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Sample records for aging affect synaptic

  1. Evolution of the aging brain transcriptome and synaptic regulation.

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    Patrick M Loerch

    Full Text Available Alzheimer's disease and other neurodegenerative disorders of aging are characterized by clinical and pathological features that are relatively specific to humans. To obtain greater insight into how brain aging has evolved, we compared age-related gene expression changes in the cortex of humans, rhesus macaques, and mice on a genome-wide scale. A small subset of gene expression changes are conserved in all three species, including robust age-dependent upregulation of the neuroprotective gene apolipoprotein D (APOD and downregulation of the synaptic cAMP signaling gene calcium/calmodulin-dependent protein kinase IV (CAMK4. However, analysis of gene ontology and cell type localization shows that humans and rhesus macaques have diverged from mice due to a dramatic increase in age-dependent repression of neuronal genes. Many of these age-regulated neuronal genes are associated with synaptic function. Notably, genes associated with GABA-ergic inhibitory function are robustly age-downregulated in humans but not in mice at the level of both mRNA and protein. Gene downregulation was not associated with overall neuronal or synaptic loss. Thus, repression of neuronal gene expression is a prominent and recently evolved feature of brain aging in humans and rhesus macaques that may alter neural networks and contribute to age-related cognitive changes.

  2. Characterizing synaptic protein development in human visual cortex enables alignment of synaptic age with rat visual cortex

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    Joshua G.A Pinto

    2015-02-01

    Full Text Available Although many potential neuroplasticity based therapies have been developed in the lab, few have translated into established clinical treatments for human neurologic or neuropsychiatric diseases. Animal models, especially of the visual system, have shaped our understanding of neuroplasticity by characterizing the mechanisms that promote neural changes and defining timing of the sensitive period. The lack of knowledge about development of synaptic plasticity mechanisms in human cortex, and about alignment of synaptic age between animals and humans, has limited translation of neuroplasticity therapies. In this study, we quantified expression of a set of highly conserved pre- and post-synaptic proteins (Synapsin, Synaptophysin, PSD-95, Gephyrin and found that synaptic development in human primary visual cortex continues into late childhood. Indeed, this is many years longer than suggested by neuroanatomical studies and points to a prolonged sensitive period for plasticity in human sensory cortex. In addition, during childhood we found waves of inter-individual variability that are different for the 4 proteins and include a stage during early development (<1 year when only Gephyrin has high inter-individual variability. We also found that pre- and post-synaptic protein balances develop quickly, suggesting that maturation of certain synaptic functions happens within the first year or two of life. A multidimensional analysis (principle component analysis showed that most of the variance was captured by the sum of the 4 synaptic proteins. We used that sum to compare development of human and rat visual cortex and identified a simple linear equation that provides robust alignment of synaptic age between humans and rats. Alignment of synaptic ages is important for age-appropriate targeting and effective translation of neuroplasticity therapies from the lab to the clinic.

  3. Characterizing synaptic protein development in human visual cortex enables alignment of synaptic age with rat visual cortex

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    Pinto, Joshua G. A.; Jones, David G.; Williams, C. Kate; Murphy, Kathryn M.

    2015-01-01

    Although many potential neuroplasticity based therapies have been developed in the lab, few have translated into established clinical treatments for human neurologic or neuropsychiatric diseases. Animal models, especially of the visual system, have shaped our understanding of neuroplasticity by characterizing the mechanisms that promote neural changes and defining timing of the sensitive period. The lack of knowledge about development of synaptic plasticity mechanisms in human cortex, and about alignment of synaptic age between animals and humans, has limited translation of neuroplasticity therapies. In this study, we quantified expression of a set of highly conserved pre- and post-synaptic proteins (Synapsin, Synaptophysin, PSD-95, Gephyrin) and found that synaptic development in human primary visual cortex (V1) continues into late childhood. Indeed, this is many years longer than suggested by neuroanatomical studies and points to a prolonged sensitive period for plasticity in human sensory cortex. In addition, during childhood we found waves of inter-individual variability that are different for the four proteins and include a stage during early development (visual cortex and identified a simple linear equation that provides robust alignment of synaptic age between humans and rats. Alignment of synaptic ages is important for age-appropriate targeting and effective translation of neuroplasticity therapies from the lab to the clinic. PMID:25729353

  4. Synaptic genes are extensively downregulated across multiple brain regions in normal human aging and Alzheimer’s disease

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    Berchtold, Nicole C.; Coleman, Paul D.; Cribbs, David H.; Rogers, Joseph; Gillen, Daniel L.; Cotman, Carl W.

    2014-01-01

    Synapses are essential for transmitting, processing, and storing information, all of which decline in aging and Alzheimer’s disease (AD). Because synapse loss only partially accounts for the cognitive declines seen in aging and AD, we hypothesized that existing synapses might undergo molecular changes that reduce their functional capacity. Microarrays were used to evaluate expression profiles of 340 synaptic genes in aging (20–99 years) and AD across 4 brain regions from 81 cases. The analysis revealed an unexpectedly large number of significant expression changes in synapse-related genes in aging, with many undergoing progressive downregulation across aging and AD. Functional classification of the genes showing altered expression revealed that multiple aspects of synaptic function are affected, notably synaptic vesicle trafficking and release, neurotransmitter receptors and receptor trafficking, postsynaptic density scaffolding, cell adhesion regulating synaptic stability, and neuromodulatory systems. The widespread declines in synaptic gene expression in normal aging suggests that function of existing synapses might be impaired, and that a common set of synaptic genes are vulnerable to change in aging and AD. PMID:23273601

  5. Role of DHA in aging-related changes in mouse brain synaptic plasma membrane proteome.

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    Sidhu, Vishaldeep K; Huang, Bill X; Desai, Abhishek; Kevala, Karl; Kim, Hee-Yong

    2016-05-01

    Aging has been related to diminished cognitive function, which could be a result of ineffective synaptic function. We have previously shown that synaptic plasma membrane proteins supporting synaptic integrity and neurotransmission were downregulated in docosahexaenoic acid (DHA)-deprived brains, suggesting an important role of DHA in synaptic function. In this study, we demonstrate aging-induced synaptic proteome changes and DHA-dependent mitigation of such changes using mass spectrometry-based protein quantitation combined with western blot or messenger RNA analysis. We found significant reduction of 15 synaptic plasma membrane proteins in aging brains including fodrin-α, synaptopodin, postsynaptic density protein 95, synaptic vesicle glycoprotein 2B, synaptosomal-associated protein 25, synaptosomal-associated protein-α, N-methyl-D-aspartate receptor subunit epsilon-2 precursor, AMPA2, AP2, VGluT1, munc18-1, dynamin-1, vesicle-associated membrane protein 2, rab3A, and EAAT1, most of which are involved in synaptic transmission. Notably, the first 9 proteins were further reduced when brain DHA was depleted by diet, indicating that DHA plays an important role in sustaining these synaptic proteins downregulated during aging. Reduction of 2 of these proteins was reversed by raising the brain DHA level by supplementing aged animals with an omega-3 fatty acid sufficient diet for 2 months. The recognition memory compromised in DHA-depleted animals was also improved. Our results suggest a potential role of DHA in alleviating aging-associated cognitive decline by offsetting the loss of neurotransmission-regulating synaptic proteins involved in synaptic function. Published by Elsevier Inc.

  6. Age-related deficits in synaptic plasticity rescued by activating PKA or PKC in sensory neurons of Aplysia californica

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    Andrew T Kempsell

    2015-09-01

    Full Text Available Brain aging is associated with declines in synaptic function that contribute to memory loss, including reduced postsynaptic response to neurotransmitters and decreased neuronal excitability. To understand how aging affects memory in a simple neural circuit, we studied neuronal proxies of memory for sensitization in mature versus advanced age Aplysia. Glutamate- (L-Glu- evoked excitatory currents were facilitated by the neuromodulator serotonin (5-HT in sensory neurons (SN isolated from mature but not aged animals. Activation of PKA and PKC signaling rescued facilitation of L-Glu currents in aged SN. Similarly, PKA and PKC activators restored increased excitability in aged tail SN. These results suggest that altered synaptic plasticity during aging involves defects in second messenger systems

  7. Age-related deficits in synaptic plasticity rescued by activating PKA or PKC in sensory neurons of Aplysia californica.

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    Kempsell, Andrew T; Fieber, Lynne A

    2015-01-01

    Brain aging is associated with declines in synaptic function that contribute to memory loss, including reduced postsynaptic response to neurotransmitters and decreased neuronal excitability. To understand how aging affects memory in a simple neural circuit, we studied neuronal proxies of memory for sensitization in mature vs. advanced age Aplysia californica (Aplysia). L-Glutamate- (L-Glu-) evoked excitatory currents were facilitated by the neuromodulator serotonin (5-HT) in sensory neurons (SN) isolated from mature but not aged animals. Activation of protein kinase A (PKA) and protein kinase C (PKC) signaling rescued facilitation of L-Glu currents in aged SN. Similarly, PKA and PKC activators restored increased excitability in aged tail SN. These results suggest that altered synaptic plasticity during aging involves defects in second messenger systems.

  8. Age-related changes in the hippocampus (loss of synaptophysin and glial-synaptic interaction) are modified by systemic treatment with an NCAM-derived peptide, FGL.

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    Ojo, Bunmi; Rezaie, Payam; Gabbott, Paul L; Davies, Heather; Colyer, Frances; Cowley, Thelma R; Lynch, Marina; Stewart, Michael G

    2012-07-01

    Altered synaptic morphology, progressive loss of synapses and glial (astrocyte and microglial) cell activation are considered as characteristic hallmarks of aging. Recent evidence suggests that there is a concomitant age-related decrease in expression of the presynaptic protein, synaptophysin, and the neuronal glycoprotein CD200, which, by interacting with its receptor, plays a role in maintaining microglia in a quiescent state. These age-related changes may be indicative of reduced neuroglial support of synapses. FG Loop (FGL) peptide synthesized from the second fibronectin type III module of neural cell adhesion molecule (NCAM), has previously been shown to attenuate age-related glial cell activation, and to 'restore' cognitive function in aged rats. The mechanisms by which FGL exerts these neuroprotective effects remain unclear, but could involve regulation of CD200, modifying glial-synaptic interactions (affecting neuroglial 'support' at synapses), or impacting directly on synaptic function. Light and electron microscopic (EM) analyses were undertaken to investigate whether systemic treatment with FGL (i) alters CD200, synaptophysin (presynaptic) and PSD-95 (postsynaptic) immunohistochemical expression levels, (ii) affects synaptic number, or (iii) exerts any effects on glial-synaptic interactions within young (4 month-old) and aged (22 month-old) rat hippocampus. Treatment with FGL attenuated the age-related loss of synaptophysin immunoreactivity (-ir) within CA3 and hilus (with no major effect on PSD-95-ir), and of CD200-ir specifically in the CA3 region. Ultrastructural morphometric analyses showed that FGL treatment (i) prevented age-related loss in astrocyte-synaptic contacts, (ii) reduced microglia-synaptic contacts in the CA3 stratum radiatum, but (iii) had no effect on the mean number of synapses in this region. These data suggest that FGL mediates its neuroprotective effects by regulating glial-synaptic interaction. Copyright © 2011 Elsevier Inc. All

  9. Age- and Sex-Dependent Impact of Repeated Social Stress on Intrinsic and Synaptic Excitability of the Rat Prefrontal Cortex.

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    Urban, Kimberly R; Valentino, Rita J

    2017-01-01

    Stress is implicated in psychiatric illnesses that are characterized by impairments in cognitive functions that are mediated by the medial prefrontal cortex (mPFC). Because sex and age determine stress vulnerability, the effects of repeated social stress occurring during early adolescence, mid-adolescence, or adulthood on the cellular properties of male and female rat mPFC Layer V neurons in vitro were examined. Repeated resident-intruder stress produced age- and sex-specific effects on mPFC intrinsic and synaptic excitability. Mid-adolescents were particularly vulnerable to effects on intrinsic excitability. The maximum number of action potentials (APs) evoked by increasing current intensity was robustly decreased in stressed male and female mid-adolescent rats compared with age-matched controls. These effects were associated with stress-induced changes in AP half-width, amplitude, threshold, and input resistance. Social stress at all ages generally decreased synaptic excitability by decreasing the amplitude of spontaneous excitatory postsynaptic potentials. The results suggest that whereas social stress throughout life can diminish the influence of afferents driving the mPFC, social stress during mid-adolescence additionally affects intrinsic characteristics of mPFC neurons that determine excitability. The depressant effects of social stress on intrinsic and synaptic mPFC neurons may underlie its ability to affect executive functions and emotional responses, particularly during adolescence. © The Author 2016. Published by Oxford University Press.

  10. Age-related synaptic loss of the medial olivocochlear efferent innervation

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    Schrader Angela

    2010-11-01

    Full Text Available Abstract Age-related functional decline of the nervous system is consistently observed, though cellular and molecular events responsible for this decline remain largely unknown. One of the most prevalent age-related functional declines is age-related hearing loss (presbycusis, a major cause of which is the loss of outer hair cells (OHCs and spiral ganglion neurons. Previous studies have also identified an age-related functional decline in the medial olivocochlear (MOC efferent system prior to age-related loss of OHCs. The present study evaluated the hypothesis that this functional decline of the MOC efferent system is due to age-related synaptic loss of the efferent innervation of the OHCs. To this end, we used a recently-identified transgenic mouse line in which the expression of yellow fluorescent protein (YFP, under the control of neuron-specific elements from the thy1 gene, permits the visualization of the synaptic connections between MOC efferent fibers and OHCs. In this model, there was a dramatic synaptic loss between the MOC efferent fibers and the OHCs in older mice. However, age-related loss of efferent synapses was independent of OHC status. These data demonstrate for the first time that age-related loss of efferent synapses may contribute to the functional decline of the MOC efferent system and that this synaptic loss is not necessary for age-related loss of OHCs.

  11. Decreased expression of vesicular glutamate transporter 1 and complexin II mRNAs in schizophrenia: further evidence for a synaptic pathology affecting glutamate neurons.

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    Eastwood, S L; Harrison, P J

    2005-03-01

    Synaptic protein gene expression is altered in schizophrenia. In the hippocampal formation there may be particular involvement of glutamatergic neurons and their synapses, but overall the profile remains unclear. In this in situ hybridization histochemistry (ISHH) study, we examined four informative synaptic protein transcripts: vesicular glutamate transporter (VGLUT) 1, VGLUT2, complexin I, and complexin II, in dorsolateral prefrontal cortex (DPFC), superior temporal cortex (STC), and hippocampal formation, in 13 subjects with schizophrenia and 18 controls. In these areas, VGLUT1 and complexin II are expressed primarily by excitatory neurons, whereas complexin I is mainly expressed by inhibitory neurons. In schizophrenia, VGLUT1 mRNA was decreased in hippocampal formation and DPFC, complexin II mRNA was reduced in DPFC and STC, and complexin I mRNA decreased in STC. Hippocampal VGLUT1 mRNA declined with age selectively in the schizophrenia group. VGLUT2 mRNA was not quantifiable due to its low level. The data provide additional evidence for a synaptic pathology in schizophrenia, in terms of a reduced expression of three synaptic protein genes. In the hippocampus, the loss of VGLUT1 mRNA supports data indicating that glutamatergic presynaptic deficits are prominent, whereas the pattern of results in temporal and frontal cortex suggests broadly similar changes may affect inhibitory and excitatory neurons. The impairment of synaptic transmission implied by the synaptic protein reductions may contribute to the dysfunction of cortical neural circuits that characterises the disorder.

  12. SYNAPTIC PLASTICITY IN THE DENTATE GYRUS OF AGED RATS IS ALTERED AFTER CHRONIC NIMODIPINE APPLICATION

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    DEJONG, GI; BUWALDA, B; SCHUURMAN, T; LUITEN, PGM

    1992-01-01

    We examined ultrastructural correlates of synaptic plasticity in the hippocampus of young (3 months) vs aged (30 months) Wistar rats and established the effects of the calcium antagonist nimodipine in animals chronically treated from 24 to 30 months. The effects of nimodipine was studied since this

  13. Low-frequency transcranial magnetic stimulation is beneficial for enhancing synaptic plasticity in the aging brain

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    Zhan-chi Zhang

    2015-01-01

    Full Text Available In the aging brain, cognitive function gradually declines and causes a progressive reduction in the structural and functional plasticity of the hippocampus. Transcranial magnetic stimulation is an emerging and novel neurological and psychiatric tool used to investigate the neurobiology of cognitive function. Recent studies have demonstrated that low-frequency transcranial magnetic stimulation (≤1 Hz ameliorates synaptic plasticity and spatial cognitive deficits in learning-impaired mice. However, the mechanisms by which this treatment improves these deficits during normal aging are still unknown. Therefore, the current study investigated the effects of transcranial magnetic stimulation on the brain-derived neurotrophic factor signal pathway, synaptic protein markers, and spatial memory behavior in the hippocampus of normal aged mice. The study also investigated the downstream regulator, Fyn kinase, and the downstream effectors, synaptophysin and growth-associated protein 43 (both synaptic markers, to determine the possible mechanisms by which transcranial magnetic stimulation regulates cognitive capacity. Transcranial magnetic stimulation with low intensity (110% average resting motor threshold intensity, 1 Hz increased mRNA and protein levels of brain-derived neurotrophic factor, tropomyosin receptor kinase B, and Fyn in the hippocampus of aged mice. The treatment also upregulated the mRNA and protein expression of synaptophysin and growth-associated protein 43 in the hippocampus of these mice. In conclusion, brain-derived neurotrophic factor signaling may play an important role in sustaining and regulating structural synaptic plasticity induced by transcranial magnetic stimulation in the hippocampus of aging mice, and Fyn may be critical during this regulation. These responses may change the structural plasticity of the aging hippocampus, thereby improving cognitive function.

  14. Low-frequency transcranial magnetic stimulation is beneficial for enhancing synaptic plasticity in the aging brain.

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    Zhang, Zhan-Chi; Luan, Feng; Xie, Chun-Yan; Geng, Dan-Dan; Wang, Yan-Yong; Ma, Jun

    2015-06-01

    In the aging brain, cognitive function gradually declines and causes a progressive reduction in the structural and functional plasticity of the hippocampus. Transcranial magnetic stimulation is an emerging and novel neurological and psychiatric tool used to investigate the neurobiology of cognitive function. Recent studies have demonstrated that low-frequency transcranial magnetic stimulation (≤1 Hz) ameliorates synaptic plasticity and spatial cognitive deficits in learning-impaired mice. However, the mechanisms by which this treatment improves these deficits during normal aging are still unknown. Therefore, the current study investigated the effects of transcranial magnetic stimulation on the brain-derived neurotrophic factor signal pathway, synaptic protein markers, and spatial memory behavior in the hippocampus of normal aged mice. The study also investigated the downstream regulator, Fyn kinase, and the downstream effectors, synaptophysin and growth-associated protein 43 (both synaptic markers), to determine the possible mechanisms by which transcranial magnetic stimulation regulates cognitive capacity. Transcranial magnetic stimulation with low intensity (110% average resting motor threshold intensity, 1 Hz) increased mRNA and protein levels of brain-derived neurotrophic factor, tropomyosin receptor kinase B, and Fyn in the hippocampus of aged mice. The treatment also upregulated the mRNA and protein expression of synaptophysin and growth-associated protein 43 in the hippocampus of these mice. In conclusion, brain-derived neurotrophic factor signaling may play an important role in sustaining and regulating structural synaptic plasticity induced by transcranial magnetic stimulation in the hippocampus of aging mice, and Fyn may be critical during this regulation. These responses may change the structural plasticity of the aging hippocampus, thereby improving cognitive function.

  15. Exocytosis of gliotransmitters from cortical astrocytes: implications for synaptic plasticity and aging.

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    Lalo, Ulyana; Rasooli-Nejad, Seyed; Pankratov, Yuriy

    2014-10-01

    Maintaining brain function during aging is very important for mental and physical health. Recent studies showed a crucial importance of communication between two major types of brain cells: neurons transmitting electrical signals, and glial cells, which maintain the well-being and function of neurons. Still, the study of age-related changes in neuron-glia signalling is far from complete. We have shown previously that cortical astrocytes are capable of releasing ATP by a quantal soluble N-ethylmaleimide-sensitive factor-attachment protein receptor (SNARE) complex-dependent mechanism. Release of ATP from cortical astrocytes can be activated via various pathways, including direct UV-uncaging of intracellular Ca²⁺ or G-protein-coupled receptors. Importantly, release of both ATP and glutamate from neocortical astrocytes was not observed in brain slices of dominant-negative SNARE (dnSNARE) mice, expressing dnSNARE domain selectively in astrocytes. We also discovered that astrocyte-driven ATP can cause significant attenuation of synaptic inhibition in the pyramidal neurons via Ca²⁺-interaction between the neuronal ATP and γ-aminobutyric acid (GABA) receptors. Furthermore, we showed that astrocyte-derived ATP can facilitate the induction of long-term potentiation of synaptic plasticity in the neocortex. Our recent data have shown that an age-related decrease in the astroglial Ca²⁺ signalling can cause a substantial decrease in the exocytosis of gliotransmitters, in particular ATP. Age-related impairment of ATP release from cortical astrocytes can cause a decrease in the extent of astroglial modulation of synaptic transmission in the neocortex and can therefore contribute to the age-related impairment of synaptic plasticity and cognitive decline. Combined, our results strongly support the physiological relevance of glial exocytosis for glia-neuron communications and brain function.

  16. Age-dependent modulation of synaptic plasticity and insulin mimetic effect of lipoic acid on a mouse model of Alzheimer's disease.

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    Harsh Sancheti

    Full Text Available Alzheimer's disease is a progressive neurodegenerative disease that entails impairments of memory, thinking and behavior and culminates into brain atrophy. Impaired glucose uptake (accumulating into energy deficits and synaptic plasticity have been shown to be affected in the early stages of Alzheimer's disease. This study examines the ability of lipoic acid to increase brain glucose uptake and lead to improvements in synaptic plasticity on a triple transgenic mouse model of Alzheimer's disease (3xTg-AD that shows progression of pathology as a function of age; two age groups: 6 months (young and 12 months (old were used in this study. 3xTg-AD mice fed 0.23% w/v lipoic acid in drinking water for 4 weeks showed an insulin mimetic effect that consisted of increased brain glucose uptake, activation of the insulin receptor substrate and of the PI3K/Akt signaling pathway. Lipoic acid supplementation led to important changes in synaptic function as shown by increased input/output (I/O and long term potentiation (LTP (measured by electrophysiology. Lipoic acid was more effective in stimulating an insulin-like effect and reversing the impaired synaptic plasticity in the old mice, wherein the impairment of insulin signaling and synaptic plasticity was more pronounced than those in young mice.

  17. Characterizing synaptic protein development in human visual cortex enables alignment of synaptic age with rat visual cortex

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    Pinto, Joshua G. A.; Jones, David G.; Williams, C. Kate; Murphy, Kathryn M.

    2015-01-01

    Although many potential neuroplasticity based therapies have been developed in the lab, few have translated into established clinical treatments for human neurologic or neuropsychiatric diseases. Animal models, especially of the visual system, have shaped our understanding of neuroplasticity by characterizing the mechanisms that promote neural changes and defining timing of the sensitive period. The lack of knowledge about development of synaptic plasticity mechanisms in human cortex, and abo...

  18. Characterizing synaptic protein development in human visual cortex enables alignment of synaptic age with rat visual cortex

    OpenAIRE

    Joshua G.A Pinto; David G Jones; Kate eWilliams; Kathryn M Murphy; Kathryn M Murphy

    2015-01-01

    Although many potential neuroplasticity based therapies have been developed in the lab, few have translated into established clinical treatments for human neurologic or neuropsychiatric diseases. Animal models, especially of the visual system, have shaped our understanding of neuroplasticity by characterizing the mechanisms that promote neural changes and defining timing of the sensitive period. The lack of knowledge about development of synaptic plasticity mechanisms in human cortex, and a...

  19. ERK pathway activation bidirectionally affects visual recognition memory and synaptic plasticity in the perirhinal cortex

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    Davide eSilingardi

    2011-12-01

    Full Text Available ERK 1,2 pathway mediates experience-dependent gene transcription in neurons and several studies have identified its pivotal role in experience-dependent synaptic plasticity and in forms of long term memory involving hippocampus, amygdala or striatum. The perirhinal cortex (PRHC plays an essential role in familiarity-based object recognition memory. It is still unknown whether ERK activation in PRHC is necessary for recognition memory consolidation. Most important, it is unknown whether by modulating the gain of the ERK pathway it is possible to bidirectionally affect visual recognition memory and PRHC synaptic plasticity.We have first pharmacologically blocked ERK activation in the PRHC of adult mice and found that this was sufficient to impair long term recognition memory in a familiarity-based task, the Object Recognition Task (ORT. We have then tested performance in the ORT in Ras-GRF1 knock-out (KO mice, which exhibit a reduced activation of ERK by neuronal activity, and in ERK1 KO mice, which have an increased activation of ERK2 and exhibit enhanced striatal plasticity and striatal mediated memory. We found that Ras-GRF1 KO mice have normal short-term memory but display a long term memory deficit; memory reconsolidation is also impaired. On the contrary, ERK1 KO mice exhibit a better performance than WT mice at 72 hour retention interval, suggesting a longer lasting recognition memory. In parallel with behavioural data, LTD was strongly reduced and LTP was significantly smaller in PRHC slices from Ras-GRF1 KO than in WT mice while enhanced LTP and LTD were found in PRHC slices from ERK1 KO mice.

  20. Loss of catecholaminergic neuromodulation of persistent forms of hippocampal synaptic plasticity with increasing age

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    Hannah Twarkowski

    2016-09-01

    Full Text Available Neuromodulation by means of the catecholaminergic system is a key component of motivation-driven learning and behaviorally modulated hippocampal synaptic plasticity. In particular, dopamine acting on D1/D5 receptors and noradrenaline acting on beta-adrenergic receptors exert a very potent regulation of forms of hippocampal synaptic plasticity that last for very long-periods of time (>24h, and occur in conjunction with novel spatial learning. Antagonism of these receptors not only prevents long-term potentiation (LTP and long-term depression (LTD, but prevents the memory of the spatial event that, under normal circumstances, leads to the perpetuation of these plasticity forms. Spatial learning behavior that normally comes easily to rats, such as object-place learning and spatial reference learning, becomes increasingly impaired with aging. Middle-aged animals display aging-related deficits of specific, but not all, components of spatial learning, and one possibility is that this initial manifestation of decrements in learning ability that become manifest in middle-age relate to changes in motivation, attention and/or the regulation by neuromodulatory systems of these behavioral states.Here, we compared the regulation by dopaminergic D1/D5 and beta-adrenergic receptors of persistent LTP in young (2-4 month old and middle-aged (8-14 month old rats. We observed in young rats, that weak potentiation that typically lasts for ca. 2h could be strengthened into persistent (>24h LTP by pharmacological activation of either D1/D5 or beta-adrenergic receptors. By contrast, no such facilitation occurred in middle-aged rats. This difference was not related to an ostensible learning deficit: a facilitation of weak potentiation into LTP by spatial learning was possible both in young and middle-aged rats. It was also not directly linked to deficits in LTP: strong afferent stimulation resulted in equivalent LTP in both age groups. We postulate that this change in

  1. The Role of GluK4 in Synaptic Plasticity and Affective Behavior in Mice

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    Catches, Justin Samuel

    Kainate receptors (KARs) are glutamate-gated ion channels that signal through both ionotropic and metabotropic pathways (Contractor et al., 2011). Combinations of five KAR subunits (GluK1-5) form tetrameric receptors with GluK1, GluK2, and GluK3 able to form functional homomeric channels. The high-affinity subunits, GluK4 and GluK5, do not form homomeric channels but modify the properties of heteromeric receptors. Expression of the GluK4 receptor subunit in the forebrain is restricted to the CA3 region of the hippocampus and dentate gyrus regions where KARs modulate synaptic plasticity. In this study, ablation of Grik4, which encodes GluK4, in mice reduced KAR synaptic currents and altered activation properties of postsynaptic receptors but left two forms of presynaptic short-term plasticity intact. Disruption of both Grik4 and Grik5 caused complete loss of the postsynaptic ionotropic KAR current and impaired presynaptic frequency facilitation. Additionally, KAR surface expression was altered at pre- and postsynaptic sites at the MF synapse. Despite the loss of ionotropic signaling, KAR-mediated inhibition of the slow afterhyperpolarization current, which is dependent on metabotropic signaling, was intact in CA3 neurons. Long-term potentiation at the MF-CA3 synapse was reduced, likely through a loss of KAR modulation of excitability of the presynaptic MF axons. Genetic variants in the human GRIK4 gene alter the susceptibility for affective disorders (Bloss and Hunter, 2010). We found that ablation of Grik4 in mice resulted in reduced anxiety and an antidepressant-like phenotype. In the elevated zero-maze, a test for anxiety and risk taking behavior, and in two anxiogenic tests, marble-burying and novelty-induced suppression of feeding, anxiety-like behavior was consistently reduced in knockout animals. In the forced swim, a test of learned helplessness used to determine depression-like behavior, knockout mice demonstrated significantly less immobility suggesting

  2. Enhancement of learning capacity and cholinergic synaptic function by carnitine in aging rats.

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    Ando, S; Tadenuma, T; Tanaka, Y; Fukui, F; Kobayashi, S; Ohashi, Y; Kawabata, T

    2001-10-15

    The effects of a carnitine derivative, acetyl-L-carnitine (ALCAR), on the cognitive and cholinergic activities of aging rats were examined. Rats were given ALCAR (100 mg/kg) per os for 3 months and were subjected to the Hebb-Williams tasks and a new maze task, AKON-1, to assess their learning capacity. The learning capacity of the ALCAR-treated group was superior to that of the control. Cholinergic activities were determined with synaptosomes isolated from the cortices. The high-affinity choline uptake by synaptosomes, acetylcholine synthesis in synaptosomes, and acetylcholine release from synaptosomes on membrane depolarization were all enhanced in the ALCAR group. This study indicates that chronic administration of ALCAR increases cholinergic synaptic transmission and consequently enhances learning capacity as a cognitive function in aging rats. Copyright 2001 Wiley-Liss, Inc.

  3. Chelation of hippocampal zinc enhances long-term potentiation and synaptic tagging/capture in CA1 pyramidal neurons of aged rats: implications to aging and memory.

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    Shetty, Mahesh Shivarama; Sharma, Mahima; Sajikumar, Sreedharan

    2017-02-01

    Aging is associated with decline in cognitive functions, prominently in the memory consolidation and association capabilities. Hippocampus plays a crucial role in the formation and maintenance of long-term associative memories, and a significant body of evidence shows that impairments in hippocampal function correlate with aging-related memory loss. A number of studies have implicated alterations in hippocampal synaptic plasticity, such as long-term potentiation (LTP), in age-related cognitive decline although exact mechanisms underlying are not completely clear. Zinc deficiency and the resultant adverse effects on cognition have been well studied. However, the role of excess of zinc in synaptic plasticity, especially in aging, is not addressed well. Here, we have investigated the hippocampal zinc levels and the impairments in synaptic plasticity, such as LTP and synaptic tagging and capture (STC), in the CA1 region of acute hippocampal slices from 82- to 84-week-old male Wistar rats. We report increased zinc levels in the hippocampus of aged rats and also deficits in the tetani-induced and dopaminergic agonist-induced late-LTP and STC. The observed deficits in synaptic plasticity were restored upon chelation of zinc using a cell-permeable chelator. These data suggest that functional plasticity and associativity can be successfully established in aged neural networks by chelating zinc with cell-permeable chelating agents. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  4. The perimenopausal aging transition in the female rat brain: decline in bioenergetic systems and synaptic plasticity.

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    Yin, Fei; Yao, Jia; Sancheti, Harsh; Feng, Tao; Melcangi, Roberto C; Morgan, Todd E; Finch, Caleb E; Pike, Christian J; Mack, Wendy J; Cadenas, Enrique; Brinton, Roberta D

    2015-07-01

    The perimenopause is an aging transition unique to the female that leads to reproductive senescence which can be characterized by multiple neurological symptoms. To better understand potential underlying mechanisms of neurological symptoms of perimenopause, the present study determined genomic, biochemical, brain metabolic, and electrophysiological transformations that occur during this transition using a rat model recapitulating fundamental characteristics of the human perimenopause. Gene expression analyses indicated two distinct aging programs: chronological and endocrine. A critical period emerged during the endocrine transition from regular to irregular cycling characterized by decline in bioenergetic gene expression, confirmed by deficits in fluorodeoxyglucose-positron emission tomography (FDG-PET) brain metabolism, mitochondrial function, and long-term potentiation. Bioinformatic analysis predicted insulin/insulin-like growth factor 1 and adenosine monophosphate-activated protein kinase/peroxisome proliferator-activated receptor gamma coactivator 1 alpha (AMPK/PGC1α) signaling pathways as upstream regulators. Onset of acyclicity was accompanied by a rise in genes required for fatty acid metabolism, inflammation, and mitochondrial function. Subsequent chronological aging resulted in decline of genes required for mitochondrial function and β-amyloid degradation. Emergence of glucose hypometabolism and impaired synaptic function in brain provide plausible mechanisms of neurological symptoms of perimenopause and may be predictive of later-life vulnerability to hypometabolic conditions such as Alzheimer's. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Lack of paternal care affects synaptic development in the anterior cingulate cortex.

    Science.gov (United States)

    Ovtscharoff, Wladimir; Helmeke, Carina; Braun, Katharina

    2006-10-20

    Exposure to enriched or impoverished environmental conditions, experience and learning are factors which influence brain development, and it has been shown that neonatal emotional experience significantly interferes with the synaptic development of higher associative forebrain areas. Here, we analyzed the impact of paternal care, i.e. the father's emotional contribution towards his offspring, on the synaptic development of the anterior cingulate cortex. Our light and electron microscopic comparison of biparentally raised control animals and animals which were raised in single-mother families revealed no significant differences in spine densities on the apical dendrites of layer II/III pyramidal neurons and of asymmetric and symmetric spine synapses. However, significantly reduced densities (-33%) of symmetric shaft synapses were found in layer II of the fatherless animals compared to controls. This finding indicates an imbalance between excitatory and inhibitory synapses in the anterior cingulate cortex of father-deprived animals. Our results query the general assumption that a father has less impact on the synaptic maturation of his offspring's brain than the mother.

  6. Inhibition of protein kinase C affects on mode of synaptic vesicle exocytosis due to cholesterol depletion

    Energy Technology Data Exchange (ETDEWEB)

    Petrov, Alexey M., E-mail: fysio@rambler.ru; Zakyrjanova, Guzalija F., E-mail: guzik121192@mail.ru; Yakovleva, Anastasia A., E-mail: nastya1234qwer@mail.ru; Zefirov, Andrei L., E-mail: zefiroval@rambler.ru

    2015-01-02

    Highlights: • We examine the involvement of PKC in MCD induced synaptic vesicle exocytosis. • PKC inhibitor does not decrease the effect MCD on MEPP frequency. • PKC inhibitor prevents MCD induced FM1-43 unloading. • PKC activation may switch MCD induced exocytosis from kiss-and-run to a full mode. • Inhibition of phospholipase C does not lead to similar change in exocytosis. - Abstract: Previous studies demonstrated that depletion of membrane cholesterol by 10 mM methyl-beta-cyclodextrin (MCD) results in increased spontaneous exocytosis at both peripheral and central synapses. Here, we investigated the role of protein kinase C in the enhancement of spontaneous exocytosis at frog motor nerve terminals after cholesterol depletion using electrophysiological and optical methods. Inhibition of the protein kinase C by myristoylated peptide and chelerythrine chloride prevented MCD-induced increases in FM1-43 unloading, whereas the frequency of spontaneous postsynaptic events remained enhanced. The increase in FM1-43 unloading still could be observed if sulforhodamine 101 (the water soluble FM1-43 quencher that can pass through the fusion pore) was added to the extracellular solution. This suggests a possibility that exocytosis of synaptic vesicles under these conditions could occur through the kiss-and-run mechanism with the formation of a transient fusion pore. Inhibition of phospholipase C did not lead to similar change in MCD-induced exocytosis.

  7. The BDNF val-66-met Polymorphism Affects Neuronal Morphology and Synaptic Transmission in Cultured Hippocampal Neurons from Rett Syndrome Mice

    Directory of Open Access Journals (Sweden)

    Xin Xu

    2017-07-01

    Full Text Available Brain-derived neurotrophic factor (Bdnf has been implicated in several neurological disorders including Rett syndrome (RTT, an X-linked neurodevelopmental disorder caused by loss-of-function mutations in the transcriptional modulator methyl-CpG-binding protein 2 (MECP2. The human BDNF gene has a single nucleotide polymorphism (SNP—a methionine (met substitution for valine (val at codon 66—that affects BDNF’s trafficking and activity-dependent release and results in cognitive dysfunction. Humans that are carriers of the met-BDNF allele have subclinical memory deficits and reduced hippocampal volume and activation. It is still unclear whether this BDNF SNP affects the clinical outcome of RTT individuals. To evaluate whether this BDNF SNP contributes to RTT pathophysiology, we examined the consequences of expression of either val-BDNF or met-BDNF on dendrite and dendritic spine morphology, and synaptic function in cultured hippocampal neurons from wildtype (WT and Mecp2 knockout (KO mice. Our findings revealed that met-BDNF does not increase dendritic growth and branching, dendritic spine density and individual spine volume, and the number of excitatory synapses in WT neurons, as val-BDNF does. Furthermore, met-BDNF reduces dendritic complexity, dendritic spine volume and quantal excitatory synaptic transmission in Mecp2 KO neurons. These results suggest that the val-BDNF variant contributes to RTT pathophysiology, and that BDNF-based therapies should take into consideration the BDNF genotype of the RTT individuals.

  8. Age dependence of the rapid antidepressant and synaptic effects of acute NMDA receptor blockade

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    Elena eNosyreva

    2014-12-01

    Full Text Available Ketamine is a NMDA receptor antagonist that produces rapid antidepressant responses in individuals with major depressive disorder. The antidepressant action of ketamine has been linked to blocking NMDA receptor activation at rest, which inhibits eukaryotic elongation factor2 kinase leading to desuppression of protein synthesis and synaptic potentiation in the CA1 region of the hippocampus. Here, we investigated ketamine mediated antidepressant response and the resulting synaptic potentiation in juvenile animals. We found that ketamine did not produce an antidepressant response in juvenile animals in the novelty suppressed feeding or the forced swim test. In addition ketamine application failed to trigger synaptic potentiation in hippocampal slices obtained from juvenile animals, unlike its action in slices from older animals (6-9 weeks old. The inability of ketamine to trigger an antidepressant response or subsequent synaptic plasticity processes suggests a developmental component to ketamine mediated antidepressant efficacy. We also show that the NMDAR antagonist AP5 triggers synaptic potentiation in mature hippocampus similar to the action of ketamine, demonstrating that global competitive blockade of NMDA receptors is sufficient to trigger this effect. These findings suggest that global blockade of NMDA receptors in developmentally mature hippocampal synapses are required for the antidepressant efficacy of ketamine.

  9. Heart Disease Affects Women of All Ages

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues Heart Disease Affects Women of All Ages Past Issues / Winter ... weeks of a heart attack. For Women with Heart Disease: About 6 million American women have coronary heart ...

  10. Cognition and Synaptic-Plasticity Related Changes in Aged Rats Supplemented with 8- and 10-Carbon Medium Chain Triglycerides.

    Directory of Open Access Journals (Sweden)

    Dongmei Wang

    Full Text Available Brain glucose hypometabolism is a common feature of Alzheimer's disease (AD. Previous studies have shown that cognition is improved by providing AD patients with an alternate energy source: ketones derived from either ketogenic diet or supplementation with medium chain triglycerides (MCT. Recently, data on the neuroprotective capacity of MCT-derived medium chain fatty acids (MCFA suggest 8-carbon and 10-carbon MCFA may have cognition-enhancing properties which are not related to ketone production. We investigated the effect of 8 week treatment with MCT8, MCT10 or sunflower oil supplementation (5% by weight of chow diet in 21 month old Wistar rats. Both MCT diets increased ketones plasma similarly compared to control diet, but MCT diets did not increase ketones in the brain. Treatment with MCT10, but not MCT8, significantly improved novel object recognition memory compared to control diet, while social recognition increased in both MCT groups. MCT8 and MCT10 diets decreased weight compared to control diet, where MCFA plasma levels were higher in MCT10 groups than in MCT8 groups. Both MCT diets increased IRS-1 (612 phosphorylation and decreased S6K phosphorylation (240/244 but only MCT10 increased Akt phosphorylation (473. MCT8 supplementation increased synaptophysin, but not PSD-95, in contrast MCT10 had no effect on either synaptic marker. Expression of Ube3a, which controls synaptic stability, was increased by both MCT diets. Cortex transcription via qPCR showed that immediate early genes related to synaptic plasticity (arc, plk3, junb, egr2, nr4a1 were downregulated by both MCT diets while MCT8 additionally down-regulated fosb and egr1 but upregulated grin1 and gba2. These results demonstrate that treatment of 8- and 10-carbon length MCTs in aged rats have slight differential effects on synaptic stability, protein synthesis and behavior that may be independent of brain ketone levels.

  11. Immune dysregulation and cognitive vulnerability in the aging brain: Interactions of microglia, IL-1β, BDNF and synaptic plasticity.

    Science.gov (United States)

    Patterson, Susan L

    2015-09-01

    Older individuals often experience declines in cognitive function after events (e.g. infection, or injury) that trigger activation of the immune system. This occurs at least in part because aging sensitizes the response of microglia (the brain's resident immune cells) to signals triggered by an immune challenge. In the aging brain, microglia respond to these signals by producing more pro-inflammatory cytokines (e.g. interleukin-1beta or IL-1β) and producing them for longer than microglia in younger brains. This exaggerated inflammatory response can compromise processes critical for optimal cognitive functioning. Interleukin-1β is central to the inflammatory response and is a key mediator and modulator of an array of associated biological functions; thus its production and release is usually very tightly regulated. This review will focus on the impact of dysregulated production of IL-1β on hippocampus dependent-memory systems and associated synaptic plasticity processes. The neurotrophin brain-derived neurotrophic factor (BNDF) helps to protect neurons from damage caused by infection or injury, and it plays a critical role in many of the same memory and hippocampal plasticity processes compromised by dysregulated production of IL-1β. This suggests that an exaggerated brain inflammatory response, arising from aging and a secondary immune challenge, may erode the capacity to provide the BDNF needed for memory-related plasticity processes at hippocampal synapses. This article is part of a Special Issue entitled 'Neuroimmunology and Synaptic Function'. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. SAD-B kinase regulates pre-synaptic vesicular dynamics at hippocampal Schaffer collateral synapses and affects contextual fear memory.

    Science.gov (United States)

    Watabe, Ayako M; Nagase, Masashi; Hagiwara, Akari; Hida, Yamato; Tsuji, Megumi; Ochiai, Toshitaka; Kato, Fusao; Ohtsuka, Toshihisa

    2016-01-01

    Synapses of amphids defective (SAD)-A/B kinases control various steps in neuronal development and differentiation, such as axon specifications and maturation in central and peripheral nervous systems. At mature pre-synaptic terminals, SAD-B is associated with synaptic vesicles and the active zone cytomatrix; however, how SAD-B regulates neurotransmission and synaptic plasticity in vivo remains unclear. Thus, we used SAD-B knockout (KO) mice to study the function of this pre-synaptic kinase in the brain. We found that the paired-pulse ratio was significantly enhanced at Shaffer collateral synapses in the hippocampal CA1 region in SAD-B KO mice compared with wild-type littermates. We also found that the frequency of the miniature excitatory post-synaptic current was decreased in SAD-B KO mice. Moreover, synaptic depression following prolonged low-frequency synaptic stimulation was significantly enhanced in SAD-B KO mice. These results suggest that SAD-B kinase regulates vesicular release probability at pre-synaptic terminals and is involved in vesicular trafficking and/or regulation of the readily releasable pool size. Finally, we found that hippocampus-dependent contextual fear learning was significantly impaired in SAD-B KO mice. These observations suggest that SAD-B kinase plays pivotal roles in controlling vesicular release properties and regulating hippocampal function in the mature brain. Synapses of amphids defective (SAD)-A/B kinases control various steps in neuronal development and differentiation, but their roles in mature brains were only partially known. Here, we demonstrated, at mature pre-synaptic terminals, that SAD-B regulates vesicular release probability and synaptic plasticity. Moreover, hippocampus-dependent contextual fear learning was significantly impaired in SAD-B KO mice, suggesting that SAD-B kinase plays pivotal roles in controlling vesicular release properties and regulating hippocampal function in the mature brain. © 2015 International

  13. Age-Related Gene Expression in the Frontal Cortex Suggests Synaptic Function Changes in Specific Inhibitory Neuron Subtypes

    Directory of Open Access Journals (Sweden)

    Leon French

    2017-05-01

    Full Text Available Genome-wide expression profiling of the human brain has revealed genes that are differentially expressed across the lifespan. Characterizing these genes adds to our understanding of both normal functions and pathological conditions. Additionally, the specific cell-types that contribute to the motor, sensory and cognitive declines during aging are unclear. Here we test if age-related genes show higher expression in specific neural cell types. Our study leverages data from two sources of murine single-cell expression data and two sources of age-associations from large gene expression studies of postmortem human brain. We used nonparametric gene set analysis to test for age-related enrichment of genes associated with specific cell-types; we also restricted our analyses to specific gene ontology groups. Our analyses focused on a primary pair of single-cell expression data from the mouse visual cortex and age-related human post-mortem gene expression information from the orbitofrontal cortex. Additional pairings that used data from the hippocampus, prefrontal cortex, somatosensory cortex and blood were used to validate and test specificity of our findings. We found robust age-related up-regulation of genes that are highly expressed in oligodendrocytes and astrocytes, while genes highly expressed in layer 2/3 glutamatergic neurons were down-regulated across age. Genes not specific to any neural cell type were also down-regulated, possibly due to the bulk tissue source of the age-related genes. A gene ontology-driven dissection of the cell-type enriched genes highlighted the strong down-regulation of genes involved in synaptic transmission and cell-cell signaling in the Somatostatin (Sst neuron subtype that expresses the cyclin dependent kinase 6 (Cdk6 and in the vasoactive intestinal peptide (Vip neuron subtype expressing myosin binding protein C, slow type (Mybpc1. These findings provide new insights into cell specific susceptibility to normal aging

  14. Mid-life environmental enrichment increases synaptic density in CA1 in a mouse model of Aβ-associated pathology and positively influences synaptic and cognitive health in healthy ageing.

    Science.gov (United States)

    Stuart, Kimberley E; King, Anna E; Fernandez-Martos, Carmen M; Dittmann, Justin; Summers, Mathew J; Vickers, James C

    2017-06-01

    Early-life cognitive enrichment may reduce the risk of experiencing cognitive deterioration and dementia in later-life. However, an intervention to prevent or delay dementia is likely to be taken up in mid to later-life. Hence, we investigated the effects of environmental enrichment in wildtype mice and in a mouse model of Aβ neuropathology (APP SWE /PS1 dE9 ) from 6 months of age. After 6 months of housing in standard laboratory cages, APP SWE /PS1 dE9 (n = 27) and healthy wildtype (n = 21) mice were randomly assigned to either enriched or standard housing. At 12 months of age, wildtype mice showed altered synaptic protein levels and relatively superior cognitive performance afforded by environmental enrichment. Environmental enrichment was not associated with alterations to Aβ plaque pathology in the neocortex or hippocampus of APP SWE /PS1 dE9 mice. However, a significant increase in synaptophysin immunolabeled puncta in the hippocampal subregion, CA1, in APP SWE /PS1 dE9 mice was detected, with no significant synaptic density changes observed in CA3, or the Fr2 region of the prefrontal cortex. Moreover, a significant increase in hippocampal BDNF was detected in APP SWE /PS1 dE9 mice exposed to EE, however, no changes were detected in neocortex or between Wt animals. These results demonstrate that mid to later-life cognitive enrichment has the potential to promote synaptic and cognitive health in ageing, and to enhance compensatory capacity for synaptic connectivity in pathological ageing associated with Aβ deposition. © 2017 Wiley Periodicals, Inc.

  15. Reduced Levels of the Synaptic Functional Regulator FMRP in Dentate Gyrus of the Aging Sprague-Dawley Rat

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    Roman Smidak

    2017-11-01

    Full Text Available Fragile X mental retardation protein (FMRP encoded by Fragile X mental retardation 1 (FMR1 gene is a RNA-binding regulator of mRNA translation, transport and stability with multiple targets responsible for proper synaptic function. Epigenetic silencing of FMR1 gene expression leads to the development of Fragile X syndrome (FXS that is characterized by intellectual disability and other behavioral problems including autism. In the rat FXS model, the lack of FMRP caused a deficit in hippocampal-dependent memory. However, the hippocampal changes of FMRP in aging rats are not fully elucidated. The current study addresses the changes in FMRP levels in dentate gyrus (DG from young (17 weeks and aging (22 months Sprague – Dawley rats. The aging animal group showed significant decline in spatial reference memory. Protein samples from five rats per each group were analyzed by quantitative proteomic analysis resulting in 153 significantly changed proteins. FMRP showed significant reduction in aging animals which was confirmed by immunoblotting and immunofluorescence microscopy. Furthermore, bioinformatic analysis of the differential protein dataset revealed several functionally related protein groups with individual interactions with FMRP. These include high representation of the RNA translation and processing machinery connected to FMRP and other RNA-binding regulators including CAPRIN1, the members of Pumilio (PUM and CUG-BP, Elav-like (CELF family, and YTH N(6-methyladenosine RNA-binding proteins (YTHDF. The results of the current study point to the important role of FMRP and regulation of RNA processing in the rat DG and memory decline during the aging process.

  16. VSNL1 Co-expression networks in aging include calcium signaling, synaptic plasticity, and Alzheimer’s disease pathways

    Directory of Open Access Journals (Sweden)

    C W Lin

    2015-03-01

    Full Text Available The Visinin-like 1 (VSNL1 gene encodes Visinin-like protein 1, a peripheral biomarker for Alzheimer disease (AD. Little is known, however, about normal VSNL1 expression in brain and the biologic networks in which it participates. Frontal cortex gray matter from 209 subjects without neurodegenerative or psychiatric illness, ranging in age from 16–91, were processed on Affymetrix GeneChip 1.1 ST and Human SNP Array 6.0. VSNL1 expression was unaffected by age and sex, and not significantly associated with SNPs in cis or trans. VSNL1 was significantly co-expressed with genes in pathways for Calcium Signaling, AD, Long Term Potentiation, Long Term Depression, and Trafficking of AMPA Receptors. The association with AD was driven, in part, by correlation with amyloid precursor protein (APP expression. These findings provide an unbiased link between VSNL1 and molecular mechanisms of AD, including pathways implicated in synaptic pathology in AD. Whether APP may drive increased VSNL1 expression, VSNL1 drives increased APP expression, or both are downstream of common pathogenic regulators will need to be evaluated in model systems.

  17. Pulmonary Function Affects Language Performance in Aging

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    Lewina O Lee

    2014-04-01

    associated with better ES performance (B = 6.64, SE = 2.43, p = .01. Higher FVC and FEV1 were related to better MN performance, but this did not reach statistical significance (FVC: B = 3.68, SE = 2.16, p = .09; FEV1: B = 4.92, SE = 2.64, p = .06. Higher FVC (B = 3.98, SE = 1.44, p = .01 and FEV1 (B = 4.79, SE = 1.75, p = .01 were associated with better ANT performance. The positive association between PF and BNT performance was marginally significant (FVC: B = 4.19, SE = 2.18, p = .06; FEV1: B = 3.51, SE = 2.66, p = .10. Discussion and Conclusion Better PF was associated with higher accuracy on sentence processing and naming-based lexical retrieval tasks, consistent with the conclusion that pulmonary function affects older adults’ language performance. Our findings support the emerging thesis that language changes in aging are influenced by health-related physiological and neural mechanisms (e.g., Albert et al., 2009; Cahana-Amitay et al., 2013. From a clinical perspective, these findings highlight the promise of targeting PF as an intervention for improving language abilities among the elderly.

  18. Low Calorie Diet Affects Aging-Related Factors

    Science.gov (United States)

    ... Current Issue Past Issues Research News From NIH Low Calorie Diet Affects Aging-Related Factors Past Issues / ... to learn more about the effects of sustained low-calorie diets in humans on factors affecting aging. ...

  19. The Networks of Genes Encoding Palmitoylated Proteins in Axonal and Synaptic Compartments Are Affected in PPT1 Overexpressing Neuronal-Like Cells

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    Francesco Pezzini

    2017-08-01

    Full Text Available CLN1 disease (OMIM #256730 is an early childhood ceroid-lipofuscinosis associated with mutated CLN1, whose product Palmitoyl-Protein Thioesterase 1 (PPT1 is a lysosomal enzyme involved in the removal of palmitate residues from S-acylated proteins. In neurons, PPT1 expression is also linked to synaptic compartments. The aim of this study was to unravel molecular signatures connected to CLN1. We utilized SH-SY5Y neuroblastoma cells overexpressing wild type CLN1 (SH-p.wtCLN1 and five selected CLN1 patients’ mutations. The cellular distribution of wtPPT1 was consistent with regular processing of endogenous protein, partially detected inside Lysosomal Associated Membrane Protein 2 (LAMP2 positive vesicles, while the mutants displayed more diffuse cytoplasmic pattern. Transcriptomic profiling revealed 802 differentially expressed genes (DEGs in SH-p.wtCLN1 (as compared to empty-vector transfected cells, whereas the number of DEGs detected in the two mutants (p.L222P and p.M57Nfs*45 was significantly lower. Bioinformatic scrutiny linked DEGs with neurite formation and neuronal transmission. Specifically, neuritogenesis and proliferation of neuronal processes were predicted to be hampered in the wtCLN1 overexpressing cell line, and these findings were corroborated by morphological investigations. Palmitoylation survey identified 113 palmitoylated protein-encoding genes in SH-p.wtCLN1, including 25 ones simultaneously assigned to axonal growth and synaptic compartments. A remarkable decrease in the expression of palmitoylated proteins, functionally related to axonal elongation (GAP43, CRMP1 and NEFM and of the synaptic marker SNAP25, specifically in SH-p.wtCLN1 cells was confirmed by immunoblotting. Subsequent, bioinformatic network survey of DEGs assigned to the synaptic annotations linked 81 DEGs, including 23 ones encoding for palmitoylated proteins. Results obtained in this experimental setting outlined two affected functional modules (connected to

  20. Age-Related Alterations in the Expression of Genes and Synaptic Plasticity Associated with Nitric Oxide Signaling in the Mouse Dorsal Striatum

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    Aisa N. Chepkova

    2015-01-01

    Full Text Available Age-related alterations in the expression of genes and corticostriatal synaptic plasticity were studied in the dorsal striatum of mice of four age groups from young (2-3 months old to old (18–24 months of age animals. A significant decrease in transcripts encoding neuronal nitric oxide (NO synthase and receptors involved in its activation (NR1 subunit of the glutamate NMDA receptor and D1 dopamine receptor was found in the striatum of old mice using gene array and real-time RT-PCR analysis. The old striatum showed also a significantly higher number of GFAP-expressing astrocytes and an increased expression of astroglial, inflammatory, and oxidative stress markers. Field potential recordings from striatal slices revealed age-related alterations in the magnitude and dynamics of electrically induced long-term depression (LTD and significant enhancement of electrically induced long-term potentiation in the middle-aged striatum (6-7 and 12-13 months of age. Corticostriatal NO-dependent LTD induced by pharmacological activation of group I metabotropic glutamate receptors underwent significant reduction with aging and could be restored by inhibition of cGMP hydrolysis indicating that its age-related deficit is caused by an altered NO-cGMP signaling cascade. It is suggested that age-related alterations in corticostriatal synaptic plasticity may result from functional alterations in receptor-activated signaling cascades associated with increasing neuroinflammation and a prooxidant state.

  1. Age Learning Factors Affecting Pilot Education.

    Science.gov (United States)

    Torbert, Brison

    This document, intended for pilot education and flight safety specialists, consists chiefly of a review of the literature on physiological factors that affect pilot education and an examination of environmental factors that should be scrutinized in order to improve the effectiveness of aviation learning facilities. The physiological factors…

  2. Citalopram Ameliorates Synaptic Plasticity Deficits in Different Cognition-Associated Brain Regions Induced by Social Isolation in Middle-Aged Rats.

    Science.gov (United States)

    Gong, Wei-Gang; Wang, Yan-Juan; Zhou, Hong; Li, Xiao-Li; Bai, Feng; Ren, Qing-Guo; Zhang, Zhi-Jun

    2017-04-01

    Our previous experiments demonstrated that social isolation (SI) caused AD-like tau hyperphosphorylation and spatial memory deficits in middle-aged rats. However, the underlying mechanisms of SI-induced spatial memory deficits remain elusive. Middle-aged rats (10 months) were group or isolation reared for 8 weeks. Following the initial 4-week period of rearing, citalopram (10 mg/kg i.p.) was administered for 28 days. Then, pathophysiological changes were assessed by performing behavioral, biochemical, and pathological analyses. We found that SI could cause cognitive dysfunction and decrease synaptic protein (synaptophysin or PSD93) expression in different brain regions associated with cognition, such as the prefrontal cortex, dorsal hippocampus, ventral hippocampus, amygdala, and caudal putamen, but not in the entorhinal cortex or posterior cingulate. Citalopram could significantly improve learning and memory and partially restore synaptophysin or PSD93 expression in the prefrontal cortex, hippocampus, and amygdala in SI rats. Moreover, SI decreased the number of dendritic spines in the prefrontal cortex, dorsal hippocampus, and ventral hippocampus, which could be reversed by citalopram. Furthermore, SI reduced the levels of BDNF, serine-473-phosphorylated Akt (active form), and serine-9-phosphorylated GSK-3β (inactive form) with no significant changes in the levels of total GSK-3β and Akt in the dorsal hippocampus, but not in the posterior cingulate. Our results suggest that decreased synaptic plasticity in cognition-associated regions might contribute to SI-induced cognitive deficits, and citalopram could ameliorate these deficits by promoting synaptic plasticity mainly in the prefrontal cortex, dorsal hippocampus, and ventral hippocampus. The BDNF/Akt/GSK-3β pathway plays an important role in regulating synaptic plasticity in SI rats.

  3. Age and disability affect dietary intake.

    Science.gov (United States)

    Bartali, Benedetta; Salvini, Simonetta; Turrini, Aida; Lauretani, Fulvio; Russo, Cosimo R; Corsi, Anna M; Bandinelli, Stefania; D'Amicis, Amleto; Palli, Domenico; Guralnik, Jack M; Ferrucci, Luigi

    2003-09-01

    The purpose of the study was to provide information on dietary intake in the InCHIANTI study population, a representative sample (n = 1453) of persons living in two towns of Tuscany (Italy), including a large number of old and very old individuals (79.5% >65 y old). We also investigated whether difficulties in nutrition-related activities were associated with inadequate intake of selected nutrients. The percentage of persons with an inadequate intake of nutrients according to Italian Recommended Nutrients Levels (LARN) was higher in the older age groups. Older persons tended to adapt their diets in response to individual functional difficulties, often leading to monotonous food consumption and, as a consequence, to inadequate nutrient intakes. Multiple logistic models were used to evaluate whether inadequate intake of selected nutrients could be predicted by nutrition-related difficulties. Reporting difficulties in three or more nutrition-related activities (chewing, self-feeding, shopping for basic necessities, carrying a shopping bag, cooking a warm meal, using fingers to grasp or handle) significantly increased the risk of inadequate intake of energy [odds ratio (OR) = 3.8, 95% CI = 1.9-7.8) and vitamin C (OR = 2.2, 95% CI = 1.2-4.2, after adjustment for energy intake). More attention to functional problems in the elderly population and the provision of formal or informal help to those who have difficulty in purchasing, processing and eating food may reduce, at least in part, the percentage of older persons with poor nutrition.

  4. Synaptic Cell Adhesion

    OpenAIRE

    Missler, Markus; Südhof, Thomas C.; Biederer, Thomas

    2012-01-01

    Chemical synapses are asymmetric intercellular junctions that mediate synaptic transmission. Synaptic junctions are organized by trans-synaptic cell adhesion molecules bridging the synaptic cleft. Synaptic cell adhesion molecules not only connect pre- and postsynaptic compartments, but also mediate trans-synaptic recognition and signaling processes that are essential for the establishment, specification, and plasticity of synapses. A growing number of synaptic cell adhesion molecules that inc...

  5. How aging affects sleep-dependent memory consolidation?

    Directory of Open Access Journals (Sweden)

    Caroline eHarand

    2012-02-01

    Full Text Available Sleep plays multiple functions among which energy conservation or recuperative processes. Besides, growing evidence indicate that sleep plays also a major role in memory consolidation, a process by which recently acquired and labile memory traces are progressively strengthened into more permanent and/or enhanced forms. Indeed, memories are not stored as they were initially encoded but rather undergo a gradual reorganization process, which is favoured by the neurochemical environment and the electrophysiological activity observed during sleep. Two putative, probably not exclusive, models (hippocampo-neocortical dialogue and synaptic homeostasis hypothesis have been proposed to explain the beneficial effect of sleep on memory processes. It is worth noting that all data gathered until now emerged from studies conducted in young subjects. The investigation of the relationships between sleep and memory in older adults has sparked off little interest until recently. Though, aging is characterized by memory impairment, changes in sleep architecture, as well as brain and neurochemical alterations. All these elements suggest that sleep-dependent memory consolidation may be impaired or occurs differently in older adults.Here, we give an overview of the mechanisms governing sleep-dependent memory consolidation, and the crucial points of this complex process that may dysfunction and result in impaired memory consolidation in aging.

  6. EDITORIAL: Synaptic electronics Synaptic electronics

    Science.gov (United States)

    Demming, Anna; Gimzewski, James K.; Vuillaume, Dominique

    2013-09-01

    Conventional computers excel in logic and accurate scientific calculations but make hard work of open ended problems that human brains handle easily. Even von Neumann—the mathematician and polymath who first developed the programming architecture that forms the basis of today's computers—was already looking to the brain for future developments before his death in 1957 [1]. Neuromorphic computing uses approaches that better mimic the working of the human brain. Recent developments in nanotechnology are now providing structures with very accommodating properties for neuromorphic approaches. This special issue, with guest editors James K Gimzewski and Dominique Vuillaume, is devoted to research at the serendipitous interface between the two disciplines. 'Synaptic electronics', looks at artificial devices with connections that demonstrate behaviour similar to synapses in the nervous system allowing a new and more powerful approach to computing. Synapses and connecting neurons respond differently to incident signals depending on the history of signals previously experienced, ultimately leading to short term and long term memory behaviour. The basic characteristics of a synapse can be replicated with around ten simple transistors. However with the human brain having around 1011 neurons and 1015 synapses, artificial neurons and synapses from basic transistors are unlikely to accommodate the scalability required. The discovery of nanoscale elements that function as 'memristors' has provided a key tool for the implementation of synaptic connections [2]. Leon Chua first developed the concept of the 'The memristor—the missing circuit element' in 1971 [3]. In this special issue he presents a tutorial describing how memristor research has fed into our understanding of synaptic behaviour and how they can be applied in information processing [4]. He also describes, 'The new principle of local activity, which uncovers a minuscule life-enabling "Goldilocks zone", dubbed the

  7. Perception of Affective Body Movements in HRI Across Age Groups

    DEFF Research Database (Denmark)

    Rehm, Matthias; Krogsager, Anders; Segato, Nicolaj

    2016-01-01

    robots and the signals they produce. In this paper we focus on affective connotations of body movements and investigate how the perception of body movements of robots is related to age. Inspired by a study from Japan, we introduce culture as a variable in the experiment and discuss the difficulties...... of cross-cultural comparisons. The results show that there are certain age-related differences in the perception of affective body movements, but not as strong as in the original study. A follow up experiment puts the affective body movements into context and shows that recognition rates deteriorate...

  8. Synaptic Plasticity, Dementia and Alzheimer Disease.

    Science.gov (United States)

    Skaper, Stephen D; Facci, Laura; Zusso, Morena; Giusti, Pietro

    2017-01-01

    Neuroplasticity is not only shaped by learning and memory but is also a mediator of responses to neuron attrition and injury (compensatory plasticity). As an ongoing process it reacts to neuronal cell activity and injury, death, and genesis, which encompasses the modulation of structural and functional processes of axons, dendrites, and synapses. The range of structural elements that comprise plasticity includes long-term potentiation (a cellular correlate of learning and memory), synaptic efficacy and remodelling, synaptogenesis, axonal sprouting and dendritic remodelling, and neurogenesis and recruitment. Degenerative diseases of the human brain continue to pose one of biomedicine's most intractable problems. Research on human neurodegeneration is now moving from descriptive to mechanistic analyses. At the same time, it is increasing apparently that morphological lesions traditionally used by neuropathologists to confirm post-mortem clinical diagnosis might furnish us with an experimentally tractable handle to understand causative pathways. Consider the aging-dependent neurodegenerative disorder Alzheimer's disease (AD) which is characterised at the neuropathological level by deposits of insoluble amyloid β-peptide (Aβ) in extracellular plaques and aggregated tau protein, which is found largely in the intracellular neurofibrillary tangles. We now appreciate that mild cognitive impairment in early AD may be due to synaptic dysfunction caused by accumulation of non-fibrillar, oligomeric Aβ, occurring well in advance of evident widespread synaptic loss and neurodegeneration. Soluble Aβ oligomers can adversely affect synaptic structure and plasticity at extremely low concentrations, although the molecular substrates by which synaptic memory mechanisms are disrupted remain to be fully elucidated. The dendritic spine constitutes a primary locus of excitatory synaptic transmission in the mammalian central nervous system. These structures protruding from dendritic

  9. Factors Affecting Sarcopenia in Korean Adults by Age Groups.

    Science.gov (United States)

    Bae, Eun-Jung; Kim, Yun-Hee

    2017-06-01

    This study aimed to investigate factors affecting sarcopenia in different age groups among Korean adults aged 20 years or older. In this secondary analysis, data were collected from records for 17,968, participants who participated in the Korea National Health and Nutrition Examination Survey during 2008-2011. Data were analyzed using multiple logistic regression to determine the associated factors of sarcopenia by age groups. The prevalence of sarcopenia increased significantly with age. Physical activity, blood pressure, waist circumference, triglycerides, vitamin D level were found to be factors significantly associated with sarcopenia in all age groups. Total energy intake was found to be a factor that is significantly associated with sarcopenia among the adults aged 20-39 years. Fasting glucose, suicidal ideation, perceived health status, mobility problem, pain/discomfort, total energy intake were found to be factors associated with sarcopenia in the adults aged 40-64 years. Sex, residential area, smoking, drinking, fasting glucose, osteoarthritis, fall experience, usual activity problem, protein intake were factors associated with sarcopenia in the adults over 65 years of age. The findings show that sarcopenia in adults and the associated factors were different by age groups. Thus, these factors should be considered in the development of intervention programs for the care and prevention of sarcopenia, and such programs should be modified according to different age groups.

  10. Myopic (HD-PTP, PTPN23) selectively regulates synaptic neuropeptide release.

    Science.gov (United States)

    Bulgari, Dinara; Jha, Anupma; Deitcher, David L; Levitan, Edwin S

    2018-02-13

    Neurotransmission is mediated by synaptic exocytosis of neuropeptide-containing dense-core vesicles (DCVs) and small-molecule transmitter-containing small synaptic vesicles (SSVs). Exocytosis of both vesicle types depends on Ca 2+ and shared secretory proteins. Here, we show that increasing or decreasing expression of Myopic (mop, HD-PTP, PTPN23), a Bro1 domain-containing pseudophosphatase implicated in neuronal development and neuropeptide gene expression, increases synaptic neuropeptide stores at the Drosophila neuromuscular junction (NMJ). This occurs without altering DCV content or transport, but synaptic DCV number and age are increased. The effect on synaptic neuropeptide stores is accounted for by inhibition of activity-induced Ca 2+ -dependent neuropeptide release. cAMP-evoked Ca 2+ -independent synaptic neuropeptide release also requires optimal Myopic expression, showing that Myopic affects the DCV secretory machinery shared by cAMP and Ca 2+ pathways. Presynaptic Myopic is abundant at early endosomes, but interaction with the endosomal sorting complex required for transport III (ESCRT III) protein (CHMP4/Shrub) that mediates Myopic's effect on neuron pruning is not required for control of neuropeptide release. Remarkably, in contrast to the effect on DCVs, Myopic does not affect release from SSVs. Therefore, Myopic selectively regulates synaptic DCV exocytosis that mediates peptidergic transmission at the NMJ.

  11. Recurrence in affective disorder. II. Effect of age and gender

    DEFF Research Database (Denmark)

    Kessing, L V

    1998-01-01

    BACKGROUND: The risk of recurrence in affective disorder has been found to increase with each new episode. It is unclear whether it is universal without regard to gender, age and type of disorder. METHOD: Survival analysis was used to estimate the risk of recurrence in a case-register study...... episodes regardless of the combination of gender, age and type of disorder. Initially in the course of illness, unipolar and bipolar women experienced an equal greater risk of recurrence than men. The risk of recurrence after the first episode was increased for middle-aged and older unipolar women compared...... with the risk for younger women, while after all other episodes younger age at first episode increased the risk of recurrence. CONCLUSIONS: The course of severe unipolar and bipolar disorder seems to be progressive in nature irrespective of gender, age and type of disorder....

  12. Estradiol attenuates ischemia-induced death of hippocampal neurons and enhances synaptic transmission in aged, long-term hormone-deprived female rats.

    Directory of Open Access Journals (Sweden)

    Tomoko Inagaki

    Full Text Available Transient global forebrain ischemia causes selective, delayed death of hippocampal CA1 pyramidal neurons, and the ovarian hormone 17β-estradiol (E2 reduces neuronal loss in young and middle-aged females. The neuroprotective efficacy of E2 after a prolonged period of hormone deprivation is controversial, and few studies examine this issue in aged animals given E2 treatment after induction of ischemia.The present study investigated the neuroprotective effects of E2 administered immediately after global ischemia in aged female rats (15-18 months after 6 months of hormone deprivation. We also used electrophysiological methods to assess whether CA1 synapses in the aging hippocampus remain responsive to E2 after prolonged hormone withdrawal. Animals were ovariohysterectomized and underwent 10 min global ischemia 6 months later. A single dose of E2 (2.25 µg infused intraventricularly after reperfusion significantly increased cell survival, with 45% of CA1 neurons surviving vs 15% in controls. Ischemia also induced moderate loss of CA3/CA4 pyramidal cells. Bath application of 1 nM E2 onto brain slices derived from non-ischemic aged females after 6 months of hormone withdrawal significantly enhanced excitatory transmission at CA1 synapses evoked by Schaffer collateral stimulation, and normal long-term potentiation (LTP was induced. The magnitude of LTP and of E2 enhancement of field excitatory postsynaptic potentials was indistinguishable from that recorded in slices from young rats.The data demonstrate that 1 acute post-ischemic infusion of E2 into the brain ventricles is neuroprotective in aged rats after 6 months of hormone deprivation; and 2 E2 enhances synaptic transmission in CA1 pyramidal neurons of aged long-term hormone deprived females. These findings provide evidence that the aging hippocampus remains responsive to E2 administered either in vivo or in vitro even after prolonged periods of hormone withdrawal.

  13. Long-term culture of astrocytes attenuates the readily releasable pool of synaptic vesicles.

    Directory of Open Access Journals (Sweden)

    Hiroyuki Kawano

    Full Text Available The astrocyte is a major glial cell type of the brain, and plays key roles in the formation, maturation, stabilization and elimination of synapses. Thus, changes in astrocyte condition and age can influence information processing at synapses. However, whether and how aging astrocytes affect synaptic function and maturation have not yet been thoroughly investigated. Here, we show the effects of prolonged culture on the ability of astrocytes to induce synapse formation and to modify synaptic transmission, using cultured autaptic neurons. By 9 weeks in culture, astrocytes derived from the mouse cerebral cortex demonstrated increases in β-galactosidase activity and glial fibrillary acidic protein (GFAP expression, both of which are characteristic of aging and glial activation in vitro. Autaptic hippocampal neurons plated on these aging astrocytes showed a smaller amount of evoked release of the excitatory neurotransmitter glutamate, and a lower frequency of miniature release of glutamate, both of which were attributable to a reduction in the pool of readily releasable synaptic vesicles. Other features of synaptogenesis and synaptic transmission were retained, for example the ability to induce structural synapses, the presynaptic release probability, the fraction of functional presynaptic nerve terminals, and the ability to recruit functional AMPA and NMDA glutamate receptors to synapses. Thus the presence of aging astrocytes affects the efficiency of synaptic transmission. Given that the pool of readily releasable vesicles is also small at immature synapses, our results are consistent with astrocytic aging leading to retarded synapse maturation.

  14. Positive affect and age as predictors of exercise compliance

    Directory of Open Access Journals (Sweden)

    Danilo Garcia

    2014-12-01

    Full Text Available Physical exercise is linked to individuals whose affect profiles are invariably positive and it induces anti-apoptotic and anti-excitotoxic effects, buttressing blood–brain barrier intactness in both healthy individuals and those suffering from disorders accompanying overweight and obesity. In this regard, exercise offers a unique non-pharmacologic, non-invasive intervention that incorporates different regimes, whether dynamic or static, endurance, or resistance. In this brief report we present a self-reported study carried out on an adolescent and adult population (N = 280, 144 males and 136 females, which indicated that the propensity and compliance for exercise, measured as the “Archer ratio”, was predicted by a positive affect. This association is discussed from the perspective of health, well-being, affect dimensions, and age.

  15. Categorical Perception of emotional faces is not affected by aging

    Directory of Open Access Journals (Sweden)

    Mandy Rossignol

    2009-11-01

    Full Text Available Effects of normal aging on categorical perception (CP of facial emotional expressions were investigated. One-hundred healthy participants (20 to 70 years old; five age groups had to identify morphed expressions ranging from neutrality to happiness, sadness and fear. We analysed percentages and latencies of correct recognition for nonmorphed emotional expressions, percentages and latencies of emotional recognition for morphed-faces, locus of the boundaries along the different continua and the number of intrusions. The results showed that unmorphed happy and fearful faces were better processed than unmorphed sad and neutral faces. For morphed faces, CP was confirmed, as latencies increased as a function of the distance between the displayed morph and the original unmorphed photograph. The locus of categorical boundaries was not affected by age. Aging did not alter the accuracy of recognition for original pictures, no more than the emotional recognition of morphed faces or the rate of intrusions. However, latencies of responses increased with age, for both unmorphed and morphed pictures. In conclusion, CP of facial expressions appears to be spared in aging.

  16. How age affects pointing with mouse and touchpad

    DEFF Research Database (Denmark)

    Hertzum, Morten; Hornbæk, Kasper

    2010-01-01

    pointing with mouse and touchpad. The goal is to provide an integrated analysis of (a) how these three age groups differ in pointing performance, (b) how these differences are affected by the two pointing devices, and (c) how the submovement structure of cursor trajectories may explain performance...... neither more nor less errors than young and adult participants. All three age groups were slower and made more errors with the touchpad than the mouse, but the touchpad slowed down elderly participants more than young participants, who in turn were slowed down more than adult participants. Adult......Effects of age on pointing performance have become increasingly important as computers have become extensively used by still larger parts of the population. This study empirically investigates young (12-14 years), adult (25-33 years), and elderly (61-69 years) participants' performance when...

  17. What affects the age of first sleeping through the night?

    Science.gov (United States)

    Adams, S M; Jones, D R; Esmail, A; Mitchell, E A

    2004-03-01

    To ascertain the age at which an infant first sleeps regularly through the night and the factors affecting this age. A representative cross sectional sample of 700 infants in south-east England were studied. Information was collected on 511 (73.0%) of the infants by parental interview. Obstetric records were also examined. Fifty per cent of babies slept through by 8 weeks and 75% by 12 weeks. Multivariate survival analysis used to investigate 61 potential factors found that a heavier birthweight, female gender and co-sleeping less than 2 hours or not at all; younger mothers, school leaving age less than 17 years, stress factors (divorce and no separation from partner for more than a month in the last 12 months); no central heating, and the baby not sharing a room with siblings were associated with an earlier age at which an infant first sleeps through the night. Little of the variation between children in age of first sleeping through the night could be explained by these nine factors.

  18. Synaptic adaptations to chronic ethanol intake in male rhesus monkey dorsal striatum depend on age of drinking onset.

    Science.gov (United States)

    Cuzon Carlson, Verginia C; Grant, Kathleen A; Lovinger, David M

    2018-03-15

    One in 12 adults suffer with alcohol use disorder (AUD). Studies suggest the younger the age in which alcohol consumption begins the higher the probability of being diagnosed with AUD. Binge/excessive alcohol drinking involves a transition from flexible to inflexible behavior likely involving the dorsal striatum (caudate and putamen nuclei). A major focus of this study was to examine the effect of age of drinking onset on subsequent chronic, voluntary ethanol intake and dorsal striatal circuitry. Data from rhesus monkeys (n = 45) that started drinking as adolescents, young adults or mature adults confirms an age-related risk for heavy drinking. Striatal neuroadaptations were examined using whole-cell patch clamp electrophysiology to record AMPA receptor-mediated miniature excitatory postsynaptic currents (mEPSCs) and GABA A receptor-mediated miniature inhibitory postsynaptic currents (mIPSCs) from medium-sized spiny projection neurons located in the caudate or putamen nuclei. In controls, greater GABAergic transmission (mIPSC frequency and amplitude) was observed in the putamen compared to the caudate. With advancing age, in the absence of ethanol, an increase in mIPSC frequency concomitant with changes in mIPSC amplitude was observed in both regions. Chronic ethanol drinking decreased mIPSC frequency in the putamen regardless of age of onset. In the caudate, an ethanol drinking-induced increase in mIPSC frequency was only observed in monkeys that began drinking as young adults. Glutamatergic transmission did not differ between the dorsal striatal subregions in controls. With chronic ethanol drinking there was a decrease in the postsynaptic characteristics of rise time and area of mEPSCs in the putamen but an increase in mEPSC frequency in the caudate. Together, the observed changes in striatal physiology indicate a combined disinhibition due to youth and ethanol leading to abnormally strong activation of the putamen that could contribute to the increased risk

  19. Curcumin enhances neurogenesis and cognition in aged rats: implications for transcriptional interactions related to growth and synaptic plasticity.

    Directory of Open Access Journals (Sweden)

    Suzhen Dong

    Full Text Available BACKGROUND: Curcumin has been demonstrated to have many neuroprotective properties, including improvement of cognition in humans and neurogenesis in animals, yet the mechanism of such effects remains unclear. METHODOLOGY: We assessed behavioural performance and hippocampal cell proliferation in aged rats after 6- and 12-week curcumin-fortified diets. Curcumin enhanced non-spatial and spatial memory, as well as dentate gyrate cell proliferation as compared to control diet rats. We also investigated underlying mechanistic pathways that might link curcumin treatment to increased cognition and neurogenesis via exon array analysis of cortical and hippocampal mRNA transcription. The results revealed a transcriptional network interaction of genes involved in neurotransmission, neuronal development, signal transduction, and metabolism in response to the curcumin treatment. CONCLUSIONS: The results suggest a neurogenesis- and cognition-enhancing potential of prolonged curcumin treatment in aged rats, which may be due to its diverse effects on genes related to growth and plasticity.

  20. Curcumin Enhances Neurogenesis and Cognition in Aged Rats: Implications for Transcriptional Interactions Related to Growth and Synaptic Plasticity

    Science.gov (United States)

    Mitchell, E. Siobhan; Xiu, Jin; Tiwari, Jyoti K.; Hu, Yinghe; Cao, Xiaohua; Zhao, Zheng

    2012-01-01

    Background Curcumin has been demonstrated to have many neuroprotective properties, including improvement of cognition in humans and neurogenesis in animals, yet the mechanism of such effects remains unclear. Methodology We assessed behavioural performance and hippocampal cell proliferation in aged rats after 6- and 12-week curcumin-fortified diets. Curcumin enhanced non-spatial and spatial memory, as well as dentate gyrate cell proliferation as compared to control diet rats. We also investigated underlying mechanistic pathways that might link curcumin treatment to increased cognition and neurogenesis via exon array analysis of cortical and hippocampal mRNA transcription. The results revealed a transcriptional network interaction of genes involved in neurotransmission, neuronal development, signal transduction, and metabolism in response to the curcumin treatment. Conclusions The results suggest a neurogenesis- and cognition-enhancing potential of prolonged curcumin treatment in aged rats, which may be due to its diverse effects on genes related to growth and plasticity. PMID:22359574

  1. The LRRK2 G2385R variant is a partial loss-of-function mutation that affects synaptic vesicle trafficking through altered protein interactions.

    Science.gov (United States)

    Carrion, Maria Dolores Perez; Marsicano, Silvia; Daniele, Federica; Marte, Antonella; Pischedda, Francesca; Di Cairano, Eliana; Piovesana, Ester; von Zweydorf, Felix; Kremmer, Elisabeth; Gloeckner, Christian Johannes; Onofri, Franco; Perego, Carla; Piccoli, Giovanni

    2017-07-14

    Mutations in the Leucine-rich repeat kinase 2 gene (LRRK2) are associated with familial Parkinson's disease (PD). LRRK2 protein contains several functional domains, including protein-protein interaction domains at its N- and C-termini. In this study, we analyzed the functional features attributed to LRRK2 by its N- and C-terminal domains. We combined TIRF microscopy and synaptopHluorin assay to visualize synaptic vesicle trafficking. We found that N- and C-terminal domains have opposite impact on synaptic vesicle dynamics. Biochemical analysis demonstrated that different proteins are bound at the two extremities, namely β3-Cav2.1 at N-terminus part and β-Actin and Synapsin I at C-terminus domain. A sequence variant (G2385R) harboured within the C-terminal WD40 domain increases the risk for PD. Complementary biochemical and imaging approaches revealed that the G2385R variant alters strength and quality of LRRK2 interactions and increases fusion of synaptic vesicles. Our data suggest that the G2385R variant behaves like a loss-of-function mutation that mimics activity-driven events. Impaired scaffolding capabilities of mutant LRRK2 resulting in perturbed vesicular trafficking may arise as a common pathophysiological denominator through which different LRRK2 pathological mutations cause disease.

  2. Genetic disorders affecting white matter in the pediatric age.

    Science.gov (United States)

    Di Rocco, Maja; Biancheri, Roberta; Rossi, Andrea; Filocamo, Mirella; Tortori-Donati, Paolo

    2004-08-15

    Pediatric white matter disorders can be distinguished into well-defined leukoencephalopathies, and undefined leukoencephalopathies. The first category may be subdivided into: (a) hypomyelinating disorders; (b) dysmyelinating disorders; (c) leukodystrophies; (d) disorders related to cystic degeneration of myelin; and (e) disorders secondary to axonal damage. The second category, representing up to 50% of leukoencephalopathies in childhood, requires a multidisciplinar approach in order to define novel homogeneous subgroups of patients, possibly representing "new genetic disorders" (such as megalencephalic leukoencepahlopathy with subcortical cysts and vanishing white matter disease that have recently been identified). In the majority of cases, pediatric white matter disorders are inherited diseases. An integrated description of the clinical, neuroimaging and pathophysiological features is crucial for categorizing myelin disorders and better understanding their genetic basis. A review of the genetic disorders affecting white matter in the pediatric age, including some novel entities, is provided. Copyright 2004 Wiley-Liss, Inc.

  3. Age-related changes in oscillatory power affect motor action.

    Directory of Open Access Journals (Sweden)

    Liqing Liu

    Full Text Available With increasing age cognitive performance slows down. This includes cognitive processes essential for motor performance. Additionally, performance of motor tasks becomes less accurate. The objective of the present study was to identify general neural correlates underlying age-related behavioral slowing and the reduction in motor task accuracy. To this end, we continuously recorded EEG activity from 18 younger and 24 older right-handed healthy participants while they were performing a simple finger tapping task. We analyzed the EEG records with respect to local changes in amplitude (power spectrum as well as phase locking between the two age groups. We found differences between younger and older subjects in the amplitude of post-movement synchronization in the β band of the sensory-motor and medial prefrontal cortex (mPFC. This post-movement β amplitude was significantly reduced in older subjects. Moreover, it positively correlated with the accuracy with which subjects performed the motor task at the electrode FCz, which detects activity of the mPFC and the supplementary motor area. In contrast, we found no correlation between the accurate timing of local neural activity, i.e. phase locking in the δ-θ frequency band, with the reaction and movement time or the accuracy with which the motor task was performed. Our results show that only post-movement β amplitude and not δ-θ phase locking is involved in the control of movement accuracy. The decreased post-movement β amplitude in the mPFC of older subjects hints at an impaired deactivation of this area, which may affect the cognitive control of stimulus-induced motor tasks and thereby motor output.

  4. Insufficient DNA methylation affects healthy aging and promotes age-related health problems.

    Science.gov (United States)

    Liu, Liang; van Groen, Thomas; Kadish, Inga; Li, Yuanyuan; Wang, Deli; James, Smitha R; Karpf, Adam R; Tollefsbol, Trygve O

    2011-08-01

    DNA methylation plays an integral role in development and aging through epigenetic regulation of genome function. DNA methyltransferase 1 (Dnmt1) is the most prevalent DNA methyltransferase that maintains genomic methylation stability. To further elucidate the function of Dnmt1 in aging and age-related diseases, we exploited the Dnmt1+/- mouse model to investigate how Dnmt1 haploinsufficiency impacts the aging process by assessing the changes of several major aging phenotypes. We confirmed that Dnmt1 haploinsufficiency indeed decreases DNA methylation as a result of reduced Dnmt1 expression. To assess the effect of Dnmt1 haploinsufficiency on general body composition, we performed dual-energy X-ray absorptiometry analysis and showed that reduced Dnmt1 activity decreased bone mineral density and body weight, but with no significant impact on mortality or body fat content. Using behavioral tests, we demonstrated that Dnmt1 haploinsufficiency impairs learning and memory functions in an age-dependent manner. Taken together, our findings point to the interesting likelihood that reduced genomic methylation activity adversely affects the healthy aging process without altering survival and mortality. Our studies demonstrated that cognitive functions of the central nervous system are modulated by Dnmt1 activity and genomic methylation, highlighting the significance of the original epigenetic hypothesis underlying memory coding and function.

  5. Influence of Synaptic Depression on Memory Storage Capacity

    Science.gov (United States)

    Otsubo, Yosuke; Nagata, Kenji; Oizumi, Masafumi; Okada, Masato

    2011-08-01

    Synaptic efficacy between neurons is known to change within a short time scale dynamically. Neurophysiological experiments show that high-frequency presynaptic inputs decrease synaptic efficacy between neurons. This phenomenon is called synaptic depression, a short term synaptic plasticity. Many researchers have investigated how the synaptic depression affects the memory storage capacity. However, the noise has not been taken into consideration in their analysis. By introducing ``temperature'', which controls the level of the noise, into an update rule of neurons, we investigate the effects of synaptic depression on the memory storage capacity in the presence of the noise. We analytically compute the storage capacity by using a statistical mechanics technique called Self Consistent Signal to Noise Analysis (SCSNA). We find that the synaptic depression decreases the storage capacity in the case of finite temperature in contrast to the case of the low temperature limit, where the storage capacity does not change.

  6. Synaptic control of motoneuronal excitability

    DEFF Research Database (Denmark)

    Rekling, J C; Funk, G D; Bayliss, D A

    2000-01-01

    important in understanding the transformation of neural activity to motor behavior. Here, we review recent studies on the control of motoneuronal excitability, focusing on synaptic and cellular properties. We first present a background description of motoneurons: their development, anatomical organization......, and membrane properties, both passive and active. We then describe the general anatomical organization of synaptic input to motoneurons, followed by a description of the major transmitter systems that affect motoneuronal excitability, including ligands, receptor distribution, pre- and postsynaptic actions...... and norepinephrine, and neuropeptides, as well as the glutamate and GABA acting at metabotropic receptors, modulate motoneuronal excitability through pre- and postsynaptic actions. Acting principally via second messenger systems, their actions converge on common effectors, e.g., leak K(+) current, cationic inward...

  7. Molecular mechanisms of synaptic remodeling in alcoholism.

    Science.gov (United States)

    Kyzar, Evan J; Pandey, Subhash C

    2015-08-05

    Alcohol use and alcohol addiction represent dysfunctional brain circuits resulting from neuroadaptive changes during protracted alcohol exposure and its withdrawal. Alcohol exerts a potent effect on synaptic plasticity and dendritic spine formation in specific brain regions, providing a neuroanatomical substrate for the pathophysiology of alcoholism. Epigenetics has recently emerged as a critical regulator of gene expression and synaptic plasticity-related events in the brain. Alcohol exposure and withdrawal induce changes in crucial epigenetic processes in the emotional brain circuitry (amygdala) that may be relevant to the negative affective state defined as the "dark side" of addiction. Here, we review the literature concerning synaptic plasticity and epigenetics, with a particular focus on molecular events related to dendritic remodeling during alcohol abuse and alcoholism. Targeting epigenetic processes that modulate synaptic plasticity may yield novel treatments for alcoholism. Published by Elsevier Ireland Ltd.

  8. Oxidative Stress, Synaptic Dysfunction, and Alzheimer's Disease.

    Science.gov (United States)

    Tönnies, Eric; Trushina, Eugenia

    2017-01-01

    Alzheimer's disease (AD) is a devastating neurodegenerative disorder without a cure. Most AD cases are sporadic where age represents the greatest risk factor. Lack of understanding of the disease mechanism hinders the development of efficacious therapeutic approaches. The loss of synapses in the affected brain regions correlates best with cognitive impairment in AD patients and has been considered as the early mechanism that precedes neuronal loss. Oxidative stress has been recognized as a contributing factor in aging and in the progression of multiple neurodegenerative diseases including AD. Increased production of reactive oxygen species (ROS) associated with age- and disease-dependent loss of mitochondrial function, altered metal homeostasis, and reduced antioxidant defense directly affect synaptic activity and neurotransmission in neurons leading to cognitive dysfunction. In addition, molecular targets affected by ROS include nuclear and mitochondrial DNA, lipids, proteins, calcium homeostasis, mitochondrial dynamics and function, cellular architecture, receptor trafficking and endocytosis, and energy homeostasis. Abnormal cellular metabolism in turn could affect the production and accumulation of amyloid-β (Aβ) and hyperphosphorylated Tau protein, which independently could exacerbate mitochondrial dysfunction and ROS production, thereby contributing to a vicious cycle. While mounting evidence implicates ROS in the AD etiology, clinical trials with antioxidant therapies have not produced consistent results. In this review, we will discuss the role of oxidative stress in synaptic dysfunction in AD, innovative therapeutic strategies evolved based on a better understanding of the complexity of molecular mechanisms of AD, and the dual role ROS play in health and disease.

  9. Synaptic Plasticity and Nociception

    Institute of Scientific and Technical Information of China (English)

    ChenJianguo

    2004-01-01

    Synaptic plasticity is one of the fields that progresses rapidly and has a lot of success in neuroscience. The two major types of synaptie plasticity: long-term potentiation ( LTP and long-term depression (LTD are thought to be the cellular mochanisms of learning and memory. Recently, accumulating evidence suggests that, besides serving as a cellular model for learning and memory, the synaptic plasticity involves in other physiological or pathophysiological processes, such as the perception of pain and the regulation of cardiovascular system. This minireview will focus on the relationship between synaptic plasticity and nociception.

  10. Banach Synaptic Algebras

    Science.gov (United States)

    Foulis, David J.; Pulmannov, Sylvia

    2018-04-01

    Using a representation theorem of Erik Alfsen, Frederic Schultz, and Erling Størmer for special JB-algebras, we prove that a synaptic algebra is norm complete (i.e., Banach) if and only if it is isomorphic to the self-adjoint part of a Rickart C∗-algebra. Also, we give conditions on a Banach synaptic algebra that are equivalent to the condition that it is isomorphic to the self-adjoint part of an AW∗-algebra. Moreover, we study some relationships between synaptic algebras and so-called generalized Hermitian algebras.

  11. Relative Age Affects Marathon Performance in Male and Female Athletes

    OpenAIRE

    Connick, Mark J.; Beckman, Emma M.; Tweedy, Sean M.

    2015-01-01

    Marathon runners are ranked in 5-year age groups. However the extent to which 5-year groupings facilitates equitable competition has not been evaluated. The aim of this study was to evaluate the effect of relative age in male and female marathon running. Marathon finishing times for the top ten male (aged 20-69 years) and female athletes (aged 20-64 years) were obtained from the 2013 New York and Chicago marathons. Intra-class and inter-class validity were evaluated by comparing performances ...

  12. Fewer ups and downs: daily stressors mediate age differences in negative affect.

    Science.gov (United States)

    Charles, Susan Turk; Luong, Gloria; Almeida, David M; Ryff, Carol; Sturm, Maggie; Love, Gayle

    2010-05-01

    The current study examined age differences in daily stressors, positive events (uplifts), and their associations with emotional experience among healthy older women. Women (N = 101, 63-93 years old) reported their daily experiences across 1 week. Older age was related to fewer stressors and less frequent negative affect. However, the association between negative affect and age was no longer significant after accounting for the occurrence of daily stressors. Older age was not significantly related to positive affect, although positive uplifts were reported less frequently with age. Findings provide a contextual explanation for emotional experience in very late life, where reduced exposure to stressors partially explains age-related reductions in negative affect.

  13. Prematurity Affects Age of Presentation of Pyloric Stenosis.

    Science.gov (United States)

    Costanzo, Caitlyn M; Vinocur, Charles; Berman, Loren

    2017-02-01

    Term infants with hypertrophic pyloric stenosis (HPS) typically present between 4 and 6 weeks. There is limited consensus, however, regarding age of presentation of premature infants. We aim to determine if there is an association between the degree of prematurity and chronological age of presentation of HPS. A total of 2988 infants who had undergone a pyloromyotomy for HPS were identified from the 2012 and 2013 NSQIP-P Participant Use Files. Two hundred seventeen infants (7.3%) were born prematurely. A greater degree of prematurity was associated with an older chronological age of presentation ( P Prematurity was significantly associated with an increase in overall postoperative morbidity, reintubation, readmission, and postoperative length of stay. When clinicians evaluate an infant with nonbilious emesis with a history of prematurity, they should consider pyloric stenosis if the calculated postconceptional age is between 44 and 50 weeks. When counseling families of premature infants, surgeons should discuss the increased incidence of postpyloromyotomy morbidity.

  14. Daily events are important for age differences in mean and duration for negative affect but not positive affect.

    Science.gov (United States)

    Charles, Susan T; Mogle, Jacqueline; Urban, Emily J; Almeida, David M

    2016-11-01

    Across midlife and into old age, older adults often report lower levels of negative affect and similar if not higher levels of positive affect than relatively younger adults. Researchers have offered a simple explanation for this result: Age is related to reductions in stressors and increases in pleasurable activities that result in higher levels of well-being. The current study examines subjective reports of emotional experience assessed across 8 days in a large sample of adults (N = 2,022) ranging from 35 to 84 years old. By modeling age differences before and after adjusting for daily positive uplifts and negative stressors, this article assesses the extent to which daily events account for age differences in positive and negative affect reports. Consistent with previous research, the authors found that older age is related to lower mean levels and shorter duration of a negative emotional experience in a model only adjusting for gender, education, and ethnicity. After adjusting for daily events, however, the linear age-related effects were no longer significant. For positive affect, adjusting for daily events did not alter age-related patterns of experiencing higher mean levels and longer positive experience duration, suggesting that other factors underlie age-related increases in positive affect. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  15. Inbreeding affects locomotor activity in Drosophila melanogaster at different ages

    DEFF Research Database (Denmark)

    Manenti, Tommaso; Pertoldi, Cino; Nasiri Moghadam, Neda

    2015-01-01

    The ability to move is essential for many behavioural traits closely related to fitness. Here we studied the effect of inbreeding on locomotor activity (LA) of Drosophila melanogaster at different ages under both dark and light regimes. We expected to find a decreased LA in inbred lines compared...

  16. Professor Age and Gender Affect Student Perceptions and Grades

    Science.gov (United States)

    Joye, Shauna W.; Wilson, Janie H.

    2015-01-01

    Student evaluations provide rich information about teaching performance, but a number of factors beyond teacher effectiveness influence student evaluations. In this study we examined the effects of professor gender and perceived age on ratings of effectiveness and rapport as well as academic performance. We also asked students to rate professor…

  17. Explant age, auxin concentrations and media type affect callus ...

    African Journals Online (AJOL)

    The effects of explant age of oil palm (Elaeis huineensis) embryo axes, 15 and 18 weeks after anthesis (WAA), media type (Eeuwens and Murashige and Skoog) supplemented with various concentrations of 2,4-D on callus production employing standard in vitro techniques were investigated. The results of the study showed ...

  18. Grape juice, berries and walnuts affect brain aging and behavior

    Science.gov (United States)

    Numerous studies have indicated that individuals consuming a diet containing high amounts of fruits and vegetables exhibit fewer age-related diseases such as Alzheimer Disease (AD). A recent report has indicated that individuals who consumed a diet containing 2.5 servings of fruit and vegetables/day...

  19. Affective Development in Advanced Old Age: Analyses of Terminal Change in Positive and Negative Affect

    Science.gov (United States)

    Schilling, Oliver K.; Wahl, Hans-Werner; Wiegering, Sarah

    2013-01-01

    Late-life development of affect may unfold terminal changes that are driven more by end-of-life processes and not so much by time since birth. This study aimed to explore time-to-death-related effects in measures of affect in a sample of the very old. We used longitudinal data (2 measurement occasions: 2002 and 2003) from 140 deceased…

  20. Does age affect prognosis in salivary gland carcinoma patients?

    DEFF Research Database (Denmark)

    Bjørndal, Kristine; Larsen, Stine R; Therkildsen, Marianne H

    2016-01-01

    in the young group were WHO performance status 0 and in disease stage I + II, and they presented with significantly more histological low grade tumors. In multivariate analysis, chronological age seemed to be of no prognostic significance to salivary gland carcinoma patients as opposed to performance status......, disease stage and histological grade. CONCLUSIONS: Salivary gland carcinoma patients over the age of 70 years have a poor prognosis compared to younger patients, which can be explained by higher disease stages, more histological high grade subtypes and a poorer performance status at the time of diagnosis.......AIM: To compare incidence, histology, treatment modalities, disease stages, and outcome in elderly patients (≥70 years) compared to younger (

  1. Perceptions of ethics in IS: How age can affect awareness

    OpenAIRE

    Wilford, S.; Wakunuma, Kutoma

    2014-01-01

    Purpose – This aim of this paper was to highlight the awareness of ethical issues across the group of information systems (IS) professionals from a range of geographical regions. Design/methodology/approach – An initial survey was conducted that informed in-depth interviews with 26 IS professionals from across the globe. The study identified that around 70 per cent of the sample were over 50 years old. This provided an opportunity to consider age-related differences in per...

  2. Elucidating key factors affecting radionuclide aging in soils

    Energy Technology Data Exchange (ETDEWEB)

    Roig, M. [Universitat Politecnica Catalunya, Institut de Tecniques Energetiques, Barcelona (Spain); Rigola, A.; Vidal, M.; Rauret, G. [Barcelona Univ., Dept. de Quimica Analitica (Spain)

    2004-07-01

    Mechanistic studies allow at present to describe the processes governing the short-term interaction of radiostrontium and radiocaesium in soils. The initial sorption step can be described through the estimation of the soil-soil solution distribution coefficient from soil parameters, as cationic exchange capacity, radiocaesium interception potential and concentration of competing ions in the soil solution. After the initial soil-radionuclide interaction, a fraction of radionuclide is no longer available for exchange with the solution, and it remains fixed in the solid fraction. At present, the initial fixed fraction of a radionuclide in a given soil cannot be predicted from soil properties. Besides, little is known about soil and environmental factors (e.g., temperature; hydric regime) provoking the increase in the fixed fraction with time, the so-called aging process. This process is considered to control the reduction of food contamination with time at contaminated scenarios. Therefore, it is crucial to be able to predict the radionuclide aging in the medium and long term for a better risk assessment, especially when a decision has to be made between relying on natural attenuation versus implementing intervention actions. Here we study radiostrontium and radiocaesium aging in a set of soils, covering a wide range of soil types of contrasting properties (e.g., loamy calcareous; podzol; chernozem, organic). Three factors are separately and simultaneously tested: time elapsed since contamination, temperature and hydric regime. Changes in the radionuclide fixed fraction are estimated with a leaching test based on the use of a mild extractant solution. In addition to this, secondary effects on the radiocaesium interception potential in various soils are also considered. (author)

  3. How age and linguistic competence affect memory for heard information

    Directory of Open Access Journals (Sweden)

    Bruce A Schneider

    2016-05-01

    Full Text Available The short-term memory performance of a group of younger adults, for whom English was a second language (young EL2 listeners, was compared to that of younger and older adults for whom English was their first language (EL1 listeners. To-be-remembered words were presented in noise and in quiet. When presented in noise, the listening situation was adjusted to insure that the likelihood of recognizing the individual words was comparable for all groups. Previous studies which used the same paradigm found memory performance of older EL1 adults on this paired-associate task to be poorer than that of their younger EL1 counterparts both in quiet and in a background of babble. The purpose of the present study was to investigate whether the less well-established semantic and linguistic skills of EL2 listeners would also lead to memory deficits even after equating for word recognition as was done for the younger and older EL1 listeners. No significant differences in memory performance were found between young EL1 and EL2 listeners after equating for word recognition, indicating that the EL2 listeners’ poorer semantic and linguistic skills had little effect on their ability to memorize and recall paired associates. This result is consistent with the hypothesis that age-related declines in memory are primarily due to age-related declines in the perceptual and attentional processes required for extracting the word pairs from a background babble of voices. Such declines are likely to increase the load on higher-order (possibly limited cognitive processes supporting memory. The problems that these results pose for the comprehension of spoken language in these three groups are discussed.

  4. How Age and Linguistic Competence Affect Memory for Heard Information.

    Science.gov (United States)

    Schneider, Bruce A; Avivi-Reich, Meital; Leung, Caterina; Heinrich, Antje

    2016-01-01

    The short-term memory performance of a group of younger adults, for whom English was a second language (young EL2 listeners), was compared to that of younger and older adults for whom English was their first language (EL1 listeners). To-be-remembered words were presented in noise and in quiet. When presented in noise, the listening situation was adjusted to ensure that the likelihood of recognizing the individual words was comparable for all groups. Previous studies which used the same paradigm found memory performance of older EL1 adults on this paired-associate task to be poorer than that of their younger EL1 counterparts both in quiet and in a background of babble. The purpose of the present study was to investigate whether the less well-established semantic and linguistic skills of EL2 listeners would also lead to memory deficits even after equating for word recognition as was done for the younger and older EL1 listeners. No significant differences in memory performance were found between young EL1 and EL2 listeners after equating for word recognition, indicating that the EL2 listeners' poorer semantic and linguistic skills had little effect on their ability to memorize and recall paired associates. This result is consistent with the hypothesis that age-related declines in memory are primarily due to age-related declines in higher-order processes supporting stream segregation and episodic memory. Such declines are likely to increase the load on higher-order (possibly limited) cognitive processes supporting memory. The problems that these results pose for the comprehension of spoken language in these three groups are discussed.

  5. Fewer Ups and Downs: Daily Stressors Mediate Age Differences in Negative Affect

    OpenAIRE

    Charles, Susan Turk; Luong, Gloria; Almeida, David M.; Ryff, Carol; Sturm, Maggie; Love, Gayle

    2010-01-01

    The current study examined age differences in daily stressors, positive events (uplifts), and their associations with emotional experience among healthy older women. Women (N = 101, 63--93 years old) reported their daily experiences across 1 week. Older age was related to fewer stressors and less frequent negative affect. However, the association between negative affect and age was no longer significant after accounting for the occurrence of daily stressors. Older age was not significantly re...

  6. Aging and intestinal motility: a review of factors that affect intestinal motility in the aged.

    LENUS (Irish Health Repository)

    O'Mahony, Denis

    2012-02-03

    Normal aging is associated with significant changes in the function of most organs and tissues. In this regard, the gastrointestinal tract is no exception. The purpose of this review is to detail the important age-related changes in motor function of the various parts of the gastrointestinal tract and to highlight some of the important motility changes that may occur, either in relation to common age-related disorders, or as a result of certain drugs commonly prescribed in the aged. A major confounding factor in the interpretation of motor phenomena throughout the gastrointestinal tract in this age group is the frequent coexistence of neurological, endocrinological and other disease states, which may be independently associated with dysmotility. Overall, current data are insufficient to implicate normal aging as a cause of dysmotility in the elderly. Normal aging is associated with various changes in gastrointestinal motility, but the clinical significance of such changes remains unclear. More important is the impact of various age-related diseases on gastrointestinal motility in the elderly: for example, long-standing diabetes mellitus may reduce gastric emptying in up to 50% of patients; depression significantly prolongs whole-gut transit time; hypothyroidism may prolong oro-caecal transit time; and chronic renal failure is associated with impaired gastric emptying. In addition, various, frequently used drugs in the elderly cause disordered gastrointestinal motility. These drugs include anticholinergics, especially antidepressants with an anticholinergic effect, opioid analgesics and calcium antagonists.

  7. Nicotinic mechanisms influencing synaptic plasticity in the hippocampus

    Institute of Scientific and Technical Information of China (English)

    Andon Nicholas PLACZEK; Tao A ZHANG; John Anthony DANI

    2009-01-01

    Nicotinic acetylcholine receptors (nAChRs) are expressed throughout the hippocampus, and nicotinic signaling plays an important role in neuronal function. In the context of learning and memory related behaviors associated with hippocampal function, a potentially significant feature of nAChR activity is the impact it has on synaptic plasticity. Synaptic plasticity in hippocampal neurons has long been considered a contributing cellular mechanism of learning and memory. These same kinds of cellular mechanisms are a factor in the development of nicotine addiction. Nicotinic signaling has been demonstrated by in vitro studies to affect synaptic plasticity in hippocampal neurons via multiple steps, and the signaling has also been shown to evoke synaptic plasticity in vivo. This review focuses on the nAChRs subtypes that contribute to hippocampal synaptic plasticity at the cellular and circuit level. It also considers nicotinic influences over long-term changes in the hippocampus that may contribute to addiction.

  8. Synaptic transmission block by presynaptic injection of oligomeric amyloid beta

    Science.gov (United States)

    Moreno, Herman; Yu, Eunah; Pigino, Gustavo; Hernandez, Alejandro I.; Kim, Natalia; Moreira, Jorge E.; Sugimori, Mutsuyuki; Llinás, Rodolfo R.

    2009-01-01

    Early Alzheimer's disease (AD) pathophysiology is characterized by synaptic changes induced by degradation products of amyloid precursor protein (APP). The exact mechanisms of such modulation are unknown. Here, we report that nanomolar concentrations of intraaxonal oligomeric (o)Aβ42, but not oAβ40 or extracellular oAβ42, acutely inhibited synaptic transmission at the squid giant synapse. Further characterization of this phenotype demonstrated that presynaptic calcium currents were unaffected. However, electron microscopy experiments revealed diminished docked synaptic vesicles in oAβ42-microinjected terminals, without affecting clathrin-coated vesicles. The molecular events of this modulation involved casein kinase 2 and the synaptic vesicle rapid endocytosis pathway. These findings open the possibility of a new therapeutic target aimed at ameliorating synaptic dysfunction in AD. PMID:19304802

  9. Cell-specific gain modulation by synaptically released zinc in cortical circuits of audition.

    Science.gov (United States)

    Anderson, Charles T; Kumar, Manoj; Xiong, Shanshan; Tzounopoulos, Thanos

    2017-09-09

    In many excitatory synapses, mobile zinc is found within glutamatergic vesicles and is coreleased with glutamate. Ex vivo studies established that synaptically released (synaptic) zinc inhibits excitatory neurotransmission at lower frequencies of synaptic activity but enhances steady state synaptic responses during higher frequencies of activity. However, it remains unknown how synaptic zinc affects neuronal processing in vivo. Here, we imaged the sound-evoked neuronal activity of the primary auditory cortex in awake mice. We discovered that synaptic zinc enhanced the gain of sound-evoked responses in CaMKII-expressing principal neurons, but it reduced the gain of parvalbumin- and somatostatin-expressing interneurons. This modulation was sound intensity-dependent and, in part, NMDA receptor-independent. By establishing a previously unknown link between synaptic zinc and gain control of auditory cortical processing, our findings advance understanding about cortical synaptic mechanisms and create a new framework for approaching and interpreting the role of the auditory cortex in sound processing.

  10. Neuronal cytoskeleton in synaptic plasticity and regeneration.

    Science.gov (United States)

    Gordon-Weeks, Phillip R; Fournier, Alyson E

    2014-04-01

    During development, dynamic changes in the axonal growth cone and dendrite are necessary for exploratory movements underlying initial axo-dendritic contact and ultimately the formation of a functional synapse. In the adult central nervous system, an impressive degree of plasticity is retained through morphological and molecular rearrangements in the pre- and post-synaptic compartments that underlie the strengthening or weakening of synaptic pathways. Plasticity is regulated by the interplay of permissive and inhibitory extracellular cues, which signal through receptors at the synapse to regulate the closure of critical periods of developmental plasticity as well as by acute changes in plasticity in response to experience and activity in the adult. The molecular underpinnings of synaptic plasticity are actively studied and it is clear that the cytoskeleton is a key substrate for many cues that affect plasticity. Many of the cues that restrict synaptic plasticity exhibit residual activity in the injured adult CNS and restrict regenerative growth by targeting the cytoskeleton. Here, we review some of the latest insights into how cytoskeletal remodeling affects neuronal plasticity and discuss how the cytoskeleton is being targeted in an effort to promote plasticity and repair following traumatic injury in the central nervous system. © 2013 International Society for Neurochemistry.

  11. Ageing/Menopausal Status in Healthy Women and Ageing in Healthy Men Differently Affect Cardiometabolic Parameters.

    Science.gov (United States)

    Campesi, Ilaria; Occhioni, Stefano; Tonolo, Giancarlo; Cherchi, Sara; Basili, Stefania; Carru, Ciriaco; Zinellu, Angelo; Franconi, Flavia

    2016-01-01

    Gender medicine requires a global analysis of an individual's life. Menopause and ageing induce variations of some cardiometabolic parameters, but, it is unknown if this occurs in a sex-specific manner. Here, some markers of oxidative stress, systemic inflammation, and endothelial dysfunction are analysed in men younger and older than 45 years and in pre- and postmenopausal women. Serum and plasma sample were assayed for TNF-α and IL-6, malondialdehyde and protein carbonyls and for methylated arginines using ELISA kits, colorimetric methods and capillary electrophoresis. Before body weight correction, men overall had higher creatinine, red blood cells and haemoglobin and lower triglycerides than women. Men younger than 45 years had lower levels of TNF-α and malondialdehyde and higher levels of arginine than age-matched women, while postmenopausal women had higher IL-6 concentrations than men, and higher total cholesterol, triglycerides, creatinine and IL-6 levels than younger women. Men younger than 45 years had lower total cholesterol and malondialdehyde than older men. After correction, some differences remained, others were amplified, others disappeared and some new differences emerged. Moreover, some parameters showed a correlation with age, and some of them correlated with each other as functions of ageing and ageing/menopausal status. Ageing/menopausal status increased many more cardiovascular risk factors in women than ageing in men, confirming that postmenopausal women had increased vascular vulnerability and indicating the need of early cardiovascular prevention in women. Sex-gender differences are also influenced by body weight, indicating as a matter of debate whether body weight should be seen as a true confounder or as part of the causal pathway.

  12. Phosphodiesterase Inhibition to Target the Synaptic Dysfunction in Alzheimer's Disease

    Science.gov (United States)

    Bales, Kelly R.; Plath, Niels; Svenstrup, Niels; Menniti, Frank S.

    Alzheimer's Disease (AD) is a disease of synaptic dysfunction that ultimately proceeds to neuronal death. There is a wealth of evidence that indicates the final common mediator of this neurotoxic process is the formation and actions on synaptotoxic b-amyloid (Aβ). The premise in this review is that synaptic dysfunction may also be an initiating factor in for AD and promote synaptotoxic Aβ formation. This latter hypothesis is consistent with the fact that the most common risk factors for AD, apolipoprotein E (ApoE) allele status, age, education, and fitness, encompass suboptimal synaptic function. Thus, the synaptic dysfunction in AD may be both cause and effect, and remediating synaptic dysfunction in AD may have acute effects on the symptoms present at the initiation of therapy and also slow disease progression. The cyclic nucleotide (cAMP and cGMP) signaling systems are intimately involved in the regulation of synaptic homeostasis. The phosphodiesterases (PDEs) are a superfamily of enzymes that critically regulate spatial and temporal aspects of cyclic nucleotide signaling through metabolic inactivation of cAMP and cGMP. Thus, targeting the PDEs to promote improved synaptic function, or 'synaptic resilience', may be an effective and facile approach to new symptomatic and disease modifying therapies for AD. There continues to be a significant drug discovery effort aimed at discovering PDE inhibitors to treat a variety of neuropsychiatric disorders. Here we review the current status of those efforts as they relate to potential new therapies for AD.

  13. Zolpidem, a clinical hypnotic that affects electronic transfer, alters synaptic activity through potential GABA receptors in the nervous system without significant free radical generation.

    Science.gov (United States)

    Kovacic, Peter; Somanathan, Ratnasamy

    2009-01-01

    Zolpidem (trade name Ambien) has attracted much interest as a sleep-inducing agent and also in research. Attention has been centered mainly on receptor binding and electrochemistry in the central nervous system which are briefly addressed herein. A novel integrated approach to mode of action is presented. The pathways to be discussed involve basicity, reduction potential, electrostatics, cell signaling, GABA receptor binding, electron transfer (ET), pharmacodynamics, structure activity relationships (SAR) and side effects. The highly conjugated pyridinium salt formed by protonation of the amidine moiety is proposed to be the active form acting as an ET agent. Extrapolation of reduction potentials for related compounds supports the premise that zolpidem may act as an ET species in vivo. From recent literature reports, electrostatics is believed to play a significant role in drug action. The pyridinium cation displays molecular electrostatic potential which may well play a role energetically or as a bridging mechanism. An SAR analysis points to analogy with other physiologically active xenobiotics, namely benzodiazepines and paraquat in the conjugated iminium category. Inactivity of metabolites indicates that the parent is the active form of zolpidem. Absence of reactive oxygen species and oxidative stress is in line with minor side effects. In contrast, generally, the prior literature contains essentially no discussion of these fundamental biochemical relationships. Pharmacodynamics may play an important role. Concerning behavior at the blood-brain barrier, useful insight can be gained from investigations of the related cationic anesthetics that are structurally related to acetyl choline. Evidently, the neutral form of the drug penetrates the neuronal membrane, with the salt form operating at the receptor. The pathways of zolpidem have several clinical implications since the agent affects sedation, electroencephalographic activity, oxidative metabolites and

  14. Decision making in the ageing brain: Changes in affective and motivational circuits

    Science.gov (United States)

    Samanez-Larkin, Gregory R.; Knutson, Brian

    2017-01-01

    As the global population ages, older decision makers will be required to take greater responsibility for their own physical, psychological and financial well-being. With this in mind, researchers have begun to examine the effects of ageing on decision making and associated neural circuits. A new “affect, integration, motivation” (or AIM) framework may help clarify how affective and motivational circuits support decision making. Recent research has shed light on whether and how ageing influences these circuits, providing an interdisciplinary account of how ageing can alter decision making. PMID:25873038

  15. Decision making in the ageing brain: changes in affective and motivational circuits.

    Science.gov (United States)

    Samanez-Larkin, Gregory R; Knutson, Brian

    2015-05-01

    As the global population ages, older decision makers will be required to take greater responsibility for their own physical, psychological and financial well-being. With this in mind, researchers have begun to examine the effects of ageing on decision making and associated neural circuits. A new 'affect-integration-motivation' (AIM) framework may help to clarify how affective and motivational circuits support decision making. Recent research has shed light on whether and how ageing influences these circuits, providing an interdisciplinary account of how ageing can alter decision making.

  16. Defective lysosomal proteolysis and axonal transport are early pathogenic events that worsen with age leading to increased APP metabolism and synaptic Abeta in transgenic APP/PS1 hippocampus.

    Science.gov (United States)

    Torres, Manuel; Jimenez, Sebastian; Sanchez-Varo, Raquel; Navarro, Victoria; Trujillo-Estrada, Laura; Sanchez-Mejias, Elisabeth; Carmona, Irene; Davila, Jose Carlos; Vizuete, Marisa; Gutierrez, Antonia; Vitorica, Javier

    2012-11-22

    Axonal pathology might constitute one of the earliest manifestations of Alzheimer disease. Axonal dystrophies were observed in Alzheimer's patients and transgenic models at early ages. These axonal dystrophies could reflect the disruption of axonal transport and the accumulation of multiple vesicles at local points. It has been also proposed that dystrophies might interfere with normal intracellular proteolysis. In this work, we have investigated the progression of the hippocampal pathology and the possible implication in Abeta production in young (6 months) and aged (18 months) PS1(M146L)/APP(751sl) transgenic mice. Our data demonstrated the existence of a progressive, age-dependent, formation of axonal dystrophies, mainly located in contact with congophilic Abeta deposition, which exhibited tau and neurofilament hyperphosphorylation. This progressive pathology was paralleled with decreased expression of the motor proteins kinesin and dynein. Furthermore, we also observed an early decrease in the activity of cathepsins B and D, progressing to a deep inhibition of these lysosomal proteases at late ages. This lysosomal impairment could be responsible for the accumulation of LC3-II and ubiquitinated proteins within axonal dystrophies. We have also investigated the repercussion of these deficiencies on the APP metabolism. Our data demonstrated the existence of an increase in the amyloidogenic pathway, which was reflected by the accumulation of hAPPfl, C99 fragment, intracellular Abeta in parallel with an increase in BACE and gamma-secretase activities. In vitro experiments, using APPswe transfected N2a cells, demonstrated that any imbalance on the proteolytic systems reproduced the in vivo alterations in APP metabolism. Finally, our data also demonstrated that Abeta peptides were preferentially accumulated in isolated synaptosomes. A progressive age-dependent cytoskeletal pathology along with a reduction of lysosomal and, in minor extent, proteasomal activity could be

  17. Agrin and synaptic laminin are required to maintain adult neuromuscular junctions.

    Directory of Open Access Journals (Sweden)

    Melanie A Samuel

    Full Text Available As synapses form and mature the synaptic partners produce organizing molecules that regulate each other's differentiation and ensure precise apposition of pre- and post-synaptic specializations. At the skeletal neuromuscular junction (NMJ, these molecules include agrin, a nerve-derived organizer of postsynaptic differentiation, and synaptic laminins, muscle-derived organizers of presynaptic differentiation. Both become concentrated in the synaptic cleft as the NMJ develops and are retained in adulthood. Here, we used mutant mice to ask whether these organizers are also required for synaptic maintenance. Deletion of agrin from a subset of adult motor neurons resulted in the loss of acetylcholine receptors and other components of the postsynaptic apparatus and synaptic cleft. Nerve terminals also atrophied and eventually withdrew from muscle fibers. On the other hand, mice lacking the presynaptic organizer laminin-α4 retained most of the synaptic cleft components but exhibited synaptic alterations reminiscent of those observed in aged animals. Although we detected no marked decrease in laminin or agrin levels at aged NMJs, we observed alterations in the distribution and organization of these synaptic cleft components suggesting that such changes could contribute to age-related synaptic disassembly. Together, these results demonstrate that pre- and post-synaptic organizers actively function to maintain the structure and function of adult NMJs.

  18. Dynamic Control of Synaptic Adhesion and Organizing Molecules in Synaptic Plasticity

    Energy Technology Data Exchange (ETDEWEB)

    Rudenko, Gabby (Texas-MED)

    2017-01-01

    Synapses play a critical role in establishing and maintaining neural circuits, permitting targeted information transfer throughout the brain. A large portfolio of synaptic adhesion/organizing molecules (SAMs) exists in the mammalian brain involved in synapse development and maintenance. SAMs bind protein partners, formingtrans-complexes spanning the synaptic cleft orcis-complexes attached to the same synaptic membrane. SAMs play key roles in cell adhesion and in organizing protein interaction networks; they can also provide mechanisms of recognition, generate scaffolds onto which partners can dock, and likely take part in signaling processes as well. SAMs are regulated through a portfolio of different mechanisms that affect their protein levels, precise localization, stability, and the availability of their partners at synapses. Interaction of SAMs with their partners can further be strengthened or weakened through alternative splicing, competing protein partners, ectodomain shedding, or astrocytically secreted factors. Given that numerous SAMs appear altered by synaptic activity, in vivo, these molecules may be used to dynamically scale up or scale down synaptic communication. Many SAMs, including neurexins, neuroligins, cadherins, and contactins, are now implicated in neuropsychiatric and neurodevelopmental diseases, such as autism spectrum disorder, schizophrenia, and bipolar disorder and studying their molecular mechanisms holds promise for developing novel therapeutics.

  19. MAGUKs: multifaceted synaptic organizers.

    Science.gov (United States)

    Won, Sehoon; Levy, Jon M; Nicoll, Roger A; Roche, Katherine W

    2017-04-01

    The PSD-95 family of proteins, known as MAGUKs, have long been recognized to be central building blocks of the PSD. They are categorized as scaffolding proteins, which link surface-expressed receptors to the intracellular signaling molecules. Although the four members of the PSD-95 family (PSD-95, PSD-93, SAP102, and SAP97) have many shared roles in regulating synaptic function, recent studies have begun to delineate specific binding partners and roles in plasticity. In the current review, we will highlight the conserved and unique roles of these proteins. Published by Elsevier Ltd.

  20. The 'disector' a tool for quantitative assessment of synaptic plasticity an example on hippocampal synapses and synapse-perforations in ageing rats

    NARCIS (Netherlands)

    Groot, D.M.G. de; Bierman, E.P.B.; Bruijnzeel, P.L.B.; Woutersen, R.A.

    1995-01-01

    The 'disector' method was used to estimate number and size of simple non-perforated and complex 'perforated' synapses and their 'perforations' in the hippocampal CA3 area of 3, 12, 24 and 30 months old rats. A decrease with age from 3 to 24 months of age in the number of non-perforated synapses per

  1. Dietary restriction of rodents decreases aging rate without affecting initial mortality rate a meta-analysis

    NARCIS (Netherlands)

    Simons, Mirre J. P.; Koch, Wouter; Verhulst, Simon

    Dietary restriction (DR) extends lifespan in multiple species from various taxa. This effect can arise via two distinct but not mutually exclusive ways: a change in aging rate and/or vulnerability to the aging process (i.e. initial mortality rate). When DR affects vulnerability, this lowers

  2. A Longitudinal Study of Cognition, Proton MR Spectroscopy and Synaptic and Neuronal Pathology in Aging Wild-type and AβPPswe-PS1dE9 Mice

    Science.gov (United States)

    Jansen, Diane; Zerbi, Valerio; Janssen, Carola I. F.; Dederen, Pieter J. W. C.; Mutsaers, Martina P. C.; Hafkemeijer, Anne; Janssen, Anna-Lena; Nobelen, Cindy L. M.; Veltien, Andor; Asten, Jack J.; Heerschap, Arend; Kiliaan, Amanda J.

    2013-01-01

    Proton magnetic resonance spectroscopy (1H MRS) is a valuable tool in Alzheimer’s disease research, investigating the functional integrity of the brain. The present longitudinal study set out to characterize the neurochemical profile of the hippocampus, measured by single voxel 1H MRS at 7 Tesla, in the brains of AβPPSswe-PS1dE9 and wild-type mice at 8 and 12 months of age. Furthermore, we wanted to determine whether alterations in hippocampal metabolite levels coincided with behavioral changes, cognitive decline and neuropathological features, to gain a better understanding of the underlying neurodegenerative processes. Moreover, correlation analyses were performed in the 12-month-old AβPP-PS1 animals with the hippocampal amyloid-β deposition, TBS-T soluble Aβ levels and high-molecular weight Aβ aggregate levels to gain a better understanding of the possible involvement of Aβ in neurochemical and behavioral changes, cognitive decline and neuropathological features in AβPP-PS1 transgenic mice. Our results show that at 8 months of age AβPPswe-PS1dE9 mice display behavioral and cognitive changes compared to age-matched wild-type mice, as determined in the open field and the (reverse) Morris water maze. However, there were no variations in hippocampal metabolite levels at this age. AβPP-PS1 mice at 12 months of age display more severe behavioral and cognitive impairment, which coincided with alterations in hippocampal metabolite levels that suggest reduced neuronal integrity. Furthermore, correlation analyses suggest a possible role of Aβ in inflammatory processes, synaptic dysfunction and impaired neurogenesis. PMID:23717459

  3. Sodium Channel Voltage-Gated Beta 2 Plays a Vital Role in Brain Aging Associated with Synaptic Plasticity and Expression of COX5A and FGF-2.

    Science.gov (United States)

    XiYang, Yan-Bin; Wang, You-Cui; Zhao, Ya; Ru, Jin; Lu, Bing-Tuan; Zhang, Yue-Ning; Wang, Nai-Chao; Hu, Wei-Yan; Liu, Jia; Yang, Jin-Wei; Wang, Zhao-Jun; Hao, Chun-Guang; Feng, Zhong-Tang; Xiao, Zhi-Cheng; Dong, Wei; Quan, Xiong-Zhi; Zhang, Lian-Feng; Wang, Ting-Hua

    2016-03-01

    The role of sodium channel voltage-gated beta 2 (SCN2B) in brain aging is largely unknown. The present study was therefore designed to determine the role of SCN2B in brain aging by using the senescence-accelerated mice prone 8 (SAMP8), a brain senescence-accelerated animal model, together with the SCN2B transgenic mice. The results showed that SAMP8 exhibited impaired learning and memory functions, assessed by the Morris water maze test, as early as 8 months of age. The messenger RNA (mRNA) and protein expressions of SCN2B were also upregulated in the prefrontal cortex at this age. Treatment with traditional Chinese anti-aging medicine Xueshuangtong (Panax notoginseng saponins, PNS) significantly reversed the SCN2B expressions in the prefrontal cortex, resulting in improved learning and memory. Moreover, SCN2B knockdown transgenic mice were generated and bred to determine the roles of SCN2B in brain senescence. A reduction in the SCN2B level by 60.68% resulted in improvement in the hippocampus-dependent spatial recognition memory and long-term potential (LTP) slope of field excitatory postsynaptic potential (fEPSP), followed by an upregulation of COX5A mRNA levels and downregulation of fibroblast growth factor-2 (FGF-2) mRNA expression. Together, the present findings indicated that SCN2B could play an important role in the aging-related cognitive deterioration, which is associated with the regulations of COX5A and FGF-2. These findings could provide the potential strategy of candidate target to develop antisenescence drugs for the treatment of brain aging.

  4. Synapse geometry and receptor dynamics modulate synaptic strength.

    Directory of Open Access Journals (Sweden)

    Dominik Freche

    Full Text Available Synaptic transmission relies on several processes, such as the location of a released vesicle, the number and type of receptors, trafficking between the postsynaptic density (PSD and extrasynaptic compartment, as well as the synapse organization. To study the impact of these parameters on excitatory synaptic transmission, we present a computational model for the fast AMPA-receptor mediated synaptic current. We show that in addition to the vesicular release probability, due to variations in their release locations and the AMPAR distribution, the postsynaptic current amplitude has a large variance, making a synapse an intrinsic unreliable device. We use our model to examine our experimental data recorded from CA1 mice hippocampal slices to study the differences between mEPSC and evoked EPSC variance. The synaptic current but not the coefficient of variation is maximal when the active zone where vesicles are released is apposed to the PSD. Moreover, we find that for certain type of synapses, receptor trafficking can affect the magnitude of synaptic depression. Finally, we demonstrate that perisynaptic microdomains located outside the PSD impacts synaptic transmission by regulating the number of desensitized receptors and their trafficking to the PSD. We conclude that geometrical modifications, reorganization of the PSD or perisynaptic microdomains modulate synaptic strength, as the mechanisms underlying long-term plasticity.

  5. Maternal aging affects oocyte resilience to carbonyl cyanide-m-chlorophenylhydrazone -induced mitochondrial dysfunction in cows.

    Directory of Open Access Journals (Sweden)

    Kazuki Kansaku

    Full Text Available Mitochondrial quality control is important for maintaining cellular and oocyte viability. In addition, aging affects mitochondrial quality in many cell types. In the present study, we examined how aging affects oocyte mitochondrial biogenesis and degeneration in response to induced mitochondrial dysfunction. Cumulus oocyte complexes were harvested from the ovaries of young (21‒45 months and aged (≥120 months cows and treated for 2 hours with 10 μM carbonyl cyanide-m- chlorophenylhydrazone (CCCP, or a vehicle control, after which cumulus oocyte complexes were subjected to in vitro fertilization and culture. CCCP treatment reduced ATP content and increased reactive oxygen species (ROS levels in the oocytes of both young and aged cows. When CCCP-treated cumulus oocyte complexes were subsequently cultured for 19 hours and/or subjected to fertilization, high ROS levels in oocytes and a low rate of blastocyst development was observed in oocytes derived from aged cows. In addition, we observed differential responses in mitochondrial biogenesis to CCCP treatment between young and aged cows. CCCP treatment enhanced mitochondrial biogenesis concomitant with upregulation of SIRT1 expression in oocytes of young, but not aged, cows. In conclusion, aging affects mitochondrial quality control and recuperation of oocytes following CCCP-induced mitochondrial dysfunction.

  6. Age effects on preattentive and early attentive auditory processing of redundant stimuli: is sensory gating affected by physiological aging?

    Science.gov (United States)

    Gmehlin, Dennis; Kreisel, Stefan H; Bachmann, Silke; Weisbrod, Matthias; Thomas, Christine

    2011-10-01

    The frontal hypothesis of aging predicts an age-related decline in cognitive functions requiring inhibitory or attentional regulation. In Alzheimer's disease, preattentive gating out of redundant information is impaired. Our study aimed to examine changes associated with physiological aging in both pre- and early attentive inhibition of recurrent acoustic information. Using a passive double-click paradigm, we recorded mid-latency (P30-P50) and late-latency (N100 and P200) evoked potentials in healthy young (26 ± 5 years) and healthy elderly subjects (72 ± 5 years). Physiological aging did not affect auditory gating in amplitude measures. Both age groups exhibited clear inhibition in preattentive P50 and attention-modulated (N100) components, whereas P30 was not attenuated. Irrespective of age, the magnitude of inhibition differed significantly, being most pronounced for N100 gating. Inhibition of redundant information seems to be preserved with physiological aging. Early attentive N100 gating showed the maximum effect. Further studies are warranted to evaluate sensory gating as a suitable biomarker of underlying neurodegenerative disease.

  7. Modulatory Effect of Aerobic Physical Activity on Synaptic Ultrastructure in the Old Mouse Hippocampus

    Directory of Open Access Journals (Sweden)

    Patrizia Fattoretti

    2018-05-01

    Full Text Available Aerobic physical exercise (APE leads to improved brain functions. To better understand the beneficial effect of APE on the aging brain, a morphometric study was carried out of changes in hippocampal synapses of old (>27 months Balb/c mice undergoing treadmill training (OTT for 4 weeks in comparison with old sedentary (OS, middle-aged sedentary (MAS and middle-aged treadmill training (MATT mice. The inner molecular layer of the hippocampal dentate gyrus (IMLDG and the molecular stratum of Ammon’s horn1 neurons (SMCA1 were investigated. The number of synapses per cubic micron of tissue (numeric density, Nv, overall synaptic area per cubic micron of tissue (surface density, Sv, average area of synaptic contact zones (S, and frequency (% of perforated synapses (PS were measured in electron micrographs of ethanol-phosphotungstic acid (E-PTA stained tissue. Data were analyzed with analysis of variance (ANOVA. In IMLDG, an effect of age was found for Nv and Sv, but not S and %PS. Similar results were found for exercise and the interaction of age and exercise. In post hoc analysis Nv was higher (60.6% to 75.1%; p < 0.001 in MATT vs. MAS, OS and OTT. Sv was higher (32.3% to 54.6%; p < 0.001 in MATT vs. MAS, OS and OTT. In SMCA1, age affected Nv, Sv and %PS, but not S. The effect of exercise was significant for Sv only. The interaction of age and exercise was significant for Nv, Sv and %PS. In post hoc analysis Nv was lower in OS vs. MAS, MATT and OTT (−26.1% to −32.1%; p < 0.038. MAS and OTT were similar. Sv was lower in OS vs. MAS, MATT and OTT (−23.4 to −30.3%, p < 0.004. MAS and OTT were similar. PS frequency was higher in OS vs. MAS, MATT and OTT (48.3% to +96.6%, p < 0.023. APE positively modulated synaptic structural dynamics in the aging hippocampus, possibly in a region-specific way. The APE-associated reduction in PS frequency in SMCA1 of old mice suggests that an increasing complement of PS is a compensatory phenomenon to maintain

  8. Association between age at onset of psychosis and age at onset of cannabis use in non-affective psychosis.

    Science.gov (United States)

    Galvez-Buccollini, Juan A; Proal, Ashley C; Tomaselli, Veronica; Trachtenberg, Melissa; Coconcea, Cristinel; Chun, Jinsoo; Manschreck, Theo; Fleming, Jerry; Delisi, Lynn E

    2012-08-01

    Several studies have associated cannabis use with the development of schizophrenia. However, it has been difficult to disentangle the effects of cannabis from that of other illicit drugs, as previous studies have not evaluated pure cannabis users. To test whether the onset of cannabis use had an effect on the initiation of psychosis, we examined the time relationship between onset of use and onset of psychosis, restricting our analysis to a cohort of individuals who only used cannabis and no other street drugs. Fifty-seven subjects with non-affective psychoses who used cannabis prior to developing a psychosis were interviewed using the Diagnostic Interview for Genetic Studies (DIGS). The Family Interview for Genetic Studies (FIGS) was also used to interview a family informant about psychiatric illness in the patient and the entire family. Multiple linear regression techniques were used to estimate the association between variables. After adjusting for potential confounding factors such as sex, age, lifetime diagnosis of alcohol abuse or dependence, and family history of schizophrenia, the age at onset of cannabis was significantly associated with age at onset of psychosis (β=0.4, 95% CI=0.1-0.7, p=0.004) and age at first hospitalization (β=0.4, 95% CI=0.1-0.8, p=0.008). The mean time between beginning to use cannabis and onset of psychosis was 7.0±4.3. Age at onset of alcohol use was not associated with age at onset of psychosis or age at first hospitalization. Age at onset of cannabis is directly associated with age at onset of psychosis and age at first hospitalization. These associations remain significant after adjusting for potential confounding factors and are consistent with the hypothesis that cannabis could cause or precipitate the onset of psychosis after a prolonged period of time. Published by Elsevier B.V.

  9. Synaptic electronics: materials, devices and applications.

    Science.gov (United States)

    Kuzum, Duygu; Yu, Shimeng; Wong, H-S Philip

    2013-09-27

    In this paper, the recent progress of synaptic electronics is reviewed. The basics of biological synaptic plasticity and learning are described. The material properties and electrical switching characteristics of a variety of synaptic devices are discussed, with a focus on the use of synaptic devices for neuromorphic or brain-inspired computing. Performance metrics desirable for large-scale implementations of synaptic devices are illustrated. A review of recent work on targeted computing applications with synaptic devices is presented.

  10. Synaptic electronics: materials, devices and applications

    International Nuclear Information System (INIS)

    Kuzum, Duygu; Yu, Shimeng; Philip Wong, H-S

    2013-01-01

    In this paper, the recent progress of synaptic electronics is reviewed. The basics of biological synaptic plasticity and learning are described. The material properties and electrical switching characteristics of a variety of synaptic devices are discussed, with a focus on the use of synaptic devices for neuromorphic or brain-inspired computing. Performance metrics desirable for large-scale implementations of synaptic devices are illustrated. A review of recent work on targeted computing applications with synaptic devices is presented. (topical review)

  11. Infant pain-related negative affect at 12 months of age: early infant and caregiver predictors.

    Science.gov (United States)

    Din Osmun, Laila; Pillai Riddell, Rebecca; Flora, David B

    2014-01-01

    To examine the predictive relationships of early infant and caregiver variables on expressed pain-related negative affect duration at the 12-month immunization. Infants and their caregivers (N = 255) were followed during immunization appointments over the first year of life. Latent growth curve modeling in a structural equation modeling context was used. Higher levels of initial infant pain reactivity at 2 months and caregiver emotional availability averaged across 2, 4, and 6 months of age were related to larger decreases in the duration of infant negative affect over the first 6 months of life. Longer duration of infant negative affect at 2 months and poorer regulation of infant negative affect over the first 6 months of life predicted longer durations of infant negative affect by 12 months. Infant negative affect at 12 months was a function of both infant factors and the quality of caregiver interactive behaviors (emotional availability) in early infancy.

  12. Factors affecting aging cognitive function among community-dwelling older adults.

    Science.gov (United States)

    Kim, Chun-Ja; Park, JeeWon; Kang, Se-Won; Schlenk, Elizabeth A

    2017-08-01

    The study purpose was to determine factors affecting aging cognitive function of 3,645 community-dwelling older adults in Korea. The Hasegawa Dementia Scale assessed aging cognitive function, blood analyses and anthropometrics assessed cardio-metabolic risk factors, and the Geriatric Depression Scale Short Form Korean Version assessed depressive symptoms. Participants with poor aging cognitive function were more likely to be in the late age group (≥75 y) and currently smoking and have a medical history of stroke, high body mass index, and high level of depressive symptoms; they were also less likely to engage in regular meals and physical activities. Regular meals and physical activities may be primary factors for clinical assessment to identify older adults at risk for aging cognitive function. With aging, depressive symptoms and other unhealthy lifestyle behaviours should be managed to prevent cognitive function disorders. © 2017 John Wiley & Sons Australia, Ltd.

  13. Re-evaluating neonatal-age models for ungulates: does model choice affect survival estimates?

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    Troy W Grovenburg

    Full Text Available New-hoof growth is regarded as the most reliable metric for predicting age of newborn ungulates, but variation in estimated age among hoof-growth equations that have been developed may affect estimates of survival in staggered-entry models. We used known-age newborns to evaluate variation in age estimates among existing hoof-growth equations and to determine the consequences of that variation on survival estimates. During 2001-2009, we captured and radiocollared 174 newborn (≤24-hrs old ungulates: 76 white-tailed deer (Odocoileus virginianus in Minnesota and South Dakota, 61 mule deer (O. hemionus in California, and 37 pronghorn (Antilocapra americana in South Dakota. Estimated age of known-age newborns differed among hoof-growth models and varied by >15 days for white-tailed deer, >20 days for mule deer, and >10 days for pronghorn. Accuracy (i.e., the proportion of neonates assigned to the correct age in aging newborns using published equations ranged from 0.0% to 39.4% in white-tailed deer, 0.0% to 3.3% in mule deer, and was 0.0% for pronghorns. Results of survival modeling indicated that variability in estimates of age-at-capture affected short-term estimates of survival (i.e., 30 days for white-tailed deer and mule deer, and survival estimates over a longer time frame (i.e., 120 days for mule deer. Conversely, survival estimates for pronghorn were not affected by estimates of age. Our analyses indicate that modeling survival in daily intervals is too fine a temporal scale when age-at-capture is unknown given the potential inaccuracies among equations used to estimate age of neonates. Instead, weekly survival intervals are more appropriate because most models accurately predicted ages within 1 week of the known age. Variation among results of neonatal-age models on short- and long-term estimates of survival for known-age young emphasizes the importance of selecting an appropriate hoof-growth equation and appropriately defining intervals (i

  14. Factors affecting age of onset of menopause and determination of quality of life in menopause

    Directory of Open Access Journals (Sweden)

    Burcu Ceylan

    2015-03-01

    Full Text Available Menopause is a process in the climacteric period, characterized by a reduction in ovarian activity, a fall in the fertility rate, and a range of symptoms including irregular menstruation intervals. Most women enter menopause in their 40s, but this can vary from one individual to another. Although there are many factors affecting the age of menopause onset, there is no general agreement on them. Studies have shown many factors to affect the age of menopause, such as the mother’s age at menopause, the age at menarche, gestational age, use of oral contraceptives, irregular menstrual cycle, number of pregnancies, body mass index, use of tobacco and alcohol, physical activity, unilateral oophorectomy, serum lead levels, consumption of polyunsaturated fat, socioeconomic status and educational level. During this period, hormonal and biochemical changes give rise to various symptoms in the woman’s body. In menopause period, physical, psychological, social and sexual changes have a negative effect on quality of life in women. Recently, different measures have been used to assess women’s quality of life in this period of change. The purpose of this review was to examine the factors affecting the onset age of menopause and the measures of quality of life related to menopause.

  15. Cross-cultural aging in cognitive and affective components of subjective well-being.

    Science.gov (United States)

    Pethtel, Olivia; Chen, Yiwei

    2010-09-01

    The present study examined age and cultural differences in cognitive and affective components of subjective well-being. A sample of 188 American and Chinese young and older adults completed surveys measuring self-life satisfaction, perceived family's life satisfaction, positive affect, and negative affect. Across cultures, older adults reported lower negative affect than did young adults. Americans reported higher self-life satisfaction, perceived family's life satisfaction, and positive affect than did Chinese. In addition, perceived family's life satisfaction was more related to self-life satisfaction for Chinese than for Americans. Findings are discussed in light of socioemotional selectivity theory and theories on culture and self-construal. (c) 2010 APA, all rights reserved.

  16. Comparison of Nutritional Status Among, Flood Affected and Unaffected School Aged Children

    International Nuclear Information System (INIS)

    Mohsin, S.N.; Aasim, M.; Ghous, R.; Fatima, M.

    2017-01-01

    Background: Natural disasters like floods affect large human populations by not only displacing them temporarily but also poses nutritional issues to women and children. Objectives: To determine the long term effects of floods, on the nutritional status of school going children in Pakistan. Study design, settings and duration: A cross sectional study which was conducted in public schools of district Nowshera which is a large district of province Khyber Pakhtunkhwa, Pakistan from February 2012 to March 2014. Subjects and Methods: A total of 353 children aged 6-14 years were enrolled. There were 190 children from flood affected areas and 163 controls from unaffected areas. Using height, weight, age and gender, malnutrition indicators like acute malnutrition, chronic malnutrition and underweight were calculated to evaluate effect of flood on these children after 20 months of the calamity. Weight for age (WAZ) was used to measure underweight, height for age (HAZ) to measure stunted growth, and weight for height (WHZ) to measure wasting or acute malnutrition. The malnutrition indicators which were positively associated with floods were further evaluated for associated factors. Results The frequency of acute malnutrition or wasting (WHZ) among flood affected children was 23.7 percent as compared to 16.5 percent among unaffected children while the frequency of underweight (WAZ) in flood affected areas was 42.1 percent as against 36.8 percent in unaffected areas (both were not significant). The frequency of chronic malnutrition or stunting (AZ) was 35.8 percent in affected and 27.6 percent in unaffected children (p< 0.041) and was the only positively associated indicator with exposure to floods. Factors associated with chronic malnutrition were age of the child, maternal education, history of fever, administration of de-worming medication and diarrhea. Conclusion: Floods had a long term effect on nutritional status of school aged children as shown by chronic malnutrition

  17. Isolation of Synaptosomes, Synaptic Plasma Membranes, and Synaptic Junctional Complexes.

    Science.gov (United States)

    Michaelis, Mary L; Jiang, Lei; Michaelis, Elias K

    2017-01-01

    Isolation of synaptic nerve terminals or synaptosomes provides an opportunity to study the process of neurotransmission at many levels and with a variety of approaches. For example, structural features of the synaptic terminals and the organelles within them, such as synaptic vesicles and mitochondria, have been elucidated with electron microscopy. The postsynaptic membranes are joined to the presynaptic "active zone" of transmitter release through cell adhesion molecules and remain attached throughout the isolation of synaptosomes. These "post synaptic densities" or "PSDs" contain the receptors for the transmitters released from the nerve terminals and can easily be seen with electron microscopy. Biochemical and cell biological studies with synaptosomes have revealed which proteins and lipids are most actively involved in synaptic release of neurotransmitters. The functional properties of the nerve terminals, such as responses to depolarization and the uptake or release of signaling molecules, have also been characterized through the use of fluorescent dyes, tagged transmitters, and transporter substrates. In addition, isolated synaptosomes can serve as the starting material for the isolation of relatively pure synaptic plasma membranes (SPMs) that are devoid of organelles from the internal environment of the nerve terminal, such as mitochondria and synaptic vesicles. The isolated SPMs can reseal and form vesicular structures in which transport of ions such as sodium and calcium, as well as solutes such as neurotransmitters can be studied. The PSDs also remain associated with the presynaptic membranes during isolation of SPM fractions, making it possible to isolate the synaptic junctional complexes (SJCs) devoid of the rest of the plasma membranes of the nerve terminals and postsynaptic membrane components. Isolated SJCs can be used to identify the proteins that constitute this highly specialized region of neurons. In this chapter, we describe the steps involved

  18. Age-Dependent Pre-Vaccination Immunity Affects the Immunogenicity of Varicella Zoster Vaccination in Middle-aged Adults

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    Marieke van der Heiden

    2018-01-01

    Full Text Available BackgroundPrevention of infectious diseases is of high priority in the rapidly aging population. Unfortunately, vaccine responses in the elderly are frequently diminished. Timely vaccination of middle-aged adults might improve the immune responses to vaccines, although knowledge on pathogen-specific immune responses and factors affecting these responses, in middle-aged adults is currently limited. We thus investigated the immune responses after vaccination with Zostavax consisting of live-attenuated varicella zoster virus (VZV.MethodsBlood samples were taken pre-, 14 days, 28 days, and 1 year after a primary VZV vaccination (Zostavax at middle age (N = 53, 50–65 years of age. VZV-specific IFNγ-producing cells were measured by ELISpot, activated T-cells by flow cytometry, antibody levels and cytokine responses by fluorescent bead-based multiplex immunoassays, and whole blood cellular kinetics by TruCOUNT analysis.ResultsRobust short-term enhancement of the VZV-specific IFNγ-producing cell numbers was observed post-vaccination in the middle-aged adults. Remarkably, long-term enhancement of VZV-specific IFNγ-producing cell numbers was induced only in participants with low numbers of VZV-specific pre-vaccination IFNγ-producing cells, who were significantly older. These participants also showed enhancement of VZV-specific activated CD4 T-cells, contrary to “exhausted” VZV-specific CD8 T-cells in participants with high numbers of VZV-specific pre-vaccination IFNγ-producing cells. Finally, a high CD4/CD8 T-cell ratio was associated with low numbers of pre-vaccination VZV-specific IFNγ-producing cells.ConclusionThese results suggest that adults in their early sixties, who showed a high CD4/CD8 T-cell ratio and low numbers of VZV-specific IFNγ-producing cells, benefit from VZV vaccination. This provides important knowledge on factors affecting VZV-specific immune responses in middle-aged adults as well as for strategies to

  19. Who is affected by neighbourhood income mix? gender, age, family, employment and income differences

    NARCIS (Netherlands)

    Galster, G.; Andersson, R.; Musterd, S.

    2010-01-01

    This paper analyses the degree to which the mixture of low-, middle- and high-income males in the neighbourhood affects the subsequent earnings of individuals, and aims to test explicitly the degree to which these impacts vary across gender, age, presence of children, employment status or income at

  20. Do Aging and Tactile Noise Stimulation Affect Responses to Support Surface Translations in Healthy Adults?

    Directory of Open Access Journals (Sweden)

    Marius Dettmer

    2016-01-01

    Full Text Available Appropriate neuromuscular responses to support surface perturbations are crucial to prevent falls, but aging-related anatomical and physiological changes affect the appropriateness and efficiency of such responses. Low-level noise application to sensory receptors has shown to be effective for postural improvement in a variety of different balance tasks, but it is unknown whether this intervention may have value for improvement of corrective postural responses. Ten healthy younger and ten healthy older adults were exposed to sudden backward translations of the support surface. Low-level noise (mechanical vibration to the foot soles was added during random trials and temporal (response latency and spatial characteristics (maximum center-of-pressure excursion and anterior-posterior path length of postural responses were assessed. Mixed-model ANOVA was applied for analysis of postural response differences based on age and vibration condition. Age affected postural response characteristics, but older adults were well able to maintain balance when exposed to a postural perturbation. Low-level noise application did not affect any postural outcomes. Healthy aging affects some specific measures of postural stability, and in high-functioning older individuals, a low-level noise intervention may not be valuable. More research is needed to investigate if recurring fallers and neuropathy patients could benefit from the intervention in postural perturbation tasks.

  1. Daily Social Exchanges and Affect in Middle and Later Adulthood: The Impact of Loneliness and Age

    Science.gov (United States)

    Russell, Alissa; Bergeman, C. S.; Scott, Stacey B.

    2012-01-01

    Although daily social exchanges are important for well-being, it is unclear how different types of exchanges affect daily well-being, as well as which factors influence the way in which individuals react to their daily social encounters. The present study included a sample of 705 adults aged 31 to 91, and using Multilevel Modeling analyses…

  2. Dietary restriction of rodents decreases aging rate without affecting initial mortality rate -- a meta-analysis.

    Science.gov (United States)

    Simons, Mirre J P; Koch, Wouter; Verhulst, Simon

    2013-06-01

    Dietary restriction (DR) extends lifespan in multiple species from various taxa. This effect can arise via two distinct but not mutually exclusive ways: a change in aging rate and/or vulnerability to the aging process (i.e. initial mortality rate). When DR affects vulnerability, this lowers mortality instantly, whereas a change in aging rate will gradually lower mortality risk over time. Unraveling how DR extends lifespan is of interest because it may guide toward understanding the mechanism(s) mediating lifespan extension and also has practical implications for the application of DR. We reanalyzed published survival data from 82 pairs of survival curves from DR experiments in rats and mice by fitting Gompertz and also Gompertz-Makeham models. The addition of the Makeham parameter has been reported to improve the estimation of Gompertz parameters. Both models separate initial mortality rate (vulnerability) from an age-dependent increase in mortality (aging rate). We subjected the obtained Gompertz parameters to a meta-analysis. We find that DR reduced aging rate without affecting vulnerability. The latter contrasts with the conclusion of a recent analysis of a largely overlapping data set, and we show how the earlier finding is due to a statistical artifact. Our analysis indicates that the biology underlying the life-extending effect of DR in rodents likely involves attenuated accumulation of damage, which contrasts with the acute effect of DR on mortality reported for Drosophila. Moreover, our findings show that the often-reported correlation between aging rate and vulnerability does not constrain changing aging rate without affecting vulnerability simultaneously. © 2013 John Wiley & Sons Ltd and the Anatomical Society.

  3. Longevity manipulations differentially affect serotonin/dopamine level and behavioral deterioration in aging Caenorhabditis elegans.

    Science.gov (United States)

    Yin, Jiang-An; Liu, Xi-Juan; Yuan, Jie; Jiang, Jing; Cai, Shi-Qing

    2014-03-12

    Aging is accompanied with behavioral and cognitive decline. Changes in the neurotransmitter level are associated with the age-related behavioral deterioration, but whether well-known longevity manipulations affect the function of neurotransmitter system in aging animals is largely unclear. Here we report that serotonin (5-HT) and dopamine (DA) level decrease with age in C. elegans. The reduction results in downregulation of the activity of neurons controlled by 5-HT/DA signaling, and deterioration of some important behaviors, including pharyngeal pumping, food-induced slowing responses, and male mating. Longevity manipulations differentially affect the age-related decline in neuronal level of 5-HT/DA. The reduction and resultant behavioral deterioration occur in long-lived worms with defective insulin signaling [daf-2(e1370), age-1(hx546)] or mitochondria function [isp-1(qm150), tpk-1(qm162)], but not in long-lived worms with dietary restriction eat-2(ad1116). A reduced expression level of dopa decarboxylase BAS-1, the shared enzyme for 5-HT/DA synthesis, is responsible for the decline in 5-HT/DA levels. RNAi assay revealed that the sustained 5-HT/DA level in neurons of aged eat-2(ad1116) worms requires PHA-4 and its effectors superoxide dismutases and catalases, suggesting the involvement of reactive oxygen species in the 5-HT/DA decline. Furthermore, we found that elevating 5-HT/DA ameliorates age-related deterioration of pharyngeal pumping, food-induced slowing responses, and male mating in both wild-type and daf-2(e1370) worms. Together, dietary restriction preserves healthy behaviors in aged worms at least partially by sustaining a high 5-HT/DA level, and elevating the 5-HT/DA level in wild-type and daf-2(e1370) worms improves their behaviors during aging.

  4. Synaptic theory of Replicator-like melioration

    Directory of Open Access Journals (Sweden)

    Yonatan Loewenstein

    2010-06-01

    Full Text Available According to the theory of Melioration, organisms in repeated choice settings shift their choice preference in favor of the alternative that provides the highest return. The goal of this paper is to explain how this learning behavior can emerge from microscopic changes in the efficacies of synapses, in the context of two-alternative repeated-choice experiment. I consider a large family of synaptic plasticity rules in which changes in synaptic efficacies are driven by the covariance between reward and neural activity. I construct a general framework that predicts the learning dynamics of any decision-making neural network that implements this synaptic plasticity rule and show that melioration naturally emerges in such networks. Moreover, the resultant learning dynamics follows the Replicator equation which is commonly used to phenomenologically describe changes in behavior in operant conditioning experiments. Several examples demonstrate how the learning rate of the network is affected by its properties and by the specifics of the plasticity rule. These results help bridge the gap between cellular physiology and learning behavior.

  5. Secreted factors as synaptic organizers.

    Science.gov (United States)

    Johnson-Venkatesh, Erin M; Umemori, Hisashi

    2010-07-01

    A critical step in synaptic development is the differentiation of presynaptic and postsynaptic compartments. This complex process is regulated by a variety of secreted factors that serve as synaptic organizers. Specifically, fibroblast growth factors, Wnts, neurotrophic factors and various other intercellular signaling molecules are proposed to regulate presynaptic and/or postsynaptic differentiation. Many of these factors appear to function at both the neuromuscular junction and in the central nervous system, although the specific function of the molecules differs between the two. Here we review secreted molecules that organize the synaptic compartments and discuss how these molecules shape synaptic development, focusing on mammalian in vivo systems. Their critical role in shaping a functional neural circuit is underscored by their possible link to a wide range of neurological and psychiatric disorders both in animal models and by mutations identified in human patients. © The Authors (2010). Journal Compilation © Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  6. Positive affect and cognitive decline: a 12-year follow-up of the Maastricht Aging Study.

    Science.gov (United States)

    Berk, Lotte; van Boxtel, Martin; Köhler, Sebastian; van Os, Jim

    2017-12-01

    In cross-sectional studies, positive affect (PA) has been associated with higher levels of cognitive functioning. This study examined whether positive affect (PA) is associated with change in cognitive function over 12 years in an adult population sample. Participants (n = 258), aged 40 to 82 years, were drawn from a subsample of the Maastricht Aging Study (MAAS) and assessed at baseline, 6 years and 12 years. PA was measured at baseline with a Dutch translation of the Positive and Negative Affect Schedule (PANAS). PA scores and associations with cognitive decline were tested in random-effects models. Controlling for demographics and depressive symptoms, there was no significant association with PA scores and decline in memory (χ 2  = 1.52; df = 2; P = 0.47), executive functions (χ 2  = 0.99; df = 2; P = 0.61), and information processing speed (χ 2  = 0.52; df = 2; P = 0.77) at 6- and 12-year follow-up. PA did not predict cognitive change over time. These findings question the extent of protective effects of PA on cognitive aging in adulthood, and are discussed in terms of age range and types of measures used for PA and cognition. Copyright © 2016 John Wiley & Sons, Ltd.

  7. Mood, motivation, and misinformation: aging and affective state influences on memory.

    Science.gov (United States)

    Hess, Thomas M; Popham, Lauren E; Emery, Lisa; Elliott, Tonya

    2012-01-01

    Normative age differences in memory have typically been attributed to declines in basic cognitive and cortical mechanisms. The present study examined the degree to which dominant everyday affect might also be associated with age-related memory errors using the misinformation paradigm. Younger and older adults viewed a positive and a negative event, and then were exposed to misinformation about each event. Older adults exhibited a higher likelihood than young adults of falsely identifying misinformation as having occurred in the events. Consistent with expectations, strength of the misinformation effect was positively associated with dominant mood, and controlling for mood eliminated any age effects. Also, motivation to engage in complex cognitive activity was negatively associated with susceptibility to misinformation, and susceptibility was stronger for negative than for positive events. We argue that motivational processes underlie all of the observed effects, and that such processes are useful in understanding age differences in memory performance.

  8. Synaptic consolidation across multiple timescales

    Directory of Open Access Journals (Sweden)

    Lorric Ziegler

    2014-03-01

    Full Text Available The brain is bombarded with a continuous stream of sensory events, but retains only a small subset in memory. The selectivity of memory formation prevents our memory from being overloaded with irrelevant items that would rapidly bring the brain to its storage limit; moreover, selectivity also prevents overwriting previously formed memories with new ones. Memory formation in the hippocampus, as well as in other brain regions, is thought to be linked to changes in the synaptic connections between neurons. In this view, sensory events imprint traces at the level of synapses that reflect potential memory items. The question of memory selectivity can therefore be reformulated as follows: what are the reasons and conditions that some synaptic traces fade away whereas others are consolidated and persist? Experimentally, changes in synaptic strength induced by 'Hebbian' protocols fade away over a few hours (early long-term potentiation or e-LTP, unless these changes are consolidated. The experiments and conceptual theory of synaptic tagging and capture (STC provide a mechanistic explanation for the processes involved in consolidation. This theory suggests that the initial trace of synaptic plasticity sets a tag at the synapse, which then serves as a marker for potential consolidation of the changes in synaptic efficacy. The actual consolidation processes, transforming e-LTP into late LTP (l-LTP, require the capture of plasticity-related proteins (PRP. We translate the above conceptual model into a compact computational model that accounts for a wealth of in vitro data including experiments on cross-tagging, tag-resetting and depotentiation. A central ingredient is that synaptic traces are described with several variables that evolve on different time scales. Consolidation requires the transmission of information from a 'fast' synaptic trace to a 'slow' one through a 'write' process, including the formation of tags and the production of PRP for the

  9. Aging and a genetic KIBRA polymorphism interactively affect feedback- and observation-based probabilistic classification learning.

    Science.gov (United States)

    Schuck, Nicolas W; Petok, Jessica R; Meeter, Martijn; Schjeide, Brit-Maren M; Schröder, Julia; Bertram, Lars; Gluck, Mark A; Li, Shu-Chen

    2018-01-01

    Probabilistic category learning involves complex interactions between the hippocampus and striatum that may depend on whether acquisition occurs via feedback or observation. Little is known about how healthy aging affects these processes. We tested whether age-related behavioral differences in probabilistic category learning from feedback or observation depend on a genetic factor known to influence individual differences in hippocampal function, the KIBRA gene (single nucleotide polymorphism rs17070145). Results showed comparable age-related performance impairments in observational as well as feedback-based learning. Moreover, genetic analyses indicated an age-related interactive effect of KIBRA on learning: among older adults, the beneficial T-allele was positively associated with learning from feedback, but negatively with learning from observation. In younger adults, no effects of KIBRA were found. Our results add behavioral genetic evidence to emerging data showing age-related differences in how neural resources relate to memory functions, namely that hippocampal and striatal contributions to probabilistic category learning may vary with age. Our findings highlight the effects genetic factors can have on differential age-related decline of different memory functions. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Synaptic vesicle exocytosis in hippocampal synaptosomes correlates directly with total mitochondrial volume

    Science.gov (United States)

    Ivannikov, Maxim V.; Sugimori, Mutsuyuki; Llinás, Rodolfo R.

    2012-01-01

    Synaptic plasticity in many regions of the central nervous system leads to the continuous adjustment of synaptic strength, which is essential for learning and memory. In this study, we show by visualizing synaptic vesicle release in mouse hippocampal synaptosomes that presynaptic mitochondria and specifically, their capacities for ATP production are essential determinants of synaptic vesicle exocytosis and its magnitude. Total internal reflection microscopy of FM1-43 loaded hippocampal synaptosomes showed that inhibition of mitochondrial oxidative phosphorylation reduces evoked synaptic release. This reduction was accompanied by a substantial drop in synaptosomal ATP levels. However, cytosolic calcium influx was not affected. Structural characterization of stimulated hippocampal synaptosomes revealed that higher total presynaptic mitochondrial volumes were consistently associated with higher levels of exocytosis. Thus, synaptic vesicle release is linked to the presynaptic ability to regenerate ATP, which itself is a utility of mitochondrial density and activity. PMID:22772899

  11. Factors affecting nocturnal enuresis amongst school-aged children: brief report

    OpenAIRE

    Ashrafalsadat Hakim; Farshid Kompani; Mohammad Bahadoram

    2015-01-01

    Enuresis is the inability to control urination during sleep. It is one of the most common childhood urologic disorders. Nocturnal enuresis refers to the occurrence of involuntary voiding at night after 5 years. Persistent nocturia can decrease self-esteem, increase anxiety and other emotional problems in children. The aim of this study is to evaluate the factors affecting nocturia amongst school-aged children. Methods: This cross- sectional study was conducted on 200 children over a period...

  12. Thermal Aging Effects on Heat Affected Zone of Alloy 600 in Dissimilar Metal Weld

    Energy Technology Data Exchange (ETDEWEB)

    Ham, Jun Hyuk; Choi, Kyoung Joon; Yoo, Seung Chang; Kim, Ji Hyun [UNIST, Ulsan (Korea, Republic of)

    2016-05-15

    Dissimilar metal weld (DMW), consists of Alloy 600, Alloy 182, and A508 Gr.3, is now being widely used as the reactor pressure vessel penetration nozzle and the steam generator tubing material for pressurized water reactors (PWR) because of its mechanical property, thermal expansion coefficient, and corrosion resistance. The heat affected zone (HAZ) on Alloy 600 which is formed by welding process is critical to crack. According to G.A. Young et al. crack growth rates (CGR) in the Alloy 600 HAZ were about 30 times faster than those in the Alloy 600 base metal tested under the same conditions [3]. And according to Z.P. Lu et al. CGR in the Alloy 600 HAZ can be more than 20 times higher than that in its base metal. To predict the life time of components, there is a model which can calculate the effective degradation years (EDYs) of the material as a function of operating temperature. This study was conducted to investigate how thermal aging affects the hardness of dissimilar metal weld from the fusion boundary to Alloy 600 base metal and the residual strain at Alloy 600 heat affected zone. Following conclusions can be drawn from this study. The hardness, measured by Vickers hardness tester, peaked near the fusion boundary between Alloy 182 and Alloy 600, and it decreases as the picked point goes to Alloy 600 base metal. Even though the formation of precipitate such as Cr carbide, thermal aging doesn't affect the value and the tendency of hardness because of reduced residual stress. According to kernel average misorientation mapping, residual strain decreases when the material thermally aged. And finally, in 30 years simulated specimen, the high residual strain almost disappears. Therefore, the influence of residual strain on primary water stress corrosion cracking can be diminished when the material undergoes thermal aging.

  13. BDNF val66met polymorphism affects aging of multiple types of memory.

    Science.gov (United States)

    Kennedy, Kristen M; Reese, Elizabeth D; Horn, Marci M; Sizemore, April N; Unni, Asha K; Meerbrey, Michael E; Kalich, Allan G; Rodrigue, Karen M

    2015-07-01

    The BDNF val66met polymorphism (rs6265) influences activity-dependent secretion of brain-derived neurotrophic factor in the synapse, which is crucial for learning and memory. Individuals homozygous or heterozygous for the met allele have lower BDNF secretion than val homozygotes and may be at risk for reduced declarative memory performance, but it remains unclear which types of declarative memory may be affected and how aging of memory across the lifespan is impacted by the BDNF val66met polymorphism. This cross-sectional study investigated the effects of BDNF polymorphism on multiple indices of memory (item, associative, prospective, subjective complaints) in a lifespan sample of 116 healthy adults aged 20-93 years. Advancing age showed a negative effect on item, associative and prospective memory, but not on subjective memory complaints. For item and prospective memory, there were significant age×BDNF group interactions, indicating the adverse effect of age on memory performance across the lifespan was much stronger in the BDNF met carriers than for the val homozygotes. BDNF met carriers also endorsed significantly greater subjective memory complaints, regardless of age, and showed a trend (pmemory performance compared to val homozygotes. These results suggest that genetic predisposition to the availability of brain-derived neurotrophic factor, by way of the BDNF val66met polymorphism, exerts an influence on multiple indices of episodic memory - in some cases in all individuals regardless of age (subjective memory and perhaps associative memory), in others as an exacerbation of age-related differences in memory across the lifespan (item and prospective memory). This article is part of a Special Issue entitled Memory & Aging. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Ageing differentially affects neural processing of different conflict types – an fMRI study

    Directory of Open Access Journals (Sweden)

    Margarethe eKorsch

    2014-04-01

    Full Text Available Interference control and conflict resolution is affected by ageing. There is increasing evidence that ageing does not compromise interference control in general but rather shows distinctive effects on different components of interference control. Different conflict types, (e.g. stimulus-stimulus (S-S or stimulus-response (S-R conflicts trigger different cognitive processes and thus activate different neural networks. In the present functional magnetic resonance imaging (fMRI study, we used a combined Flanker and Stimulus Response Conflict (SRC task to investigate the effect of ageing on S-S and S-R conflicts. Behavioral data analysis revealed larger SRC effects in elderly. fMRI Results show that both age groups recruited similar regions (caudate nucleus, cingulate gyrus and middle occipital gyrus during Flanker conflict processing. Furthermore, elderly show an additional activation pattern in parietal and frontal areas. In contrast, no common activation of both age groups was found in response to the SRC. These data suggest that ageing has distinctive effects on S-S and S-R conflicts.

  15. Ageing differentially affects neural processing of different conflict types-an fMRI study.

    Science.gov (United States)

    Korsch, Margarethe; Frühholz, Sascha; Herrmann, Manfred

    2014-01-01

    Interference control and conflict resolution is affected by ageing. There is increasing evidence that ageing does not compromise interference control in general but rather shows distinctive effects on different components of interference control. Different conflict types, [e.g., stimulus-stimulus (S-S) or stimulus-response (S-R) conflicts] trigger different cognitive processes and thus activate different neural networks. In the present functional magnetic resonance imaging (fMRI) study, we used a combined Flanker and Stimulus Response Conflict (SRC) task to investigate the effect of ageing on S-S and S-R conflicts. Behavioral data analysis revealed larger SRC effects in elderly. fMRI Results show that both age groups recruited similar regions [caudate nucleus, cingulate gyrus and middle occipital gyrus (MOG)] during Flanker conflict processing. Furthermore, elderly show an additional activation pattern in parietal and frontal areas. In contrast, no common activation of both age groups was found in response to the SRC. These data suggest that ageing has distinctive effects on S-S and S-R conflicts.

  16. Factors affecting red blood cell storage age at the time of transfusion.

    Science.gov (United States)

    Dzik, Walter H; Beckman, Neil; Murphy, Michael F; Delaney, Meghan; Flanagan, Peter; Fung, Mark; Germain, Marc; Haspel, Richard L; Lozano, Miguel; Sacher, Ronald; Szczepiorkowski, Zbigniew; Wendel, Silvano

    2013-12-01

    Clinical trials are investigating the potential benefit resulting from a reduced maximum storage interval for red blood cells (RBCs). The key drivers that determine RBC age at the time of issue vary among individual hospitals. Although progressive reduction in the maximum storage period of RBCs would be expected to result in smaller hospital inventories and reduced blood availability, the magnitude of the effect is unknown. Data on current hospital blood inventories were collected from 11 hospitals and three blood centers in five nations. A general predictive model for the age of RBCs at the time of issue was developed based on considerations of demand for RBCs in the hospital. Age of RBCs at issue is sensitive to the following factors: ABO group, storage age at the time of receipt by the hospital, the restock interval, inventory reserve, mean demand, and variation in demand. A simple model, based on hospital demand, may serve as the basis for examining factors affecting the storage age of RBCs in hospital inventories. The model suggests that the age of RBCs at the time of their issue to the patient depends on factors external to the hospital transfusion service. Any substantial change in the expiration date of stored RBCs will need to address the broad variation in demand for RBCs while attempting to balance considerations of availability and blood wastage. © 2013 American Association of Blood Banks.

  17. Chronic intermittent exposure to ayahuasca during aging does not affect memory in mice

    Directory of Open Access Journals (Sweden)

    N.F. Correa-Netto

    Full Text Available The Quechua term ayahuasca refers to a beverage obtained from decoctions of the liana Banisteriopsis caapi with leaves of Psychotria viridis. The ritualistic use of ayahuasca is becoming a global phenomenon, with some individuals using this beverage throughout life, including in old age. Cognitive impairment is a common manifestation during aging. There are conflicting reports on the ability of some ayahuasca compounds to exert neuroprotective or neurotoxic effects that could improve or impair learning and memory. Animal models provide a relevant and accessible means of investigating the behavioral effects of ayahuasca without the environmental conditions associated with the ritualistic use of the beverage. In this study, we investigated the influence of chronic ayahuasca exposure throughout aging on the spatial reference and habituation memories of mice. Twenty-eight male c57bl/6 mice (6 months old received ayahuasca or water (1.5 mL/kg, orally twice a week for 12 months and were tested in the Morris water maze (MWM, open field and elevated plus maze (EPM tasks before and after treatment. During aging, there was significant impairment in the evocation (but not acquisition of spatial reference memory and in habituation to the open field. There was also a decrease in locomotor activity in the open field and EPM tests, whereas the anxiety parameters were unaltered. Ayahuasca treatment did not alter any of these parameters associated with aging. These findings indicate that chronic exposure to ayahuasca during aging did not affect memory in mice.

  18. Chronic intermittent exposure to ayahuasca during aging does not affect memory in mice.

    Science.gov (United States)

    Correa-Netto, N F; Coelho, L S; Galfano, G S; Nishide, F; Tamura, F; Shimizu, M K; Santos, J G; Linardi, A

    2017-06-05

    The Quechua term ayahuasca refers to a beverage obtained from decoctions of the liana Banisteriopsis caapi with leaves of Psychotria viridis. The ritualistic use of ayahuasca is becoming a global phenomenon, with some individuals using this beverage throughout life, including in old age. Cognitive impairment is a common manifestation during aging. There are conflicting reports on the ability of some ayahuasca compounds to exert neuroprotective or neurotoxic effects that could improve or impair learning and memory. Animal models provide a relevant and accessible means of investigating the behavioral effects of ayahuasca without the environmental conditions associated with the ritualistic use of the beverage. In this study, we investigated the influence of chronic ayahuasca exposure throughout aging on the spatial reference and habituation memories of mice. Twenty-eight male c57bl/6 mice (6 months old) received ayahuasca or water (1.5 mL/kg, orally) twice a week for 12 months and were tested in the Morris water maze (MWM), open field and elevated plus maze (EPM) tasks before and after treatment. During aging, there was significant impairment in the evocation (but not acquisition) of spatial reference memory and in habituation to the open field. There was also a decrease in locomotor activity in the open field and EPM tests, whereas the anxiety parameters were unaltered. Ayahuasca treatment did not alter any of these parameters associated with aging. These findings indicate that chronic exposure to ayahuasca during aging did not affect memory in mice.

  19. Maternal and Neonatal Birth Factors Affecting the Age of ASD Diagnosis.

    Science.gov (United States)

    Darcy-Mahoney, Ashley; Minter, Bonnie; Higgins, Melinda; Guo, Ying; Zauche, Lauren Head; Hirst, Jessica

    2016-12-01

    Early diagnosis of autism spectrum disorders (ASD) enables early intervention that improves long term functioning of children with ASD but is often delayed until age of school entry. Few studies have identified factors that affect timely diagnosis. This study addressed how maternal education, race, age, marital status as well as neonatal birth factors affect the age at which a child is diagnosed with ASD. This study involved a retrospective analysis of 664 records of children treated at one of the largest autism treatment centers in the United States from March 1, 2009 to December 30, 2010. Logistic regression and Cox proportional hazards regression were used to identify maternal and neonatal factors associated with age of diagnosis. Infant gender, maternal race, marital status, and maternal age were identified as significant factors for predicting the age of ASD diagnosis. In the Cox proportional hazards regression model, only maternal race and marital status were included. Median survival age till diagnosis of children born to married mothers was 53.4 months compared to 57.8 months and 63.7 months of children born to single and divorced or widowed mothers respectively. Median survival age till diagnosis for children of African American mothers was 53.8 months compared to 57.2 months for children of Caucasian mothers. No statistically significant difference of timing of ASD diagnosis was found for children of varying gestational age. Children born to older or married mothers and mothers of minority races were more likely to have an earlier ASD diagnosis. No statistically significant differences in timing of ASD diagnosis were found for children born at varying gestational ages. Identification of these factors has the potential to inform public health outreach aimed at promoting timely ASD diagnosis. This work could enhance clinical practice for timelier diagnoses of ASD by supporting parents and clinicians around the world in identifying risk factors beyond gender

  20. Acute Stress Affects the Expression of Hippocampal Mu Oscillations in an Age-Dependent Manner

    Directory of Open Access Journals (Sweden)

    Samir Takillah

    2017-09-01

    Full Text Available Anxiolytic drugs are widely used in the elderly, a population particularly sensitive to stress. Stress, aging and anxiolytics all affect low-frequency oscillations in the hippocampus and prefrontal cortex (PFC independently, but the interactions between these factors remain unclear. Here, we compared the effects of stress (elevated platform, EP and anxiolytics (diazepam, DZP on extracellular field potentials (EFP in the PFC, parietal cortex and hippocampus (dorsal and ventral parts of adult (8 months and aged (18 months Wistar rats. A potential source of confusion in the experimental studies in rodents comes from locomotion-related theta (6–12 Hz oscillations, which may overshadow the direct effects of anxiety on low-frequency and especially on the high-amplitude oscillations in the Mu range (7–12 Hz, related to arousal. Animals were restrained to avoid any confound and isolate the direct effects of stress from theta oscillations related to stress-induced locomotion. We identified transient, high-amplitude oscillations in the 7–12 Hz range (“Mu-bursts” in the PFC, parietal cortex and only in the dorsal part of hippocampus. At rest, aged rats displayed more Mu-bursts than adults. Stress acted differently on Mu-bursts depending on age: it increases vs. decreases burst, in adult and aged animals, respectively. In contrast DZP (1 mg/kg acted the same way in stressed adult and age animal: it decreased the occurrence of Mu-bursts, as well as their co-occurrence. This is consistent with DZP acting as a positive allosteric modulator of GABAA receptors, which globally potentiates inhibition and has anxiolytic effects. Overall, the effect of benzodiazepines on stressed animals was to restore Mu burst activity in adults but to strongly diminish them in aged rats. This work suggests Mu-bursts as a neural marker to study the impact of stress and DZP on age.

  1. Mutation types and aging differently affect revertant fiber expansion in dystrophic mdx and mdx52 mice.

    Directory of Open Access Journals (Sweden)

    Yusuke Echigoya

    Full Text Available Duchenne muscular dystrophy (DMD, one of the most common and lethal genetic disorders, and the mdx mouse myopathies are caused by a lack of dystrophin protein. These dystrophic muscles contain sporadic clusters of dystrophin-expressing revertant fibers (RFs, as detected by immunohistochemistry. RFs are known to arise from muscle precursor cells with spontaneous exon skipping (alternative splicing and clonally expand in size with increasing age through the process of muscle degeneration/regeneration. The expansion of revertant clusters is thought to represent the cumulative history of muscle regeneration and proliferation of such precursor cells. However, the precise mechanisms by which RFs arise and expand are poorly understood. Here, to test the effects of mutation types and aging on RF expansion and muscle regeneration, we examined the number of RFs in mdx mice (containing a nonsense mutation in exon 23 and mdx52 mice (containing deletion mutation of exon 52 with the same C57BL/6 background at 2, 6, 12, and 18months of age. Mdx mice displayed a significantly higher number of RFs compared to mdx52 mice in all age groups, suggesting that revertant fiber expansion largely depends on the type of mutation and/or location in the gene. A significant increase in the expression and clustering levels of RFs was found beginning at 6months of age in mdx mice compared with mdx52 mice. In contrast to the significant expansion of RFs with increasing age, the number of centrally nucleated fibers and embryonic myosin heavy chain-positive fibers (indicative of cumulative and current muscle regeneration, respectively decreased with age in both mouse strains. These results suggest that mutation types and aging differently affect revertant fiber expansion in mdx and mdx52 mice.

  2. Acute Stress Affects the Expression of Hippocampal Mu Oscillations in an Age-Dependent Manner.

    Science.gov (United States)

    Takillah, Samir; Naudé, Jérémie; Didienne, Steve; Sebban, Claude; Decros, Brigitte; Schenker, Esther; Spedding, Michael; Mourot, Alexandre; Mariani, Jean; Faure, Philippe

    2017-01-01

    Anxiolytic drugs are widely used in the elderly, a population particularly sensitive to stress. Stress, aging and anxiolytics all affect low-frequency oscillations in the hippocampus and prefrontal cortex (PFC) independently, but the interactions between these factors remain unclear. Here, we compared the effects of stress (elevated platform, EP) and anxiolytics (diazepam, DZP) on extracellular field potentials (EFP) in the PFC, parietal cortex and hippocampus (dorsal and ventral parts) of adult (8 months) and aged (18 months) Wistar rats. A potential source of confusion in the experimental studies in rodents comes from locomotion-related theta (6-12 Hz) oscillations, which may overshadow the direct effects of anxiety on low-frequency and especially on the high-amplitude oscillations in the Mu range (7-12 Hz), related to arousal. Animals were restrained to avoid any confound and isolate the direct effects of stress from theta oscillations related to stress-induced locomotion. We identified transient, high-amplitude oscillations in the 7-12 Hz range ("Mu-bursts") in the PFC, parietal cortex and only in the dorsal part of hippocampus. At rest, aged rats displayed more Mu-bursts than adults. Stress acted differently on Mu-bursts depending on age: it increases vs. decreases burst, in adult and aged animals, respectively. In contrast DZP (1 mg/kg) acted the same way in stressed adult and age animal: it decreased the occurrence of Mu-bursts, as well as their co-occurrence. This is consistent with DZP acting as a positive allosteric modulator of GABA A receptors, which globally potentiates inhibition and has anxiolytic effects. Overall, the effect of benzodiazepines on stressed animals was to restore Mu burst activity in adults but to strongly diminish them in aged rats. This work suggests Mu-bursts as a neural marker to study the impact of stress and DZP on age.

  3. Affect

    NARCIS (Netherlands)

    Cetinic, M.; Diamanti, J.; Szeman, I.; Blacker, S.; Sully, J.

    2017-01-01

    This chapter historicizes four divergent but historically contemporaneous genres of affect theory – romantic, realist, speculative, and materialist. While critics credited with the turn to affect in the 1990s wrote largely in the wake of poststructuralism from the perspective of gender and queer

  4. Daily interactions with aging parents and adult children: Associations with negative affect and diurnal cortisol.

    Science.gov (United States)

    Birditt, Kira S; Manalel, Jasmine A; Kim, Kyungmin; Zarit, Steven H; Fingerman, Karen L

    2017-09-01

    Midlife adults report greater investment in their children than in their parents, and these ties have important implications for well-being. To date, little research has addressed daily experiences in these ties. The present study examines daily experiences (negative and positive) with aging parents and adult children and their associations with daily negative affect and diurnal cortisol rhythms. Participants were middle-aged adults (N = 156; 56% women) from Wave 2 of the Family Exchanges Study, conducted in 2013, who completed a 7-day daily diary study, which included assessments of daily negative and positive social encounters and negative affect, and 4 days of saliva collection, which was collected 3 times a day (upon waking, 30 min after waking, and at bedtime) and assayed for cortisol. Multilevel models revealed that individuals were more likely to have contact with adult children than with parents but more likely to have negative experiences (negative interactions, avoidance, negative thoughts) with parents than with adult children. Nevertheless, contact and negative experiences with adult children were more consistently associated with negative affect and daily cortisol patterns than were interactions with parents. Findings are consistent with the intergenerational stake hypothesis, which suggests that individuals have a greater stake in their children than in their parents. Indeed, negative experiences with adult children may be more salient because tensions with adult children occur less frequently than do tensions with parents. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  5. Synaptic Effects of Electric Fields

    Science.gov (United States)

    Rahman, Asif

    Learning and sensory processing in the brain relies on the effective transmission of information across synapses. The strength and efficacy of synaptic transmission is modifiable through training and can be modulated with noninvasive electrical brain stimulation. Transcranial electrical stimulation (TES), specifically, induces weak intensity and spatially diffuse electric fields in the brain. Despite being weak, electric fields modulate spiking probability and the efficacy of synaptic transmission. These effects critically depend on the direction of the electric field relative to the orientation of the neuron and on the level of endogenous synaptic activity. TES has been used to modulate a wide range of neuropsychiatric indications, for various rehabilitation applications, and cognitive performance in diverse tasks. How can a weak and diffuse electric field, which simultaneously polarizes neurons across the brain, have precise changes in brain function? Designing therapies to maximize desired outcomes and minimize undesired effects presents a challenging problem. A series of experiments and computational models are used to define the anatomical and functional factors leading to specificity of TES. Anatomical specificity derives from guiding current to targeted brain structures and taking advantage of the direction-sensitivity of neurons with respect to the electric field. Functional specificity originates from preferential modulation of neuronal networks that are already active. Diffuse electric fields may recruit connected brain networks involved in a training task and promote plasticity along active synaptic pathways. In vitro, electric fields boost endogenous synaptic plasticity and raise the ceiling for synaptic learning with repeated stimulation sessions. Synapses undergoing strong plasticity are preferentially modulated over weak synapses. Therefore, active circuits that are involved in a task could be more susceptible to stimulation than inactive circuits

  6. Synaptic vesicle dynamic changes in a model of fragile X.

    Science.gov (United States)

    Broek, Jantine A C; Lin, Zhanmin; de Gruiter, H Martijn; van 't Spijker, Heleen; Haasdijk, Elize D; Cox, David; Ozcan, Sureyya; van Cappellen, Gert W A; Houtsmuller, Adriaan B; Willemsen, Rob; de Zeeuw, Chris I; Bahn, Sabine

    2016-01-01

    Fragile X syndrome (FXS) is a single-gene disorder that is the most common heritable cause of intellectual disability and the most frequent monogenic cause of autism spectrum disorders (ASD). FXS is caused by an expansion of trinucleotide repeats in the promoter region of the fragile X mental retardation gene (Fmr1). This leads to a lack of fragile X mental retardation protein (FMRP), which regulates translation of a wide range of messenger RNAs (mRNAs). The extent of expression level alterations of synaptic proteins affected by FMRP loss and their consequences on synaptic dynamics in FXS has not been fully investigated. Here, we used an Fmr1 knockout (KO) mouse model to investigate the molecular mechanisms underlying FXS by monitoring protein expression changes using shotgun label-free liquid-chromatography mass spectrometry (LC-MS(E)) in brain tissue and synaptosome fractions. FXS-associated candidate proteins were validated using selected reaction monitoring (SRM) in synaptosome fractions for targeted protein quantification. Furthermore, functional alterations in synaptic release and dynamics were evaluated using live-cell imaging, and interpretation of synaptic dynamics differences was investigated using electron microscopy. Key findings relate to altered levels of proteins involved in GABA-signalling, especially in the cerebellum. Further exploration using microscopy studies found reduced synaptic vesicle unloading of hippocampal neurons and increased vesicle unloading in cerebellar neurons, which suggests a general decrease of synaptic transmission. Our findings suggest that FMRP is a regulator of synaptic vesicle dynamics, which supports the role of FMRP in presynaptic functions. Taken together, these studies provide novel insights into the molecular changes associated with FXS.

  7. Ictal affective symptoms in temporal lobe epilepsy are related to gender and age.

    Science.gov (United States)

    Toth, Vanda; Fogarasi, Andras; Karadi, Kazmer; Kovacs, Norbert; Ebner, Alois; Janszky, Jozsef

    2010-07-01

    We systematically analyzed the video-recorded and patient-reported, as well as positive and negative ictal affective symptoms (IAS) in temporal lobe epilepsy (TLE). Our aim was to assess (1) frequency, (2) gender effect, (3) lateralizing significance, (4) localizing value, and (5) prognostic significance in epilepsy surgery of IAS in patients with video-registered seizures. We reviewed ictal video recordings of 184 patients (99 women, aged 16-63). All patients had surgery for intractable TLE with video-recorded complex partial seizures (CPS) due to temporal lobe lesions visualized by high-resolution magnetic resonance imaging (MRI). Affective auras (AAs) were categorized into two groups: positive or negative. We registered AAs in 18% of patients: positive in 3%, negative in 15%. We saw ictal affective behavior (IAB) in 22% of patients; 10% had positive, whereas 14% had negative IAB. Two patients had both positive and negative IAB. AAs showed an association with IAB in case of fear expression versus fear auras (p = 0.018). IAB, especially negative IAB, occurred more often in women than in men. Patients with negative IAB were younger than others. We could not demonstrate an association between IAS and the localization, lateralization, or hemispheric dominance. Surgical outcome did not associate with IAS. Patient-reported and video-recorded negative-but not positive-affective signs are related to each other. Video-recorded negative AAs occur more often in women and young patients.

  8. Methamphetamine reduces LTP and increases baseline synaptic transmission in the CA1 region of mouse hippocampus.

    Directory of Open Access Journals (Sweden)

    Jarod Swant

    2010-06-01

    Full Text Available Methamphetamine (METH is an addictive psychostimulant whose societal impact is on the rise. Emerging evidence suggests that psychostimulants alter synaptic plasticity in the brain--which may partly account for their adverse effects. While it is known that METH increases the extracellular concentration of monoamines dopamine, serotonin, and norepinephrine, it is not clear how METH alters glutamatergic transmission. Within this context, the aim of the present study was to investigate the effects of acute and systemic METH on basal synaptic transmission and long-term potentiation (LTP; an activity-induced increase in synaptic efficacy in CA1 sub-field in the hippocampus. Both the acute ex vivo application of METH to hippocampal slices and systemic administration of METH decreased LTP. Interestingly, the acute ex vivo application of METH at a concentration of 30 or 60 microM increased baseline synaptic transmission as well as decreased LTP. Pretreatment with eticlopride (D2-like receptor antagonist did not alter the effects of METH on synaptic transmission or LTP. In contrast, pretreatment with D1/D5 dopamine receptor antagonist SCH23390 or 5-HT1A receptor antagonist NAN-190 abrogated the effect of METH on synaptic transmission. Furthermore, METH did not increase baseline synaptic transmission in D1 dopamine receptor haploinsufficient mice. Our findings suggest that METH affects excitatory synaptic transmission via activation of dopamine and serotonin receptor systems in the hippocampus. This modulation may contribute to synaptic maladaption induced by METH addiction and/or METH-mediated cognitive dysfunction.

  9. Age affects not only metabolome but also metal toxicity in Scenedesmus quadricauda cultures

    Energy Technology Data Exchange (ETDEWEB)

    Kováčik, Jozef, E-mail: jozkovacik@yahoo.com [Institute of Chemistry and Biochemistry, Faculty of Agronomy, Mendel University in Brno, Zemědělská 1, 613 00 Brno (Czech Republic); CEITEC—Central European Institute of Technology, Mendel University in Brno, Zemědělská 1, 613 00 Brno (Czech Republic); Klejdus, Bořivoj [Institute of Chemistry and Biochemistry, Faculty of Agronomy, Mendel University in Brno, Zemědělská 1, 613 00 Brno (Czech Republic); CEITEC—Central European Institute of Technology, Mendel University in Brno, Zemědělská 1, 613 00 Brno (Czech Republic); Babula, Petr [Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 753/5, 625 00 Brno (Czech Republic); Hedbavny, Josef [Institute of Chemistry and Biochemistry, Faculty of Agronomy, Mendel University in Brno, Zemědělská 1, 613 00 Brno (Czech Republic)

    2016-04-05

    Highlights: • Vitality was lower in old than in young culture and amount of sucrose differed. • Cd stimulated ROS more than Ni in both cultures but NO was not extensively affected. • Cd accumulated more than Ni but old culture contained more Cd and Ni than young. • Phytochelatin 2 strongly increased under Cd and ascorbic acid under Cd and high Ni. • Young culture contained more acids and mainly citrate differed under metal excess. - Abstract: Responses of Scenedesmus quadricauda grown in vitro and differing in age (old culture—13 months, young culture—1 month) to short-term cadmium (Cd) or nickel (Ni) excess (24 h) were compared. Higher age of the culture led to lower amount of chlorophylls, ascorbic acid and glutathione but higher signal of ROS. Surprisingly, sucrose was detected using DART-Orbitrap MS in both old and young culture and subsequent quantification confirmed its higher amount (ca. 3-times) in the old culture. Cd affected viability and ROS amount more negatively than Ni that could arise from excessive Cd uptake which was also higher in all treatments than in respective Ni counterparts. Surprisingly, nitric oxide was not extensively different in response to age or metals. Strong induction of phytochelatin 2 is certainly Cd-specific response while Ni also elevated ascorbate content. Krebs cycle acids were more accumulated in the young culture but they were rather elevated in the old culture (citric acid under Ni excess). We conclude that organic solid ‘Milieu Bristol’ medium we tested is suitable for long-term storage of unicellular green algae (also successfully tested for Coccomyxa sp. and Parachlorella sp.) and the impact of age on metal uptake may be useful for bioremediation purposes.

  10. Age affects not only metabolome but also metal toxicity in Scenedesmus quadricauda cultures

    International Nuclear Information System (INIS)

    Kováčik, Jozef; Klejdus, Bořivoj; Babula, Petr; Hedbavny, Josef

    2016-01-01

    Highlights: • Vitality was lower in old than in young culture and amount of sucrose differed. • Cd stimulated ROS more than Ni in both cultures but NO was not extensively affected. • Cd accumulated more than Ni but old culture contained more Cd and Ni than young. • Phytochelatin 2 strongly increased under Cd and ascorbic acid under Cd and high Ni. • Young culture contained more acids and mainly citrate differed under metal excess. - Abstract: Responses of Scenedesmus quadricauda grown in vitro and differing in age (old culture—13 months, young culture—1 month) to short-term cadmium (Cd) or nickel (Ni) excess (24 h) were compared. Higher age of the culture led to lower amount of chlorophylls, ascorbic acid and glutathione but higher signal of ROS. Surprisingly, sucrose was detected using DART-Orbitrap MS in both old and young culture and subsequent quantification confirmed its higher amount (ca. 3-times) in the old culture. Cd affected viability and ROS amount more negatively than Ni that could arise from excessive Cd uptake which was also higher in all treatments than in respective Ni counterparts. Surprisingly, nitric oxide was not extensively different in response to age or metals. Strong induction of phytochelatin 2 is certainly Cd-specific response while Ni also elevated ascorbate content. Krebs cycle acids were more accumulated in the young culture but they were rather elevated in the old culture (citric acid under Ni excess). We conclude that organic solid ‘Milieu Bristol’ medium we tested is suitable for long-term storage of unicellular green algae (also successfully tested for Coccomyxa sp. and Parachlorella sp.) and the impact of age on metal uptake may be useful for bioremediation purposes.

  11. Does the Age of Donor Kidneys Affect Nocturnal Polyuria in Patients With Successful Real Transplantation?

    Science.gov (United States)

    Mitsui, T; Morita, K; Iwami, D; Kitta, T; Kanno, Y; Moriya, K; Takeda, M; Shinohara, N

    We investigated whether the age of donor kidneys influences the incidence of nocturnal polyuria in patients with successful renal transplantation (RTX). Eighty-five patients (45 men and 40 women) undergoing RTX (median age, 47 years) were included in this study. Twenty-four-hour bladder diaries were kept for 3 days, and nocturnal polyuria was defined as a nocturnal polyuria index (nocturnal urine volume/24-hour urine volume) of >0.33. Risk factors for nocturnal polyuria were analyzed in patients with RTX by means of the Mann-Whitney U test, χ 2 test, and a logistic regression analysis. End-stage renal disease (ESRD) developed from diabetes mellitus in 16 patients (19%). Sixty-five patients (76%) received pre-transplant dialysis, with a median duration of 5 years. The median serum creatinine level and body mass index at the most recent visit were 1.2 mg/dL and 21.2 kg/m 2 , respectively. On the basis of the 24-hour bladder diaries, nocturnal polyuria was identified in 48 patients (56%). A logistic regression analysis revealed that diabetes mellitus as the original disease for ESRD was the only risk factor for nocturnal polyuria (odds ratio, 8.95; 95% confidence interval, 2.01-65.3; P = .0028). The age of donor kidneys at examination did not affect the incidence of nocturnal polyuria (P = .9402). Nocturnal polyuria was not uncommon in patients with successful RTX. Diabetes mellitus as the original disease for ESRD was the only risk factor for nocturnal polyuria, whereas the age of donor kidneys at examination did not affect the incidence of nocturnal polyuria. Thus, nocturnal polyuria is caused by recipient factors but not donor factors. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Age affects not only metabolome but also metal toxicity in Scenedesmus quadricauda cultures.

    Science.gov (United States)

    Kováčik, Jozef; Klejdus, Bořivoj; Babula, Petr; Hedbavny, Josef

    2016-04-05

    Responses of Scenedesmus quadricauda grown in vitro and differing in age (old culture-13 months, young culture-1 month) to short-term cadmium (Cd) or nickel (Ni) excess (24h) were compared. Higher age of the culture led to lower amount of chlorophylls, ascorbic acid and glutathione but higher signal of ROS. Surprisingly, sucrose was detected using DART-Orbitrap MS in both old and young culture and subsequent quantification confirmed its higher amount (ca. 3-times) in the old culture. Cd affected viability and ROS amount more negatively than Ni that could arise from excessive Cd uptake which was also higher in all treatments than in respective Ni counterparts. Surprisingly, nitric oxide was not extensively different in response to age or metals. Strong induction of phytochelatin 2 is certainly Cd-specific response while Ni also elevated ascorbate content. Krebs cycle acids were more accumulated in the young culture but they were rather elevated in the old culture (citric acid under Ni excess). We conclude that organic solid 'Milieu Bristol' medium we tested is suitable for long-term storage of unicellular green algae (also successfully tested for Coccomyxa sp. and Parachlorella sp.) and the impact of age on metal uptake may be useful for bioremediation purposes. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. [Mixed affective states in the juvenile age (historical aspects, current state of the problem, psychopathology)].

    Science.gov (United States)

    Kopeĭko, G I

    2011-01-01

    The author analyzed the problem in historical, diagnostic and psychopathological aspects and presented the results of his own study. The aim was to study the structure and dynamics of endogenous juvenile mixed states in order to work out the psychopathological typology and to clarify the criteria of diagnosis, differential treatment and clinical-social prognosis. The study included 174 patients, 118 men and 56 women, aged from 17 to 25 years (mean age 20, 4 years). Depressive states were found in 65%, mania in 16% and mixed in 19% of patients. The clinical differentiation of mixed states was carried out basing on the dominating pole of affective disorders and the following types were singled out and described: mania type (dysphoria-like mania)--34%, depressive type (association-driven depression)--38%; alternating type of mixed states--28%. The preference of the formation of alternating and atypical variants of mixed states in the juvenile age demonstrated in the study may reflect the pathogenetic and pathoplastic effect of biological features characteristic of this age--lability and polymorphism of clinical presentations as well as immaturity of emotional and cognitive spheres.

  14. Feeling old today? Daily health, stressors, and affect explain day-to-day variability in subjective age.

    Science.gov (United States)

    Kotter-Grühn, Dana; Neupert, Shevaun D; Stephan, Yannick

    2015-01-01

    Subjective age is an important correlate of health, well-being, and longevity. So far, little is known about short-term variability in subjective age and the circumstances under which individuals feel younger/older in daily life. This study examined whether (a) older adults' felt age fluctuates on a day-to-day basis, (b) daily changes in health, stressors, and affect explain fluctuations in felt age, and (c) the daily associations between felt age and health, stressors, or affect are time-ordered. Using an eight-day daily diary approach, N = 43 adults (60-96 years, M = 74.65, SD = 8.19) filled out daily questionnaires assessing subjective age, health, daily stressors, and affect. Data were analysed using multilevel modelling. Subjective age, health, daily stressors, affect. Intra-individual variability in felt age was not explained by time but by short-term variability in other variables. Specifically, on days when participants experienced more than average health problems, stress, or negative affect they felt older than on days with average health, stress, or negative affect. No time-ordered effects were found. Bad health, many stressors, and negative affective experiences constitute circumstances under which older adults feel older than they typically do. Thus, daily measures of subjective age could be markers of health and well-being.

  15. The selective antagonism of P2X7 and P2Y1 receptors prevents synaptic failure and affects cell proliferation induced by oxygen and glucose deprivation in rat dentate gyrus.

    Directory of Open Access Journals (Sweden)

    Giovanna Maraula

    Full Text Available Purinergic P2X and P2Y receptors are broadly expressed on both neurons and glial cells in the central nervous system (CNS, including dentate gyrus (DG. The aim of this research was to determine the synaptic and proliferative response of the DG to severe oxygen and glucose deprivation (OGD in acute rat hippocampal slices and to investigate the contribution of P2X7 and P2Y1 receptor antagonism to recovery of synaptic activity after OGD. Extracellular field excitatory post-synaptic potentials (fEPSPs in granule cells of the DG were recorded from rat hippocampal slices. Nine-min OGD elicited an irreversible loss of fEPSP and was invariably followed by the appearance of anoxic depolarization (AD. Application of MRS2179 (selective antagonist of P2Y1 receptor and BBG (selective antagonist of P2X7 receptor, before and during OGD, prevented AD appearance and allowed a significant recovery of neurotransmission after 9-min OGD. The effects of 9-min OGD on proliferation and maturation of cells localized in the subgranular zone (SGZ of slices prepared from rats treated with 5-Bromo-2'-deoxyuridine (BrdU were investigated. Slices were further incubated with an immature neuron marker, doublecortin (DCX. The number of BrdU+ cells in the SGZ was significantly decreased 6 hours after OGD. This effect was antagonized by BBG, but not by MRS2179. Twenty-four hours after 9-min OGD, the number of BrdU+ cells returned to control values and a significant increase of DCX immunofluorescence was observed. This phenomenon was still evident when BBG, but not MRS2179, was applied during OGD. Furthermore, the P2Y1 antagonist reduced the number of BrdU+ cells at this time. The data demonstrate that P2X7 and P2Y1 activation contributes to early damage induced by OGD in the DG. At later stages after the insult, P2Y1 receptors might play an additional and different role in promoting cell proliferation and maturation in the DG.

  16. Limited distal organelles and synaptic function in extensive monoaminergic innervation.

    Science.gov (United States)

    Tao, Juan; Bulgari, Dinara; Deitcher, David L; Levitan, Edwin S

    2017-08-01

    Organelles such as neuropeptide-containing dense-core vesicles (DCVs) and mitochondria travel down axons to supply synaptic boutons. DCV distribution among en passant boutons in small axonal arbors is mediated by circulation with bidirectional capture. However, it is not known how organelles are distributed in extensive arbors associated with mammalian dopamine neuron vulnerability, and with volume transmission and neuromodulation by monoamines and neuropeptides. Therefore, we studied presynaptic organelle distribution in Drosophila octopamine neurons that innervate ∼20 muscles with ∼1500 boutons. Unlike in smaller arbors, distal boutons in these arbors contain fewer DCVs and mitochondria, although active zones are present. Absence of vesicle circulation is evident by proximal nascent DCV delivery, limited impact of retrograde transport and older distal DCVs. Traffic studies show that DCV axonal transport and synaptic capture are not scaled for extensive innervation, thus limiting distal delivery. Activity-induced synaptic endocytosis and synaptic neuropeptide release are also reduced distally. We propose that limits in organelle transport and synaptic capture compromise distal synapse maintenance and function in extensive axonal arbors, thereby affecting development, plasticity and vulnerability to neurodegenerative disease. © 2017. Published by The Company of Biologists Ltd.

  17. Synaptic contacts impaired by styrene-7,8-oxide toxicity

    International Nuclear Information System (INIS)

    Corsi, P.; D'Aprile, A.; Nico, B.; Costa, G.L.; Assennato, G.

    2007-01-01

    Styrene-7,8-oxide (SO), a chemical compound widely used in industrial applications, is a potential hazard for humans, particularly in occupational settings. Neurobehavioral changes are consistently observed in occupationally exposed individuals and alterations of neurotransmitters associated with neuronal loss have been reported in animal models. Although the toxic effects of styrene have been extensively documented, the molecular mechanisms responsible for SO-induced neurotoxicity are still unclear. A possible dopamine-mediated effect of styrene neurotoxicity has been previously demonstrated, since styrene oxide alters dopamine neurotransmission in the brain. Thus, the present study hypothesizes that styrene neurotoxicity may involve synaptic contacts. Primary striatal neurons were exposed to styrene oxide at different concentrations (0.1-1 mM) for different time periods (8, 16, and 24 h) to evaluate the dose able to induce synaptic impairments. The expression of proteins crucial for synaptic transmission such as Synapsin, Synaptophysin, and RAC-1 were considered. The levels of Synaptophysin and RAC-1 decreased in a dose-dependent manner. Accordingly, morphological alterations, observed at the ultrastructural level, primarily involved the pre-synaptic compartment. In SO-exposed cultures, the biochemical cascade of caspases was activated affecting the cytoskeleton components as their target. Thus the impairments in synaptic contacts observed in SO-exposed cultures might reflect a primarily morphological alteration of neuronal cytoskeleton. In addition, our data support the hypothesis developed by previous authors of reactive oxygen species (ROS) initiating events of SO cytotoxicity

  18. Synaptic clustering within dendrites: an emerging theory of memory formation

    Science.gov (United States)

    Kastellakis, George; Cai, Denise J.; Mednick, Sara C.; Silva, Alcino J.; Poirazi, Panayiota

    2015-01-01

    It is generally accepted that complex memories are stored in distributed representations throughout the brain, however the mechanisms underlying these representations are not understood. Here, we review recent findings regarding the subcellular mechanisms implicated in memory formation, which provide evidence for a dendrite-centered theory of memory. Plasticity-related phenomena which affect synaptic properties, such as synaptic tagging and capture, synaptic clustering, branch strength potentiation and spinogenesis provide the foundation for a model of memory storage that relies heavily on processes operating at the dendrite level. The emerging picture suggests that clusters of functionally related synapses may serve as key computational and memory storage units in the brain. We discuss both experimental evidence and theoretical models that support this hypothesis and explore its advantages for neuronal function. PMID:25576663

  19. Shank synaptic scaffold proteins: keys to understanding the pathogenesis of autism and other synaptic disorders.

    Science.gov (United States)

    Sala, Carlo; Vicidomini, Cinzia; Bigi, Ilaria; Mossa, Adele; Verpelli, Chiara

    2015-12-01

    Shank/ProSAP proteins are essential to synaptic formation, development, and function. Mutations in the family of SHANK genes are strongly associated with autism spectrum disorders (ASD) and other neurodevelopmental and neuropsychiatric disorders, such as intellectual disability (ID), and schizophrenia. Thus, the term 'Shankopathies' identifies a number of neuronal diseases caused by alteration of Shank protein expression leading to abnormal synaptic development. With this review we want to summarize the major genetic, molecular, behavior and electrophysiological studies that provide new clues into the function of Shanks and pave the way for the discovery of new therapeutic drugs targeted to treat patients with SHANK mutations and also patients affected by other neurodevelopmental and neuropsychiatric disorders. Shank/ProSAP proteins are essential to synaptic formation, development, and function. Mutations in the family of SHANK genes are strongly associated with autism spectrum disorders (ASD) and other neurodevelopmental and neuropsychiatric disorders, such as intellectual disability (ID), and schizophrenia (SCZ). With this review we want to summarize the major genetic, molecular, behavior and electrophysiological studies that provide new clues into the function of Shanks and pave the way for the discovery of new therapeutic drugs targeted to treat patients with SHANK mutations. © 2015 International Society for Neurochemistry.

  20. Does artificial aging affect mechanical properties of CAD/CAM composite materials.

    Science.gov (United States)

    Egilmez, Ferhan; Ergun, Gulfem; Cekic-Nagas, Isil; Vallittu, Pekka K; Lassila, Lippo V J

    2018-01-01

    The purpose of this study was to determine the flexural strength and Weibull characteristics of different CAD/CAM materials after different in vitro aging conditions. The specimens were randomly assigned to one of the six in vitro aging conditions: (1) water storage (37°C, 3 weeks), (2) boiling water (24h), (3) hydrochloric acid exposure (pH: 1.2, 24h), (4) autoclave treatment (134°C, 200kPa, 12h), (5) thermal cycling (5000 times, 5-55°C), (6) cyclic loading (100N, 50,000 cycles). No treatment was applied to the specimens in control group. Three-point bending test was used for the calculation of flexural strength. The reliability of the strength was assessed by Weibull distribution. Surface roughness and topography was examined by coherence scanning interferometry. Evaluated parameters were compared using the Kruskall-Wallis or Mann-Whitney U test. Water storage, autoclave treatment and thermal cycling significantly decreased the flexural strength of all materials (p0.05). Weibull moduli of Cerasmart™ and Lava™ Ultimate were similar with control. Vita Enamic ® exhibited similar Weibull moduli in all aging groups except the HCl treated group (p>0.05). R a values of Cerasmart™ and Lava™ Ultimate were in the range of 0.053-0.088μm in the aged groups. However R a results of Vita Enamic ® were larger than 0.2μm. Flexural strength of newly developed restorative CAD/CAM materials was significantly decreased by artificial aging. Cyclic loading or HCl exposure does not affect to the flexural strength and structural reliability of Cerasmart™ and Lava™ Ultimate. Copyright © 2017 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

  1. Lung vitamin E transport processes are affected by both age and environmental oxidants in mice

    International Nuclear Information System (INIS)

    Valacchi, Giuseppe; Vasu, Vihas T.; Yokohama, Wallace; Corbacho, Ana M.; Phung, Anh; Lim, Yunsook; Aung, Hnin Hnin; Cross, Carroll E.; Davis, Paul A.

    2007-01-01

    Despite the physiological importance of alpha-tocopherol (AT), the molecular mechanisms involved in maintaining cellular and tissue tocopherol levels remain to be fully characterized. Scavenger receptor B1 (SRB1), one of a large family of scavenger receptors, has been shown to facilitate AT transfer from HDL to peripheral tissues via apo A-1-mediated processes and to be important in the delivery of AT to the lung cells. In the present studies the effects of age and two environmental oxidants ozone (O 3 ) (0.25 ppm 6 h/day) and cigarette smoke (CS) (60 mg/m 3 6 h/day) for 4 days on selected aspects of AT transport in murine lung tissues were assessed. While AT levels were 25% higher (p 3 or CS at the doses used had no effect. Gene expression levels, determined by RT-PCR of AT transport protein (ATTP), SRB1, CD36, ATP binding cassette 3 (ABCA3) and ABCA1 and protein levels, determined by Western blots for SRB1, ATTP and ABCA1 were assessed. Aged mouse lung showed a lower levels of ATTP, ABCA3 and SRB1 and a higher level CD36 and ABCA1. Acute exposure to either O 3 or CS induced declines in ATTP and SRB1 in both aged and young mice lung. CD36 increased in both young and aged mice lung upon exposure to O 3 and CS. These findings suggest that both age and environmental oxidant exposure affect pathways related to lung AT homeostasis and do so in a way that favors declines in lung AT. However, given the approach taken, the effects cannot be traced to changes in these pathways or AT content in any specific lung associated cell type and thus highlight the need for further follow-up studies looking at specific lung associated cell types

  2. Donor age of human platelet lysate affects proliferation and differentiation of mesenchymal stem cells.

    Directory of Open Access Journals (Sweden)

    Michael Lohmann

    Full Text Available The regenerative potential declines upon aging. This might be due to cell-intrinsic changes in stem and progenitor cells or to influences by the microenvironment. Mesenchymal stem cells (MSC raise high hopes in regenerative medicine. They are usually culture expanded in media with fetal calf serum (FCS or other serum supplements such as human platelet lysate (HPL. In this study, we have analyzed the impact of HPL-donor age on culture expansion. 31 single donor derived HPLs (25 to 57 years old were simultaneously compared for culture of MSC. Proliferation of MSC did not reveal a clear association with platelet counts of HPL donors or growth factors concentrations (PDGF-AB, TGF-β1, bFGF, or IGF-1, but it was significantly higher with HPLs from younger donors (45 years. Furthermore, HPLs from older donors increased activity of senescence-associated beta-galactosidase (SA-βgal. HPL-donor age did not affect the fibroblastoid colony-forming unit (CFU-f frequency, immunophenotype or induction of adipogenic differentiation, whereas osteogenic differentiation was significantly lower with HPLs from older donors. Concentrations of various growth factors (PDGF-AB, TGF-β1, bFGF, IGF-1 or hormones (estradiol, parathormone, leptin, 1,25 vitamin D3 were not associated with HPL-donor age or MSC growth. Taken together, our data support the notion that aging is associated with systemic feedback mechanisms acting on stem and progenitor cells, and this is also relevant for serum supplements in cell culture: HPLs derived from younger donors facilitate enhanced expansion and more pronounced osteogenic differentiation.

  3. Donor Age of Human Platelet Lysate Affects Proliferation and Differentiation of Mesenchymal Stem Cells

    Science.gov (United States)

    Lohmann, Michael; Walenda, Gudrun; Hemeda, Hatim; Joussen, Sylvia; Drescher, Wolf; Jockenhoevel, Stefan; Hutschenreuter, Gabriele; Zenke, Martin; Wagner, Wolfgang

    2012-01-01

    The regenerative potential declines upon aging. This might be due to cell-intrinsic changes in stem and progenitor cells or to influences by the microenvironment. Mesenchymal stem cells (MSC) raise high hopes in regenerative medicine. They are usually culture expanded in media with fetal calf serum (FCS) or other serum supplements such as human platelet lysate (HPL). In this study, we have analyzed the impact of HPL-donor age on culture expansion. 31 single donor derived HPLs (25 to 57 years old) were simultaneously compared for culture of MSC. Proliferation of MSC did not reveal a clear association with platelet counts of HPL donors or growth factors concentrations (PDGF-AB, TGF-β1, bFGF, or IGF-1), but it was significantly higher with HPLs from younger donors (45 years). Furthermore, HPLs from older donors increased activity of senescence-associated beta-galactosidase (SA-βgal). HPL-donor age did not affect the fibroblastoid colony-forming unit (CFU-f) frequency, immunophenotype or induction of adipogenic differentiation, whereas osteogenic differentiation was significantly lower with HPLs from older donors. Concentrations of various growth factors (PDGF-AB, TGF-β1, bFGF, IGF-1) or hormones (estradiol, parathormone, leptin, 1,25 vitamin D3) were not associated with HPL-donor age or MSC growth. Taken together, our data support the notion that aging is associated with systemic feedback mechanisms acting on stem and progenitor cells, and this is also relevant for serum supplements in cell culture: HPLs derived from younger donors facilitate enhanced expansion and more pronounced osteogenic differentiation. PMID:22662236

  4. Different postconditioning cycles affect prognosis of aged patients undergoing primary percutaneous coronary intervention.

    Science.gov (United States)

    Zhang, Jie; Zhang, Xin; Cui, Yuqi; Ferdous, Misbahul; Cui, Lianqun; Zhao, Peng

    2017-07-17

    Postconditioning can affect the infarct size in acute myocardial infarction (AMI). However, few studies show an effect of different postconditioning cycles on AMI aged patients. This study sought to assess the effect of different postconditioning cycles on prognosis in aged patients with AMI who underwent primary percutaneous coronary intervention (PCI). 74 aged patients were randomly assigned to three groups. Control group; PC-1 group accepted postconditioning 4 cycles of 30 s inflation and 30 s deflation; PC-2 group accepted postconditioning 4 cycles of 60 s. Creatine kinase MB (CK-MB), troponin I (cTnI), high-sensitive C-reactive protein (hs-CRP) and corrected Thrombolysis in Myocardial Infarction (TIMI) frame counts (CTFC) were analyzed before andafter treatment. All patients received an echocardiographic examination for whole heart function, wall motion score index (WMSI) and single-photon emission computed tomography (SPECT) examination at 7 days and 6 months after treatment. S: The peak of CK-MB, postoperative 72 h cTnI and CTFC were significantly attenuated by postconditioning when compared with the control group. The hs-CRP of the postconditioning group was lower than the control group 24 h postoperative. No difference was observed between PC-1 and PC-2 group about the effect described above. At 7 days, heart function in the postconditioning group was improved when compared with the control group. At 6 months, the WMSI and SPECT score significantly reduced in the PC-2 group compared with the control and PC-1 groups, but there was no difference among the three groups about echo data except the left ventricular end-systolic diameter. Postconditioning is significantly beneficial to prognosis in aged patients with AMI. The cardiac protective effect of 4 cycles of 60 s procedure was observed in WMSI and SPECT. It is favorable to implement this procedure in aged patients with AMI in clinic.

  5. How accelerated biological aging can affect solar reflective polymeric based building materials

    Science.gov (United States)

    Ferrari, C.; Santunione, G.; Libbra, A.; Muscio, A.; Sgarbi, E.

    2017-11-01

    Among the main issues concerning building materials, in particular outdoor ones, one can identify the colonization by microorganisms referred to as biological aggression. This can affect not only the aesthetical aspect but also the thermal performance of solar reflective materials. In order to improve the reliability of tests aimed to assess the resistance to biological aggression and contextually reduce the test duration, an accelerated test method has been developed. It is based on a lab reproducible setup where specific and controlled environmental and boundary conditions are imposed to accelerate as much as possible biological growth on building materials. Due to their widespread use, polymeric materials have been selected for the present analysis, in the aim of reaching an advanced bio-aged level in a relatively short time (8 weeks or less) and at the same time comparatively evaluate different materials under a given set of ageing conditions. Surface properties before, during and after ageing have been investigated by surface, microstructural and chemical analyses, as well as by examination of time progressive images to assess bacterial and algal growth rate.

  6. Aging affects the balance between goal-guided and habitual spatial attention.

    Science.gov (United States)

    Twedell, Emily L; Koutstaal, Wilma; Jiang, Yuhong V

    2017-08-01

    Visual clutter imposes significant challenges to older adults in everyday tasks and often calls on selective processing of relevant information. Previous research has shown that both visual search habits and task goals influence older adults' allocation of spatial attention, but has not examined the relative impact of these two sources of attention when they compete. To examine how aging affects the balance between goal-driven and habitual attention, and to inform our understanding of different attentional subsystems, we tested young and older adults in an adapted visual search task involving a display laid flat on a desk. To induce habitual attention, unbeknownst to participants, the target was more often placed in one quadrant than in the others. All participants rapidly acquired habitual attention toward the high-probability quadrant. We then informed participants where the high-probability quadrant was and instructed them to search that screen location first-but pitted their habit-based, viewer-centered search against this instruction by requiring participants to change their physical position relative to the desk. Both groups prioritized search in the instructed location, but this effect was stronger in young adults than in older adults. In contrast, age did not influence viewer-centered search habits: the two groups showed similar attentional preference for the visual field where the target was most often found before. Aging disrupted goal-guided but not habitual attention. Product, work, and home design for people of all ages--but especially for older individuals--should take into account the strong viewer-centered nature of habitual attention.

  7. Aging Affects Adaptation to Sound-Level Statistics in Human Auditory Cortex.

    Science.gov (United States)

    Herrmann, Björn; Maess, Burkhard; Johnsrude, Ingrid S

    2018-02-21

    Optimal perception requires efficient and adaptive neural processing of sensory input. Neurons in nonhuman mammals adapt to the statistical properties of acoustic feature distributions such that they become sensitive to sounds that are most likely to occur in the environment. However, whether human auditory responses adapt to stimulus statistical distributions and how aging affects adaptation to stimulus statistics is unknown. We used MEG to study how exposure to different distributions of sound levels affects adaptation in auditory cortex of younger (mean: 25 years; n = 19) and older (mean: 64 years; n = 20) adults (male and female). Participants passively listened to two sound-level distributions with different modes (either 15 or 45 dB sensation level). In a control block with long interstimulus intervals, allowing neural populations to recover from adaptation, neural response magnitudes were similar between younger and older adults. Critically, both age groups demonstrated adaptation to sound-level stimulus statistics, but adaptation was altered for older compared with younger people: in the older group, neural responses continued to be sensitive to sound level under conditions in which responses were fully adapted in the younger group. The lack of full adaptation to the statistics of the sensory environment may be a physiological mechanism underlying the known difficulty that older adults have with filtering out irrelevant sensory information. SIGNIFICANCE STATEMENT Behavior requires efficient processing of acoustic stimulation. Animal work suggests that neurons accomplish efficient processing by adjusting their response sensitivity depending on statistical properties of the acoustic environment. Little is known about the extent to which this adaptation to stimulus statistics generalizes to humans, particularly to older humans. We used MEG to investigate how aging influences adaptation to sound-level statistics. Listeners were presented with sounds drawn from

  8. Aging differentially affects male and female neural stem cell neurogenic properties

    Directory of Open Access Journals (Sweden)

    Jay Waldron

    2010-09-01

    Full Text Available Jay Waldron1, Althea McCourty1, Laurent Lecanu1,21The Research Institute of the McGill University Health Centre, Montreal, Canada; 2Department of Medicine, McGill University, Montreal, Quebec, CanadaPurpose: Neural stem cell transplantation as a brain repair strategy is a very promising technology. However, despite many attempts, the clinical success remains very deceiving. Despite clear evidence that sexual dimorphism rules many aspects of human biology, the occurrence of a sex difference in neural stem cell biology is largely understudied. Herein, we propose to determine whether gender is a dimension that drives the fate of neural stem cells through aging. Should it occur, we believe that neural stem cell sexual dimorphism and its variation during aging should be taken into account to refine clinical approaches of brain repair strategies.Methods: Neural stem cells were isolated from the subventricular zone of three- and 20-month-old male and female Long-Evans rats. Expression of the estrogen receptors, ERα and ERβ, progesterone receptor, androgen receptor, and glucocorticoid receptor was analyzed and quantified by Western blotting on undifferentiated neural stem cells. A second set of neural stem cells was treated with retinoic acid to trigger differentiation, and the expression of neuronal, astroglial, and oligodendroglial markers was determined using Western blotting.Conclusion: We provided in vitro evidence that the fate of neural stem cells is affected by sex and aging. Indeed, young male neural stem cells mainly expressed markers of neuronal and oligodendroglial fate, whereas young female neural stem cells underwent differentiation towards an astroglial phenotype. Aging resulted in a lessened capacity to express neuron and astrocyte markers. Undifferentiated neural stem cells displayed sexual dimorphism in the expression of steroid receptors, in particular ERα and ERβ, and the expression level of several steroid receptors increased

  9. Depression as a Glial-Based Synaptic Dysfunction

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    Daniel eRial

    2016-01-01

    Full Text Available Recent studies combining pharmacological, behavioral, electrophysiological and molecular approaches indicate that depression results from maladaptive neuroplastic processing occurring in defined frontolimbic circuits responsible for emotional processing such as the prefrontal cortex, hippocampus, amygdala and ventral striatum. However, the exact mechanisms controlling synaptic plasticity that are disrupted to trigger depressive conditions have not been elucidated. Since glial cells (astrocytes and microglia tightly and dynamically interact with synapses, engaging a bi-directional communication critical for the processing of synaptic information, we now revisit the role of glial cells in the etiology of depression focusing on a dysfunction of the ‘quad-partite’ synapse. This interest is supported by the observations that depressive-like conditions are associated with a decreased density and hypofunction of astrocytes and with an increase microglia ‘activation’ in frontolimbic regions, which is expected to contribute for the synaptic dysfunction present in depression. Furthermore, the traditional culprits of depression (glucocorticoids, biogenic amines, BDNF affect glia functioning, whereas antidepressant treatments (SSRIs, electroshock, deep brain stimulation recover glia functioning. In this context of a quad-partite synapse, systems modulating glia-synapse bidirectional communication - such as the purinergic neuromodulation system operated by ATP and adenosine - emerge as promising candidates to re-normalize synaptic function by combining direct synaptic effects with an ability to also control astrocyte and microglia function. This proposed triple action of purines to control aberrant synaptic function illustrates the rationale to consider the interference with glia dysfunction as a mechanism of action driving the design of future pharmacological tools to manage depression.

  10. Hardwiring of fine synaptic layers in the zebrafish visual pathway

    Directory of Open Access Journals (Sweden)

    Taylor Michael R

    2008-12-01

    Full Text Available Abstract Background Neuronal connections are often arranged in layers, which are divided into sublaminae harboring synapses with similar response properties. It is still debated how fine-grained synaptic layering is established during development. Here we investigated two stratified areas of the zebrafish visual pathway, the inner plexiform layer (IPL of the retina and the neuropil of the optic tectum, and determined if activity is required for their organization. Results The IPL of 5-day-old zebrafish larvae is composed of at least nine sublaminae, comprising the connections between different types of amacrine, bipolar, and ganglion cells (ACs, BCs, GCs. These sublaminae were distinguished by their expression of cell type-specific transgenic fluorescent reporters and immunohistochemical markers, including protein kinase Cβ (PKC, parvalbumin (Parv, zrf3, and choline acetyltransferase (ChAT. In the tectum, four retinal input layers abut a laminated array of neurites of tectal cells, which differentially express PKC and Parv. We investigated whether these patterns were affected by experimental disruptions of retinal activity in developing fish. Neither elimination of light inputs by dark rearing, nor a D, L-amino-phosphono-butyrate-induced reduction in the retinal response to light onset (but not offset altered IPL or tectal lamination. Moreover, thorough elimination of chemical synaptic transmission with Botulinum toxin B left laminar synaptic arrays intact. Conclusion Our results call into question a role for activity-dependent mechanisms – instructive light signals, balanced on and off BC activity, Hebbian plasticity, or a permissive role for synaptic transmission – in the synaptic stratification we examined. We propose that genetically encoded cues are sufficient to target groups of neurites to synaptic layers in this vertebrate visual system.

  11. Analysis of Factors Affecting Women of Childbearing Age to Screen Using Visual Inspection with Acetic Acid.

    Science.gov (United States)

    Sidabutar, Sondang; Martini, Santi; Wahyuni, Chatarina Umbul

    2017-02-01

    The purpose of this study was to evaluate patient factors such as knowledge, attitude, motivation, perception, socio-economic status and travel time to health facilities and assess how these factors affected patients' decision to pursue cervical cancer screening with visual inspection with acetic acid (VIA). A total of 80 women of childbearing age who visited Kenjeran and Balongsari Public Health Centers for health assessments were involved in this study. Patients who agreed to participate in the study underwent a verbal questionnaire to evaluate various factors. Bivariate analysis concluded that knowledge, attitude, motivation, perception, socioeconomic status, and travel time to health facilities were significantly different between women who received VIA screening and women who did not receive VIA screening ( p motivation, perception, socio-economic status, and the travel time to health facilities accounted for 2.920-fold, 2.043-fold, 3.704-fold, 2.965-fold, 3.198-fold and 2.386-fold possibility, respectively, of patients to pursue cervical cancer screening with VIA. Multivariate analysis showed that perception, socio-economic status, and travel time to health facilities were the most important factors influencing whether or not women pursued VIA screening. Knowledge, attitude, motivation, perception, socio-economic status, and travel time to health facilities appears to affect women's' decision to pursue cervical cancer screening with VIA, with the largest intake being the motivational factor.

  12. How does context affect assessments of facial emotion? The role of culture and age.

    Science.gov (United States)

    Ko, Seon-Gyu; Lee, Tae-Ho; Yoon, Hyea-Young; Kwon, Jung-Hye; Mather, Mara

    2011-03-01

    People from Asian cultures are more influenced by context in their visual processing than people from Western cultures. In this study, we examined how these cultural differences in context processing affect how people interpret facial emotions. We found that younger Koreans were more influenced than younger Americans by emotional background pictures when rating the emotion of a central face, especially those younger Koreans with low self-rated stress. In contrast, among older adults, neither Koreans nor Americans showed significant influences of context in their face emotion ratings. These findings suggest that cultural differences in reliance on context to interpret others' emotions depend on perceptual integration processes that decline with age, leading to fewer cultural differences in perception among older adults than among younger adults. Furthermore, when asked to recall the background pictures, younger participants recalled more negative pictures than positive pictures, whereas older participants recalled similar numbers of positive and negative pictures. These age differences in the valence of memory were consistent across culture. (c) 2011 APA, all rights reserved.

  13. Do social networks affect the use of residential aged care among older Australians?

    Directory of Open Access Journals (Sweden)

    Glonek Gary FV

    2007-10-01

    Full Text Available Abstract Background Older people's social networks with family and friends can affect residential aged care use. It remains unclear if there are differences in the effects of specific (with children, other relatives, friends and confidants and total social networks upon use of low-level residential care and nursing homes. Methods Data were drawn from the Australian Longitudinal Study of Ageing. Six waves of data from 1477 people aged ≥ 70 collected over nine years of follow-up were used. Multinomial logistic regressions of the effects of specific and total social networks on residential care use were carried out. Propensity scores were used in the analyses to adjust for differences in participant's health, demographic and lifestyle characteristics with respect to social networks. Results Higher scores for confidant networks were protective against nursing home use (odds ratio [OR] upper versus lower tertile of confidant networks = 0.50; 95%CI 0.33–0.75. Similarly, a significant effect of upper versus lower total network tertile on nursing home use was observed (OR = 0.62; 95%CI 0.43–0.90. Evidence of an effect of children networks on nursing home use was equivocal. Nursing home use was not predicted by other relatives or friends social networks. Use of lower-level residential care was unrelated to social networks of any type. Social networks of any type did not have a significant effect upon low-level residential care use. Discussion Better confidant and total social networks predict nursing home use in a large cohort of older Australians. Policy needs to reflect the importance of these particular relationships in considering where older people want to live in the later years of life.

  14. Spike Train Auto-Structure Impacts Post-Synaptic Firing and Timing-Based Plasticity

    Science.gov (United States)

    Scheller, Bertram; Castellano, Marta; Vicente, Raul; Pipa, Gordon

    2011-01-01

    Cortical neurons are typically driven by several thousand synapses. The precise spatiotemporal pattern formed by these inputs can modulate the response of a post-synaptic cell. In this work, we explore how the temporal structure of pre-synaptic inhibitory and excitatory inputs impact the post-synaptic firing of a conductance-based integrate and fire neuron. Both the excitatory and inhibitory input was modeled by renewal gamma processes with varying shape factors for modeling regular and temporally random Poisson activity. We demonstrate that the temporal structure of mutually independent inputs affects the post-synaptic firing, while the strength of the effect depends on the firing rates of both the excitatory and inhibitory inputs. In a second step, we explore the effect of temporal structure of mutually independent inputs on a simple version of Hebbian learning, i.e., hard bound spike-timing-dependent plasticity. We explore both the equilibrium weight distribution and the speed of the transient weight dynamics for different mutually independent gamma processes. We find that both the equilibrium distribution of the synaptic weights and the speed of synaptic changes are modulated by the temporal structure of the input. Finally, we highlight that the sensitivity of both the post-synaptic firing as well as the spike-timing-dependent plasticity on the auto-structure of the input of a neuron could be used to modulate the learning rate of synaptic modification. PMID:22203800

  15. Age-related differences in affective responses to and memory for emotions conveyed by music: a cross-sectional study

    OpenAIRE

    Vieillard , Sandrine; Gilet , Anne-Laure ,

    2013-01-01

    International audience; There is mounting evidence that aging is associated with the maintenance of positive affect and the decrease of negative affect to ensure emotion regulation goals. Previous empirical studies have primarily focused on a visual or autobiographical form of emotion communication. To date, little investigation has been done on musical emotions. The few studies that have addressed aging and emotions in music were mainly interested in emotion recognition, thus leaving unexplo...

  16. Factors Affecting Age at ASD Diagnosis in UK: No Evidence That Diagnosis Age Has Decreased between 2004 and 2014

    Science.gov (United States)

    Brett, Denise; Warnell, Frances; McConachie, Helen; Parr, Jeremy R.

    2016-01-01

    Clinical initiatives have aimed to reduce the age at ASD diagnosis in the UK. This study investigated whether the median age at diagnosis in childhood has reduced in recent years, and identified the factors associated with earlier diagnosis in the UK. Data on 2,134 children with ASD came from two large family databases. Results showed that the age…

  17. The moderating effects of aging and cognitive abilities on the association between work stress and negative affect.

    Science.gov (United States)

    Hyun, Jinshil; Sliwinski, Martin J; Almeida, David M; Smyth, Joshua M; Scott, Stacey B

    2018-05-01

    Given that the association between work stress and negative affect can exacerbate negative health and workplace outcomes, it is important to identify the protective and risk factors that moderate this association. Socioemotional aging and cognitive abilities might influence how people utilize emotion regulation skills and engage in practical problem solving to manage their work stress. The aim of this study is to examine whether age and cognitive abilities independently and interactively moderate the association between work-related stress and negative affect. A diverse working adult sample (N = 139, age 25-65, 69% of females) completed a cross-sectional survey that assessed chronic work stress, negative affect, and fluid and crystallized cognitive abilities. Results from regression analyses suggested that both fluid and crystallized cognitive abilities, but not age, moderated the association between work stress and negative affect. Further, we found that crystallized cognition had a stronger attenuating effect on the work stress-negative affect association for older compared to younger workers. The moderating effect of fluid cognition was invariant across age. Our findings demonstrate that cognitive abilities are an important personal resource that might protect individuals against the negative impacts of work stress and negative affect. Although the role that fluid cognition plays in work stress-negative affect association is comparably important for both younger and older workers, crystallized cognition might play a more valuable role for older than younger workers.

  18. Leisure Activity Engagement and Positive Affect Partially Mediate the Relationship Between Positive Views on Aging and Physical Health.

    Science.gov (United States)

    Hicks, Stephanie A; Siedlecki, Karen L

    2017-03-01

    To examine leisure activity engagement and positive affect as potential mediators for the relationships between positive views on aging (PVA) and two health outcomes: subjective health and physical limitations. Data from 5,194 participants from the German Ageing Survey (aged 40-91 years) were used to examine relationships between PVA to subjective health (assessed by self-rated health and perceived health change from past) and physical limitations (assessed via self-reported limitations on 10 activities). Leisure activity engagement and positive affect were examined as potential mediators in latent variable path analyses. Age moderation among these relationships was also examined. Leisure activity engagement and positive affect separately and jointly served to partially mediate the relationships between PVA and the health outcomes. When entered as joint mediators, positive affect no longer significantly predicted physical limitations, indicating a shared variance with leisure activity engagement. Age moderated the relationship between PVA and physical limitations; the relationship was stronger among older adults than among middle-aged adults. Leisure activity engagement and positive affect were shown to help explain the relationship between PVA and health, but differently for different health constructs and also among middle-aged and older adults. Findings provide further insight into ways in which PVA influence health. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. Sex, age, and sex hormones affect recall of words in a directed forgetting paradigm.

    Science.gov (United States)

    Kerschbaum, Hubert H; Hofbauer, Ildiko; Gföllner, Anna; Ebner, Birgit; Bresgen, Nikolaus; Bäuml, Karl-Heinz T

    2017-01-02

    During the course of serious discussion, an unexpected interruption may induce forgetting of the original topic of a conversation. Sex, age, and sex hormone levels may affect frequency and extension of forgetting. In a list-method directed forgetting paradigm, subjects have to learn two word lists. After learning list 1, subjects receive either a forget or a remember list 1 cue. When the participants had learned list 2 and completed a distraction task, they were asked to write down as many recalled items as possible, starting either with list 1 or list 2 items. In the present study, 96 naturally cycling women, 60 oral contraceptive users, 56 postmenopausal women, and 41 young men were assigned to one of these different experimental conditions. Forget-cued young subjects recall fewer list 1 items (list 1 forgetting) but more list 2 items (list 2 enhancement) compared with remember-cued subjects. However, forget-cued postmenopausal women showed reduced list 1 forgetting but enhanced list 2 retention. Remember-cued naturally cycling women recalled more list 1 items than oral contraceptive users, young men, and postmenopausal women. In forget-cued follicular women, salivary progesterone correlated positively with recalled list 2 items. Salivary 17β-estradiol did not correlate with recalled list 1 or list 2 items in either remember- or forget-cued young women. However, salivary 17β-estradiol correlated with item recall in remember-cued postmenopausal women. Our findings suggest that sex hormones do not globally modulate verbal memory or forgetting, but selectively affect cue-specific processing. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. Synaptogenesis in visual cortex of normal and preterm monkeys: evidence for intrinsic regulation of synaptic overproduction.

    Science.gov (United States)

    Bourgeois, J P; Jastreboff, P J; Rakic, P

    1989-01-01

    We used quantitative electron microscopy to determine the effect of precocious visual experience on the time course, magnitude, and pattern of perinatal synaptic overproduction in the primary visual cortex of the rhesus monkey. Fetuses were delivered by caesarean section 3 weeks before term, exposed to normal light intensity and day/night cycles, and killed within the first postnatal month, together with age-matched controls that were delivered at term. We found that premature visual stimulation does not affect the rate of synaptic accretion and overproduction. Both of these processes proceed in relation to the time of conception rather than to the time of delivery. In contrast, the size, type, and laminar distribution of synapses were significantly different between preterm and control infants. The changes and differences in these parameters correlate with the duration of visual stimulation and become less pronounced with age. If visual experience in infancy influences the maturation of the visual cortex, it must do so predominantly by strengthening, modifying, and/or eliminating synapses that have already been formed, rather than by regulating the rate of synapse production. Images PMID:2726773

  1. Variation in Honey Bee Gut Microbial Diversity Affected by Ontogenetic Stage, Age and Geographic Location

    Science.gov (United States)

    Hroncova, Zuzana; Havlik, Jaroslav; Killer, Jiri; Doskocil, Ivo; Tyl, Jan; Kamler, Martin; Titera, Dalibor; Hakl, Josef; Mrazek, Jakub; Bunesova, Vera; Rada, Vojtech

    2015-01-01

    Social honey bees, Apis mellifera, host a set of distinct microbiota, which is similar across the continents and various honey bee species. Some of these bacteria, such as lactobacilli, have been linked to immunity and defence against pathogens. Pathogen defence is crucial, particularly in larval stages, as many pathogens affect the brood. However, information on larval microbiota is conflicting. Seven developmental stages and drones were sampled from 3 colonies at each of the 4 geographic locations of A. mellifera carnica, and the samples were maintained separately for analysis. We analysed the variation and abundance of important bacterial groups and taxa in the collected bees. Major bacterial groups were evaluated over the entire life of honey bee individuals, where digestive tracts of same aged bees were sampled in the course of time. The results showed that the microbial tract of 6-day-old 5th instar larvae were nearly equally rich in total microbial counts per total digestive tract weight as foraging bees, showing a high percentage of various lactobacilli (Firmicutes) and Gilliamella apicola (Gammaproteobacteria 1). However, during pupation, microbial counts were significantly reduced but recovered quickly by 6 days post-emergence. Between emergence and day 6, imago reached the highest counts of Firmicutes and Gammaproteobacteria, which then gradually declined with bee age. Redundancy analysis conducted using denaturing gradient gel electrophoresis identified bacterial species that were characteristic of each developmental stage. The results suggest that 3-day 4th instar larvae contain low microbial counts that increase 2-fold by day 6 and then decrease during pupation. Microbial succession of the imago begins soon after emergence. We found that bacterial counts do not show only yearly cycles within a colony, but vary on the individual level. Sampling and pooling adult bees or 6th day larvae may lead to high errors and variability, as both of these stages may

  2. Divergent Trajectories in the Aging Mind: Changes in Working Memory for Affective Versus Visual Information With Age

    OpenAIRE

    Mikels, Joseph A.; Larkin, Gregory R.; Reuter-Lorenz, Patricia A.; Carstensen, Laura L.

    2005-01-01

    Working memory mediates the short-term maintenance of information. Virtually all empirical research on working memory involves investigations of working memory for verbal and visual information. Whereas aging is typically associated with a deficit in working memory for these types of information, recent findings suggestive of relatively well-preserved long-term memory for emotional information in older adults raise questions about working memory for emotional material. This study examined age...

  3. Study on Developing Degradation Model for Nuclear Power Plants With Ageing Elements Affected on Operation Parameter

    International Nuclear Information System (INIS)

    Choi, Yong Won; Lim, Sung Won; Lee, Un Chul; Kim, Man Woong; Kim, Kab; Ryu, Yong Ho

    2009-01-01

    As a part of development the evaluation system of safety margin effects for degradation of CANDU reactors, it is required that the degradation model represents the distribution of each ageing factor's value during operating year. Unfortunately, it is not easy to make an explicit relation between the RELAP-CANDU parameters and ageing mechanism because of insufficient data and lack of applicable models. So, operating parameter related with ageing is used for range determination of ageing factor. Then, relation between operating parameter and ageing elements is analyzed and ageing constant values for degradation model are determined. Also the other ageing factor is derived for more accurate ageing analysis

  4. Seasonality affects dietary diversity of school-age children in northern Ghana.

    Directory of Open Access Journals (Sweden)

    Abdul-Razak Abizari

    Full Text Available Dietary diversity score (DDS is relatively easy to measure and is shown to be a very useful indicator of the probability of adequate micronutrient intake. Dietary diversity, however, is usually assessed during a single period and little is known about the effect of seasonality on it. This study investigates whether dietary diversity is influenced by seasonality.Two cross-sectional surveys were conducted in two different seasons-dry season (October 2010 and rainy season (May 2011 among the same school-age children (SAC in two rural schools in northern Ghana. The study population consisted of 228 school-age children. A qualitative 24-hour dietary recall was conducted in both seasons. Based on 13 food groups, a score of 1 was given if a child consumed a food item belonging to a particular food group, else 0. Individual scores were aggregated into DDS for each child. Differences in mean DDS between seasons were compared using linear mixed model analysis.The dietary pattern of the SAC was commonly plant foods with poor consumption of animal source foods. The mean DDS was significantly higher (P < 0.001 in the rainy season (6.95 ± 0.55 compared to the dry season (6.44 ± 0.55 after adjusting for potential confounders such as age, sex, occupation (household head and mother and education of household head. The difference in mean DDS between dry and rainy seasons was mainly due to the difference in the consumption of Vitamin A-rich fruits and vegetables between the seasons. While vitamin A-rich fruits (64.0% vs. 0.9%; P < 0.0001 and vitamin A rich dark green leafy vegetables (52.6% vs. 23.3%, P < .0001 were consumed more during the rainy season than the dry season, more children consumed vitamin A-rich deep yellow, orange and red vegetables during the dry season than during the rainy season (73.7% vs. 36.4%, P <0.001.Seasonality has an effect on DDS and may affect the quality of dietary intake of SAC; in such a context, it would be useful to measure DDS

  5. Inflammation subverts hippocampal synaptic plasticity in experimental multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Robert Nisticò

    Full Text Available Abnormal use-dependent synaptic plasticity is universally accepted as the main physiological correlate of memory deficits in neurodegenerative disorders. It is unclear whether synaptic plasticity deficits take place during neuroinflammatory diseases, such as multiple sclerosis (MS and its mouse model, experimental autoimmune encephalomyelitis (EAE. In EAE mice, we found significant alterations of synaptic plasticity rules in the hippocampus. When compared to control mice, in fact, hippocampal long-term potentiation (LTP induction was favored over long-term depression (LTD in EAE, as shown by a significant rightward shift in the frequency-synaptic response function. Notably, LTP induction was also enhanced in hippocampal slices from control mice following interleukin-1β (IL-1β perfusion, and both EAE and IL-1β inhibited GABAergic spontaneous inhibitory postsynaptic currents (sIPSC without affecting glutamatergic transmission and AMPA/NMDA ratio. EAE was also associated with selective loss of GABAergic interneurons and with reduced gamma-frequency oscillations in the CA1 region of the hippocampus. Finally, we provided evidence that microglial activation in the EAE hippocampus was associated with IL-1β expression, and hippocampal slices from control mice incubated with activated microglia displayed alterations of GABAergic transmission similar to those seen in EAE brains, through a mechanism dependent on enhanced IL-1β signaling. These data may yield novel insights into the basis of cognitive deficits in EAE and possibly of MS.

  6. Inflammation Subverts Hippocampal Synaptic Plasticity in Experimental Multiple Sclerosis

    Science.gov (United States)

    Mandolesi, Georgia; Piccinin, Sonia; Berretta, Nicola; Pignatelli, Marco; Feligioni, Marco; Musella, Alessandra; Gentile, Antonietta; Mori, Francesco; Bernardi, Giorgio; Nicoletti, Ferdinando; Mercuri, Nicola B.; Centonze, Diego

    2013-01-01

    Abnormal use-dependent synaptic plasticity is universally accepted as the main physiological correlate of memory deficits in neurodegenerative disorders. It is unclear whether synaptic plasticity deficits take place during neuroinflammatory diseases, such as multiple sclerosis (MS) and its mouse model, experimental autoimmune encephalomyelitis (EAE). In EAE mice, we found significant alterations of synaptic plasticity rules in the hippocampus. When compared to control mice, in fact, hippocampal long-term potentiation (LTP) induction was favored over long-term depression (LTD) in EAE, as shown by a significant rightward shift in the frequency–synaptic response function. Notably, LTP induction was also enhanced in hippocampal slices from control mice following interleukin-1β (IL-1β) perfusion, and both EAE and IL-1β inhibited GABAergic spontaneous inhibitory postsynaptic currents (sIPSC) without affecting glutamatergic transmission and AMPA/NMDA ratio. EAE was also associated with selective loss of GABAergic interneurons and with reduced gamma-frequency oscillations in the CA1 region of the hippocampus. Finally, we provided evidence that microglial activation in the EAE hippocampus was associated with IL-1β expression, and hippocampal slices from control mice incubated with activated microglia displayed alterations of GABAergic transmission similar to those seen in EAE brains, through a mechanism dependent on enhanced IL-1β signaling. These data may yield novel insights into the basis of cognitive deficits in EAE and possibly of MS. PMID:23355887

  7. Intense synaptic activity enhances temporal resolution in spinal motoneurons.

    Directory of Open Access Journals (Sweden)

    Rune W Berg

    Full Text Available In neurons, spike timing is determined by integration of synaptic potentials in delicate concert with intrinsic properties. Although the integration time is functionally crucial, it remains elusive during network activity. While mechanisms of rapid processing are well documented in sensory systems, agility in motor systems has received little attention. Here we analyze how intense synaptic activity affects integration time in spinal motoneurons during functional motor activity and report a 10-fold decrease. As a result, action potentials can only be predicted from the membrane potential within 10 ms of their occurrence and detected for less than 10 ms after their occurrence. Being shorter than the average inter-spike interval, the AHP has little effect on integration time and spike timing, which instead is entirely determined by fluctuations in membrane potential caused by the barrage of inhibitory and excitatory synaptic activity. By shortening the effective integration time, this intense synaptic input may serve to facilitate the generation of rapid changes in movements.

  8. Facets of negative affectivity and blood pressure in middle-aged men

    Directory of Open Access Journals (Sweden)

    Cornel V. Igna

    2013-04-01

    Full Text Available Research results suggesting that facets of negative affectivity, i.e. anxiety, anger-hostility, and depression, relate to incident cardiovascular diseases have been steadily increasing. Evidence for depression has been especially extensive. Elevated blood pressure, a major risk factor of cardiovascular diseases, is one probable mediator in this context. The purpose of this study was to clarify the relationship of specific key elements of depressive disposition, i.e. depressive symptoms, hopelessness and vital exhaustion, with health behavior and blood pressure. Study sample was comprised of 710 middle-aged men. Participants completed self-report questionnaires assessing health behavior, depressive symptoms, vital exhaustion and hopelessness. Statistical analyses involved descriptive analyses, correlations and path analysis. Depressive symptoms and vital exhaustion associated with several unfavorable lifestyles such as smoking, alcohol consumption, and inactivity (standardized solution coefficients: 0.10, 0.14, 0.17, accordingly. However, no significant direct associations with blood pressure could be found for depressive symptoms or vital exhaustion. Hopelessness associated only with unhealthy diet (standardized solution coefficient -0.10 Moreover, for hopelessness, results showed a direct but inverse association with systolic blood pressure (standardized solution coefficient -0.08. Results suggest that the previously reported relations of depression and vital exhaustion with blood pressure could be mediated by unfavorable lifestyles. The relation of hopelessness with adverse health behaviors seems to be less significant. Also, the role of hopelessness as a risk factor of elevated blood pressure is not supported by the results of this study.

  9. Geographical location and age affects the incidence of parasitic infestations in school children

    Directory of Open Access Journals (Sweden)

    Rayan Paran

    2010-07-01

    Full Text Available Environmental factors affect the dissemination and distribution of intestinal parasites in human communities. To comprehend the prevalence of parasitic infestation and to examine whether geographical location and age also influence the prevalence of infection, fecal samples from 195 school children (rural = 95; male = 39; female = 56 (urban = 100; male = 60; female = 40 of five age groups ranging from 5 to 11 years in two different socio-economic zones (rural and urban were screened for specific intestinal parasites using standard histological techniques. Percentage incidences of parasitic species found in fecal wet mounts and concentrates in rural children were Entamoeba coli (25.3%, Giardia lamblia (17.9%, Blastocystis hominis (14.7%, Entamoeba histolytica (4.2%, Iodamoeba butschlii (1.1%, Hymenolepis nana (1.1% and Ascaris lumbricoides (1.1%. Whereas the percentage incidences among urban children were E. coli (26%, A. lumbricoides (21%, B. hominis (18%, G. lamblia (14%, T. trichiura (8%, I. butschlii (4% and A. duodenale (1%. Such findings may be related to dietary differences, living conditions and the greater use of natural anti-helminthic medicinal plants in rural communities. These results are important for both epidemiological data collection and for correlating dietary differences to intestinal parasitic diseases. Aims: We chose to investigate whether geographical location and age affect the prevalence and distribution of intestinal parasites among school children from two separate regions (rural and urban in areas surrounding, Chennai, Tamil Nadu, India. Settings and Design: A study of the prevalence of parasitic infestations was undertaken among primary school children, in rural and urban communities around Chennai, Tamil Nadu, India. Materials and Methods: Faecal sample collection, direct microscopic techniques, macroscopic examination and concentration techniques for identifying the parasites. Statistical analysis used: Percentage

  10. Aβ-Induced Synaptic Alterations Require the E3 Ubiquitin Ligase Nedd4-1.

    Science.gov (United States)

    Rodrigues, Elizabeth M; Scudder, Samantha L; Goo, Marisa S; Patrick, Gentry N

    2016-02-03

    Alzheimer's disease (AD) is a neurodegenerative disease in which patients experience progressive cognitive decline. A wealth of evidence suggests that this cognitive impairment results from synaptic dysfunction in affected brain regions caused by cleavage of amyloid precursor protein into the pathogenic peptide amyloid-β (Aβ). Specifically, it has been shown that Aβ decreases surface AMPARs, dendritic spine density, and synaptic strength, and also alters synaptic plasticity. The precise molecular mechanisms by which this occurs remain unclear. Here we demonstrate a role for ubiquitination in Aβ-induced synaptic dysfunction in cultured rat neurons. We find that Aβ promotes the ubiquitination of AMPARs, as well as the redistribution and recruitment of Nedd4-1, a HECT E3 ubiquitin ligase we previously demonstrated to target AMPARs for ubiquitination and degradation. Strikingly, we show that Nedd4-1 is required for Aβ-induced reductions in surface AMPARs, synaptic strength, and dendritic spine density. Our findings, therefore, indicate an important role for Nedd4-1 and ubiquitin in the synaptic alterations induced by Aβ. Synaptic changes in Alzheimer's disease (AD) include surface AMPAR loss, which can weaken synapses. In a cell culture model of AD, we found that AMPAR loss correlates with increased AMPAR ubiquitination. In addition, the ubiquitin ligase Nedd4-1, known to ubiquitinate AMPARs, is recruited to synapses in response to Aβ. Strikingly, reducing Nedd4-1 levels in this model prevented surface AMPAR loss and synaptic weakening. These findings suggest that, in AD, Nedd4-1 may ubiquitinate AMPARs to promote their internalization and weaken synaptic strength, similar to what occurs in Nedd4-1's established role in homeostatic synaptic scaling. This is the first demonstration of Aβ-mediated control of a ubiquitin ligase to regulate surface AMPAR expression. Copyright © 2016 the authors 0270-6474/16/361590-06$15.00/0.

  11. Mechanisms of Synaptic Alterations in a Neuroinflammation Model of Autism

    Science.gov (United States)

    2015-10-01

    inhibitory presynaptic input in the cortex of MIA offspring To determine if the altered number, shape and dynamic proper- ties of spines are...affects synaptic function in the cortex . We performed whole-cell voltage -clamp recordings from layer 2 pyramidal neurons in the somatosensory cortex ...highly dynamic struc- tures with new spines forming and others disappearing on a time scale of minutes (Dailey and Smith, 1996; Dunaevsky et al., 1999

  12. Pinpointing Synaptic Loss Caused by Alzheimer?s Disease with fMRI

    OpenAIRE

    Brickman, Adam M.; Small, Scott A.; Fleisher, Adam

    2009-01-01

    During its earliest stage, before cell loss and independent of amyloid plaques and neurofibrillary tangles, Alzheimer's disease (AD) causes synaptic loss affecting the basal functional properties of neurons. In principle, synaptic loss can be detected by measuring AD-induced changes in basal function, or by measuring stimulus-evoked responses on top of basal changes. Functional magnetic resonance imaging (fMRI) is sensitive to both basal changes and evoked-responses, and there are therefore t...

  13. The Impact of Audience Age and Familiarity on Children's Drawings of Themselves in Contrasting Affective States

    Science.gov (United States)

    Burkitt, Esther; Watling, Dawn

    2013-01-01

    The present study was designed to investigate the impact of familiarity and audience age on children's self-presentation in self-drawings of happy, sad and neutral figures. Two hundred children (100 girls and 100 boys) with the average age of 8 years 2 months, ranging from 6 years 3 months to 10 years 1 month, formed two age groups and five…

  14. Maternal age and in vitro culture affect mitochondrial number and function in equine oocytes and embryos

    NARCIS (Netherlands)

    Hendriks, W Karin; Colleoni, Silvia; Galli, Cesare; Paris, Damien B B P; Colenbrander, Ben; Roelen, Bernard A J; Stout, Tom A E

    2015-01-01

    Advanced maternal age and in vitro embryo production (IVP) predispose to pregnancy loss in horses. We investigated whether mare age and IVP were associated with alterations in mitochondrial (mt) DNA copy number or function that could compromise oocyte and embryo development. Effects of mare age

  15. Development and growth potential of axillary buds in roses as affected by bud age.

    NARCIS (Netherlands)

    Marcelis-van Acker, C.A.M.

    1994-01-01

    The effect of axillary bud age on the development and potential for growth of the bud into a shoot was studied in roses. Age of the buds occupying a similar position on the plant varied from 'subtending leaf just unfolded' up to 1 year later. With increasing age of the axillary bud its dry mass,

  16. Optogenetic Examination of Prefrontal-Amygdala Synaptic Development.

    Science.gov (United States)

    Arruda-Carvalho, Maithe; Wu, Wan-Chen; Cummings, Kirstie A; Clem, Roger L

    2017-03-15

    A brain network comprising the medial prefrontal cortex (mPFC) and amygdala plays important roles in developmentally regulated cognitive and emotional processes. However, very little is known about the maturation of mPFC-amygdala circuitry. We conducted anatomical tracing of mPFC projections and optogenetic interrogation of their synaptic connections with neurons in the basolateral amygdala (BLA) at neonatal to adult developmental stages in mice. Results indicate that mPFC-BLA projections exhibit delayed emergence relative to other mPFC pathways and establish synaptic transmission with BLA excitatory and inhibitory neurons in late infancy, events that coincide with a massive increase in overall synaptic drive. During subsequent adolescence, mPFC-BLA circuits are further modified by excitatory synaptic strengthening as well as a transient surge in feedforward inhibition. The latter was correlated with increased spontaneous inhibitory currents in excitatory neurons, suggesting that mPFC-BLA circuit maturation culminates in a period of exuberant GABAergic transmission. These findings establish a time course for the onset and refinement of mPFC-BLA transmission and point to potential sensitive periods in the development of this critical network. SIGNIFICANCE STATEMENT Human mPFC-amygdala functional connectivity is developmentally regulated and figures prominently in numerous psychiatric disorders with a high incidence of adolescent onset. However, it remains unclear when synaptic connections between these structures emerge or how their properties change with age. Our work establishes developmental windows and cellular substrates for synapse maturation in this pathway involving both excitatory and inhibitory circuits. The engagement of these substrates by early life experience may support the ontogeny of fundamental behaviors but could also lead to inappropriate circuit refinement and psychopathology in adverse situations. Copyright © 2017 the authors 0270-6474/17/372976-10$15.00/0.

  17. Affective Norms for Italian Words in Older Adults: Age Differences in Ratings of Valence, Arousal and Dominance.

    Science.gov (United States)

    Fairfield, Beth; Ambrosini, Ettore; Mammarella, Nicola; Montefinese, Maria

    2017-01-01

    In line with the dimensional theory of emotional space, we developed affective norms for words rated in terms of valence, arousal and dominance in a group of older adults to complete the adaptation of the Affective Norms for English Words (ANEW) for Italian and to aid research on aging. Here, as in the original Italian ANEW database, participants evaluated valence, arousal, and dominance by means of the Self-Assessment Manikin (SAM) in a paper-and-pencil procedure. We observed high split-half reliabilities within the older sample and high correlations with the affective ratings of previous research, especially for valence, suggesting that there is large agreement among older adults within and across-languages. More importantly, we found high correlations between younger and older adults, showing that our data are generalizable across different ages. However, despite this across-ages accord, we obtained age-related differences on three affective dimensions for a great number of words. In particular, older adults rated as more arousing and more unpleasant a number of words that younger adults rated as moderately unpleasant and arousing in our previous affective norms. Moreover, older participants rated negative stimuli as more arousing and positive stimuli as less arousing than younger participants, thus leading to a less-curved distribution of ratings in the valence by arousal space. We also found more extreme ratings for older adults for the relationship between dominance and arousal: older adults gave lower dominance and higher arousal ratings for words rated by younger adults with middle dominance and arousal values. Together, these results suggest that our affective norms are reliable and can be confidently used to select words matched for the affective dimensions of valence, arousal and dominance across younger and older participants for future research in aging.

  18. Somatic and cognitive-affective depressive symptoms among patients with heart disease: differences by sex and age

    Directory of Open Access Journals (Sweden)

    Carina Aparecida Marosti Dessotte

    2015-04-01

    Full Text Available OBJECTIVE: this study investigated the association of somatic and cognitive-affective symptoms with sex and age, among patients hospitalized with heart disease. METHOD: this study was a secondary analysis of two previous observational studies totaling 531 patients with heart disease, hospitalized from 2005 to 2011 in two public hospitals in Ribeirão Preto, state of São Paulo, Brazil. Somatic and cognitive-affective symptoms were assessed using the subscales of the Beck Depression Inventory - I (BDI-I. RESULTS: of 531 participants, 62.7% were male, with a mean age 57.3 years (SD= 13.0 for males and 56.2 years (SD= 12.1 for females. Analyses of variance showed an effect of sex (p<0.001 for somatic and p=0.005 for cognitive-affective symptoms, but no effect of age. Women presented with higher mean values than men in both BDI-I subscales: 7.1 (4.5 vs. 5.4 (4.3 for somatic, and 8.3 (7.9 vs. 6.7 (7.2 for cognitive-affective symptoms. There were no differences by age for somatic (p=0.84 or cognitive-affective symptoms (p=0.84. CONCLUSION: women hospitalized with heart disease had more somatic and cognitive-affective symptoms than men. We found no association of somatic and cognitive-affective symptoms with age. Future research for these patients could reveal whether these differences according to sex continue throughout the rehabilitation process.

  19. Sexual selection affects the evolution of lifespan and ageing in the decorated cricket Gryllodes sigillatus.

    Science.gov (United States)

    Archer, C R; Zajitschek, F; Sakaluk, S K; Royle, N J; Hunt, J

    2012-10-01

    Recent work suggests that sexual selection can influence the evolution of ageing and lifespan by shaping the optimal timing and relative costliness of reproductive effort in the sexes. We used inbred lines of the decorated cricket, Gryllodes sigillatus, to estimate the genetic (co)variance between age-dependent reproductive effort, lifespan, and ageing within and between the sexes. Sexual selection theory predicts that males should die sooner and age more rapidly than females. However, a reversal of this pattern may be favored if reproductive effort increases with age in males but not in females. We found that male calling effort increased with age, whereas female fecundity decreased, and that males lived longer and aged more slowly than females. These divergent life-history strategies were underpinned by a positive genetic correlation between early-life reproductive effort and ageing rate in both sexes, although this relationship was stronger in females. Despite these sex differences in life-history schedules, age-dependent reproductive effort, lifespan, and ageing exhibited strong positive intersexual genetic correlations. This should, in theory, constrain the independent evolution of these traits in the sexes and may promote intralocus sexual conflict. Our study highlights the importance of sexual selection to the evolution of sex differences in ageing and lifespan in G. sigillatus. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

  20. Synaptic vesicle distribution by conveyor belt.

    Science.gov (United States)

    Moughamian, Armen J; Holzbaur, Erika L F

    2012-03-02

    The equal distribution of synaptic vesicles among synapses along the axon is critical for robust neurotransmission. Wong et al. show that the continuous circulation of synaptic vesicles throughout the axon driven by molecular motors ultimately yields this even distribution. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Spontaneous Vesicle Recycling in the Synaptic Bouton

    Directory of Open Access Journals (Sweden)

    Sven eTruckenbrodt

    2014-12-01

    Full Text Available The trigger for synaptic vesicle exocytosis is Ca2+, which enters the synaptic bouton following action potential stimulation. However, spontaneous release of neurotransmitter also occurs in the absence of stimulation in virtually all synaptic boutons. It has long been thought that this represents exocytosis driven by fluctuations in local Ca2+ levels. The vesicles responding to these fluctuations are thought to be the same ones that release upon stimulation, albeit potentially triggered by different Ca2+ sensors. This view has been challenged by several recent works, which have suggested that spontaneous release is driven by a separate pool of synaptic vesicles. Numerous articles appeared during the last few years in support of each of these hypotheses, and it has been challenging to bring them into accord. We speculate here on the origins of this controversy, and propose a solution that is related to developmental effects. Constitutive membrane traffic, needed for the biogenesis of vesicles and synapses, is responsible for high levels of spontaneous membrane fusion in young neurons, probably independent of Ca2+. The vesicles releasing spontaneously in such neurons are not related to other synaptic vesicle pools and may represent constitutively releasing vesicles (CRVs rather than bona fide synaptic vesicles. In mature neurons, constitutive traffic is much dampened, and the few remaining spontaneous release events probably represent bona fide spontaneously releasing synaptic vesicles (SRSVs responding to Ca2+ fluctuations, along with a handful of CRVs that participate in synaptic vesicle turnover.

  2. Active hippocampal networks undergo spontaneous synaptic modification.

    Directory of Open Access Journals (Sweden)

    Masako Tsukamoto-Yasui

    Full Text Available The brain is self-writable; as the brain voluntarily adapts itself to a changing environment, the neural circuitry rearranges its functional connectivity by referring to its own activity. How the internal activity modifies synaptic weights is largely unknown, however. Here we report that spontaneous activity causes complex reorganization of synaptic connectivity without any external (or artificial stimuli. Under physiologically relevant ionic conditions, CA3 pyramidal cells in hippocampal slices displayed spontaneous spikes with bistable slow oscillations of membrane potential, alternating between the so-called UP and DOWN states. The generation of slow oscillations did not require fast synaptic transmission, but their patterns were coordinated by local circuit activity. In the course of generating spontaneous activity, individual neurons acquired bidirectional long-lasting synaptic modification. The spontaneous synaptic plasticity depended on a rise in intracellular calcium concentrations of postsynaptic cells, but not on NMDA receptor activity. The direction and amount of the plasticity varied depending on slow oscillation patterns and synapse locations, and thus, they were diverse in a network. Once this global synaptic refinement occurred, the same neurons now displayed different patterns of spontaneous activity, which in turn exhibited different levels of synaptic plasticity. Thus, active networks continuously update their internal states through ongoing synaptic plasticity. With computational simulations, we suggest that with this slow oscillation-induced plasticity, a recurrent network converges on a more specific state, compared to that with spike timing-dependent plasticity alone.

  3. Old and Unemployable? How Age-Based Stereotypes Affect Willingness to Hire Job Candidates.

    Science.gov (United States)

    Abrams, Dominic; Swift, Hannah J; Drury, Lisbeth

    2016-03-01

    Across the world, people are required, or want, to work until an increasingly old age. But how might prospective employers view job applicants who have skills and qualities that they associate with older adults? This article draws on social role theory, age stereotypes and research on hiring biases, and reports three studies using age-diverse North American participants. These studies reveal that: (1) positive older age stereotype characteristics are viewed less favorably as criteria for job hire, (2) even when the job role is low-status, a younger stereotype profile tends to be preferred, and (3) an older stereotype profile is only considered hirable when the role is explicitly cast as subordinate to that of a candidate with a younger age profile. Implications for age-positive selection procedures and ways to reduce the impact of implicit age biases are discussed.

  4. Synaptic plasticity in drug reward circuitry.

    Science.gov (United States)

    Winder, Danny G; Egli, Regula E; Schramm, Nicole L; Matthews, Robert T

    2002-11-01

    Drug addiction is a major public health issue worldwide. The persistence of drug craving coupled with the known recruitment of learning and memory centers in the brain has led investigators to hypothesize that the alterations in glutamatergic synaptic efficacy brought on by synaptic plasticity may play key roles in the addiction process. Here we review the present literature, examining the properties of synaptic plasticity within drug reward circuitry, and the effects that drugs of abuse have on these forms of plasticity. Interestingly, multiple forms of synaptic plasticity can be induced at glutamatergic synapses within the dorsal striatum, its ventral extension the nucleus accumbens, and the ventral tegmental area, and at least some of these forms of plasticity are regulated by behaviorally meaningful administration of cocaine and/or amphetamine. Thus, the present data suggest that regulation of synaptic plasticity in reward circuits is a tractable candidate mechanism underlying aspects of addiction.

  5. Does Maternal Prenatal Stress Adversely Affect the Child's Learning and Memory at Age Six?

    Science.gov (United States)

    Gutteling, Barbara M.; de Weerth, Carolina; Zandbelt, Noortje; Mulder, Eduard J. H.; Visser, Gerard H. A.; Buitelaar, Jan K.

    2006-01-01

    Prenatal maternal stress has been shown to affect postnatal development in animals and humans. In animals, the morphology and function of the offspring's hippocampus is negatively affected by prenatal maternal stress. The present study prospectively investigated the influence of prenatal maternal stress on learning and memory of 112 children (50…

  6. Time-Dependent Behavior of Shrinkage Strain for Early Age Concrete Affected by Temperature Variation

    OpenAIRE

    Qin, Yu; Yi, Zhijian; Wang, Weina; Wang, Di

    2017-01-01

    Shrinkage has been proven to be an important property of early age concrete. The shrinkage strain leads to inherent engineering problems, such as cracking and loss of prestress. Atmospheric temperature is an important factor in shrinkage strain. However, current research does not provide much attention to the effect of atmospheric temperature on shrinkage of early age concrete. In this paper, a laboratory study was undertaken to present the time-dependent shrinkage of early age concrete under...

  7. Neuromodulation, development and synaptic plasticity.

    Science.gov (United States)

    Foehring, R C; Lorenzon, N M

    1999-03-01

    We discuss parallels in the mechanisms underlying use-dependent synaptic plasticity during development and long-term potentiation (LTP) and long-term depression (LTD) in neocortical synapses. Neuromodulators, such as norepinephrine, serotonin, and acetylcholine have also been implicated in regulating both developmental plasticity and LTP/LTD. There are many potential levels of interaction between neuromodulators and plasticity. Ion channels are substrates for modulation in many cell types. We discuss examples of modulation of voltage-gated Ca2+ channels and Ca(2+)-dependent K+ channels and the consequences for neocortical pyramidal cell firing behaviour. At the time when developmental plasticity is most evident in rat cortex, the substrate for modulation is changing as the densities and relative proportions of various ion channels types are altered during ontogeny. We discuss examples of changes in K+ and Ca2+ channels and the consequence for modulation of neuronal activity.

  8. Synaptic transmission modulates while non-synaptic processes govern the transition from pre-ictal to seizure activity in vitro

    OpenAIRE

    Jefferys, John; Fox, John; Jiruska, Premysl; Kronberg, Greg; Miranda, Dolores; Ruiz-Nuño, Ana; Bikson, Marom

    2018-01-01

    It is well established that non-synaptic mechanisms can generate electrographic seizures after blockade of synaptic function. We investigated the interaction of intact synaptic activity with non-synaptic mechanisms in the isolated CA1 region of rat hippocampal slices using the 'elevated-K+' model of epilepsy. Elevated K+ ictal bursts share waveform features with other models of electrographic seizures, including non-synaptic models where chemical synaptic transmission is suppressed, such as t...

  9. Age Differences in Affective Decision Making as Indexed by Performance on the Iowa Gambling Task

    Science.gov (United States)

    Cauffman, Elizabeth; Shulman, Elizabeth P.; Steinberg, Laurence; Claus, Eric; Banich, Marie T.; Graham, Sandra; Woolard, Jennifer

    2010-01-01

    Contemporary perspectives on age differences in risk taking, informed by advances in developmental neuroscience, have emphasized the need to examine the ways in which emotional and cognitive factors interact to influence decision making. In the present study, a diverse sample of 901 individuals between the ages of 10 and 30 were administered a…

  10. Stronger Association Between Valence- and Arousal Ratings of Affective Pictures with Older Age: Evidence for Variation Across Emotion Categories

    DEFF Research Database (Denmark)

    Mikkelsen, Mai Bjørnskov; Mehlsen, Mimi Yung; Lyby, Marlene Skovgaard

    A sample of older and younger adults rated affective pictures according to valence, arousal and emotion category (happiness, sadness and disgust). Results indicate that older age is associated with a stronger linear association between ratings of arousal and valence. Further, the strength...... of the association vary according to emotion category....

  11. Age at onset of non-affective psychosis in relation to cannabis use, other drug use and gender

    NARCIS (Netherlands)

    Dekker, N.; Meijer, J.; Koeter, M.; van den Brink, W.; van Beveren, N.; Kahn, R. S.; Linszen, D. H.; van Os, J.; Wiersma, D.; Bruggeman, R.; Cahn, W.; de Haan, L.; Krabbendam, L.; Myin-Germeys, I.

    Background. Cannabis use is associated with an earlier age at onset of psychotic illness. The aim of the present study was to examine whether this association is confounded by gender or other substance use in a large cohort of patients with a non-affective psychotic disorder. Method. In 785 patients

  12. Inter-individual differences in how presentation modality affects verbal learning performance in children aged 5 to 16

    NARCIS (Netherlands)

    Meijs, Celeste; Hurks, Petra P M; Wassenberg, Renske; Feron, Frans J M; Jolles, Jelle

    2016-01-01

    This study examines inter-individual differences in how presentation modality affects verbal learning performance. Children aged 5 to 16 performed a verbal learning test within one of three presentation modalities: pictorial, auditory, or textual. The results indicated that a beneficial effect of

  13. Arteriolosclerosis that affects multiple brain regions is linked to hippocampal sclerosis of ageing

    Science.gov (United States)

    Neltner, Janna H.; Abner, Erin L.; Baker, Steven; Schmitt, Frederick A.; Kryscio, Richard J.; Jicha, Gregory A.; Smith, Charles D.; Hammack, Eleanor; Kukull, Walter A.; Brenowitz, Willa D.; Van Eldik, Linda J.

    2014-01-01

    Hippocampal sclerosis of ageing is a prevalent brain disease that afflicts older persons and has been linked with cerebrovascular pathology. Arteriolosclerosis is a subtype of cerebrovascular pathology characterized by concentrically thickened arterioles. Here we report data from multiple large autopsy series (University of Kentucky Alzheimer’s Disease Centre, Nun Study, and National Alzheimer’s Coordinating Centre) showing a specific association between hippocampal sclerosis of ageing pathology and arteriolosclerosis. The present analyses incorporate 226 cases of autopsy-proven hippocampal sclerosis of ageing and 1792 controls. Case–control comparisons were performed including digital pathological assessments for detailed analyses of blood vessel morphology. We found no evidence of associations between hippocampal sclerosis of ageing pathology and lacunar infarcts, large infarcts, Circle of Willis atherosclerosis, or cerebral amyloid angiopathy. Individuals with hippocampal sclerosis of ageing pathology did not show increased rates of clinically documented hypertension, diabetes, or other cardiac risk factors. The correlation between arteriolosclerosis and hippocampal sclerosis of ageing pathology was strong in multiple brain regions outside of the hippocampus. For example, the presence of arteriolosclerosis in the frontal cortex (Brodmann area 9) was strongly associated with hippocampal sclerosis of ageing pathology (P ageing (n = 15) and control (n = 42) cases. Following technical studies to optimize immunostaining methods for small blood vessel visualization, our analyses focused on sections immunostained for smooth muscle actin (a marker of arterioles) and CD34 (an endothelial marker), with separate analyses on grey and white matter. A total of 43 834 smooth muscle actin-positive vascular profiles and 603 798 CD34-positive vascular profiles were evaluated. In frontal cortex of cases with hippocampal sclerosis of ageing, smooth muscle actin

  14. Carbon dioxide inhalation induces dose-dependent and age-related negative affectivity.

    Directory of Open Access Journals (Sweden)

    Eric J Griez

    Full Text Available BACKGROUND: Carbon dioxide inhalation is known to induce an emotion similar to spontaneous panic in Panic Disorder patients. The affective response to carbon dioxide in healthy subjects was not clearly characterized yet. METHODOLOGY/PRINCIPAL FINDINGS: Sixty-four healthy subjects underwent a double inhalation of four mixtures containing respectively 0, 9, 17.5 and 35% CO(2 in compressed air, following a double blind, cross-over, randomized design. Affective responses were assessed according to DSM IV criteria for panic, using an Electronic Visual Analogue Scale and the Panic Symptom List. It was demonstrated that carbon dioxide challenges induced a dose dependent negative affect (p<0.0001. This affect was semantically identical to the DSM IV definition of panic. Older individuals were subjectively less sensitive to Carbon Dioxide (p<0.05. CONCLUSIONS/SIGNIFICANCE: CO(2 induced affectivity may lay on a continuum with pathological panic attacks. Consistent with earlier suggestions that panic is a false biological alarm, the affective response to CO(2 may be part of a protective system triggered by suffocation and acute metabolic distress.

  15. Implications of advancing paternal age: does it affect offspring school performance?

    Directory of Open Access Journals (Sweden)

    Anna C Svensson

    Full Text Available Average paternal age is increasing in many high income countries, but the implications of this demographic shift for child health and welfare are poorly understood. There is equivocal evidence that children of older fathers are at increased risk of neurodevelopmental disorders and reduced IQ. We therefore report here on the relationship between paternal age and a composite indicator of scholastic achievement during adolescence, i.e. compulsory school leaving grades, among recent birth cohorts in Stockholm County where delayed paternity is notably common. We performed a record-linkage study comprising all individuals in Stockholm County who finished 9 years of compulsory school from 2000 through 2007 (n = 155,875. Data on school leaving grades and parental characteristics were retrieved from administrative and health service registers and analyzed using multiple linear regression. Advancing paternal age at birth was not associated with a decrease in school leaving grades in adolescent offspring. After adjustment for year of graduation, maternal age and parental education, country of birth and parental mental health service use, offspring of fathers aged 50 years or older had on average 0.3 (95% CI -3.8, 4.4 points higher grades than those of fathers aged 30-34 years. In conclusion, advancing paternal age is not associated with poorer school performance in adolescence. Adverse effects of delayed paternity on offspring cognitive function, if any, may be counterbalanced by other potential advantages for children born to older fathers.

  16. Arteriolosclerosis that affects multiple brain regions is linked to hippocampal sclerosis of ageing.

    Science.gov (United States)

    Neltner, Janna H; Abner, Erin L; Baker, Steven; Schmitt, Frederick A; Kryscio, Richard J; Jicha, Gregory A; Smith, Charles D; Hammack, Eleanor; Kukull, Walter A; Brenowitz, Willa D; Van Eldik, Linda J; Nelson, Peter T

    2014-01-01

    Hippocampal sclerosis of ageing is a prevalent brain disease that afflicts older persons and has been linked with cerebrovascular pathology. Arteriolosclerosis is a subtype of cerebrovascular pathology characterized by concentrically thickened arterioles. Here we report data from multiple large autopsy series (University of Kentucky Alzheimer's Disease Centre, Nun Study, and National Alzheimer's Coordinating Centre) showing a specific association between hippocampal sclerosis of ageing pathology and arteriolosclerosis. The present analyses incorporate 226 cases of autopsy-proven hippocampal sclerosis of ageing and 1792 controls. Case-control comparisons were performed including digital pathological assessments for detailed analyses of blood vessel morphology. We found no evidence of associations between hippocampal sclerosis of ageing pathology and lacunar infarcts, large infarcts, Circle of Willis atherosclerosis, or cerebral amyloid angiopathy. Individuals with hippocampal sclerosis of ageing pathology did not show increased rates of clinically documented hypertension, diabetes, or other cardiac risk factors. The correlation between arteriolosclerosis and hippocampal sclerosis of ageing pathology was strong in multiple brain regions outside of the hippocampus. For example, the presence of arteriolosclerosis in the frontal cortex (Brodmann area 9) was strongly associated with hippocampal sclerosis of ageing pathology (P studies to optimize immunostaining methods for small blood vessel visualization, our analyses focused on sections immunostained for smooth muscle actin (a marker of arterioles) and CD34 (an endothelial marker), with separate analyses on grey and white matter. A total of 43 834 smooth muscle actin-positive vascular profiles and 603 798 CD34-positive vascular profiles were evaluated. In frontal cortex of cases with hippocampal sclerosis of ageing, smooth muscle actin-immunoreactive arterioles had thicker walls (P < 0.05), larger perimeters (P < 0

  17. Longitudinal Relationships Between Positive Affect, Loneliness, and Suicide Ideation: Age-Specific Factors in a General Population.

    Science.gov (United States)

    Bennardi, Marco; Caballero, Francisco Félix; Miret, Marta; Ayuso-Mateos, Jose Luis; Haro, Josep Maria; Lara, Elvira; Arensman, Ella; Cabello, Maria

    2017-12-06

    The aims of this study were to analyze whether positive and negative affect, social support, and loneliness are factors longitudinally related to suicide ideation in the general population in different age groups. A total of 2,392 individuals from a nationally representative sample of the Spanish general population were evaluated in 2011-2012 and in 2014-2015. After including relevant control variables in the analyses, lower positive affect was prospectively related to ideation in 18- to 59-year-old individuals, whereas feelings of loneliness were related to ideation in 60-year-and-older individuals. Social support was not associated with suicide ideation in any age group. These results are in line with the need for age-tailored suicide prevention programs. The present findings might also suggest that health care professionals should consider feelings of loneliness rather than social support to assess the presence of suicide ideation in older people. © 2017 The American Association of Suicidology.

  18. Aging affects the transcriptional regulation of human skeletal muscle disuse atrophy

    DEFF Research Database (Denmark)

    Suetta, Charlotte Arneboe; Frandsen, Ulrik; Jensen, Line

    2012-01-01

    Important insights concerning the molecular basis of skeletal muscle disuse-atrophy and aging related muscle loss have been obtained in cell culture and animal models, but these regulatory signaling pathways have not previously been studied in aging human muscle. In the present study, muscle...... atrophy was induced by immobilization in healthy old and young individuals to study the time-course and transcriptional factors underlying human skeletal muscle atrophy. The results reveal that irrespectively of age, mRNA expression levels of MuRF-1 and Atrogin-1 increased in the very initial phase (2......-4 days) of human disuse-muscle atrophy along with a marked reduction in PGC-1α and PGC-1β (1-4 days) and a ∼10% decrease in myofiber size (4 days). Further, an age-specific decrease in Akt and S6 phosphorylation was observed in young muscle within the first days (1-4 days) of immobilization. In contrast...

  19. Chronological age affects the permeation of fentanyl through human skin in vitro

    DEFF Research Database (Denmark)

    Holmgaard, R; Benfeldt, E; Sorensen, J A

    2013-01-01

    AIM: To study the influence of chronological age on fentanyl permeation through human skin in vitro using static diffusion cells. Elderly individuals are known to be more sensitive to opioids and obtain higher plasma concentrations following dermal application of fentanyl compared to younger...... individuals. The influence of age - as an isolated pharmacokinetic term - on the absorption of fentanyl has not been previously studied. METHOD: Human skin from 30 female donors was mounted in static diffusion cells, and samples were collected during 48 h. Donors were divided into three age groups: ... and old age groups: 5,922 and 4,050 ng, respectively). Furthermore, the lag time and absorption rate were different between the three groups, with a significantly higher rate in the young participants versus the oldest participants. CONCLUSION: We demonstrate that fentanyl permeates the skin of young...

  20. aging affects morphology but not stimulated secretion of saliva in rats

    African Journals Online (AJOL)

    initial food digestion, taste perception, maintenance of ... salivary gland weights, salivary flow rates, pH and salivary levels of sodium, ... free flow into sterile plain tubes for a period of 10 .... composition are largely age independent in human. In.

  1. Factors Affecting Age at Initial Autism Spectrum Disorder Diagnosis in a National Survey

    OpenAIRE

    Rosenberg, Rebecca E.; Landa, Rebecca; Law, J. Kiely; Stuart, Elizabeth A.; Law, Paul A.

    2011-01-01

    Entry into early intervention depends on both age of first parent concern (AOC) and age at initial autism spectrum disorder (ASD) diagnosis (AOD). Using data collected from a national online registry from 6214 children diagnosed with an ASD between 1994 and 2010 in the US, we analyzed the effect of individual, family, and geographic covariates on AOC and AOD in a multivariate linear regression model with random effects. Overall, no single modifiable factor associated with AOC or AOD emerged ...

  2. Brain processing of emotional scenes in aging: effect of arousal and affective context.

    Directory of Open Access Journals (Sweden)

    Nicolas Gilles Mathieu

    Full Text Available Research on emotion showed an increase, with age, in prevalence of positive information relative to negative ones. This effect is called positivity effect. From the cerebral analysis of the Late Positive Potential (LPP, sensitive to attention, our study investigated to which extent the arousal level of negative scenes is differently processed between young and older adults and, to which extent the arousal level of negative scenes, depending on its value, may contextually modulate the cerebral processing of positive (and neutral scenes and favor the observation of a positivity effect with age. With this aim, two negative scene groups characterized by two distinct arousal levels (high and low were displayed into two separate experimental blocks in which were included positive and neutral pictures. The two blocks only differed by their negative pictures across participants, as to create two negative global contexts for the processing of the positive and neutral pictures. The results show that the relative processing of different arousal levels of negative stimuli, reflected by LPP, appears similar between the two age groups. However, a lower activity for negative stimuli is observed with the older group for both tested arousal levels. The processing of positive information seems to be preserved with age and is also not contextually impacted by negative stimuli in both younger and older adults. For neutral stimuli, a significantly reduced activity is observed for older adults in the contextual block of low-arousal negative stimuli. Globally, our study reveals that the positivity effect is mainly due to a modulation, with age, in processing of negative stimuli, regardless of their arousal level. It also suggests that processing of neutral stimuli may be modulated with age, depending on negative context in which they are presented to. These age-related effects could contribute to justify the differences in emotional preference with age.

  3. An analysis of vascular surgery in elderly patients to determine whether age affects treatment strategy.

    LENUS (Irish Health Repository)

    O'Brien, G

    2012-03-01

    The incidence of arterial disease increases with age. Increasing life expectancy in the western world will intensify demands on vascular surgeons with regard to increasing caseload, expanding patient selection criteria, and more complex and minimally-invasive treatment options. We analysed our arterial cases over the past 31 years (n = 6,144) and compared our methods of intervention and complication rates in the elderly population (>75) with the younger cohort, in order to determine whether age should influence our management strategies.

  4. Modulatory role of androgenic and estrogenic neurosteroids in determining the direction of synaptic plasticity in the CA1 hippocampal region of male rats.

    Science.gov (United States)

    Pettorossi, Vito Enrico; Di Mauro, Michela; Scarduzio, Mariangela; Panichi, Roberto; Tozzi, Alessandro; Calabresi, Paolo; Grassi, Silvarosa

    2013-12-01

    Estrogenic and androgenic neurosteroids can rapidly modulate synaptic plasticity in the brain through interaction with membrane receptors for estrogens (ERs) and androgens (ARs). We used electrophysiological recordings in slices of young and adolescent male rats to explore the influence of sex neurosteroids on synaptic plasticity in the CA1 hippocampal region, by blocking ARs or ERs during induction of long-term depression (LTD) and depotentiation (DP) by low-frequency stimulation (LFS) and long-term potentiation (LTP) by high-frequency stimulation (HFS). We found that LTD and DP depend on ARs, while LTP on ERs in both age groups. Accordingly, the AR blocker flutamide affected induction of LTD reverting it into LTP, and prevented DP, while having no effect on HFS-dependent LTP. Conversely, ER blockade with ICI 182,780 (ICI) markedly reduced LTP, but did not influence LTD and DP. However, the receptor blockade did not affect the maintenance of either LTD or LTP. Moreover, we found that similar to LTP and LTD induced in control condition, the LTP unveiled by flutamide during LFS and residual LTP induced by HFS under ICI depended on N-methyl-d aspartate receptor (NMDAR) activation. Furthermore, as the synaptic paired-pulse facilitation (PPF) was not affected by either AR or ER blockade, we suggest that sex neurosteroids act primarily at a postsynaptic level. This study demonstrates for the first time the crucial role of estrogenic and androgenic neurosteroids in determining the sign of hippocampal synaptic plasticity in male rat and the activity-dependent recruitment of androgenic and estrogenic pathways leading to LTD and LTP, respectively.

  5. How age affects memory task performance in clinically normal hearing persons.

    Science.gov (United States)

    Vercammen, Charlotte; Goossens, Tine; Wouters, Jan; van Wieringen, Astrid

    2017-05-01

    The main objective of this study is to investigate memory task performance in different age groups, irrespective of hearing status. Data are collected on a short-term memory task (WAIS-III Digit Span forward) and two working memory tasks (WAIS-III Digit Span backward and the Reading Span Test). The tasks are administered to young (20-30 years, n = 56), middle-aged (50-60 years, n = 47), and older participants (70-80 years, n = 16) with normal hearing thresholds. All participants have passed a cognitive screening task (Montreal Cognitive Assessment (MoCA)). Young participants perform significantly better than middle-aged participants, while middle-aged and older participants perform similarly on the three memory tasks. Our data show that older clinically normal hearing persons perform equally well on the memory tasks as middle-aged persons. However, even under optimal conditions of preserved sensory processing, changes in memory performance occur. Based on our data, these changes set in before middle age.

  6. Factors affecting age at first dental exam for children seen at Federally Qualified Health Centers

    Science.gov (United States)

    Kuthy, Raymond A.; Pendharkar, Bhagyashree; Momany, Elizabeth T.; Jones, Michael P.; Askelson, Natoshia M.; Chi, Donald L.; Wehby, George L.; Damiano, Peter C.

    2014-01-01

    Objective To estimate age at first dental visit (FDV) and identify variables predicting earlier visits for Medicaid-enrolled children at Federally Qualified Health Centers (FQHC). Methods Statewide Medicaid claims data were used to draw a random sample of children who received their FDV prior to 6 years of age at a FQHC, were Medicaid-enrolled within the first two months of life, and remained continuously enrolled over the study period. Forty children from each of 5 FQHCs had their dental charts abstracted and merged with other Medicaid records and birth certificate data. The logarithmic age at FDV was regressed against several predictor variables. Results Mean and median ages for FDV were 25.6 and 23 months, respectively. When controlling for other variables, there were differences in FDV age by mother’s marital status (p=0.003), number of medical well-child visits (MCV) at a FQHC prior to the FDV (p1MCV at the FQHC. Conclusion Medicaid enrolled children who visited FQHCs for FDV were seen at an earlier age than previously recorded for such health centers (i.e., mean-4 years). Children who also received their MCVs at FQHCs were more likely to have earlier FDVs. PMID:23756303

  7. Incidence of diseases primarily affecting the skin by age group: population-based epidemiologic study in Olmsted County, Minnesota, and comparison with age-specific incidence rates worldwide.

    Science.gov (United States)

    Wessman, Laurel L; Andersen, Louise K; Davis, Mark D P

    2018-01-29

    Understanding the effects of age on the epidemiology of diseases primarily affecting the skin is important to the practice of dermatology, both for proper allocation of resources and for optimal patient-centered care. To fully appreciate the effect that age may have on the population-based calculations of incidence of diseases primarily affecting the skin in Olmsted County, Minnesota, and worldwide, we performed a review of all relevant Rochester Epidemiology Project-published data and compared them to similar reports in the worldwide English literature. Using the Rochester Epidemiology Project, population-based epidemiologic studies have been performed to estimate the incidence of specific skin diseases over the past 50 years. In older persons (>65 years), nonmelanoma skin cancer, lentigo maligna, herpes zoster, delusional infestation, venous stasis syndrome, venous ulcer, and burning mouth syndrome were more commonly diagnosed. In those younger than 65 years, atypical nevi, psoriatic arthritis, pityriasis rosea, herpes progenitalis, genital warts, alopecia areata, hidradenitis suppurativa, infantile hemangioma, Behçet's disease, and sarcoidosis (isolated cutaneous, with sarcoidosis-specific cutaneous lesions and with erythema nodosum) had a higher incidence. Many of the incidence rates by age group of diseases primarily affecting the skin derived from the Rochester Epidemiology Project were similar to those reported elsewhere. © 2018 The International Society of Dermatology.

  8. Age-related compaction of lens fibers affects the structure and optical properties of rabbit lenses

    Directory of Open Access Journals (Sweden)

    Al-Ghoul Walid M

    2007-12-01

    Full Text Available Abstract Background The goal of this investigation was to correlate particular age-related structural changes (compaction to the amount of scatter in rabbit lenses and to determine if significant fiber compaction occurred in the nuclear and inner cortical regions. Methods New Zealand White rabbits at 16–20 months old (adult; n = 10 and at 3.5–4 years old (aged; n = 10 were utilized for this study. Immediately after euthanising, scatter was assessed in fresh lenses by low power helium-neon laser scan analysis. Scatter data was analyzed both for whole lenses and regionally, to facilitate correlation with morphometric data. After functional analysis, lenses were fixed and processed for scanning electron microcopy (SEM; right eyes and light microscopy (LM; left eyes. Morphometric analysis of SEM images was utilized to evaluate compaction of nuclear fibers. Similarly, measurements from LM images were used to assess compaction of inner cortical fibers. Results Scatter was significantly greater in aged lenses as compared to adult lenses in all regions analyzed, however the difference in the mean was slightly more pronounced in the inner cortical region. The anterior and posterior elliptical angles at 1 mm (inner fetal nucleus were significantly decreased in aged vs. adult lenses (anterior, p = 0.040; posterior, p = 0.036. However, the average elliptical angles at 2.5 mm (outer fetal nucleus were not significantly different in adult and aged lenses since all lenses examined had comparable angles to inner fetal fibers of aged lenses, i.e. they were all compacted. In cortical fibers, measures of average cross-sectional fiber area were significantly different at diameters of both 6 and 7 mm as a function of age (p = 0.011 and p = 0.005, respectively. Accordingly, the estimated fiber volume was significantly decreased in aged as compared to adult lenses at both 6 mm diameter (p = 0.016 and 7 mm diameter (p = 0.010. Conclusion Morphometric data indicates

  9. Aging affects the interaction between attentional control and source memory: an fMRI study.

    Science.gov (United States)

    Dulas, Michael R; Duarte, Audrey

    2014-12-01

    Age-related source memory impairments may be due, at least in part, to deficits in executive processes mediated by the PFC at both study and test. Behavioral work suggests that providing environmental support at encoding, such as directing attention toward item-source associations, may improve source memory and reduce age-related deficits in the recruitment of these executive processes. The present fMRI study investigated the effects of directed attention and aging on source memory encoding and retrieval. At study, participants were shown pictures of objects. They were either asked to attend to the objects and their color (source) or to their size. At test, participants determined if objects were seen before, and if so, whether they were the same color as previously. Behavioral results showed that direction of attention improved source memory for both groups; however, age-related deficits persisted. fMRI results revealed that, across groups, direction of attention facilitated medial temporal lobe-mediated contextual binding processes during study and attenuated right PFC postretrieval monitoring effects at test. However, persistent age-related source memory deficits may be related to increased recruitment of medial anterior PFC during encoding, indicative of self-referential processing, as well as underrecruitment of lateral anterior PFC-mediated relational processes. Taken together, this study suggests that, even when supported, older adults may fail to selectively encode goal-relevant contextual details supporting source memory performance.

  10. Age Differences in Affective and Cardiovascular Responses to a Negative Social Interaction: The Role of Goals, Appraisals, and Emotion Regulation

    Science.gov (United States)

    Luong, Gloria; Charles, Susan T.

    2014-01-01

    Older adults often report less affective reactivity to interpersonal tensions than younger individuals, but few studies have directly investigated mechanisms explaining this effect. The current study examined whether older adults’ differential endorsement of goals, appraisals, and emotion regulation strategies (i.e., conflict avoidance/de-escalation, self-distraction) during a controlled negative social interaction may explain age differences in affective and cardiovascular responses to the conflict discussion. Participants (N=159; 80 younger adults, 79 older adults) discussed hypothetical dilemmas with disagreeable confederates. Throughout the laboratory session, participants’ subjective emotional experience, blood pressure, and pulse rate were assessed. Older adults generally exhibited less reactivity (negative affect reactivity, diastolic blood pressure reactivity, and pulse rate reactivity) to the task, and more pronounced positive and negative affect recovery following the task, than did younger adults. Older adults appraised the task as more enjoyable and the confederate as more likeable, and more strongly endorsed goals to perform well on the task, which mediated age differences in negative affect reactivity, pulse rate reactivity, and positive affect recovery (i.e., increases in post-task positive affect), respectively. In addition, younger adults showed increased negative affect reactivity with greater use of self-distraction, whereas older adults did not. Together, findings suggest that older adults respond less negatively to unpleasant social interactions than younger adults, and these responses are explained in part by older adults’ pursuit of different motivational goals, less threatening appraisals of the social interaction, and more effective use of self-distraction, compared to younger adults. PMID:24773101

  11. Free amino acids in synaptic vesicles isolated from the cerebellum and cerebral hemispheres of control and neonatally X-irradiated rats

    International Nuclear Information System (INIS)

    Valcana, T.; Hudson, D.B.; Timiras, P.S.

    1984-01-01

    X-irradiation of the rat brain (1000R, at two days of age), suppresses the normal age-related increase in the weight of the cerebellum and cerebral hemispheres and influences amino acid levels. The decrease in glutamic acid concentration, particularly in the cerebellum, supports the previously advanced proposition that this amino acid may be associated with or may be the transmitter of, the rat cerebellar granule cells. Subfractionation of the cerebellar tissue reveals that the decrease in the glutamic acid level consequent to the loss of granule cells, is reflected in the cytoplasmic fraction but not in the synaptic vesicle subfraction, where glutamic acid was increased. The reduced weight gain in the cerebral hemispheres after irradiation, is accompanied by a significant decrease of aspartate in the cytoplasmic fraction, changes which suggest that a specific cell type, with aspartic acid as its neurotransmitter (possibly in the hippocampus), may also be radiosensitive in the early postnatal period. In contrast, in the synaptic vesicle fraction from cerebral hemispheres, all free amino acids, with the exception of glutamine, increased significantly. Overall, the changes in free amino acid concentration induced by X-irradiation in the cytoplasmic fraction in both brain regions studied are opposite to those found in the synaptic vesicle fraction and although they may indicate changes in specific cell populations, as proposed above, they could also reflect changes in cellular compartmentalization and metabolism or changes in the relative axonal arborization of the affected regions

  12. An Intron 7 Polymorphism in APP Affects the Age of Onset of Dementia in Down Syndrome

    Directory of Open Access Journals (Sweden)

    Emma L. Jones

    2011-01-01

    Full Text Available People with Down syndrome (DS develop Alzheimer's disease (AD with an early age of onset. A tetranucleotide repeat, attt5−8, in intron 7 of the amyloid precursor protein has been associated with the age of onset of AD in DS in a preliminary study. The authors examine the impact of this polymorphism in a larger cohort of individuals with DS. Adults with DS were genotyped for attt5−8 and APOE. The results were analysed with respect to the age of onset of dementia. The presence of three copies of the six-repeat allele resulted in onset of dementia seven years earlier than in the presence of other genotypes. Further study is essential to elucidate the mechanism by which this polymorphism functions, with an exciting opportunity to identify novel treatment targets relevant for people with DS and AD.

  13. Aging affects hemispheric asymmetry in the neural representation of speech sounds.

    Science.gov (United States)

    Bellis, T J; Nicol, T; Kraus, N

    2000-01-15

    Hemispheric asymmetries in the processing of elemental speech sounds appear to be critical for normal speech perception. This study investigated the effects of age on hemispheric asymmetry observed in the neurophysiological responses to speech stimuli in three groups of normal hearing, right-handed subjects: children (ages, 8-11 years), young adults (ages, 20-25 years), and older adults (ages > 55 years). Peak-to-peak response amplitudes of the auditory cortical P1-N1 complex obtained over right and left temporal lobes were examined to determine the degree of left/right asymmetry in the neurophysiological responses elicited by synthetic speech syllables in each of the three subject groups. In addition, mismatch negativity (MMN) responses, which are elicited by acoustic change, were obtained. Whereas children and young adults demonstrated larger P1-N1-evoked response amplitudes over the left temporal lobe than over the right, responses from elderly subjects were symmetrical. In contrast, MMN responses, which reflect an echoic memory process, were symmetrical in all subject groups. The differences observed in the neurophysiological responses were accompanied by a finding of significantly poorer ability to discriminate speech syllables involving rapid spectrotemporal changes in the older adult group. This study demonstrates a biological, age-related change in the neural representation of basic speech sounds and suggests one possible underlying mechanism for the speech perception difficulties exhibited by aging adults. Furthermore, results of this study support previous findings suggesting a dissociation between neural mechanisms underlying those processes that reflect the basic representation of sound structure and those that represent auditory echoic memory and stimulus change.

  14. 2017 Accomplishments – Tritium Aging Studies on Stainless Steel Weldments and Heat-Affected Zones

    Energy Technology Data Exchange (ETDEWEB)

    Morgan, Michael J. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Hitchcock, Dale [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Krentz, Tim [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); McNamara, Joy [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Duncan, Andrew [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2018-01-31

    In this study, the combined effects tritium and decay helium in forged and welded Types 304L and 21-6-9 stainless steels were studied. To measure these effects, fracture mechanic specimens were thermally precharged with tritium and aged for approximately 17 years to build in decay helium from tritium decay prior to testing. The results are compared to earlier measurements on the same alloys and weldments (4-5, 8-9). In support of Enhanced Surveillance, “Tritium Effects on Materials”, the fracture toughness properties of long-aged tritium-charged stainless-steel base metals and weldments were measured and compared to earlier measurements. The fracture-toughness data were measured by thermally precharging as-forged and as-welded specimens with tritium gas at 34.5 MPa and 350°C and aging for approximately 17 years to build-in decay helium prior to testing. These data result from the longest aged specimens ever tested in the history of the tritium effects programs at Savannah River and the fracture toughness values measured were the lowest ever recorded for tritium-exposed stainless steel. For Type 21-6-9 stainless steel, fracture toughness values were reduced to less than 2-4% of the as-forged values to 41 lbs / in specimens that contained more than 1300 appm helium from tritium decay. The fracture toughness properties of long-aged weldments were also measured. The fracture toughness reductions were not as severe because the specimens did not retain as much tritium from the charging and aging as did the base metals. For Type 304L weldments, the specimens in this study contained approximately 600 appm helium and their fracture toughness values averaged 750 lbs / in. The results for other steels and weldments are reported and additional tests will be conducted during FY18.

  15. Dynamic of age structure and the number of population in Ozyorsk and affecting factors

    International Nuclear Information System (INIS)

    Panchenko, O.; Rtischeva, M.

    2001-01-01

    In connection with serious social-economic and ecological problems in our country an analysis of demographic processes in cities of atomic industry causes a big of interest. The aim of this work was an evaluation of dynamic of age structure of population of city Ozyorsk, based in connection with creation of nuclear plant 'Mayak' of 'first-born' of atomic industry in Russia. Data received in city's administration, included the information about number of population, its age composition taking into account of natural increase and of migration processes for a period from 1959 to 1997. (authors)

  16. Exercise counteracts aging-related memory impairment: a potential role for the astrocytic metabolic shuttle

    Directory of Open Access Journals (Sweden)

    Sheng-Feng eTsai

    2016-03-01

    Full Text Available Age-related cognitive impairment has become one of the most common health threats in many countries. The biological substrate of cognition is the interconnection of neurons to form complex information processing networks. Experience-based alterations in the activities of these information processing networks lead to neuroadaptation, which is physically represented at the cellular level as synaptic plasticity. Although synaptic plasticity is known to be affected by aging, the underlying molecular mechanisms are not well described. Astrocytes, a glial cell type that is infrequently investigated in cognitive science, have emerged as energy suppliers which are necessary for meeting the abundant energy demand resulting from glutamatergic synaptic activity. Moreover, the concerted action of an astrocyte-neuron metabolic shuttle is essential for cognitive function; whereas, energetic incoordination between astrocytes and neurons may contribute to cognitive impairment. Whether altered function of the astrocyte-neuron metabolic shuttle links aging to reduced synaptic plasticity is unexplored. However, accumulated evidence documents significant beneficial effects of long-term, regular exercise on cognition and synaptic plasticity. Furthermore, exercise increases the effectiveness of astrocyte-neuron metabolic shuttle by upregulation of astrocytic lactate transporter levels. This review summarizes previous findings related to the neuronal activity-dependent astrocyte-neuron metabolic shuttle. Moreover, we discuss how aging and exercise may shape the astrocyte-neuron metabolic shuttle in cognition-associated brain areas.

  17. GxE Interactions Between FOXO Genotypes and Tea Drinking Significantly Affect Cognitive Disability at Advanced Ages in China

    DEFF Research Database (Denmark)

    Zeng, Yi; Chen, Huashuai; Ni, Ting

    2015-01-01

    Logistic regression analysis based on data from 822 Han Chinese oldest old aged 92+ demonstrated that interactions between carrying FOXO1A-266 or FOXO3-310 or FOXO3-292 and tea drinking at around age 60 or at present time were significantly associated with lower risk of cognitive disability...... at advanced ages. Associations between tea drinking and reduced cognitive disability were much stronger among carriers of the genotypes of FOXO1A-266 or FOXO3-310 or FOXO3-292 compared with noncarriers, and it was reconfirmed by analysis of three-way interactions across FOXO genotypes, tea drinking at around...... age 60, and at present time. Based on prior findings from animal and human cell models, we postulate that intake of tea compounds may activate FOXO gene expression, which in turn may positively affect cognitive function in the oldest old population. Our empirical findings imply that the health...

  18. Age group differences in positive and negative affect among oldest-old adults: findings from the Georgia Centenarian Study.

    Science.gov (United States)

    Cho, Jinmyoung; Martin, Peter; Poon, Leonard W; MacDonald, M; Jazwinski, S M; Green, R C; Gearing, M; Johnson, M A; Markesbery, W R; Woodard, J L; Tenover, J S; Siegler, L C; Rott, C; Rodgers, W L; Hausman, D; Arnold, J; Davey, A

    2013-01-01

    The developmental adaptation model (Martin & Martin, 2002) provides insights into how current experiences and resources (proximal variables) and past experiences (distal variables) are correlated with outcomes (e.g., well-being) in later life. Applying this model, the current study examined proximal and distal variables associated with positive and negative affect in oldest-old adults, investigating age differences. Data from 306 octogenarians and centenarians who participated in Phase III of the Georgia Centenarian Study were used. Proximal variables included physical functioning, cognitive functioning, self-rated health, number of chronic conditions, social resources, and perceived economic status; distal variables included education, social productive activities, management of personal assets, and other learning experiences. Analysis of variance and block-wise regression analyses were conducted. Octogenarians showed significantly higher levels of positive emotion than centenarians. Cognitive functioning was significantly associated with positive affect, and number of health problems was significantly associated with negative affect after controlling for gender, ethnicity, residence, and marital status. Furthermore, four significant interaction effects suggested that positive affect significantly depended on the levels of cognitive and physical functioning among centenarians, whereas positive affect was dependent on the levels of physical health problems and learning experiences among octogenarians. Findings of this study addressed the importance of current and past experiences and resources in subjective well-being among oldest-old adults as a life-long process. Mechanisms connecting aging processes at the end of a long life to subjective well-being should be explored in future studies.

  19. Vector competence of Aedes aegypti mosquitoes for filarial nematodes is affected by age and nutrient limitation.

    Science.gov (United States)

    Ariani, Cristina V; Juneja, Punita; Smith, Sophia; Tinsley, Matthew C; Jiggins, Francis M

    2015-01-01

    Mosquitoes are one of the most important vectors of human disease. The ability of mosquitoes to transmit disease is dependent on the age structure of the population, as mosquitoes must survive long enough for the parasites to complete their development and infect another human. Age could have additional effects due to mortality rates and vector competence changing as mosquitoes senesce, but these are comparatively poorly understood. We have investigated these factors using the mosquito Aedes aegypti and the filarial nematode Brugia malayi. Rather than observing any effects of immune senescence, we found that older mosquitoes were more resistant, but this only occurred if they had previously been maintained on a nutrient-poor diet of fructose. Constant blood feeding reversed this decline in vector competence, meaning that the number of parasites remained relatively unchanged as mosquitoes aged. Old females that had been maintained on fructose also experienced a sharp spike in mortality after an infected blood meal ("refeeding syndrome") and few survived long enough for the parasite to develop. Again, this effect was prevented by frequent blood meals. Our results indicate that old mosquitoes may be inefficient vectors due to low vector competence and high mortality, but that frequent blood meals can prevent these effects of age. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Natural (auto)antibodies in calves are affected by age and diet

    NARCIS (Netherlands)

    Khobondo, J.O.; Nieuwland, M.G.B.; Webb, L.E.; Bokkers, E.A.M.; Parmentier, H.K.

    2015-01-01

    Background: Natural autoantibodies (N(a)ab) were found in every species tested so far, and are likely important in maintaining homeostasis. Objectives: (1) To determine N(a)ab in Bos taurus calves, (2) evaluate effects of diet and age on N(a)ab binding repertoires in calves, and (3) delineate bovine

  1. How Can Gender Affect Psychopathology in Lebanese School-Age Children?

    Science.gov (United States)

    Khamis, Vivian

    2018-01-01

    This study investigated the extent to which gender differences in coping, school and family environments could account for variation in psychopathology among school-age children. Participants were 665 middle school students. Results showed no gender differences for PTSD. Females scored higher on emotional problems and prosocial behavior whereas…

  2. Does Relative Age Affect Career Length in North American Professional Sports?

    Science.gov (United States)

    Steingröver, C; Wattie, N; Baker, J; Schorer, J

    Relative age effects (RAEs) typically favour older members within a cohort; however, research suggests that younger players may experience some long-term advantages, such as longer career length. The purposes of this study were to replicate previous findings on RAEs among National Hockey League (NHL) ice hockey players, National Basketball Association (NBA) basketball players and National Football League (NFL) football players and to investigate the influence of relative age on career length in all three sports. Using official archives, birthdates and number of games played were collected for players drafted into the NBA ( N  = 407), NFL ( N  = 2380) and NHL ( N  = 1028) from 1980 to 1989. We investigated the possibility that younger players might be able to maximize their career length by operationalizing career length as players' number of games played throughout their careers. There was a clear RAE for the NHL, but effects were not significant for the NBA or NFL. Moreover, there was a significant difference in matches played between birth quartiles in the NHL favouring relatively younger players. There were no significant quartiles by career length effects in the NBA or NFL. The significant relationship between relative age and career length provides further support for relative age as an important constraint on expertise development in ice hockey but not basketball or football. Currently, the reason why relatively younger players have longer careers is not known. However, it may be worth exploring the influence of injury risk or the development of better playing skills.

  3. The posterior parahippocampal gyrus is preferentially affected in age-related memory decline.

    NARCIS (Netherlands)

    Burgmans, S.; van Boxtel, M.P.J.; van den Berg, K.E.M.; Gronenschild, E.H.B.M.; Jacobs, H.I.L.; Jolles, J.; Uylings, H.B.M.

    2011-01-01

    Atrophy in the medial temporal lobe is generally considered to be highly associated with age-related memory decline. Volume loss in the hippocampus and entorhinal cortex has extensively been investigated, but the posterior parts of the parahippocampal gyrus have received little attention. The

  4. The posterior parahippocampal gyrus is preferentially affected in age-related memory decline

    NARCIS (Netherlands)

    Burgmans, S.; van Boxtel, M.P.J.; van den Berg, K.E.M.; Gronenschild, E.H.; Jacobs, H.I.L.; Jolles, J.; Uylings, H.B.M.

    2009-01-01

    Atrophy in the medial temporal lobe is generally considered to be highly associated with age-related memory decline. Volume loss in the hippocampus and entorhinal cortex has extensively been investigated, but the posterior parts of the parahippocampal gyrus have received little attention. The

  5. Feature Binding of Common Everyday Items Is Not Affected by Age

    Directory of Open Access Journals (Sweden)

    Serge Hoefeijzers

    2017-05-01

    Full Text Available There is a surge of studies confirming that old age spares the ability to bind in visual working memory (VWM multiple features within singular object representations. Furthermore, it has been suggested that such ability may also be independent of the cultural background of the assessed individual. However, this evidence has been gathered with tasks that use arbitrary bindings of unfamiliar features. Whether age spares memory binding functions when the memoranda are features of everyday life objects remains less well explored. The present study investigated the influence of age, memory delay, and education, on conjunctive binding functions responsible for representing everyday items in VWM. We asked 32 healthy young and 41 healthy older adults to perform a memory binding task. During the task, participants saw visual arrays of objects, colours, or coloured objects presented for 6 s. Immediately after they were asked either to select the objects or the colours that were presented during the study display from larger sets of objects or colours, or to recombine them by selecting from such sets the objects and their corresponding colours. This procedure was repeated immediately after but this time providing a 30 s unfiled delay. We manipulated familiarity by presenting congruent and incongruent object-colour pairings. The results showed that the ability to bind intrinsic features in VWM does not decline with age even when these features belong to everyday items and form novel or well-known associations. Such preserved memory binding abilities held across memory delays. The impact of feature congruency on item-recognition appears to be greater in older than in younger adults. This suggests that long-term memory (LTM supports binding functions carried out in VWM for familiar everyday items and older adults still benefit from this LTM support. We have expanded the evidence supporting the lack of age effects on VWM binding functions to new feature and

  6. Deficiency in LRP6-Mediated Wnt Signaling Contributes to Synaptic Abnormalities and Amyloid Pathology in Alzheimer’s Disease

    OpenAIRE

    Liu, Chia-Chen; Tsai, Chih-Wei; Deak, Ferenc; Rogers, Justin; Penuliar, Michael; Sung, You Me; Maher, James N.; Fu, Yuan; Li, Xia; Xu, Huaxi; Estus, Steven; Hoe, Hyang-Sook; Fryer, John D.; Kanekiyo, Takahisa; Bu, Guojun

    2014-01-01

    Alzheimer’s disease (AD) is an age-related neurological disorder characterized by synaptic loss and dementia. The low-density lipoprotein receptor-related protein 6 (LRP6) is an essential co-receptor for Wnt signaling and its genetic variants have been linked to AD risk. Here we report that neuronal LRP6-mediated Wnt signaling is critical for synaptic function and cognition. Conditional deletion of Lrp6 gene in mouse forebrain neurons leads to age-dependent deficits in synaptic integrity and ...

  7. Cholesterol asymmetry in synaptic plasma membranes.

    Science.gov (United States)

    Wood, W Gibson; Igbavboa, Urule; Müller, Walter E; Eckert, Gunter P

    2011-03-01

    Lipids are essential for the structural and functional integrity of membranes. Membrane lipids are not randomly distributed but are localized in different domains. A common characteristic of these membrane domains is their association with cholesterol. Lipid rafts and caveolae are examples of cholesterol enriched domains, which have attracted keen interest. However, two other important cholesterol domains are the exofacial and cytofacial leaflets of the plasma membrane. The two leaflets that make up the bilayer differ in their fluidity, electrical charge, lipid distribution, and active sites of certain proteins. The synaptic plasma membrane (SPM) cytofacial leaflet contains over 85% of the total SPM cholesterol as compared with the exofacial leaflet. This asymmetric distribution of cholesterol is not fixed or immobile but can be modified by different conditions in vivo: (i) chronic ethanol consumption; (ii) statins; (iii) aging; and (iv) apoE isoform. Several potential candidates have been proposed as mechanisms involved in regulation of SPM cholesterol asymmetry: apoE, low-density lipoprotein receptor, sterol carrier protein-2, fatty acid binding proteins, polyunsaturated fatty acids, P-glycoprotein and caveolin-1. This review examines cholesterol asymmetry in SPM, potential mechanisms of regulation and impact on membrane structure and function. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

  8. Convergent synaptic and circuit substrates underlying autism genetic risks.

    Science.gov (United States)

    McGee, Aaron; Li, Guohui; Lu, Zhongming; Qiu, Shenfeng

    2014-02-01

    There has been a surge of diagnosis of autism spectrum disorders (ASD) over the past decade. While large, high powered genome screening studies of children with ASD have identified numerous genetic risk factors, research efforts to understanding how each of these risk factors contributes to the development autism has met with limited success. Revealing the mechanisms by which these genetic risk factors affect brain development and predispose a child to autism requires mechanistic understanding of the neurobiological changes underlying this devastating group of developmental disorders at multifaceted molecular, cellular and system levels. It has been increasingly clear that the normal trajectory of neurodevelopment is compromised in autism, in multiple domains as much as aberrant neuronal production, growth, functional maturation, patterned connectivity, and balanced excitation and inhibition of brain networks. Many autism risk factors identified in humans have been now reconstituted in experimental mouse models to allow mechanistic interrogation of the biological role of the risk gene. Studies utilizing these mouse models have revealed that underlying the enormous heterogeneity of perturbed cellular events, mechanisms directing synaptic and circuit assembly may provide a unifying explanation for the pathophysiological changes and behavioral endophenotypes seen in autism, although synaptic perturbations are far from being the only alterations relevant for ASD. In this review, we discuss synaptic and circuit abnormalities obtained from several prevalent mouse models, particularly those reflecting syndromic forms of ASD that are caused by single gene perturbations. These compiled results reveal that ASD risk genes contribute to proper signaling of the developing gene networks that maintain synaptic and circuit homeostasis, which is fundamental to normal brain development.

  9. Factors Affecting Age at Initial Autism Spectrum Disorder Diagnosis in a National Survey

    Directory of Open Access Journals (Sweden)

    Rebecca E. Rosenberg

    2011-01-01

    Full Text Available Entry into early intervention depends on both age of first parent concern (AOC and age at initial autism spectrum disorder (ASD diagnosis (AOD. Using data collected from a national online registry from 6214 children diagnosed with an ASD between 1994 and 2010 in the US, we analyzed the effect of individual, family, and geographic covariates on AOC and AOD in a multivariate linear regression model with random effects. Overall, no single modifiable factor associated with AOC or AOD emerged but cumulative variation in certain individual- and family-based features, as well as some geographic factors, all contribute to AOC and AOD variation. A multipronged strategy is needed for targeted education and awareness campaigns to maximize outcomes and decrease disparities in ASD care.

  10. Lateral regulation of synaptic transmission by astrocytes.

    Science.gov (United States)

    Covelo, A; Araque, A

    2016-05-26

    Fifteen years ago the concept of the "tripartite synapse" was proposed to conceptualize the functional view that astrocytes are integral elements of synapses. The signaling exchange between astrocytes and neurons within the tripartite synapse results in the synaptic regulation of synaptic transmission and plasticity through an autocrine form of communication. However, recent evidence indicates that the astrocyte synaptic regulation is not restricted to the active tripartite synapse but can be manifested through astrocyte signaling at synapses relatively distant from active synapses, a process termed lateral astrocyte synaptic regulation. This phenomenon resembles the classical heterosynaptic modulation but is mechanistically different because it involves astrocytes and its properties critically depend on the morphological and functional features of astrocytes. Therefore, the functional concept of the tripartite synapse as a fundamental unit must be expanded to include the interaction between tripartite synapses. Through lateral synaptic regulation, astrocytes serve as an active processing bridge for synaptic interaction and crosstalk between synapses with no direct neuronal connectivity, supporting the idea that neural network function results from the coordinated activity of astrocytes and neurons. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  11. Genetics, Synergists, and Age Affect Insecticide Sensitivity of the Honey Bee, Apis mellifera

    Science.gov (United States)

    Rinkevich, Frank D.; Margotta, Joseph W.; Pittman, Jean M.; Danka, Robert G.; Tarver, Matthew R.; Ottea, James A.; Healy, Kristen B.

    2015-01-01

    The number of honey bee colonies in the United States has declined to half of its peak level in the 1940s, and colonies lost over the winter have reached levels that are becoming economically unstable. While the causes of these losses are numerous and the interaction between them is very complex, the role of insecticides has garnered much attention. As a result, there is a need to better understand the risk of insecticides to bees, leading to more studies on both toxicity and exposure. While much research has been conducted on insecticides and bees, there have been very limited studies to elucidate the role that bee genotype and age has on the toxicity of these insecticides. The goal of this study was to determine if there are differences in insecticide sensitivity between honey bees of different genetic backgrounds (Carniolan, Italian, and Russian stocks) and assess if insecticide sensitivity varies with age. We found that Italian bees were the most sensitive of these stocks to insecticides, but variation was largely dependent on the class of insecticide tested. There were almost no differences in organophosphate bioassays between honey bee stocks (bees aged, the sensitivity to phenothrin significantly decreased, but the sensitivity to naled significantly increased. These results demonstrate the variation arising from the genetic background and physiological transitions in honey bees as they age. This information can be used to determine risk assessment, as well as establishing baseline data for future comparisons to explain the variation in toxicity differences for honey bees reported in the literature. PMID:26431171

  12. Antioxidant enzymatic protection during tobacco leaf ageing is affected by cytokinin depletion

    Czech Academy of Sciences Publication Activity Database

    Mýtinová, Zuzana; Motyka, Václav; Haisel, Daniel; Lubovská, Zuzana; Trávníčková, Alena; Dobrev, Petre; Holík, Josef; Wilhelmová, Naděžda

    2011-01-01

    Roč. 65, č. 1 (2011), s. 23-34 ISSN 0167-6903 R&D Projects: GA ČR GA522/03/0312; GA AV ČR IAA600380701; GA MŠk(CZ) LC06034 Institutional research plan: CEZ:AV0Z50380511 Keywords : Ageing * Antioxidant enzymes * Cytokinins Subject RIV: CE - Biochemistry Impact factor: 1.604, year: 2011

  13. Colour Changes in Meat of Foals as Affected by Slaughtering Age and Post-thawing Time

    Directory of Open Access Journals (Sweden)

    P. De Palo

    2012-12-01

    Full Text Available The aim of the present work was to investigate how colour changes of foal meat can vary after thawing out in relation to the slaughtering age of the horses and to the post-thawing time. Eighteen Italian Heavy Draught Horse (IHDH foals were used for the trial. They were subdivided in three groups according to their slaughtering age (6, 11 and 18 months. Two different surfaces were investigated for each sample: a fresh cut surface (daily renewed cutting surface: DRCS, and not-renewed cutting surface (NRCS. The redness of both investigated surfaces increased with slaughtering age (p<0.01. Moreover, this parameter decreased during post-thawing time (p<0.01 only on the NRCS, probably due to the myoglobin oxidation processes. Colour is an important visual cue denoting perceived quality by consumers. So, by a chromatic perspective the thawed meat of IHDH foals slaughtered at 6 and 11 months proved to be that which best meets the market requirements.

  14. Age and individual sleep characteristics affect cognitive performance in anesthesiology residents after a 24-hour shift.

    Science.gov (United States)

    Tadinac, Meri; Sekulić, Ante; Hromatko, Ivana; Mazul-Sunko, Branka; Ivancić, Romina

    2014-03-01

    Previous research has shown that both shift work and sleep deprivation have an adverse influence on various aspects of human cognitive performance. The aim of this study was to explore changes in cognitive functioning and subjective sleepiness of anesthesiology residents after a 24-hour shift. Twenty-six anesthesiology residents completed a set of psychological instruments at the beginning and at the end of the shift, as well as a questionnaire regarding information about the shift, Stanford Sleepiness Scale, and Circadian Type Questionnaire. There was a significant decline in cognitive performance measured by the Auditory Verbal Learning Test after the shift. The effect was stronger in older participants and in those with high scores on rigidity of sleep scale and low scores on the ability to overcome sleepiness scale. There were no differences in the digits forward test (a measure of concentration), while digits backward test (a measure of working memory) even showed an improved performance after the shift. Although participants reported being significantly sleepier after the shift, the subjective sleepiness did not correlate with any of the objective measures of cognitive performance. In conclusion, the performance in short tasks involving concentration and working memory was not impaired, while performance in long-term and monotone tasks declined after sleep deprivation, and the magnitude of this decline depended on the specific individual characteristics of sleep and on age Surprisingly, age seemed to have an important impact on cognitive functions after shift work even in the relatively age-homogeneous population of young anesthesiology residents.

  15. Diet and weaning age affect the growth and condition of Dover sole (Solea solea L.

    Directory of Open Access Journals (Sweden)

    2005-01-01

    Full Text Available The effect of diet type (frozen Artemia biomass and two inert diets: micro-bound [MB] and micro-extruded [ME] and two weaning ages (early weaning and late weaning, 50 and 64 days after hatching, respectively were studied in Solea solea larvae. The experiment lasted 56 and 42 days for early and late weaning, respectively. The mortality results showed the highest values for late weaning (39% in the Artemia treatment. No significant differences in mortality were observed between the inert diets. The final dry weight values were higher for late weaning than for early weaning. At both weaning ages, fish receiving the same treatments had similar tendencies for dry weight and standard length. Fish fed with MB presented significantly higher dry weight and standard length, followed by ME, while the lowest values at both weaning ages were recorded for the Artemia treatment. Similar amounts of highly unsaturated fatty acid fractions among the inert diets were reflected by the absence of significant differences in the susceptibility to oxidation (thiobarbituric acid reactive substances testing; however, significant differences were found in carbohydrate, protein and lipid contents of whole-body homogenates for both early and late weaning. At the end of the experiment no significant differences in biochemical contents were observed between the two inert diets. The results of this study suggest that weaning starting on day 50 (early weaning, using a good quality inert diet, leads to higher survival, growth and fish condition.

  16. Age effects in emotional prospective memory: cue valence differentially affects the prospective and retrospective component.

    Science.gov (United States)

    Schnitzspahn, Katharina M; Horn, Sebastian S; Bayen, Ute J; Kliegel, Matthias

    2012-06-01

    While first studies suggested that emotional task material may enhance prospective memory performance in young and older adults, the extent and mechanisms of this effect are under debate. The authors explored possible differential effects of cue valence on the prospective and retrospective component of prospective memory in young and older adults. Forty-five young and 41 older adults performed a prospective memory task in which emotional valence of the prospective memory cue was manipulated (positive, negative, neutral). The multinomial model of event-based prospective memory was used to analyze effects of valence and age on the two prospective memory components separately. Results revealed an interaction indicating that age differences were smaller in both emotional valence conditions. For older adults positive cues improved the prospective component, while negative cues improved the retrospective component. No main effect of valence was found for younger adults on an overt accuracy measure, but model-based analyses showed that the retrospective component was enhanced in the positive compared with the negative cue condition. The study extends the literature in demonstrating that processes underlying emotional effects on prospective memory may differ depending on valence and age. PsycINFO Database Record (c) 2012 APA, all rights reserved

  17. Does age affect the relationship between control at work and sleep disturbance for shift workers?

    Science.gov (United States)

    Loudoun, Rebecca Jane; Muurlink, Olav; Peetz, David; Murray, Georgina

    2014-12-01

    Among miners, shift work, aging and lack of control at work may be factors leading to increased sleep problems. Such risk factors may also operate in interaction, resulting in an even increased harm for sleep disruption. The present study aims at evaluating these relationships drawing on a sample of Australian mine and energy workers and their partners. The workers were mainly men. All performed shift work that included either nights (95%) or multiple shifts (92%), usually both (87%), while 36% were aged 50 years or above. The results show that low latitude over work activities is associated with higher sleep disturbances across the sample, though the effects are clearer amongst younger workers. By contrast, for younger workers, control over shift scheduling is not associated with sleep disturbances but for workers aged 50 or more, low control results in more sleep disturbance. Misalignment between shift workers and partner work schedules, and partner dissatisfaction with shift worker's employment and shift worker's work-life balance, are also associated with more sleep disturbances amongst shift workers.

  18. Colour Changes in Meat of Foals as Affected by Slaughtering Age and Post-thawing Time

    Science.gov (United States)

    De Palo, P.; Maggiolino, A.; Centoducati, P.; Tateo, A.

    2012-01-01

    The aim of the present work was to investigate how colour changes of foal meat can vary after thawing out in relation to the slaughtering age of the horses and to the post-thawing time. Eighteen Italian Heavy Draught Horse (IHDH) foals were used for the trial. They were subdivided in three groups according to their slaughtering age (6, 11 and 18 months). Two different surfaces were investigated for each sample: a fresh cut surface (daily renewed cutting surface: DRCS), and not-renewed cutting surface (NRCS). The redness of both investigated surfaces increased with slaughtering age (p<0.01). Moreover, this parameter decreased during post-thawing time (p<0.01) only on the NRCS, probably due to the myoglobin oxidation processes. Colour is an important visual cue denoting perceived quality by consumers. So, by a chromatic perspective the thawed meat of IHDH foals slaughtered at 6 and 11 months proved to be that which best meets the market requirements. PMID:25049544

  19. Presynaptic Active Zone Density during Development and Synaptic Plasticity.

    Science.gov (United States)

    Clarke, Gwenaëlle L; Chen, Jie; Nishimune, Hiroshi

    2012-01-01

    Neural circuits transmit information through synapses, and the efficiency of synaptic transmission is closely related to the density of presynaptic active zones, where synaptic vesicles are released. The goal of this review is to highlight recent insights into the molecular mechanisms that control the number of active zones per presynaptic terminal (active zone density) during developmental and stimulus-dependent changes in synaptic efficacy. At the neuromuscular junctions (NMJs), the active zone density is preserved across species, remains constant during development, and is the same between synapses with different activities. However, the NMJ active zones are not always stable, as exemplified by the change in active zone density during acute experimental manipulation or as a result of aging. Therefore, a mechanism must exist to maintain its density. In the central nervous system (CNS), active zones have restricted maximal size, exist in multiple numbers in larger presynaptic terminals, and maintain a constant density during development. These findings suggest that active zone density in the CNS is also controlled. However, in contrast to the NMJ, active zone density in the CNS can also be increased, as observed in hippocampal synapses in response to synaptic plasticity. Although the numbers of known active zone proteins and protein interactions have increased, less is known about the mechanism that controls the number or spacing of active zones. The following molecules are known to control active zone density and will be discussed herein: extracellular matrix laminins and voltage-dependent calcium channels, amyloid precursor proteins, the small GTPase Rab3, an endocytosis mechanism including synaptojanin, cytoskeleton protein spectrins and β-adducin, and a presynaptic web including spectrins. The molecular mechanisms that organize the active zone density are just beginning to be elucidated.

  20. Communication, support and psychosocial work environment affecting psychological distress among working women aged 20 to 39 years in Japan

    OpenAIRE

    HONDA, Ayumi; DATE, Yutaka; ABE, Yasuyo; AOYAGI, Kiyoshi; HONDA, Sumihisa

    2015-01-01

    When compared with their older counterparts, younger women are more likely to have depressive symptoms because they more often experience interrupted work history and a heavy childrearing burden. The purposes of the present study were 1) to investigate the possible association of psychosocial work environment with psychological distress and 2) to examine the way by which communication and support in the workplace affect to psychological distress among young women. We studied 198 women aged 20...

  1. Long-term relationships between cholinergic tone, synchronous bursting and synaptic remodeling.

    Directory of Open Access Journals (Sweden)

    Maya Kaufman

    Full Text Available Cholinergic neuromodulation plays key roles in the regulation of neuronal excitability, network activity, arousal, and behavior. On longer time scales, cholinergic systems play essential roles in cortical development, maturation, and plasticity. Presumably, these processes are associated with substantial synaptic remodeling, yet to date, long-term relationships between cholinergic tone and synaptic remodeling remain largely unknown. Here we used automated microscopy combined with multielectrode array recordings to study long-term relationships between cholinergic tone, excitatory synapse remodeling, and network activity characteristics in networks of cortical neurons grown on multielectrode array substrates. Experimental elevations of cholinergic tone led to the abrupt suppression of episodic synchronous bursting activity (but not of general activity, followed by a gradual growth of excitatory synapses over hours. Subsequent blockage of cholinergic receptors led to an immediate restoration of synchronous bursting and the gradual reversal of synaptic growth. Neither synaptic growth nor downsizing was governed by multiplicative scaling rules. Instead, these occurred in a subset of synapses, irrespective of initial synaptic size. Synaptic growth seemed to depend on intrinsic network activity, but not on the degree to which bursting was suppressed. Intriguingly, sustained elevations of cholinergic tone were associated with a gradual recovery of synchronous bursting but not with a reversal of synaptic growth. These findings show that cholinergic tone can strongly affect synaptic remodeling and synchronous bursting activity, but do not support a strict coupling between the two. Finally, the reemergence of synchronous bursting in the presence of elevated cholinergic tone indicates that the capacity of cholinergic neuromodulation to indefinitely suppress synchronous bursting might be inherently limited.

  2. Long-term Relationships between Cholinergic Tone, Synchronous Bursting and Synaptic Remodeling

    Science.gov (United States)

    Kaufman, Maya; Corner, Michael A.; Ziv, Noam E.

    2012-01-01

    Cholinergic neuromodulation plays key roles in the regulation of neuronal excitability, network activity, arousal, and behavior. On longer time scales, cholinergic systems play essential roles in cortical development, maturation, and plasticity. Presumably, these processes are associated with substantial synaptic remodeling, yet to date, long-term relationships between cholinergic tone and synaptic remodeling remain largely unknown. Here we used automated microscopy combined with multielectrode array recordings to study long-term relationships between cholinergic tone, excitatory synapse remodeling, and network activity characteristics in networks of cortical neurons grown on multielectrode array substrates. Experimental elevations of cholinergic tone led to the abrupt suppression of episodic synchronous bursting activity (but not of general activity), followed by a gradual growth of excitatory synapses over hours. Subsequent blockage of cholinergic receptors led to an immediate restoration of synchronous bursting and the gradual reversal of synaptic growth. Neither synaptic growth nor downsizing was governed by multiplicative scaling rules. Instead, these occurred in a subset of synapses, irrespective of initial synaptic size. Synaptic growth seemed to depend on intrinsic network activity, but not on the degree to which bursting was suppressed. Intriguingly, sustained elevations of cholinergic tone were associated with a gradual recovery of synchronous bursting but not with a reversal of synaptic growth. These findings show that cholinergic tone can strongly affect synaptic remodeling and synchronous bursting activity, but do not support a strict coupling between the two. Finally, the reemergence of synchronous bursting in the presence of elevated cholinergic tone indicates that the capacity of cholinergic neuromodulation to indefinitely suppress synchronous bursting might be inherently limited. PMID:22911726

  3. Long-term relationships between cholinergic tone, synchronous bursting and synaptic remodeling.

    Science.gov (United States)

    Kaufman, Maya; Corner, Michael A; Ziv, Noam E

    2012-01-01

    Cholinergic neuromodulation plays key roles in the regulation of neuronal excitability, network activity, arousal, and behavior. On longer time scales, cholinergic systems play essential roles in cortical development, maturation, and plasticity. Presumably, these processes are associated with substantial synaptic remodeling, yet to date, long-term relationships between cholinergic tone and synaptic remodeling remain largely unknown. Here we used automated microscopy combined with multielectrode array recordings to study long-term relationships between cholinergic tone, excitatory synapse remodeling, and network activity characteristics in networks of cortical neurons grown on multielectrode array substrates. Experimental elevations of cholinergic tone led to the abrupt suppression of episodic synchronous bursting activity (but not of general activity), followed by a gradual growth of excitatory synapses over hours. Subsequent blockage of cholinergic receptors led to an immediate restoration of synchronous bursting and the gradual reversal of synaptic growth. Neither synaptic growth nor downsizing was governed by multiplicative scaling rules. Instead, these occurred in a subset of synapses, irrespective of initial synaptic size. Synaptic growth seemed to depend on intrinsic network activity, but not on the degree to which bursting was suppressed. Intriguingly, sustained elevations of cholinergic tone were associated with a gradual recovery of synchronous bursting but not with a reversal of synaptic growth. These findings show that cholinergic tone can strongly affect synaptic remodeling and synchronous bursting activity, but do not support a strict coupling between the two. Finally, the reemergence of synchronous bursting in the presence of elevated cholinergic tone indicates that the capacity of cholinergic neuromodulation to indefinitely suppress synchronous bursting might be inherently limited.

  4. Axonal accumulation of synaptic markers in APP transgenic Drosophila depends on the NPTY motif and is paralleled by defects in synaptic plasticity

    DEFF Research Database (Denmark)

    Rusu, Patricia; Jansen, Anna; Soba, Peter

    2007-01-01

    . Specifically, axonal transport defects have been reported in AD animal models, including mice and flies that overexpress APP and tau. Here we demonstrate that the APP-induced traffic jam of vesicles in peripheral nerves of Drosophila melanogaster larvae depends on the four residues NPTY motif in the APP...... neurotransmission at the neuromuscular junction in transgenic larvae that express human APP. Consistent with the observation that these larvae do not show any obvious movement deficits, we found no changes in basal synaptic transmission. However, short-term synaptic plasticity was affected by overexpression of APP...

  5. Tree age affects physicochemical, functional quality and storability of Amrapali mango (Mangifera indica L.) fruits.

    Science.gov (United States)

    Meena, Nirmal Kumar; Asrey, Ram

    2017-12-12

    The effect of tree age on physicochemical quality attributes and storage behaviour of Amrapali mango fruit was evaluated. Physiologically mature fruits were harvested from 6-, 18- and 30-year-old trees and kept for ripening under ambient conditions (temperature 35 ± 3 °C, relative humidity 60 ± 5%). Observations were recorded at 3-day intervals. Highest total soluble solids and total sugars were found in the fruit sourced from 18-year-old trees. At the end of storage, least titratable acidity (0.17%) and higher carotenoids (10.86 mg 100 g -1 ) were found in 30-year-old tree fruits during the last day of storage. Highest total phenols (TP) (251.33 μg gallic acid g -1 ), antioxidant capacity (AC) (5.63 μmol Trolox g -1 ) and ascorbic acid (AA) (31.13 mg 100 g -1 ) were reported in fruits from younger trees of 6 years old. Maximum respiratory and ethylene evolution peak was observed in fruits obtained from oldest trees, whereas least activities of pectin methyl esterase (0.31 μmol min -1 g -1 fresh weight) and polygalacturonase (53.67 μg galacturonic acid g -1 h -1 ) were observed in 6-year-old tree fruits at the end of the 9-day storage period. Higher total soluble solids and total sugars were found in fruit harvested from middle-age-group (18-year-old) trees during the entire storage period of 9 days. Most of the functional parameters, such as TP, AC and AA, were observed to be higher in fruits from younger (6-year-old) trees. The obtained results revealed that produce from middle-age-group (18-year-old) Amrapali mango orchards suit consumers' and processors' requirements. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  6. Astrocytic β2 Adrenergic Receptor Gene Deletion Affects Memory in Aged Mice.

    Directory of Open Access Journals (Sweden)

    Cathy Joanna Jensen

    Full Text Available In vitro and in vivo studies suggest that the astrocytic adrenergic signalling enhances glycogenolysis which provides energy to be transported to nearby cells and in the form of lactate. This energy source is important for motor and cognitive functioning. While it is suspected that the β2-adrenergic receptor on astrocytes might contribute to this energy balance, it has not yet been shown conclusively in vivo. Inducible astrocyte specific β2-adrenergic receptor knock-out mice were generated by crossing homozygous β2-adrenergic receptor floxed mice (Adrb2flox and mice with heterozygous tamoxifen-inducible Cre recombinase-expression driven by the astrocyte specific L-glutamate/L-aspartate transporter promoter (GLAST-CreERT2. Assessments using the modified SHIRPA (SmithKline/Harwell/Imperial College/Royal Hospital/Phenotype Assessment test battery, swimming ability test, and accelerating rotarod test, performed at 1, 2 and 4 weeks, 6 and 12 months after tamoxifen (or vehicle administration did not reveal any differences in physical health or motor functions between the knock-out mice and controls. However deficits were found in the cognitive ability of aged, but not young adult mice, reflected in impaired learning in the Morris Water Maze. Similarly, long-term potentiation (LTP was impaired in hippocampal brain slices of aged knock-out mice maintained in low glucose media. Using microdialysis in cerebellar white matter we found no significant differences in extracellular lactate or glucose between the young adult knock-out mice and controls, although trends were detected. Our results suggest that β2-adrenergic receptor expression on astrocytes in mice may be important for maintaining cognitive health at advanced age, but is dispensable for motor function.

  7. Acute stress affects free recall and recognition of pictures differently depending on age and sex.

    Science.gov (United States)

    Hidalgo, Vanesa; Pulopulos, Matias M; Puig-Perez, Sara; Espin, Laura; Gomez-Amor, Jesus; Salvador, Alicia

    2015-10-01

    Little is known about age differences in the effects of stress on memory retrieval. Our aim was to perform an in-depth examination of acute psychosocial stress effects on memory retrieval, depending on age and sex. For this purpose, data from 52 older subjects (27 men and 25 women) were reanalyzed along with data from a novel group of 50 young subjects (26 men and 24 women). Participants were exposed to an acute psychosocial stress task (Trier Social Stress Test) or a control task. After the experimental manipulation, the retrieval of positive, negative and neutral pictures learned the previous day was tested. As expected, there was a significant response to the exposure to the stress task, but the older participants had a lower cortisol response to TSST than the younger ones. Stress impaired free recall of emotional (positive and negative) and neutral pictures only in the group of young men. Also in this group, correlation analyses showed a marginally significant association between cortisol and free recall. However, exploratory analyses revealed only a negative relationship between the stress-induced cortisol response and free recall of negative pictures. Moreover, stress impaired recognition memory of positive pictures in all participants, although this effect was not related to the cortisol or alpha-amylase response. These results indicate that both age and sex are critical factors in acute stress effects on specific aspects of long-term memory retrieval of emotional and neutral material. They also point out that more research is needed to better understand their specific role. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Age and Menopausal Status Affect Osteoprotegerin and Osteocalcin Levels in Women Differently, Irrespective of Thyroid Function

    Directory of Open Access Journals (Sweden)

    Alexander D. Shinkov

    2014-01-01

    Full Text Available Osteoprotegerin (OPG and osteocalcin (OC are essential bone proteins. Recent studies have demonstrated that they are not secreted solely by bone cells; they play roles in the vascular function and energy metabolism, and they are influenced by multiple factors. The aim of the current study was to investigate the influence of menopause and age on OPG and OC in women with different thyroid-stimulating hormone (TSH levels. Material and Methods We studied 49 women with elevated TSH, 26 with suppressed TSH, and 67 age-matched euthyroid controls. Of them 64 were menstruating and 78 postmenopausal. Body weight, height, waist circumference (WC, body mass index (BMI, serum TSH, free thyroxin (FT4, OPG, and OC were measured. Results Generally, both OPG and OC were higher in the postmenopausal women than in the menstruating subjects (OPG 3.85 ± 1.49 pmol/L vs. 5.84 ± 2.42 pmol/L, P < 0.001; OC 8.84 ± 3.70 ng/dL vs. 12.87 ± 6.45 ng/dL, P < 0.001, and within the two thyroid dysfunction subgroups and the controls (all P < 0.05. OPG correlated with age (postmenopausal rho = 0.57, P < 0.001; premenopausal rho = 0.31, P = 0.015. Among the premenopausal subjects, OPG was higher in those with low TSH than in the controls ( P = 0.048. OC correlated negatively with BMI and WC in the postmenopausal group (Spearman rho = –-0.25, P = 0.03 and rho = –-0.42, P < 0.001 respectively. OC was higher in the postmenopausal subjects with low TSH than in those with elevated TSH ( P = 0.024, and correlated positively with FT4 (rho = 0.40, P = 0.002 and negatively with TSH (rho = -0.29, P = 0.013. CONCLUSIONS In women, OPG and OC depended differently on age and menopause and, to a lesser extent, on the thyroid function and body composition.

  9. Age-related differences in affective responses to and memory for emotions conveyed by music: a cross-sectional study

    Science.gov (United States)

    Vieillard, Sandrine; Gilet, Anne-Laure

    2013-01-01

    There is mounting evidence that aging is associated with the maintenance of positive affect and the decrease of negative affect to ensure emotion regulation goals. Previous empirical studies have primarily focused on a visual or autobiographical form of emotion communication. To date, little investigation has been done on musical emotions. The few studies that have addressed aging and emotions in music were mainly interested in emotion recognition, thus leaving unexplored the question of how aging may influence emotional responses to and memory for emotions conveyed by music. In the present study, eighteen older (60–84 years) and eighteen younger (19–24 years) listeners were asked to evaluate the strength of their experienced emotion on happy, peaceful, sad, and scary musical excerpts (Vieillard et al., 2008) while facial muscle activity was recorded. Participants then performed an incidental recognition task followed by a task in which they judged to what extent they experienced happiness, peacefulness, sadness, and fear when listening to music. Compared to younger adults, older adults (a) reported a stronger emotional reactivity for happiness than other emotion categories, (b) showed an increased zygomatic activity for scary stimuli, (c) were more likely to falsely recognize happy music, and (d) showed a decrease in their responsiveness to sad and scary music. These results are in line with previous findings and extend them to emotion experience and memory recognition, corroborating the view of age-related changes in emotional responses to music in a positive direction away from negativity. PMID:24137141

  10. Age-related differences in affective responses to and memory for emotions conveyed by music: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Sandrine eVieillard

    2013-10-01

    Full Text Available There is mounting evidence that aging is associated with the maintenance of positive affect and the decrease of negative affect to ensure emotion regulation goals. Previous empirical studies have primarily focused on a visual or autobiographical form of emotion communication. To date, little investigation has been done on musical emotions. The few studies that have addressed aging and emotions in music were mainly interested in emotion recognition, thus leaving unexplored the question of how aging may influence emotional responses to and memory for music. In the present study, eighteen older (60-84 years and eighteen younger (19-24 years listeners were asked to evaluate the strength of their experienced emotion on happy, peaceful, sad, and scary musical excerpts (Vieillard, et al., 2008 while facial muscle activity was recorded. Participants then performed an incidental recognition task followed by a task in which they judged to what extent they experienced happiness, peacefulness, sadness, and fear when listening to music. Compared to younger adults, older adults (a reported a stronger emotional reactivity for happiness than other emotion categories, (b showed an increased zygomatic activity for scary stimuli, (c were more likely to falsely recognize happy music, and (d showed a decrease in their responsiveness to sad and scary music. These results are in line with previous findings and extend them to emotion experience and memory recognition, corroborating the view of age-related changes in emotional responses to music in a positive direction away from negativity.

  11. Age-related differences in affective responses to and memory for emotions conveyed by music: a cross-sectional study.

    Science.gov (United States)

    Vieillard, Sandrine; Gilet, Anne-Laure

    2013-01-01

    There is mounting evidence that aging is associated with the maintenance of positive affect and the decrease of negative affect to ensure emotion regulation goals. Previous empirical studies have primarily focused on a visual or autobiographical form of emotion communication. To date, little investigation has been done on musical emotions. The few studies that have addressed aging and emotions in music were mainly interested in emotion recognition, thus leaving unexplored the question of how aging may influence emotional responses to and memory for emotions conveyed by music. In the present study, eighteen older (60-84 years) and eighteen younger (19-24 years) listeners were asked to evaluate the strength of their experienced emotion on happy, peaceful, sad, and scary musical excerpts (Vieillard et al., 2008) while facial muscle activity was recorded. Participants then performed an incidental recognition task followed by a task in which they judged to what extent they experienced happiness, peacefulness, sadness, and fear when listening to music. Compared to younger adults, older adults (a) reported a stronger emotional reactivity for happiness than other emotion categories, (b) showed an increased zygomatic activity for scary stimuli, (c) were more likely to falsely recognize happy music, and (d) showed a decrease in their responsiveness to sad and scary music. These results are in line with previous findings and extend them to emotion experience and memory recognition, corroborating the view of age-related changes in emotional responses to music in a positive direction away from negativity.

  12. Depletion of Pax7+ satellite cells does not affect diaphragm adaptations to running in young or aged mice.

    Science.gov (United States)

    Murach, Kevin A; Confides, Amy L; Ho, Angel; Jackson, Janna R; Ghazala, Lina S; Peterson, Charlotte A; Dupont-Versteegden, Esther E

    2017-10-01

    Satellite cell depletion does not affect diaphragm adaptations to voluntary wheel running in young or aged mice. Satellite cell depletion early in life (4 months of age) has minimal effect on diaphragm phenotype by old age (24 months). Prolonged satellite cell depletion in the diaphragm does not result in excessive extracellular matrix accumulation, in contrast to what has been reported in hind limb muscles. Up-regulation of Pax3 mRNA+ cells after satellite cell depletion in young and aged mice suggests that Pax3+ cells may compensate for a loss of Pax7+ satellite cells in the diaphragm. Future investigations should focus on the role of Pax3+ cells in the diaphragm during adaptation to exercise and ageing. Satellite cell contribution to unstressed diaphragm is higher compared to hind limb muscles, which is probably attributable to constant activation of this muscle to drive ventilation. Whether satellite cell depletion negatively impacts diaphragm quantitative and qualitative characteristics under stressed conditions in young and aged mice is unknown. We therefore challenged the diaphragm with prolonged running activity in the presence and absence of Pax7+ satellite cells in young and aged mice using an inducible Pax7 CreER -R26R DTA model. Mice were vehicle (Veh, satellite cell-replete) or tamoxifen (Tam, satellite cell-depleted) treated at 4 months of age and were then allowed to run voluntarily at 6 months (young) and 22 months (aged). Age-matched, cage-dwelling, Veh- and Tam-treated mice without wheel access served as activity controls. Diaphragm muscles were analysed from young (8 months) and aged (24 months) mice. Satellite cell depletion did not alter diaphragm mean fibre cross-sectional area, fibre type distribution or extracellular matrix content in young or aged mice, regardless of running activity. Resting in vivo diaphragm function was also unaffected by satellite cell depletion. Myonuclear density was maintained in young satellite cell

  13. The stories we tell: how age, gender, and forgiveness affect the emotional content of autobiographical narratives.

    Science.gov (United States)

    Robertson, Sarah M C; Swickert, Rhonda J

    2018-04-01

    Researchers have been attempting to understand the variables that predict differences in autobiographical narratives, given that these differences often reveal important information about the psychological characteristics of the person providing the narrative. A sample of young adults (n = 80) and older adults (n = 80) completed a battery of self-report measures in addition to an autobiographical narrative task in which they described a negative emotional experience. These narratives were transcribed and entered into a text analysis program. Results indicated a significant three-way interaction (age × gender × forgiveness) for negative emotion words. Results also indicated two significant two-way interactions (age × forgiveness and gender × forgiveness) and one significant main effect for anger words. There were no significant findings related to anxiety or sad words. Results are discussed in the context of Socioemotional Selectivity Theory, which asserts that social and emotional goals shift throughout the lifespan such that older adults are more motivated to regulate their emotions than young adults. Clinical applications and future directions are discussed.

  14. Factors that affect skin aging: a cohort-based survey on twins.

    Science.gov (United States)

    Martires, Kathryn J; Fu, Pingfu; Polster, Amy M; Cooper, Kevin D; Baron, Elma D

    2009-12-01

    To identify environmental factors that correlate with skin photoaging, controlling for genetic susceptibility by using a questionnaire administered to twins. The survey collected information about each participant's Fitzpatrick type, history of skin cancer, smoking and drinking habits, and weight from a cohort of twins. Clinicians then assigned a clinical photodamage score to each participant. The annual Twins Days Festival in Twinsburg, Ohio. A voluntary cohort of twins from the general community, mostly from Ohio, Pennsylvania, and the northeastern United States. The survey was completed on a voluntary basis by sets of monozygotic (MZ) and dizygotic (DZ) twins. A total of 130 surveys taken by 65 complete twin pairs were analyzed. Skin aging was assessed using a validated photographic scale of photodamage, graded by such characteristics as wrinkling and pigmentation change. Photodamage scores among twins of a pair, whether MZ or DZ, were highly correlated (P = .92). Factors found to predict higher photodamage include history of skin cancer (P < .001), zygosity status (MZ vs DZ) (P = .001), weight (P = .02), and cigarette smoking (P = .046). Alcohol consumption was significantly associated with lower photodamage scores (P = .003). The study of twins provides a unique opportunity to control for genetic susceptibility in order to elucidate environmental influences on skin aging. The relationships found between smoking, weight, sunscreen use, skin cancer, and photodamage in these twin pairs may help to motivate the reduction of risky behaviors.

  15. Fecal overflow often affects children with chronic constipation that appears after the age of 2 years.

    Science.gov (United States)

    Kammacher Guerreiro, Mélissa; Bettinville, Aurore; Herzog, Denise

    2014-08-01

    Chronic functional constipation with or without encopresis is a common problem in the pediatric population, and the prevalence of encopresis may be underestimated. The aim of this study was to assess the prevalence and risk factors for overflow incontinence in patients with chronic constipation seen at a pediatric gastroenterology consultation. A retrospective study of 270 files of patients seen between 1997 and 2012 was conducted, and a classification according to Rome III criteria was done. Among 145 (53.7%) boys and 125 (46.2%) girls, 117 had overflow incontinence (43.3%) - 41 (35%) girls and 76 (65%) boys. The first symptoms of chronic constipation appeared at a median age of 30 and 33 months in encopretic and 16 and 12 months in nonencopretic girls and boys, respectively. The first specialized consultation took place after a median disease duration of 26.5 and 24 months in encopretic and 16 and 9 months in nonencopretic girls and boys, respectively. A history of stool retention and the presence of scybala at examination, but not of pain at defecation or anal fissure, were associated with encopresis. The onset of chronic constipation after the age of 2 years, a longer disease duration, male gender, and a history of stool retention were seen as risk factors for the development of encopresis in patients with chronic functional constipation. © The Author(s) 2014.

  16. Work load and individual factors affecting work ability among aging municipal employees.

    Science.gov (United States)

    Tuomi, K; Eskelinen, L; Toikkanen, J; Jarvinen, E; Ilmarinen, J; Klockars, M

    1991-01-01

    The effects of work stressors, individual characteristics, symptoms, and diseases on work ability were studied among 4255 municipal employees. Work ability was assessed by a work ability index in two cross-sectional inquiries, one in 1981 and the other in 1985. The most impairing for work ability were mental symptoms and musculoskeletal disease. Among the work stressors, high physical demands at work, poor physical work environment, and lack of freedom were associated with impaired work ability. Muscular work, disturbing temperatures at the workplace, and lack of freedom particularly affected employees with disease, whereas poor work postures and role conflicts at work were particularly injurious for healthy employees. The worst situation was observed when a worker with many symptoms and disease was exposed to many different work stressors. Life satisfaction, sitting work posture, a good basic education, and physical exercise during leisure time were associated with good work ability.

  17. Dynamic of age structure and the number of population in Ozersk and affecting factors

    International Nuclear Information System (INIS)

    Panchenko, O.; Rtischeva, M.

    2000-01-01

    The aim of this work was an evaluation of the dynamics of age structure and population for the city of Ozyorsk, based in connection with creation of the nuclear plant Mayak, the 'first-born' of the Russian atomic industry. The obtained results indicate that since 1950 demographic processes in Ozyorsk were more favorable, in spite of fact that it was in this period workers of Mayak nuclear plant and population as a whole, got comparatively greater radiation doses than in the following years. However, dynamics the number of population has an unfavorable trend to reduce, connected with sharp worsening of social-economic situation in the town as a whole, as a result of the economic reforms in the country. Reduction of the number of population in the town is expressed by the negative natural growth and by reducing migration processes, which resulted in sharp decrease of the general growth of population, and in its stopping in 1998. (authors)

  18. Milestone Age Affects the Role of Health and Emotions in Life Satisfaction: A Preliminary Inquiry

    Science.gov (United States)

    Miron-Shatz, Talya; Bhargave, Rajesh; Doniger, Glen M.

    2015-01-01

    Jill turns 40. Should this change how she evaluates her life, and would a similar change occur when she turns 41? Milestone age (e.g., 30, 40, 50)—a naturally occurring feature in personal timelines—has received much attention is popular culture, but little attention in academic inquiry. This study examines whether milestone birthdays change the way people evaluate their life. We show that life outlook is impacted by this temporal landmark, which appears to punctuate people’s mental maps of their life cycle. At these milestone junctures, people take stock of where they stand and have a more evaluative perspective towards their lives when making life satisfaction judgments. Correspondingly, they place less emphasis on daily emotional experiences. We find that milestone agers (vs. other individuals) place greater weight on health satisfaction and BMI and lesser weight on daily positive emotions in their overall life satisfaction judgments, whereas negative emotions remain influential. PMID:26244348

  19. Attitude of Reproductive Age Women towards Factors Affecting Induced Abortion in Hamedan, Iran

    Directory of Open Access Journals (Sweden)

    Seyede Zahra Masoumi

    2016-07-01

    Full Text Available Background & aim: Abortion is the third leading cause of maternal mortality. The attitude of women towards abortion is one of the most important factors involved in this issue. This study aimed to evaluate the attitude of women of reproductive age towards induced abortion. Methods This cross-sectional study was performed on 450 women of reproductive age in Fatemieh Hospital in Hamedan, Iran in 2014. Data was collected using abortion attitude scale consisting of five sections: socioeconomic status, family status, maternal and fetal health status, psycho -cultural background, and fertility status. Mean score less than three in each domain was considered as negative attitude, while scores higher or equal to three indicated positive attitude towards induced abortion. To analyze the data, logistic regression analysis, Chi-square and Fisher's exact tests were performed using SPSS version 21. P value of less than 0.05 was considered statistically significant. Results: In this study, induced abortion had no significant relationship with family status, maternal and fetal health, and fertility domains (82.1%, 77.3%, and 64.4%, respectively. A relationship was observed between induced abortion and socioeconomic and psycho-cultural domains (61.8% and 56%, respectively. Logistic regression analysis showed that the predictors of induced abortion were the attitude towards the effect of abortion on the health of mother and fetus (P= 0.01, as well as the psychocultural status of the mothers (P= 0.02. Conclusion: Evaluation of the results indicated a strong belief in the majority of the participants in psychocultural and socioeconomic domains as the most significant predictive factors for induced abortion. Since it is difficult to alter the socioeconomic and psychocultural domains of individuals, changes are recommended in predominant attitudes towards induced abortion.

  20. Age affects the contraction-induced mitochondrial redox response in skeletal muscle

    Directory of Open Access Journals (Sweden)

    Dennis R Claflin

    2015-02-01

    Full Text Available Compromised mitochondrial respiratory function is associated with advancing age. Damage due to an increase in reactive oxygen species (ROS with age is thought to contribute to the mitochondrial deficits. The coenzyme nicotinamide adenine dinucleotide in its reduced (NADH and oxidized (NAD+ forms plays an essential role in the cyclic sequence of reactions that result in the regeneration of ATP by oxidative phosphorylation in mitochondria. Monitoring mitochondrial NADH/NAD+ redox status during recovery from an episode of high energy demand thus allows assessment of mitochondrial function. NADH fluoresces when excited with ultraviolet light in the UV-A band and NAD+ does not, allowing NADH/NAD+ to be monitored in real time using fluorescence microscopy. Our goal was to assess mitochondrial function by monitoring the NADH fluorescence response following a brief period of high energy demand in muscle from adult and old wild-type (WT mice. This was accomplished by isolating whole lumbrical muscles from the hind paws of 7- and 28-month-old WT mice and making simultaneous measurements of force and NADH fluorescence responses during and after a 5 s maximum isometric contraction. All muscles exhibited fluorescence oscillations that were qualitatively similar and consisted of a brief transient increase followed by a longer transient period of reduced fluorescence and, finally, an increase that included an overshoot before recovering to resting level. Compared with the adult WT mice, muscles from the 28 mo WT mice exhibited a delayed peak during the first fluorescence transient and an attenuated recovery following the second transient. These findings indicate an impaired mitochondrial capacity to maintain NADH/NAD+ redox homeostasis during contractile activity in skeletal muscles of old mice.

  1. Factors affecting vocabulary acquisition at age 2 in children born between 23 and 28 weeks' gestation.

    Science.gov (United States)

    Marston, Louise; Peacock, Janet L; Calvert, Sandra A; Greenough, Anne; Marlow, Neil

    2007-08-01

    Language development is often slower in preterm children compared with their term peers. We investigated factors associated with vocabulary acquisition at 2 years in a cohort of children born at 28 weeks' gestation or less. For children entered into the United Kingdom Oscillation Study, language development was evaluated by using the MacArthur-Bates Communicative Development Inventories score, completed by parents as part of a developmental questionnaire. The effect of demographic, neonatal, socioeconomic factors, growth, and disability were investigated using multifactorial random effects modelling. Questionnaires were returned by 288 participants (148 males, 140 females). The mean number of words vocalized was 42 (SD 29). Multifactorial analysis showed only four factors were significantly associated with vocabulary acquisition. These were: (1) level of disability (mean words: no disability, 45; other disability, 38; severe disability, 30 [severe disability is defined as at least one extreme response in one of the following clinical domains: neuromotor, vision, hearing, communication, or other physical disabilities]; 95% confidence interval [CI] for the difference between no and severe disability 7- 23); (2) sex (39 males, 44 females; 95% CI 0.4-11); (3) length of hospital stay (lower quartile, 47; upper quartile, 38; 95% CI -12 to -4); and (4) weight SD score at 12 months (lower quartile, 39; upper quartile, 44; 95% CI 1-9). There was no significant association between gestational age and vocabulary after multifactorial analysis. There was no significant effect of any socioeconomic factor on vocabulary acquisition. We conclude that clinical factors, particularly indicators of severe morbidity, dominate the correlates of vocabulary acquisition at age 2 in children born very preterm.

  2. Timing of phosphate application affects arsenic phytoextraction by Pteris vittata L. of different ages

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Jorge A.G.; Gonzaga, Maria I.S. [Department of Soil Chemistry, Universidade Federal da Bahia, Cruz das Almas, 44380000 (Brazil); Ma, Lena Q. [Soil and Water Science Department, University of Florida, Gainesville, FL 32611-0290 (United States)], E-mail: lqma@ufl.edu; Srivastava, M. [Soil and Water Science Department, University of Florida, Gainesville, FL 32611-0290 (United States)

    2008-07-15

    The effects of timing in phosphate application on plant growth and arsenic removal by arsenic hyperaccumulator Pteris vittata L. of different ages were evaluated. The hydroponic experiment consisted of three plant ages (A{sub 45d}, A{sub 90d} and A{sub 180d}) and three P feeding regimens (P{sub 200+0}, P{sub 134+66} and P{sub 66+134}) growing for 45 d in 0.2-strength Hoagland-Arnon solution containing 145 {mu}g L{sup -1} As. While all plants received 200 {mu}M P, P was added in two phases: during acclimation and after arsenic exposure. High initial P-supply (P{sub 200+0}) favored frond biomass production and plant P uptake, while split-P application (P{sub 134+66} and P{sub 66+134}) favored plant root production. Single P addition favored arsenic accumulation in the roots while split-P addition increased frond arsenic accumulation. Young ferns (A{sub 45d}) in treatment P{sub 134+66} were the most efficient in arsenic removal, reducing arsenic concentration to below 10 {mu}g L{sup -1} in 35 d. The results indicated that the use of young ferns, coupled with feeding of low initial P or split-P application, increased the efficiency of arsenic removal by P. vittata. - Young ferns coupled with split-P application were effective in arsenic removal by Pteris vittata.

  3. How does aging affect recognition-based inference? A hierarchical Bayesian modeling approach.

    Science.gov (United States)

    Horn, Sebastian S; Pachur, Thorsten; Mata, Rui

    2015-01-01

    The recognition heuristic (RH) is a simple strategy for probabilistic inference according to which recognized objects are judged to score higher on a criterion than unrecognized objects. In this article, a hierarchical Bayesian extension of the multinomial r-model is applied to measure use of the RH on the individual participant level and to re-evaluate differences between younger and older adults' strategy reliance across environments. Further, it is explored how individual r-model parameters relate to alternative measures of the use of recognition and other knowledge, such as adherence rates and indices from signal-detection theory (SDT). Both younger and older adults used the RH substantially more often in an environment with high than low recognition validity, reflecting adaptivity in strategy use across environments. In extension of previous analyses (based on adherence rates), hierarchical modeling revealed that in an environment with low recognition validity, (a) older adults had a stronger tendency than younger adults to rely on the RH and (b) variability in RH use between individuals was larger than in an environment with high recognition validity; variability did not differ between age groups. Further, the r-model parameters correlated moderately with an SDT measure expressing how well people can discriminate cases where the RH leads to a correct vs. incorrect inference; this suggests that the r-model and the SDT measures may offer complementary insights into the use of recognition in decision making. In conclusion, younger and older adults are largely adaptive in their application of the RH, but cognitive aging may be associated with an increased tendency to rely on this strategy. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Health beliefs of school-age rural children in podoconiosis-affected families: A qualitative study in Southern Ethiopia.

    Directory of Open Access Journals (Sweden)

    Abebayehu Tora

    2017-05-01

    Full Text Available Several studies have suggested investigation of health beliefs in children to be an important pre-condition for primary prevention of disease. However, little effort has been made to understand these in the context of podoconiosis. This study therefore aimed to explore the health beliefs of school-age rural children in podoconiosis-affected families.A cross sectional qualitative study was conducted in March 2016 in Wolaita Zone, Southern Ethiopia. Data were collected through in-depth individual interviews (IDIs and focus group discussions (FGDs, with a total of one hundred seventeen 9 to15-year-old children recruited from podoconiosis affected families. The study revealed various misconceptions regarding risk factors for podoconiosis. Most children believed barefoot exposure to dew, worms, snake bite, frog urine, other forms of poison, and contact with affected people to be major causes of the disease. Their knowledge about the role of heredity and that of long term barefoot exposure to irritant mineral particles was also weak. Though most participants correctly appraised their susceptibility to podoconiosis in relation to regular use of footwear and foot hygiene, others based their risk perceptions on factors they think beyond their control. They described several barriers to preventive behaviour, including uncomfortable footwear, shortage and poor adaptability of footwear for farm activities and sports, and shortage of soap for washing. Children also perceived low self-efficacy to practice preventive behaviour in spite of the barriers.Health education interventions may enhance school-age children's health literacy and be translated to preventive action. Overcoming practical challenges such as shortage of footwear and other hygiene facilities requires other forms of interventions such as livelihood strengthening activities. Linking podoconiosis-affected families with local governmental or non-governmental organizations providing socio

  5. Field establishment and grain yield of maize affected by hydro-priming of differentially aged seeds

    Directory of Open Access Journals (Sweden)

    Kazem Ghassemi-Golezani

    2017-02-01

    Full Text Available A sub-sample of maize seeds (cv. SC-AR68 with a 100% germination was kept as control, and two other sub-samples were artificially deteriorated at 40 °C for 2 and 3 days, reducing normal germination to 98% and 93%, respectively. Consequently, three seed lots of maize with different levels of vigor were provided. Each seed lot was then divided into four sub-samples, one unprimed and the other three lots were primed in distilled water at 15 °C for 7, 14 and 21 hours, and then dried back to initial moisture content (about 20% at a room temperature of 20–22 °C for 24 hours. The field experiment was arranged as factorial based on randomized complete block design with three replications. Although germination percentage of seed lots was not significantly affected by hydro-priming, germination rate and seedling dry weight were considerably enhanced as a result of seed priming. Hydro-priming for 21 hours enhanced seedling emergence rate of all seed lots with different levels of vigor. This hydro-priming duration also increased grain yield of maize by about 32%, although this superiority was not statistically significant. This advantage in grain yield of plants from primed seeds was related with rapid germination and seedling growth and early emergence in the field.

  6. NPY gene transfer in the hippocampus attenuates synaptic plasticity and learning

    DEFF Research Database (Denmark)

    Sørensen, Andreas T; Kanter-Schlifke, Irene; Carli, Mirjana

    2008-01-01

    -mediated mechanisms. In addition, transgene NPY seems to be released during high frequency neuronal activity, leading to decreased glutamate release in excitatory synapses. Importantly, memory consolidation appears to be affected by the treatment. We found that long-term potentiation (LTP) in the CA1 area...... processing. Here we show, by electrophysiological recordings in CA1 of the hippocampal formation of rats, that hippocampal NPY gene transfer into the intact brain does not affect basal synaptic transmission, but slightly alters short-term synaptic plasticity, most likely via NPY Y2 receptor....... Future clinical progress, however, requires more detailed evaluation of possible side effects of this treatment. Until now it has been unknown whether rAAV vector-based NPY overexpression in the hippocampus alters normal synaptic transmission and plasticity, which could disturb learning and memory...

  7. Do Age and Anticoagulants Affect the Natural History of Acute Subdural Hematomas?

    Science.gov (United States)

    Lucke-Wold, Brandon P.; Turner, Ryan C.; Josiah, Darnell; Knotts, Chelsea; Bhatia, Sanjay

    2016-01-01

    Acute subdural hematoma is a serious complication following traumatic brain injury. Large volume hematomas or those with underlying brain injury can cause mass effect, midline shift, and eventually herniation of the brain. Acute subdural hematomas in the young are associated with high-energy trauma and often have underlying contusions, while acute subdural hematomas in the elderly are associated with minor trauma and an absence of underlying contusions, even though the elderly are more likely to be on anticoagulants or anti-platelet therapy. In the young patients with high impact injuries the hematomas tend to be small and the underlying brain injury and swelling is responsible for the increased intracranial pressure and midline shift. In the elderly, the injuries are low impact (e.g fall from standing), the underlying brain is intact, and the volume of the hematoma itself produces symptoms. In addition the use of anticoagulants and antiplatelet agents in the elderly population has been thought to be a poor prognostic indicator and is considered to be responsible for larger hematomas and poor outcome. When managed conservatively, acute subdural hematomas can sometimes progress to chronic subdural hematoma formation, further enlargement, seizures, and progressive midline shift. Another potential difference in the young and the elderly is brain atrophy, which increases the potential space to accommodate a larger hematoma. It is not known if these two groups differ in other ways that might have implications for treatment or prognosis. In this paper, we investigate the clinical course of 80 patients admitted to our institution with acute subdural hematomas, to identify differences in patients above or below the age of 65 years. The natural progression/resolution of acute subdural hematomas was mapped by measuring volume expansion/regression over time. In this retrospective chart review, we investigated clinical baseline metrics and subsequent volumetric expansion

  8. Do Age and Anticoagulants Affect the Natural History of Acute Subdural Hematomas?

    Science.gov (United States)

    Lucke-Wold, Brandon P; Turner, Ryan C; Josiah, Darnell; Knotts, Chelsea; Bhatia, Sanjay

    2016-01-01

    Acute subdural hematoma is a serious complication following traumatic brain injury. Large volume hematomas or those with underlying brain injury can cause mass effect, midline shift, and eventually herniation of the brain. Acute subdural hematomas in the young are associated with high-energy trauma and often have underlying contusions, while acute subdural hematomas in the elderly are associated with minor trauma and an absence of underlying contusions, even though the elderly are more likely to be on anticoagulants or anti-platelet therapy. In the young patients with high impact injuries the hematomas tend to be small and the underlying brain injury and swelling is responsible for the increased intracranial pressure and midline shift. In the elderly, the injuries are low impact (e.g fall from standing), the underlying brain is intact, and the volume of the hematoma itself produces symptoms. In addition the use of anticoagulants and antiplatelet agents in the elderly population has been thought to be a poor prognostic indicator and is considered to be responsible for larger hematomas and poor outcome. When managed conservatively, acute subdural hematomas can sometimes progress to chronic subdural hematoma formation, further enlargement, seizures, and progressive midline shift. Another potential difference in the young and the elderly is brain atrophy, which increases the potential space to accommodate a larger hematoma. It is not known if these two groups differ in other ways that might have implications for treatment or prognosis. In this paper, we investigate the clinical course of 80 patients admitted to our institution with acute subdural hematomas, to identify differences in patients above or below the age of 65 years. The natural progression/resolution of acute subdural hematomas was mapped by measuring volume expansion/regression over time. In this retrospective chart review, we investigated clinical baseline metrics and subsequent volumetric expansion

  9. Catechol-O-methyltransferase (COMT Genotype Affects Age-Related Changes in Plasticity in Working Memory: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Stephan Heinzel

    2014-01-01

    Full Text Available Objectives. Recent work suggests that a genetic variation associated with increased dopamine metabolism in the prefrontal cortex (catechol-O-methyltransferase Val158Met; COMT amplifies age-related changes in working memory performance. Research on younger adults indicates that the influence of dopamine-related genetic polymorphisms on working memory performance increases when testing the cognitive limits through training. To date, this has not been studied in older adults. Method. Here we investigate the effect of COMT genotype on plasticity in working memory in a sample of 14 younger (aged 24–30 years and 25 older (aged 60–75 years healthy adults. Participants underwent adaptive training in the n-back working memory task over 12 sessions under increasing difficulty conditions. Results. Both younger and older adults exhibited sizeable behavioral plasticity through training (P<.001, which was larger in younger as compared to older adults (P<.001. Age-related differences were qualified by an interaction with COMT genotype (P<.001, and this interaction was due to decreased behavioral plasticity in older adults carrying the Val/Val genotype, while there was no effect of genotype in younger adults. Discussion. Our findings indicate that age-related changes in plasticity in working memory are critically affected by genetic variation in prefrontal dopamine metabolism.

  10. Do Gender and Age Affect the Level of Digital Competence? A Study with University Students

    Directory of Open Access Journals (Sweden)

    Marcos CABEZAS GONZÁLEZ

    2017-12-01

    Full Text Available The characteristics of Information and Communication Technologies (ICT and their implementation at the global level have led to significant changes in different areas, especially institutional ones. This article presents the results of a research study whose purpose was to learn the level of digital competence of university students of education and to verify whether the variables of gender and age have any influence on it. A quantitative methodology was used, with a non-experimental, descriptive and inferential method, and the digital questionnaire was employed as an instrument for collecting information on the dimensions of knowledge and management of ICTs as well as attitudes towards them. The data were analysed based on a comparison of means, using non-parametric tests. The results show that the sample studied self-evaluated negatively their knowledge of ICT concepts, considered positive their management of devices, tools and services, and showed a very positive attitude toward technology. Regarding the variables studied, significant differences were found in favour of men in relation to knowledge and management, and in favour of older subjects with regard to attitude.

  11. Ethanol and Acetate Acting as Carbon/Energy Sources Negatively Affect Yeast Chronological Aging

    Directory of Open Access Journals (Sweden)

    Ivan Orlandi

    2013-01-01

    Full Text Available In Saccharomyces cerevisiae, the chronological lifespan (CLS is defined as the length of time that a population of nondividing cells can survive in stationary phase. In this phase, cells remain metabolically active, albeit at reduced levels, and responsive to environmental signals, thus simulating the postmitotic quiescent state of mammalian cells. Many studies on the main nutrient signaling pathways have uncovered the strong influence of growth conditions, including the composition of culture media, on CLS. In this context, two byproducts of yeast glucose fermentation, ethanol and acetic acid, have been proposed as extrinsic proaging factors. Here, we report that ethanol and acetic acid, at physiological levels released in the exhausted medium, both contribute to chronological aging. Moreover, this combined proaging effect is not due to a toxic environment created by their presence but is mainly mediated by the metabolic pathways required for their utilization as carbon/energy sources. In addition, measurements of key enzymatic activities of the glyoxylate cycle and gluconeogenesis, together with respiration assays performed in extreme calorie restriction, point to a long-term quiescent program favoured by glyoxylate/gluconeogenesis flux contrary to a proaging one based on the oxidative metabolism of ethanol/acetate via TCA and mitochondrial respiration.

  12. Age and reproductive status of adult Varroa mites affect grooming success of honey bees.

    Science.gov (United States)

    Kirrane, Maria J; de Guzman, Lilia I; Rinderer, Thomas E; Frake, Amanda M; Wagnitz, Jeremy; Whelan, Pádraig M

    2012-12-01

    This study evaluated for the first time the grooming response of honey bees to Varroa mites of different ages and reproductive statuses in the laboratory. Plastic cages containing a section of dark comb and about 200 bees were inoculated with groups of four classes of mites: gravid, phoretic foundresses, phoretic daughters and a combination of gravid and phoretic foundress mites. Each cage received 20 mites belonging to one of these classes. Our results showed that, 1 day after mite inoculation, phoretic daughter mites were the most prone to grooming by honey bees with an average mite drop of 49.8 ± 2.6 %. The lowest mite drop was recorded for bees inoculated with phoretic foundresses (30.3 ± 3.6 %) but was comparable to bees inoculated with gravid mites (31.8 ± 3.8 %) and the combination of gravid and phoretic foundress mites (34.2 ± 3.2 %). No differences among mite types were detected during the second and third days of observation. Regardless of mite type, the highest mite drop was recorded on the first day (35 ± 2.1 %) compared to the drop for any subsequent day (grooming behaviour may increase our insight into the importance of grooming in mite resistance.

  13. Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

    Science.gov (United States)

    Machiela, Mitchell J.; Zhou, Weiyin; Karlins, Eric; Sampson, Joshua N.; Freedman, Neal D.; Yang, Qi; Hicks, Belynda; Dagnall, Casey; Hautman, Christopher; Jacobs, Kevin B.; Abnet, Christian C.; Aldrich, Melinda C.; Amos, Christopher; Amundadottir, Laufey T.; Arslan, Alan A.; Beane-Freeman, Laura E.; Berndt, Sonja I.; Black, Amanda; Blot, William J.; Bock, Cathryn H.; Bracci, Paige M.; Brinton, Louise A.; Bueno-de-Mesquita, H Bas; Burdett, Laurie; Buring, Julie E.; Butler, Mary A.; Canzian, Federico; Carreón, Tania; Chaffee, Kari G.; Chang, I-Shou; Chatterjee, Nilanjan; Chen, Chu; Chen, Constance; Chen, Kexin; Chung, Charles C.; Cook, Linda S.; Crous Bou, Marta; Cullen, Michael; Davis, Faith G.; De Vivo, Immaculata; Ding, Ti; Doherty, Jennifer; Duell, Eric J.; Epstein, Caroline G.; Fan, Jin-Hu; Figueroa, Jonine D.; Fraumeni, Joseph F.; Friedenreich, Christine M.; Fuchs, Charles S.; Gallinger, Steven; Gao, Yu-Tang; Gapstur, Susan M.; Garcia-Closas, Montserrat; Gaudet, Mia M.; Gaziano, J. Michael; Giles, Graham G.; Gillanders, Elizabeth M.; Giovannucci, Edward L.; Goldin, Lynn; Goldstein, Alisa M.; Haiman, Christopher A.; Hallmans, Goran; Hankinson, Susan E.; Harris, Curtis C.; Henriksson, Roger; Holly, Elizabeth A.; Hong, Yun-Chul; Hoover, Robert N.; Hsiung, Chao A.; Hu, Nan; Hu, Wei; Hunter, David J.; Hutchinson, Amy; Jenab, Mazda; Johansen, Christoffer; Khaw, Kay-Tee; Kim, Hee Nam; Kim, Yeul Hong; Kim, Young Tae; Klein, Alison P.; Klein, Robert; Koh, Woon-Puay; Kolonel, Laurence N.; Kooperberg, Charles; Kraft, Peter; Krogh, Vittorio; Kurtz, Robert C.; LaCroix, Andrea; Lan, Qing; Landi, Maria Teresa; Marchand, Loic Le; Li, Donghui; Liang, Xiaolin; Liao, Linda M.; Lin, Dongxin; Liu, Jianjun; Lissowska, Jolanta; Lu, Lingeng; Magliocco, Anthony M.; Malats, Nuria; Matsuo, Keitaro; McNeill, Lorna H.; McWilliams, Robert R.; Melin, Beatrice S.; Mirabello, Lisa; Moore, Lee; Olson, Sara H.; Orlow, Irene; Park, Jae Yong; Patiño-Garcia, Ana; Peplonska, Beata; Peters, Ulrike; Petersen, Gloria M.; Pooler, Loreall; Prescott, Jennifer; Prokunina-Olsson, Ludmila; Purdue, Mark P.; Qiao, You-Lin; Rajaraman, Preetha; Real, Francisco X.; Riboli, Elio; Risch, Harvey A.; Rodriguez-Santiago, Benjamin; Ruder, Avima M.; Savage, Sharon A.; Schumacher, Fredrick; Schwartz, Ann G.; Schwartz, Kendra L.; Seow, Adeline; Wendy Setiawan, Veronica; Severi, Gianluca; Shen, Hongbing; Sheng, Xin; Shin, Min-Ho; Shu, Xiao-Ou; Silverman, Debra T.; Spitz, Margaret R.; Stevens, Victoria L.; Stolzenberg-Solomon, Rachael; Stram, Daniel; Tang, Ze-Zhong; Taylor, Philip R.; Teras, Lauren R.; Tobias, Geoffrey S.; Van Den Berg, David; Visvanathan, Kala; Wacholder, Sholom; Wang, Jiu-Cun; Wang, Zhaoming; Wentzensen, Nicolas; Wheeler, William; White, Emily; Wiencke, John K.; Wolpin, Brian M.; Wong, Maria Pik; Wu, Chen; Wu, Tangchun; Wu, Xifeng; Wu, Yi-Long; Wunder, Jay S.; Xia, Lucy; Yang, Hannah P.; Yang, Pan-Chyr; Yu, Kai; Zanetti, Krista A.; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Zhou, Baosen; Ziegler, Regina G.; Perez-Jurado, Luis A.; Caporaso, Neil E.; Rothman, Nathaniel; Tucker, Margaret; Dean, Michael C.; Yeager, Meredith; Chanock, Stephen J.

    2016-01-01

    To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases. PMID:27291797

  14. Diacylglycerol kinases in the coordination of synaptic plasticity

    Directory of Open Access Journals (Sweden)

    Dongwon Lee

    2016-08-01

    Full Text Available Synaptic plasticity is activity-dependent modification of the efficacy of synaptic transmission. Although detailed mechanisms underlying synaptic plasticity are diverse and vary at different types of synapses, diacylglycerol (DAG-associated signaling has been considered as an important regulator of many forms of synaptic plasticity, including long-term potentiation (LTP and long-term depression (LTD. Recent evidence indicate that DAG kinases (DGKs, which phosphorylate DAG to phosphatidic acid to terminate DAG signaling, are important regulators of LTP and LTD, as supported by the results from mice lacking specific DGK isoforms. This review will summarize these studies and discuss how specific DGK isoforms distinctly regulate different forms of synaptic plasticity at pre- and postsynaptic sites. In addition, we propose a general role of DGKs as coordinators of synaptic plasticity that make local synaptic environments more permissive for synaptic plasticity by regulating DAG concentration and interacting with other synaptic proteins.

  15. Metabolic Turnover of Synaptic Proteins: Kinetics, Interdependencies and Implications for Synaptic Maintenance

    Science.gov (United States)

    Cohen, Laurie D.; Zuchman, Rina; Sorokina, Oksana; Müller, Anke; Dieterich, Daniela C.; Armstrong, J. Douglas; Ziv, Tamar; Ziv, Noam E.

    2013-01-01

    Chemical synapses contain multitudes of proteins, which in common with all proteins, have finite lifetimes and therefore need to be continuously replaced. Given the huge numbers of synaptic connections typical neurons form, the demand to maintain the protein contents of these connections might be expected to place considerable metabolic demands on each neuron. Moreover, synaptic proteostasis might differ according to distance from global protein synthesis sites, the availability of distributed protein synthesis facilities, trafficking rates and synaptic protein dynamics. To date, the turnover kinetics of synaptic proteins have not been studied or analyzed systematically, and thus metabolic demands or the aforementioned relationships remain largely unknown. In the current study we used dynamic Stable Isotope Labeling with Amino acids in Cell culture (SILAC), mass spectrometry (MS), Fluorescent Non–Canonical Amino acid Tagging (FUNCAT), quantitative immunohistochemistry and bioinformatics to systematically measure the metabolic half-lives of hundreds of synaptic proteins, examine how these depend on their pre/postsynaptic affiliation or their association with particular molecular complexes, and assess the metabolic load of synaptic proteostasis. We found that nearly all synaptic proteins identified here exhibited half-lifetimes in the range of 2–5 days. Unexpectedly, metabolic turnover rates were not significantly different for presynaptic and postsynaptic proteins, or for proteins for which mRNAs are consistently found in dendrites. Some functionally or structurally related proteins exhibited very similar turnover rates, indicating that their biogenesis and degradation might be coupled, a possibility further supported by bioinformatics-based analyses. The relatively low turnover rates measured here (∼0.7% of synaptic protein content per hour) are in good agreement with imaging-based studies of synaptic protein trafficking, yet indicate that the metabolic load

  16. Basic abnormalities in visual processing affect face processing at an early age in autism spectrum disorder.

    Science.gov (United States)

    Vlamings, Petra Hendrika Johanna Maria; Jonkman, Lisa Marthe; van Daalen, Emma; van der Gaag, Rutger Jan; Kemner, Chantal

    2010-12-15

    A detailed visual processing style has been noted in autism spectrum disorder (ASD); this contributes to problems in face processing and has been directly related to abnormal processing of spatial frequencies (SFs). Little is known about the early development of face processing in ASD and the relation with abnormal SF processing. We investigated whether young ASD children show abnormalities in low spatial frequency (LSF, global) and high spatial frequency (HSF, detailed) processing and explored whether these are crucially involved in the early development of face processing. Three- to 4-year-old children with ASD (n = 22) were compared with developmentally delayed children without ASD (n = 17). Spatial frequency processing was studied by recording visual evoked potentials from visual brain areas while children passively viewed gratings (HSF/LSF). In addition, children watched face stimuli with different expressions, filtered to include only HSF or LSF. Enhanced activity in visual brain areas was found in response to HSF versus LSF information in children with ASD, in contrast to control subjects. Furthermore, facial-expression processing was also primarily driven by detail in ASD. Enhanced visual processing of detailed (HSF) information is present early in ASD and occurs for neutral (gratings), as well as for socially relevant stimuli (facial expressions). These data indicate that there is a general abnormality in visual SF processing in early ASD and are in agreement with suggestions that a fast LSF subcortical face processing route might be affected in ASD. This could suggest that abnormal visual processing is causative in the development of social problems in ASD. Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  17. Early-life seizures alter synaptic calcium-permeable AMPA receptor function and plasticity

    Science.gov (United States)

    Lippman-Bell, Jocelyn J.; Zhou, Chengwen; Sun, Hongyu; Feske, Joel S.; Jensen, Frances E.

    2016-01-01

    Calcium (Ca2+)-mediated1 signaling pathways are critical to synaptic plasticity. In adults, the NMDA glutamate receptor (NMDAR) represents a major route for activity-dependent synaptic Ca2+ entry. However, during neonatal development, when synaptic plasticity is high, many AMPA glutamate receptors (AMPARs) are also permeable to Ca2+ (CP-AMPAR) due to low GluA2 subunit expression, providing an additional route for activity- and glutamate-dependent Ca2+ influx and subsequent signaling. Therefore, altered hippocampal Ca2+ signaling may represent an age-specific pathogenic mechanism. We thus aimed to assess Ca2+ responses 48 hours after hypoxia-induced neonatal seizures (HS) in postnatal day (P)10 rats, a post-seizure time point at which we previously reported LTP attenuation. We found that Ca2+ responses were higher in brain slices from post-HS rats than in controls and this increase was CP-AMPAR-dependent. To determine whether synaptic CP-AMPAR expression was also altered post-HS, we assessed the expression of GluA2 at hippocampal synapses and the expression of long-term depression (LTD), which has been linked to the presence of synaptic GluA2. Here we report a decrease 48 hours after HS in synaptic GluA2 expression at synapses and LTD in hippocampal CA1. Given the potentially critical role of AMPAR trafficking in disease progression, we aimed to establish whether post-seizure in vivo AMPAR antagonist treatment prevented the enhanced Ca2+ responses, changes in GluA2 synaptic expression, and diminished LTD. We found that NBQX treatment prevents all three of these post-seizure consequences, further supporting a critical role for AMPARs as an age-specific therapeutic target. PMID:27521497

  18. Soil sterilization affects aging-related sequestration and bioavailability of p,p'-DDE and anthracene to earthworms

    International Nuclear Information System (INIS)

    Slizovskiy, Ilya B.; Kelsey, Jason W.

    2010-01-01

    Laboratory experiments investigated the effects of soil sterilization and compound aging on the bioaccumulation of spiked p,p'-DDE and anthracene by Eisenia fetida and Lumbricus terrestris. Declines in bioavailability occurred as pollutant residence time in both sterile and non-sterile soils increased from 3 to 203 d. Accumulation was generally higher in sterile soils during initial periods of aging (from 3-103 d). By 203 d, however, bioavailability of the compounds was unaffected by sterilization. Gamma irradiation and autoclaving may have altered bioavailability by inducing changes in the chemistry of soil organic matter (SOM). The results support a dual-mode partitioning sorption model in which the SOM components associated with short-term sorption (the 'soft' or 'rubbery' phases) are more affected than are the components associated with long-term sorption (the 'glassy' or microcrystalline phases). Risk assessments based on data from experiments in which sterile soil was used could overestimate exposure and bioaccumulation of pollutants. - Soil sterilization affects aging-related sequestration of organic contaminants.

  19. Soil sterilization affects aging-related sequestration and bioavailability of p,p'-DDE and anthracene to earthworms

    Energy Technology Data Exchange (ETDEWEB)

    Slizovskiy, Ilya B. [Program in Environmental Science and Department of Chemistry, Muhlenberg College, Allentown, PA 18104 (United States); Kelsey, Jason W., E-mail: Kelsey@muhlenberg.ed [Program in Environmental Science and Department of Chemistry, Muhlenberg College, Allentown, PA 18104 (United States)

    2010-10-15

    Laboratory experiments investigated the effects of soil sterilization and compound aging on the bioaccumulation of spiked p,p'-DDE and anthracene by Eisenia fetida and Lumbricus terrestris. Declines in bioavailability occurred as pollutant residence time in both sterile and non-sterile soils increased from 3 to 203 d. Accumulation was generally higher in sterile soils during initial periods of aging (from 3-103 d). By 203 d, however, bioavailability of the compounds was unaffected by sterilization. Gamma irradiation and autoclaving may have altered bioavailability by inducing changes in the chemistry of soil organic matter (SOM). The results support a dual-mode partitioning sorption model in which the SOM components associated with short-term sorption (the 'soft' or 'rubbery' phases) are more affected than are the components associated with long-term sorption (the 'glassy' or microcrystalline phases). Risk assessments based on data from experiments in which sterile soil was used could overestimate exposure and bioaccumulation of pollutants. - Soil sterilization affects aging-related sequestration of organic contaminants.

  20. Age and gender affect likely manometric diagnosis: Audit of a tertiary referral hospital clinical esophageal manometry service.

    Science.gov (United States)

    Andrews, Jane M; Heddle, Richard; Hebbard, Geoffrey S; Checklin, Helen; Besanko, Laura; Fraser, Robert J

    2009-01-01

    Awareness of patient demographics, common diagnoses and associations between these may improve the use and interpretation of manometric investigations. The aim of the present study therefore was to determine whether age and/or gender affect manometric diagnosis in a clinical motility service. An audit of all 452 clinical manometry reports issued from December 2003 to July 2005 with respect to age, gender and diagnosis was carried out. Patients were divided by age (17-24 years n = 14, 25-44 years n = 87, 45-64 years n = 216 and >or=65 years n = 135), and gender and data compared using contingency tables. Women were more commonly referred overall (59%) and in each age bracket except motor problems P = 0.01. With aging, normal motor function became less common (P = 0.013), with non-specific motor disorder, ineffective/hypotensive peristalsis and 'achalasia-like' conditions each more common (individual P = NS). Increasing age showed a trend for increased spastic motor disorders (P = 0.06). Gender did not, however, influence whether motility was abnormal (P = 0.5), spastic (P = 0.7) or whether a non-specific motor disorder was present (P = 0.1). In the total cohort, the principal manometric diagnoses were: non-specific motor disorder 33%, normal motility 29%, low basal lower esophageal sphincter pressure 18%, hypotensive/ineffective peristalsis 10%, achalasia/achalasia-like 6%, diffuse esophageal spasm 3% and other 1%. Aging leads to increasing esophageal motor abnormalities. Men and women have similar rates of dysfunction, although 'low-pressure problems' were more common in men.

  1. Factors affecting unmet need for family planning in married women of reproductive age group in urban slums of Lucknow

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    Anjali Pal

    2014-03-01

    Full Text Available Background: Unmet need for family planning signifies the gap between the reproductive intentions of couples and their actual contraceptive behaviour. The National Family Health Surveys carried out in India in 1992-93, 1998-99 and 2004-2005 have revealed that for a sizable proportion of the population in the reproductive age group, the need for contraceptive services are not met with despite the existence of a National Policy on family planning since 1983. This study was carried out to assess the extent of unmet need for family planning among married women of reproductive age group in urban slums of Lucknow and identify the various factors affecting it. Study design: Cross sectional Setting: four urban slums of Lucknow Participants: 414 married women in the age group of 15- 44 years Study variables: age, education, occupation, religion, parity Statistical analysis: chi- square test, logistic regression analysis, fisher’s exact test Results: the extent of unmet need among married women of reproductive age group was 53.1%. The unmet need was found to be significantly associated with age, number of living sons, discussion of family planning with husband, perception of husband’s view on family planning and husbands’ behaviour towards use of family planning method. Logistic regression analysis of unmet need showed that the lower age of the woman, lesser number of living sons and husband’s discouragement towards the use of FP method were correlated with the unmet need for Family Planning.

  2. Synaptic damage underlies EEG abnormalities in postanoxic encephalopathy: A computational study.

    Science.gov (United States)

    Ruijter, B J; Hofmeijer, J; Meijer, H G E; van Putten, M J A M

    2017-09-01

    In postanoxic coma, EEG patterns indicate the severity of encephalopathy and typically evolve in time. We aim to improve the understanding of pathophysiological mechanisms underlying these EEG abnormalities. We used a mean field model comprising excitatory and inhibitory neurons, local synaptic connections, and input from thalamic afferents. Anoxic damage is modeled as aggravated short-term synaptic depression, with gradual recovery over many hours. Additionally, excitatory neurotransmission is potentiated, scaling with the severity of anoxic encephalopathy. Simulations were compared with continuous EEG recordings of 155 comatose patients after cardiac arrest. The simulations agree well with six common categories of EEG rhythms in postanoxic encephalopathy, including typical transitions in time. Plausible results were only obtained if excitatory synapses were more severely affected by short-term synaptic depression than inhibitory synapses. In postanoxic encephalopathy, the evolution of EEG patterns presumably results from gradual improvement of complete synaptic failure, where excitatory synapses are more severely affected than inhibitory synapses. The range of EEG patterns depends on the excitation-inhibition imbalance, probably resulting from long-term potentiation of excitatory neurotransmission. Our study is the first to relate microscopic synaptic dynamics in anoxic brain injury to both typical EEG observations and their evolution in time. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  3. Effects of active conductance distribution over dendrites on the synaptic integration in an identified nonspiking interneuron.

    Directory of Open Access Journals (Sweden)

    Akira Takashima

    Full Text Available The synaptic integration in individual central neuron is critically affected by how active conductances are distributed over dendrites. It has been well known that the dendrites of central neurons are richly endowed with voltage- and ligand-regulated ion conductances. Nonspiking interneurons (NSIs, almost exclusively characteristic to arthropod central nervous systems, do not generate action potentials and hence lack voltage-regulated sodium channels, yet having a variety of voltage-regulated potassium conductances on their dendritic membrane including the one similar to the delayed-rectifier type potassium conductance. It remains unknown, however, how the active conductances are distributed over dendrites and how the synaptic integration is affected by those conductances in NSIs and other invertebrate neurons where the cell body is not included in the signal pathway from input synapses to output sites. In the present study, we quantitatively investigated the functional significance of active conductance distribution pattern in the spatio-temporal spread of synaptic potentials over dendrites of an identified NSI in the crayfish central nervous system by computer simulation. We systematically changed the distribution pattern of active conductances in the neuron's multicompartment model and examined how the synaptic potential waveform was affected by each distribution pattern. It was revealed that specific patterns of nonuniform distribution of potassium conductances were consistent, while other patterns were not, with the waveform of compound synaptic potentials recorded physiologically in the major input-output pathway of the cell, suggesting that the possibility of nonuniform distribution of potassium conductances over the dendrite cannot be excluded as well as the possibility of uniform distribution. Local synaptic circuits involving input and output synapses on the same branch or on the same side were found to be potentially affected under

  4. Aging and soil organic matter content affect the fate of silver nanoparticles in soil

    International Nuclear Information System (INIS)

    Coutris, Claire; Joner, Erik Jautris; Oughton, Deborah Helen

    2012-01-01

    Sewage sludge application on soils represents an important potential source of silver nanoparticles (Ag NPs) to terrestrial ecosystems, and it is thus important to understand the fate of Ag NPs once in contact with soil components. Our aim was to compare the behavior of three different forms of silver, namely silver nitrate, citrate stabilized Ag NPs (5 nm) and uncoated Ag NPs (19 nm), in two soils with contrasting organic matter content, and to follow changes in binding strength over time. Soil samples were spiked with silver and left to age for 2 h, 2 days, 5 weeks or 10 weeks before they were submitted to sequential extraction. The ionic silver solution and the two Ag NP types were radiolabeled so that silver could be quantified by gamma spectrometry by measuring the 110m Ag tracer in the different sequential extraction fractions. Different patterns of partitioning of silver were observed for the three forms of silver. All types of silver were more mobile in the mineral soil than in the soil rich in organic matter, although the fractionation patterns were very different for the three silver forms in both cases. Over 20% of citrate stabilized Ag NPs was extractible with water in both soils the first two days after spiking (compared to 1–3% for AgNO 3 and uncoated Ag NPs), but the fraction decreased to trace levels thereafter. Regarding the 19 nm uncoated Ag NPs, 80% was not extractible at all, but contrary to AgNO 3 and citrate stabilized Ag NPs, the bioaccessible fraction increased over time, and by day 70 was between 8 and 9 times greater than that seen in the other two treatments. This new and unexpected finding demonstrates that some Ag NPs can act as a continuous source of bioaccessible Ag, while AgNO 3 is rapidly immobilized in soil. - Highlights: ► We compared the behavior of AgNO 3 and two types of Ag NPs in soil over time. ► AgNO 3 is rapidly immobilized in soil. ► Larger Ag NPs can act as a continuous source of bioaccessible Ag, which calls for

  5. Molecular hydrogen affects body composition, metabolic profiles, and mitochondrial function in middle-aged overweight women.

    Science.gov (United States)

    Korovljev, D; Trivic, T; Drid, P; Ostojic, S M

    2018-02-01

    Molecular hydrogen (H 2 ) effectively treats obesity-related disorders in animal models, yet no studies have investigated the effectiveness and safety of H 2 for improving biomarkers of obesity in humans. In this double blind, placebo-controlled, crossover pilot trial, we evaluated the effects of H 2 intervention on body composition, hormonal status, and mitochondrial function in ten (n = 10) middle-aged overweight women. Volunteers received either hydrogen-generating minerals (supplying ~6 ppm of H 2 per day) or placebo by oral administration of caplets for 4 weeks. The primary end-point of treatment efficacy was the change in the body fat percentage from baseline to 4 weeks. In addition, assessment of other body composition indices, screening laboratory studies, and evaluation of side effects were performed before and at follow-up. Clinical trial registration www.clinicaltrials.gov , ID number NCT02832219. No significant differences were observed between treatment groups for changes in weight, body mass index, and body circumferences at 4-week follow-up (P > 0.05). H 2 treatment significantly reduced body fat percentage (3.2 vs. 0.9%, P = 0.05) and arm fat index (9.7 vs. 6.0%, P = 0.01) compared to placebo administration, respectively. This was accompanied by a significant drop in serum triglycerides after H 2 intervention comparing to placebo (21.3 vs. 6.5%; P = 0.04), while other blood lipids remained stable during the study (P > 0.05). Fasting serum insulin levels dropped by 5.4% after H 2 administration, while placebo intervention augmented insulin response by 29.3% (P = 0.01). It appears that orally administered H 2 as a blend of hydrogen-generating minerals might be a beneficial agent in the management of body composition and insulin resistance in obesity.

  6. Role of the adhesion molecule F3/Contactin in synaptic plasticity and memory.

    Science.gov (United States)

    Gulisano, Walter; Bizzoca, Antonella; Gennarini, Gianfranco; Palmeri, Agostino; Puzzo, Daniela

    2017-06-01

    Cell adhesion molecules (CAMs) have a pivotal role in building and maintaining synaptic structures during brain development participating in axonal elongation and pathfinding, glial guidance of neuronal migration, as well as myelination. CAMs expression persists in the adult brain particularly in structures undergoing postnatal neurogenesis and involved in synaptic plasticity and memory as the hippocampus. Among the neural CAMs, we have recently focused on F3/Contactin, a glycosylphosphatidyl inositol-anchored glycoprotein belonging to the immunoglobulin superfamily, involved in neuronal development, synaptic maintenance and organization of neuronal networks. Here, we discuss our recent data suggesting that F3/Contactin exerts a role in hippocampal synaptic plasticity and memory in adult and aged mice. In particular, we have studied long-term potentiation (LTP), spatial and object recognition memory, and phosphorylation of the transcription factor cAMP-Responsive-Element Binding protein (CREB) in a transgenic mouse model of F3/Contactin overexpression. We also investigated whether F3/Contactin might influence neuronal apoptosis and the production of amyloid-beta peptide (Aβ), known to be one of the main pathogenetic hallmarks of Alzheimer's disease (AD). In conclusion, a further understanding of F3/Contactin role in synaptic plasticity and memory might have interesting clinical outcomes in cognitive disorders, such as aging and AD, offering innovative therapeutic opportunities. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Synaptic Correlates of Working Memory Capacity.

    Science.gov (United States)

    Mi, Yuanyuan; Katkov, Mikhail; Tsodyks, Misha

    2017-01-18

    Psychological studies indicate that human ability to keep information in readily accessible working memory is limited to four items for most people. This extremely low capacity severely limits execution of many cognitive tasks, but its neuronal underpinnings remain unclear. Here we show that in the framework of synaptic theory of working memory, capacity can be analytically estimated to scale with characteristic time of short-term synaptic depression relative to synaptic current time constant. The number of items in working memory can be regulated by external excitation, enabling the system to be tuned to the desired load and to clear the working memory of currently held items to make room for new ones. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. The Corticohippocampal Circuit, Synaptic Plasticity, and Memory

    Science.gov (United States)

    Basu, Jayeeta; Siegelbaum, Steven A.

    2015-01-01

    Synaptic plasticity serves as a cellular substrate for information storage in the central nervous system. The entorhinal cortex (EC) and hippocampus are interconnected brain areas supporting basic cognitive functions important for the formation and retrieval of declarative memories. Here, we discuss how information flow in the EC–hippocampal loop is organized through circuit design. We highlight recently identified corticohippocampal and intrahippocampal connections and how these long-range and local microcircuits contribute to learning. This review also describes various forms of activity-dependent mechanisms that change the strength of corticohippocampal synaptic transmission. A key point to emerge from these studies is that patterned activity and interaction of coincident inputs gives rise to associational plasticity and long-term regulation of information flow. Finally, we offer insights about how learning-related synaptic plasticity within the corticohippocampal circuit during sensory experiences may enable adaptive behaviors for encoding spatial, episodic, social, and contextual memories. PMID:26525152

  9. Electric Dipole Theory of Chemical Synaptic Transmission

    Science.gov (United States)

    Wei, Ling Y.

    1968-01-01

    In this paper we propose that chemicals such as acetylcholine are electric dipoles which when oriented and arranged in a large array could produce an electric field strong enough to drive positive ions over the junction barrier of the post-synaptic membrane and thus initiate excitation or produce depolarization. This theory is able to explain a great number of facts such as cleft size, synaptic delay, nonregeneration, subthreshold integration, facilitation with repetition, and the calcium and magnesium effects. It also shows why and how acetylcholine could act as excitatory or inhibitory transmitters under different circumstances. Our conclusion is that the nature of synaptic transmission is essentially electrical, be it mediated by electrical or chemical transmitters. PMID:4296121

  10. Astroglial Metabolic Networks Sustain Hippocampal Synaptic Transmission

    Science.gov (United States)

    Rouach, Nathalie; Koulakoff, Annette; Abudara, Veronica; Willecke, Klaus; Giaume, Christian

    2008-12-01

    Astrocytes provide metabolic substrates to neurons in an activity-dependent manner. However, the molecular mechanisms involved in this function, as well as its role in synaptic transmission, remain unclear. Here, we show that the gap-junction subunit proteins connexin 43 and 30 allow intercellular trafficking of glucose and its metabolites through astroglial networks. This trafficking is regulated by glutamatergic synaptic activity mediated by AMPA receptors. In the absence of extracellular glucose, the delivery of glucose or lactate to astrocytes sustains glutamatergic synaptic transmission and epileptiform activity only when they are connected by gap junctions. These results indicate that astroglial gap junctions provide an activity-dependent intercellular pathway for the delivery of energetic metabolites from blood vessels to distal neurons.

  11. Astroglial metabolic networks sustain hippocampal synaptic transmission.

    Science.gov (United States)

    Rouach, Nathalie; Koulakoff, Annette; Abudara, Veronica; Willecke, Klaus; Giaume, Christian

    2008-12-05

    Astrocytes provide metabolic substrates to neurons in an activity-dependent manner. However, the molecular mechanisms involved in this function, as well as its role in synaptic transmission, remain unclear. Here, we show that the gap-junction subunit proteins connexin 43 and 30 allow intercellular trafficking of glucose and its metabolites through astroglial networks. This trafficking is regulated by glutamatergic synaptic activity mediated by AMPA receptors. In the absence of extracellular glucose, the delivery of glucose or lactate to astrocytes sustains glutamatergic synaptic transmission and epileptiform activity only when they are connected by gap junctions. These results indicate that astroglial gap junctions provide an activity-dependent intercellular pathway for the delivery of energetic metabolites from blood vessels to distal neurons.

  12. Loss of synaptic zinc transport in progranulin deficient mice may contribute to progranulin-associated psychopathology and chronic pain.

    Science.gov (United States)

    Hardt, Stefanie; Heidler, Juliana; Albuquerque, Boris; Valek, Lucie; Altmann, Christine; Wilken-Schmitz, Annett; Schäfer, Michael K E; Wittig, Ilka; Tegeder, Irmgard

    2017-11-01

    Affective and cognitive processing of nociception contributes to the development of chronic pain and vice versa, pain may precipitate psychopathologic symptoms. We hypothesized a higher risk for the latter with immanent neurologic diseases and studied this potential interrelationship in progranulin-deficient mice, which are a model for frontotemporal dementia, a disease dominated by behavioral abnormalities in humans. Young naïve progranulin deficient mice behaved normal in tests of short-term memory, anxiety, depression and nociception, but after peripheral nerve injury, they showed attention-deficit and depression-like behavior, over-activity, loss of shelter-seeking, reduced impulse control and compulsive feeding behavior, which did not occur in equally injured controls. Hence, only the interaction of 'pain x progranulin deficiency' resulted in the complex phenotype at young age, but neither pain nor progranulin deficiency alone. A deep proteome analysis of the prefrontal cortex and olfactory bulb revealed progranulin-dependent alterations of proteins involved in synaptic transport, including neurotransmitter transporters of the solute carrier superfamily. In particular, progranulin deficiency was associated with a deficiency of nuclear and synaptic zinc transporters (ZnT9/Slc30a9; ZnT3/Slc30a3) with low plasma zinc. Dietary zinc supplementation partly normalized the attention deficit of progranulin-deficient mice, which was in part reminiscent of autism-like and compulsive behavior of synaptic zinc transporter Znt3-knockout mice. Hence, the molecular studies point to defective zinc transport possibly contributing to progranulin-deficiency-associated psychopathology. Translated to humans, our data suggest that neuropathic pain may precipitate cognitive and psychopathological symptoms of an inherent, still silent neurodegenerative disease. Copyright © 2017. Published by Elsevier B.V.

  13. Synaptic Vesicle Endocytosis in Different Model Systems

    Directory of Open Access Journals (Sweden)

    Quan Gan

    2018-06-01

    Full Text Available Neurotransmission in complex animals depends on a choir of functionally distinct synapses releasing neurotransmitters in a highly coordinated manner. During synaptic signaling, vesicles fuse with the plasma membrane to release their contents. The rate of vesicle fusion is high and can exceed the rate at which synaptic vesicles can be re-supplied by distant sources. Thus, local compensatory endocytosis is needed to replenish the synaptic vesicle pools. Over the last four decades, various experimental methods and model systems have been used to study the cellular and molecular mechanisms underlying synaptic vesicle cycle. Clathrin-mediated endocytosis is thought to be the predominant mechanism for synaptic vesicle recycling. However, recent studies suggest significant contribution from other modes of endocytosis, including fast compensatory endocytosis, activity-dependent bulk endocytosis, ultrafast endocytosis, as well as kiss-and-run. Currently, it is not clear whether a universal model of vesicle recycling exist for all types of synapses. It is possible that each synapse type employs a particular mode of endocytosis. Alternatively, multiple modes of endocytosis operate at the same synapse, and the synapse toggles between different modes depending on its activity level. Here we compile review and research articles based on well-characterized model systems: frog neuromuscular junctions, C. elegans neuromuscular junctions, Drosophila neuromuscular junctions, lamprey reticulospinal giant axons, goldfish retinal ribbon synapses, the calyx of Held, and rodent hippocampal synapses. We will compare these systems in terms of their known modes and kinetics of synaptic vesicle endocytosis, as well as the underlying molecular machineries. We will also provide the future development of this field.

  14. Effect of miR-138 on the antioxidant function of lens epithelial cells affected by age-related cataracts

    Directory of Open Access Journals (Sweden)

    Bo Lu

    2018-03-01

    Full Text Available AIM: To investigate the effects and mechanism of miR-138 in mediating the antioxidant function of lens epithelial cells affected by age-related cataracts. METHODS: Real-time quantitative PCR(RT-qPCRwas used to detect miR-138 expression in the anterior lens capsules of healthy people, the anterior lens capsules of patients with age-related cataracts, and human epithelial cell line(SRA01/04cells exposed to oxidative stress. A 2', 7'-dichloro-fluorescein diacetate(DCFH-DAprobe was used to measure the levels of endogenous reactive oxygen species(ROSin human lens epithelial cells(hLECsexposed to 400μmol/L H2O2 for 1h. SRA01/04 cells were transfected with either miR-138 mimics, mimic controls, miR-138 inhibitors or inhibitor controls. After 72h, these cells were exposed to 400μmol/L H2O2 for 1h, then p53 and Bax mRNA expression were measured using RT-qPCR. Expression of p53 and Bax protein were also measured by western blotting analysis. Finally, cell viability was assessed using an MTS assay. RESULTS: Compared to the control group, expression of miR-138 in the anterior lens capsules of age-related cataract patients and in SRA01/04 cells exposed to oxidative stress significantly increased(PPPPCONCLUSION: The expression of miR-138 is upregulated in the anterior lens capsules of age-related cataract patients. MiR-138 decreases the anti-oxidative stress capacity of lens epithelial cells by upregulating p53 and Bax, while inhibiting cell proliferation and repair. This finding suggests that miR-138 may play a key role in the development of age-related cataracts.

  15. As long as you've got your health: Longitudinal relationships between positive affect and functional health in old age.

    Science.gov (United States)

    Gana, Kamel; Saada, Yaël; Broc, Guillaume; Quintard, Bruno; Amieva, Hélène; Dartigues, Jean-François

    2016-02-01

    Reciprocal relationships between positive affect (PA) and health are now subject of a heuristic debate in psychology and behavioral medicine. Two radically opposed approaches address the link between subjective well being (SWB) and physical health: top-down (i.e., psychosomatic hypothesis) and bottom-up (i.e., disability/ability hypothesis) approaches. The aim of the present study was to test these two approaches by investigating thirteen-year longitudinal relationships between PA, as an affective dimension of SWB, and functional health in older people. The study included 3754 participants aged 62-101 years assessed 6 times over a thirteen-year period. PA was measured by the mean of the positive affect subscale of the CES-D scale. Functional health was assessed by four composite items: a single-item self-rating of hearing impairment, a single-item self-rating of vision impairment, the number of medically prescribed drugs, and a single-item self-rating of dyspnoea. We used cross-lagged modeling with latent variables, which is appropriate for testing specific theories. Mean arterial pressure, diabetes mellitus and hypercholesterolemia status, sequelae of stroke, gender, level of education, and age at baseline were use as control variables in the models. Results indicated that good health significantly predicted subsequent levels of PA (average β = -0.58, p got your health". Limitations of this finding are reviewed and discussed. Models including longitudinal mediators, such as biomarkers and life style patterns, are needed to clarify the nature of the link between these constructs. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Flexible Proton-Gated Oxide Synaptic Transistors on Si Membrane.

    Science.gov (United States)

    Zhu, Li Qiang; Wan, Chang Jin; Gao, Ping Qi; Liu, Yang Hui; Xiao, Hui; Ye, Ji Chun; Wan, Qing

    2016-08-24

    Ion-conducting materials have received considerable attention for their applications in fuel cells, electrochemical devices, and sensors. Here, flexible indium zinc oxide (InZnO) synaptic transistors with multiple presynaptic inputs gated by proton-conducting phosphorosilicate glass-based electrolyte films are fabricated on ultrathin Si membranes. Transient characteristics of the proton gated InZnO synaptic transistors are investigated, indicating stable proton-gating behaviors. Short-term synaptic plasticities are mimicked on the proposed proton-gated synaptic transistors. Furthermore, synaptic integration regulations are mimicked on the proposed synaptic transistor networks. Spiking logic modulations are realized based on the transition between superlinear and sublinear synaptic integration. The multigates coupled flexible proton-gated oxide synaptic transistors may be interesting for neuroinspired platforms with sophisticated spatiotemporal information processing.

  17. Leaf age affects the responses of foliar injury and gas exchange to tropospheric ozone in Prunus serotina seedlings

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Jianwei, E-mail: jianweizhang@fs.fed.u [Environmental Resources Research Institute, Pennsylvania State University, University Park, PA 16802 (United States); School of Forest Resources, Pennsylvania State University, University Park, PA 16802 (United States); Schaub, Marcus; Ferdinand, Jonathan A. [Environmental Resources Research Institute, Pennsylvania State University, University Park, PA 16802 (United States); Skelly, John M. [Department of Plant Pathology, Pennsylvania State University, University Park, PA 16802 (United States); Steiner, Kim C. [School of Forest Resources, Pennsylvania State University, University Park, PA 16802 (United States); Savage, James E. [Department of Plant Pathology, Pennsylvania State University, University Park, PA 16802 (United States)

    2010-08-15

    We investigated the effect of leaf age on the response of net photosynthesis (A), stomatal conductance (g{sub wv}), foliar injury, and leaf nitrogen concentration (N{sub L}) to tropospheric ozone (O{sub 3}) on Prunus serotina seedlings grown in open-plots (AA) and open-top chambers, supplied with either carbon-filtered or non-filtered air. We found significant variation in A, g{sub wv}, foliar injury, and N{sub L} (P < 0.05) among O{sub 3} treatments. Seedlings in AA showed the highest A and g{sub wv} due to relatively low vapor pressure deficit (VPD). Older leaves showed significantly lower A, g{sub wv}, N{sub L}, and higher foliar injury (P < 0.001) than younger leaves. Leaf age affected the response of A, g{sub wv}, and foliar injury to O{sub 3}. Both VPD and N{sub L} had a strong influence on leaf gas exchange. Foliar O{sub 3}-induced injury appeared when cumulative O{sub 3} uptake reached 8-12 mmol m{sup -2}, depending on soil water availability. The mechanistic assessment of O{sub 3}-induced injury is a valuable approach for a biologically relevant O{sub 3} risk assessment for forest trees. - Ozone effects on symptom development and leaf gas exchange interacted with leaf age and N-content on black cherry seedlings.

  18. Levetiracetam reverses synaptic deficits produced by overexpression of SV2A.

    Directory of Open Access Journals (Sweden)

    Amy Nowack

    Full Text Available Levetiracetam is an FDA-approved drug used to treat epilepsy and other disorders of the nervous system. Although it is known that levetiracetam binds the synaptic vesicle protein SV2A, how drug binding affects synaptic functioning remains unknown. Here we report that levetiracetam reverses the effects of excess SV2A in autaptic hippocampal neurons. Expression of an SV2A-EGFP fusion protein produced a ∼1.5-fold increase in synaptic levels of SV2, and resulted in reduced synaptic release probability. The overexpression phenotype parallels that seen in neurons from SV2 knockout mice, which experience severe seizures. Overexpression of SV2A also increased synaptic levels of the calcium-sensor protein synaptotagmin, an SV2-binding protein whose stability and trafficking are regulated by SV2. Treatment with levetiracetam rescued normal neurotransmission and restored normal levels of SV2 and synaptotagmin at the synapse. These results indicate that changes in SV2 expression in either direction impact neurotransmission, and suggest that levetiracetam may modulate SV2 protein interactions.

  19. The Chemokine MIP-1α/CCL3 impairs mouse hippocampal synaptic transmission, plasticity and memory.

    Science.gov (United States)

    Marciniak, Elodie; Faivre, Emilie; Dutar, Patrick; Alves Pires, Claire; Demeyer, Dominique; Caillierez, Raphaëlle; Laloux, Charlotte; Buée, Luc; Blum, David; Humez, Sandrine

    2015-10-29

    Chemokines are signaling molecules playing an important role in immune regulations. They are also thought to regulate brain development, neurogenesis and neuroendocrine functions. While chemokine upsurge has been associated with conditions characterized with cognitive impairments, their ability to modulate synaptic plasticity remains ill-defined. In the present study, we specifically evaluated the effects of MIP1-α/CCL3 towards hippocampal synaptic transmission, plasticity and spatial memory. We found that CCL3 (50 ng/ml) significantly reduced basal synaptic transmission at the Schaffer collateral-CA1 synapse without affecting NMDAR-mediated field potentials. This effect was ascribed to post-synaptic regulations, as CCL3 did not impact paired-pulse facilitation. While CCL3 did not modulate long-term depression (LTD), it significantly impaired long-term potentiation (LTP), an effect abolished by Maraviroc, a CCR5 specific antagonist. In addition, sub-chronic intracerebroventricular (icv) injections of CCL3 also impair LTP. In accordance with these electrophysiological findings, we demonstrated that the icv injection of CCL3 in mouse significantly impaired spatial memory abilities and long-term memory measured using the two-step Y-maze and passive avoidance tasks. These effects of CCL3 on memory were inhibited by Maraviroc. Altogether, these data suggest that the chemokine CCL3 is an hippocampal neuromodulator able to regulate synaptic plasticity mechanisms involved in learning and memory functions.

  20. Survival motor neuron protein in motor neurons determines synaptic integrity in spinal muscular atrophy.

    Science.gov (United States)

    Martinez, Tara L; Kong, Lingling; Wang, Xueyong; Osborne, Melissa A; Crowder, Melissa E; Van Meerbeke, James P; Xu, Xixi; Davis, Crystal; Wooley, Joe; Goldhamer, David J; Lutz, Cathleen M; Rich, Mark M; Sumner, Charlotte J

    2012-06-20

    The inherited motor neuron disease spinal muscular atrophy (SMA) is caused by deficient expression of survival motor neuron (SMN) protein and results in severe muscle weakness. In SMA mice, synaptic dysfunction of both neuromuscular junctions (NMJs) and central sensorimotor synapses precedes motor neuron cell death. To address whether this synaptic dysfunction is due to SMN deficiency in motor neurons, muscle, or both, we generated three lines of conditional SMA mice with tissue-specific increases in SMN expression. All three lines of mice showed increased survival, weights, and improved motor behavior. While increased SMN expression in motor neurons prevented synaptic dysfunction at the NMJ and restored motor neuron somal synapses, increased SMN expression in muscle did not affect synaptic function although it did improve myofiber size. Together these data indicate that both peripheral and central synaptic integrity are dependent on motor neurons in SMA, but SMN may have variable roles in the maintenance of these different synapses. At the NMJ, it functions at the presynaptic terminal in a cell-autonomous fashion, but may be necessary for retrograde trophic signaling to presynaptic inputs onto motor neurons. Importantly, SMN also appears to function in muscle growth and/or maintenance independent of motor neurons. Our data suggest that SMN plays distinct roles in muscle, NMJs, and motor neuron somal synapses and that restored function of SMN at all three sites will be necessary for full recovery of muscle power.

  1. The Roles of Cortical Slow Waves in Synaptic Plasticity and Memory Consolidation.

    Science.gov (United States)

    Miyamoto, Daisuke; Hirai, Daichi; Murayama, Masanori

    2017-01-01

    Sleep plays important roles in sensory and motor memory consolidation. Sleep oscillations, reflecting neural population activity, involve the reactivation of learning-related neurons and regulate synaptic strength and, thereby affect memory consolidation. Among sleep oscillations, slow waves (0.5-4 Hz) are closely associated with memory consolidation. For example, slow-wave power is regulated in an experience-dependent manner and correlates with acquired memory. Furthermore, manipulating slow waves can enhance or impair memory consolidation. During slow wave sleep, inter-areal interactions between the cortex and hippocampus (HC) have been proposed to consolidate declarative memory; however, interactions for non-declarative (HC-independent) memory remain largely uninvestigated. We recently showed that the directional influence in a slow-wave range through a top-down cortical long-range circuit is involved in the consolidation of non-declarative memory. At the synaptic level, the average cortical synaptic strength is known to be potentiated during wakefulness and depressed during sleep. Moreover, learning causes plasticity in a subset of synapses, allocating memory to them. Sleep may help to differentiate synaptic strength between allocated and non-allocated synapses (i.e., improving the signal-to-noise ratio, which may facilitate memory consolidation). Herein, we offer perspectives on inter-areal interactions and synaptic plasticity for memory consolidation during sleep.

  2. The Roles of Cortical Slow Waves in Synaptic Plasticity and Memory Consolidation

    Directory of Open Access Journals (Sweden)

    Daisuke Miyamoto

    2017-11-01

    Full Text Available Sleep plays important roles in sensory and motor memory consolidation. Sleep oscillations, reflecting neural population activity, involve the reactivation of learning-related neurons and regulate synaptic strength and, thereby affect memory consolidation. Among sleep oscillations, slow waves (0.5–4 Hz are closely associated with memory consolidation. For example, slow-wave power is regulated in an experience-dependent manner and correlates with acquired memory. Furthermore, manipulating slow waves can enhance or impair memory consolidation. During slow wave sleep, inter-areal interactions between the cortex and hippocampus (HC have been proposed to consolidate declarative memory; however, interactions for non-declarative (HC-independent memory remain largely uninvestigated. We recently showed that the directional influence in a slow-wave range through a top-down cortical long-range circuit is involved in the consolidation of non-declarative memory. At the synaptic level, the average cortical synaptic strength is known to be potentiated during wakefulness and depressed during sleep. Moreover, learning causes plasticity in a subset of synapses, allocating memory to them. Sleep may help to differentiate synaptic strength between allocated and non-allocated synapses (i.e., improving the signal-to-noise ratio, which may facilitate memory consolidation. Herein, we offer perspectives on inter-areal interactions and synaptic plasticity for memory consolidation during sleep.

  3. Stress-triggered synaptic malfunction: a gate along the path from depression to dementia

    Directory of Open Access Journals (Sweden)

    Ioannis Sotiropoulos

    2014-03-01

    Full Text Available Clinical and experimental studies suggest a causal role of chronic stress for brain pathology and diseases e.g. depression and Alzheimer´s disease (AD as stress is strongly associated with neuronal and synaptic atrophy/loss resulting in impaired mood and/or cognition. Indeed, synaptic loss is a key underlying pathomechanism in both disorders while growing clinical evidence supports a pathological link between depression and AD pointing to shared neurobiological underpinnings and pathogenic mechanisms e.g. AD-related mechanisms, such as APP misprocessing, are also found to be affected in depression while depression predisposes individuals to develop AD. Based on the above, our studies have been conceived to contribute towards bridging the current gap monitoring AD-related mechanisms in the CMS (chronic mild stress animal model of depression before and after antidepressant treatment. We found that depressive status in these animals was accompanied by increased APP misprocessing and tau accumulation as well as neuronal atrophy in hippocampus and prefrontal cortex. Interestingly, antidepressant treatment with two different antidepressants reversed both biochemical and synaptic changes. Furthermore, we demonstrate the blockage of stress-triggered depressive behavior and neuronal/synaptic atrophy in animals lacking APP misprocessing and amyloid beta generation, further supporting the involvement of APP misprocessing in depressive pathology and behavior. Thus, this study forms the first in vivo approach to clarify the involvement of AD-related APP misprocessing on stress-driven synaptic pathology underlying depressive pathology.

  4. Loss of Cdc42 leads to defects in synaptic plasticity and remote memory recall.

    Science.gov (United States)

    Kim, Il Hwan; Wang, Hong; Soderling, Scott H; Yasuda, Ryohei

    2014-07-08

    Cdc42 is a signaling protein important for reorganization of actin cytoskeleton and morphogenesis of cells. However, the functional role of Cdc42 in synaptic plasticity and in behaviors such as learning and memory are not well understood. Here we report that postnatal forebrain deletion of Cdc42 leads to deficits in synaptic plasticity and in remote memory recall using conditional knockout of Cdc42. We found that deletion of Cdc42 impaired LTP in the Schaffer collateral synapses and postsynaptic structural plasticity of dendritic spines in CA1 pyramidal neurons in the hippocampus. Additionally, loss of Cdc42 did not affect memory acquisition, but instead significantly impaired remote memory recall. Together these results indicate that the postnatal functions of Cdc42 may be crucial for the synaptic plasticity in hippocampal neurons, which contribute to the capacity for remote memory recall.

  5. Recent advances in understanding synaptic abnormalities in Rett syndrome [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Michael Johnston

    2015-12-01

    Full Text Available Rett syndrome is an extremely disabling X-linked nervous system disorder that mainly affects girls in early childhood and causes autism-like behavior, severe intellectual disability, seizures, sleep disturbances, autonomic instability, and other disorders due to mutations in the MeCP2 (methyl CpG-binding protein 2 transcription factor. The disorder targets synapses and synaptic plasticity and has been shown to disrupt the balance between glutamate excitatory synapses and GABAergic inhibitory synapses. In fact, it can be argued that Rett syndrome is primarily a disorder of synaptic plasticity and that agents that can correct this imbalance may have beneficial effects on brain development. This review briefly summarizes the link between disrupted synaptic plasticity mechanisms and Rett syndrome and early clinical trials that aim to target these abnormalities to improve the outcome for these severely disabled children.

  6. Synaptic molecular imaging in spared and deprived columns of mouse barrel cortex with array tomography.

    Science.gov (United States)

    Weiler, Nicholas C; Collman, Forrest; Vogelstein, Joshua T; Burns, Randal; Smith, Stephen J

    2014-01-01

    A major question in neuroscience is how diverse subsets of synaptic connections in neural circuits are affected by experience dependent plasticity to form the basis for behavioral learning and memory. Differences in protein expression patterns at individual synapses could constitute a key to understanding both synaptic diversity and the effects of plasticity at different synapse populations. Our approach to this question leverages the immunohistochemical multiplexing capability of array tomography (ATomo) and the columnar organization of mouse barrel cortex to create a dataset comprising high resolution volumetric images of spared and deprived cortical whisker barrels stained for over a dozen synaptic molecules each. These dataset has been made available through the Open Connectome Project for interactive online viewing, and may also be downloaded for offline analysis using web, Matlab, and other interfaces.

  7. Synaptic ribbon. Conveyor belt or safety belt?

    Science.gov (United States)

    Parsons, T D; Sterling, P

    2003-02-06

    The synaptic ribbon in neurons that release transmitter via graded potentials has been considered as a conveyor belt that actively moves vesicles toward their release sites. But evidence has accumulated to the contrary, and it now seems plausible that the ribbon serves instead as a safety belt to tether vesicles stably in mutual contact and thus facilitate multivesicular release by compound exocytosis.

  8. P2X Receptors and Synaptic Plasticity

    Czech Academy of Sciences Publication Activity Database

    Pankratov, Y.; Lalo, U.; Krishtal, A.; Verkhratsky, Alexei

    2009-01-01

    Roč. 158, č. 1 (2009), s. 137-148 ISSN 0306-4522 Institutional research plan: CEZ:AV0Z50390512 Keywords : ATP * P2X receptors * synaptic plasticity Subject RIV: FH - Neurology Impact factor: 3.292, year: 2009

  9. Synaptic plasticity and the warburg effect

    KAUST Repository

    Magistretti, Pierre J.

    2014-01-01

    Functional brain imaging studies show that in certain brain regions glucose utilization exceeds oxygen consumption, indicating the predominance of aerobic glycolysis. In this issue, Goyal et al. (2014) report that this metabolic profile is associated with an enrichment in the expression of genes involved in synaptic plasticity and remodeling processes. © 2014 Elsevier Inc.

  10. Synaptic remodeling, synaptic growth and the storage of long-term memory in Aplysia.

    Science.gov (United States)

    Bailey, Craig H; Kandel, Eric R

    2008-01-01

    Synaptic remodeling and synaptic growth accompany various forms of long-term memory. Storage of the long-term memory for sensitization of the gill-withdrawal reflex in Aplysia has been extensively studied in this respect and is associated with the growth of new synapses by the sensory neurons onto their postsynaptic target neurons. Recent time-lapse imaging studies of living sensory-to-motor neuron synapses in culture have monitored both functional and structural changes simultaneously so as to follow remodeling and growth at the same specific synaptic connections continuously over time and to examine the functional contribution of these learning-related structural changes to the different time-dependent phases of memory storage. Insights provided by these studies suggest the synaptic differentiation and growth induced by learning in the mature nervous system are highly dynamic and often rapid processes that can recruit both molecules and mechanisms used for de novo synapse formation during development.

  11. Deficits in synaptic function occur at medial perforant path-dentate granule cell synapses prior to Schaffer collateral-CA1 pyramidal cell synapses in the novel TgF344-Alzheimer's Disease Rat Model.

    Science.gov (United States)

    Smith, Lindsey A; McMahon, Lori L

    2018-02-01

    Alzheimer's disease (AD) pathology begins decades prior to onset of clinical symptoms, and the entorhinal cortex and hippocampus are among the first and most extensively impacted brain regions. The TgF344-AD rat model, which more fully recapitulates human AD pathology in an age-dependent manner, is a next generation preclinical rodent model for understanding pathophysiological processes underlying the earliest stages of AD (Cohen et al., 2013). Whether synaptic alterations occur in hippocampus prior to reported learning and memory deficit is not known. Furthermore, it is not known if specific hippocampal synapses are differentially affected by progressing AD pathology, or if synaptic deficits begin to appear at the same age in males and females in this preclinical model. Here, we investigated the time-course of synaptic changes in basal transmission, paired-pulse ratio, as an indirect measure of presynaptic release probability, long-term potentiation (LTP), and dendritic spine density at two hippocampal synapses in male and ovariectomized female TgF344-AD rats and wildtype littermates, prior to reported behavioral deficits. Decreased basal synaptic transmission begins at medial perforant path-dentate granule cell (MPP-DGC) synapses prior to Schaffer-collateral-CA1 (CA3-CA1) synapses, in the absence of a change in paired-pulse ratio (PPR) or dendritic spine density. N-methyl-d-aspartate receptor (NMDAR)-dependent LTP magnitude is unaffected at CA3-CA1 synapses at 6, 9, and 12months of age, but is significantly increased at MPP-DGC synapses in TgF344-AD rats at 6months only. Sex differences were only observed at CA3-CA1 synapses where the decrease in basal transmission occurs at a younger age in males versus females. These are the first studies to define presymptomatic alterations in hippocampal synaptic transmission in the TgF344-AD rat model. The time course of altered synaptic transmission mimics the spread of pathology through hippocampus in human AD and provides

  12. Overexpression of guanylate cyclase activating protein 2 in rod photoreceptors in vivo leads to morphological changes at the synaptic ribbon.

    Directory of Open Access Journals (Sweden)

    Natalia López-del Hoyo

    Full Text Available Guanylate cyclase activating proteins are EF-hand containing proteins that confer calcium sensitivity to retinal guanylate cyclase at the outer segment discs of photoreceptor cells. By making the rate of cGMP synthesis dependent on the free intracellular calcium levels set by illumination, GCAPs play a fundamental role in the recovery of the light response and light adaptation. The main isoforms GCAP1 and GCAP2 also localize to the synaptic terminal, where their function is not known. Based on the reported interaction of GCAP2 with Ribeye, the major component of synaptic ribbons, it was proposed that GCAP2 could mediate the synaptic ribbon dynamic changes that happen in response to light. We here present a thorough ultrastructural analysis of rod synaptic terminals in loss-of-function (GCAP1/GCAP2 double knockout and gain-of-function (transgenic overexpression mouse models of GCAP2. Rod synaptic ribbons in GCAPs-/- mice did not differ from wildtype ribbons when mice were raised in constant darkness, indicating that GCAPs are not required for ribbon early assembly or maturation. Transgenic overexpression of GCAP2 in rods led to a shortening of synaptic ribbons, and to a higher than normal percentage of club-shaped and spherical ribbon morphologies. Restoration of GCAP2 expression in the GCAPs-/- background (GCAP2 expression in the absence of endogenous GCAP1 had the striking result of shortening ribbon length to a much higher degree than overexpression of GCAP2 in the wildtype background, as well as reducing the thickness of the outer plexiform layer without affecting the number of rod photoreceptor cells. These results indicate that preservation of the GCAP1 to GCAP2 relative levels is relevant for maintaining the integrity of the synaptic terminal. Our demonstration of GCAP2 immunolocalization at synaptic ribbons at the ultrastructural level would support a role of GCAPs at mediating the effect of light on morphological remodeling changes of

  13. BACE1 Is Necessary for Experience-Dependent Homeostatic Synaptic Plasticity in Visual Cortex

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    Emily Petrus

    2014-01-01

    Full Text Available Alzheimer’s disease (AD is the most common form of age-related dementia, which is thought to result from overproduction and/or reduced clearance of amyloid-beta (Aβ peptides. Studies over the past few decades suggest that Aβ is produced in an activity-dependent manner and has physiological relevance to normal brain functions. Similarly, physiological functions for β- and γ-secretases, the two key enzymes that produce Aβ by sequentially processing the amyloid precursor protein (APP, have been discovered over recent years. In particular, activity-dependent production of Aβ has been suggested to play a role in homeostatic regulation of excitatory synaptic function. There is accumulating evidence that activity-dependent immediate early gene Arc is an activity “sensor,” which acts upstream of Aβ production and triggers AMPA receptor endocytosis to homeostatically downregulate the strength of excitatory synaptic transmission. We previously reported that Arc is critical for sensory experience-dependent homeostatic reduction of excitatory synaptic transmission in the superficial layers of visual cortex. Here we demonstrate that mice lacking the major neuronal β-secretase, BACE1, exhibit a similar phenotype: stronger basal excitatory synaptic transmission and failure to adapt to changes in visual experience. Our results indicate that BACE1 plays an essential role in sensory experience-dependent homeostatic synaptic plasticity in the neocortex.

  14. Analysis of synaptic growth and function in Drosophila with an extended larval stage.

    Science.gov (United States)

    Miller, Daniel L; Ballard, Shannon L; Ganetzky, Barry

    2012-10-03

    The Drosophila larval neuromuscular junction (NMJ) is a powerful system for the genetic and molecular analysis of neuronal excitability, synaptic transmission, and synaptic development. However, its use for studying age-dependent processes, such as maintenance of neuronal viability and synaptic stability, are temporally limited by the onset of pupariation and metamorphosis. Here we characterize larval NMJ growth, growth regulation, structure, and function in a developmental variant with an extended third instar (ETI). RNAi-knockdown of the prothoracicotropic hormone receptor, torso, in the ring gland of developing larvae leaves the timing of first and second instar molts largely unchanged, but triples duration of the third instar from 3 to 9.5 d (McBrayer et al., 2007; Rewitz et al., 2009). During this ETI period, NMJs undergo additional growth (adding >50 boutons/NMJ), and this growth remains under the control of the canonical regulators Highwire and the TGFβ/BMP pathway. NMJ growth during the ETI period occurs via addition of new branches, satellite boutons, and interstitial boutons, and continues even after muscle growth levels off. Throughout the ETI, organization of synapses and active zones remains normal, and synaptic transmission is unchanged. These results establish the ETI larval system as a viable model for studying motor neuron diseases and for investigating time-dependent effects of perturbations that impair mechanisms of neuroprotection, synaptic maintenance, and response to neural injury.

  15. How Children Aged 0 to 6 Benefits from Health Services, Permanent Service Resources and the Factors Affecting Them

    Directory of Open Access Journals (Sweden)

    Saliha Altiparmak

    2012-10-01

    Full Text Available Abstract Aim: Aim of the research is “How children aged 0 to 6 benefit from health services, permanent service resources and the factors affecting them”. Material and Methods: The 3839 children aged 0-72 months and followed by the 3rd Family Health Center in Manisa comprise the population of this descriptive study. The sample size was determined as 192 based on the Epi info Statcalc statistical program with a prevalence of 8.3%, a sampling error of 12:05, and a confidence limit of 99%. In the study, the following two forms were used: socio-demographic questionnaire, evaluation form for the use of health services. The data were evaluated with the 15.00 SPSS package program. To assess the data points, chi-square test and descriptive statistics such as percentage were used. Results: The distribution of age groups of the children participating in the study is 37.4 ± 22.3 months (min: 0 months, max: 72 months. Of the children in the study, 52.1% were male. Of the 0-6 age group children in the study, 28.6% had a health problem and 20.8% presented to a medical facility. The institutions preferred most were state institutions. All of the children received at least one preventive health service. Of the children, 78.1% had permanent health care and 57.3% of them received health care from family health centers. There was a statistically significant difference between children with and without a congenital disease, and between children with and without social security. Conclusion: One of the results obtained from this study suggests that children with a congenital disease are expected to apply to health facilities more often. Another result is that having health insurance is an important factor which increases the use of health services. [TAF Prev Med Bull 2012; 11(5.000: 599-608

  16. Physical exercise in aging human skeletal muscle increases mitochondrial calcium uniporter expression levels and affects mitochondria dynamics.

    Science.gov (United States)

    Zampieri, Sandra; Mammucari, Cristina; Romanello, Vanina; Barberi, Laura; Pietrangelo, Laura; Fusella, Aurora; Mosole, Simone; Gherardi, Gaia; Höfer, Christian; Löfler, Stefan; Sarabon, Nejc; Cvecka, Jan; Krenn, Matthias; Carraro, Ugo; Kern, Helmut; Protasi, Feliciano; Musarò, Antonio; Sandri, Marco; Rizzuto, Rosario

    2016-12-01

    Age-related sarcopenia is characterized by a progressive loss of muscle mass with decline in specific force, having dramatic consequences on mobility and quality of life in seniors. The etiology of sarcopenia is multifactorial and underlying mechanisms are currently not fully elucidated. Physical exercise is known to have beneficial effects on muscle trophism and force production. Alterations of mitochondrial Ca 2+ homeostasis regulated by mitochondrial calcium uniporter (MCU) have been recently shown to affect muscle trophism in vivo in mice. To understand the relevance of MCU-dependent mitochondrial Ca 2+ uptake in aging and to investigate the effect of physical exercise on MCU expression and mitochondria dynamics, we analyzed skeletal muscle biopsies from 70-year-old subjects 9 weeks trained with either neuromuscular electrical stimulation (ES) or leg press. Here, we demonstrate that improved muscle function and structure induced by both trainings are linked to increased protein levels of MCU Ultrastructural analyses by electron microscopy showed remodeling of mitochondrial apparatus in ES-trained muscles that is consistent with an adaptation to physical exercise, a response likely mediated by an increased expression of mitochondrial fusion protein OPA1. Altogether these results indicate that the ES-dependent physiological effects on skeletal muscle size and force are associated with changes in mitochondrial-related proteins involved in Ca 2+ homeostasis and mitochondrial shape. These original findings in aging human skeletal muscle confirm the data obtained in mice and propose MCU and mitochondria-related proteins as potential pharmacological targets to counteract age-related muscle loss. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  17. How does aging affect the types of error made in a visual short-term memory 'object-recall' task?

    Science.gov (United States)

    Sapkota, Raju P; van der Linde, Ian; Pardhan, Shahina

    2014-01-01

    This study examines how normal aging affects the occurrence of different types of incorrect responses in a visual short-term memory (VSTM) object-recall task. Seventeen young (Mean = 23.3 years, SD = 3.76), and 17 normally aging older (Mean = 66.5 years, SD = 6.30) adults participated. Memory stimuli comprised two or four real world objects (the memory load) presented sequentially, each for 650 ms, at random locations on a computer screen. After a 1000 ms retention interval, a test display was presented, comprising an empty box at one of the previously presented two or four memory stimulus locations. Participants were asked to report the name of the object presented at the cued location. Errors rates wherein participants reported the names of objects that had been presented in the memory display but not at the cued location (non-target errors) vs. objects that had not been presented at all in the memory display (non-memory errors) were compared. Significant effects of aging, memory load and target recency on error type and absolute error rates were found. Non-target error rate was higher than non-memory error rate in both age groups, indicating that VSTM may have been more often than not populated with partial traces of previously presented items. At high memory load, non-memory error rate was higher in young participants (compared to older participants) when the memory target had been presented at the earliest temporal position. However, non-target error rates exhibited a reversed trend, i.e., greater error rates were found in older participants when the memory target had been presented at the two most recent temporal positions. Data are interpreted in terms of proactive interference (earlier examined non-target items interfering with more recent items), false memories (non-memory items which have a categorical relationship to presented items, interfering with memory targets), slot and flexible resource models, and spatial coding deficits.

  18. Sleep Homeostasis and Synaptic Plasticity

    Science.gov (United States)

    2017-06-01

    Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202...circuit (a homeostat) that operates in concert with the circadian circuitry or does sleep drive accumulate everywhere in the brain? To answer these...neurons is capable of generating sleep drive. RNAi-mediated knockdown of insomniac in R2 neurons abolished sleep homeostasis without affecting baseline

  19. Effect of Neuroinflammation on Synaptic Organization and Function in the Developing Brain: Implications for Neurodevelopmental and Neurodegenerative Disorders

    Directory of Open Access Journals (Sweden)

    Amin Mottahedin

    2017-07-01

    Full Text Available The brain is a plastic organ where both the intrinsic CNS milieu and extrinsic cues play important roles in shaping and wiring neural connections. The perinatal period constitutes a critical time in central nervous system development with extensive refinement of neural connections, which are highly sensitive to fetal and neonatal compromise, such as inflammatory challenges. Emerging evidence suggests that inflammatory cells in the brain such as microglia and astrocytes are pivotal in regulating synaptic structure and function. In this article, we will review the role of glia cells in synaptic physiology and pathophysiology, including microglia-mediated elimination of synapses. We propose that activation of the immune system dynamically affects synaptic organization and function in the developing brain. We will discuss the role of neuroinflammation in altered synaptic plasticity following perinatal inflammatory challenges and potential implications for neurodevelopmental and neurodegenerative disorders.

  20. Curcuma longa L. extract improves the cortical neural connectivity during the aging process.

    Science.gov (United States)

    Flores, Gonzalo

    2017-06-01

    Turmeric or Curcuma is a natural product that has anti-inflammatory, antioxidant and anti-apoptotic pharmacological properties. It can be used in the control of the aging process that involves oxidative stress, inflammation, and apoptosis. Aging is a physiological process that affects higher cortical and cognitive functions with a reduction in learning and memory, limited judgment and deficits in emotional control and social behavior. Moreover, aging is a major risk factor for the appearance of several disorders such as cerebrovascular disease, diabetes mellitus, and hypertension. At the brain level, the aging process alters the synaptic intercommunication by a reduction in the dendritic arbor as well as the number of the dendritic spine in the pyramidal neurons of the prefrontal cortex, hippocampus and basolateral amygdala, consequently reducing the size of these regions. The present review discusses the synaptic changes caused by the aging process and the neuroprotective role the Curcuma has through its anti-inflammatory, antioxidant and anti-apoptotic actions.

  1. Altered synaptic plasticity in Tourette's syndrome and its relationship to motor skill learning.

    Directory of Open Access Journals (Sweden)

    Valerie Cathérine Brandt

    Full Text Available Gilles de la Tourette syndrome is a neuropsychiatric disorder characterized by motor and phonic tics that can be considered motor responses to preceding inner urges. It has been shown that Tourette patients have inferior performance in some motor learning tasks and reduced synaptic plasticity induced by transcranial magnetic stimulation. However, it has not been investigated whether altered synaptic plasticity is directly linked to impaired motor skill acquisition in Tourette patients. In this study, cortical plasticity was assessed by measuring motor-evoked potentials before and after paired associative stimulation in 14 Tourette patients (13 male; age 18-39 and 15 healthy controls (12 male; age 18-33. Tic and urge severity were assessed using the Yale Global Tic Severity Scale and the Premonitory Urges for Tics Scale. Motor learning was assessed 45 minutes after inducing synaptic plasticity and 9 months later, using the rotary pursuit task. On average, long-term potentiation-like effects in response to the paired associative stimulation were present in healthy controls but not in patients. In Tourette patients, long-term potentiation-like effects were associated with more and long-term depression-like effects with less severe urges and tics. While motor learning did not differ between patients and healthy controls 45 minutes after inducing synaptic plasticity, the learning curve of the healthy controls started at a significantly higher level than the Tourette patients' 9 months later. Induced synaptic plasticity correlated positively with motor skills in healthy controls 9 months later. The present study confirms previously found long-term improvement in motor performance after paired associative stimulation in healthy controls but not in Tourette patients. Tourette patients did not show long-term potentiation in response to PAS and also showed reduced levels of motor skill consolidation after 9 months compared to healthy controls. Moreover

  2. Mammalian Vestibular Macular Synaptic Plasticity: Results from SLS-2 Spaceflight

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    Ross, Muriel D.D.

    1994-01-01

    The effects of exposure to microgravity were studied in rat utricular maculas collected inflight (IF, day 13), post-flight on day of orbiter landing (day 14, R+O) and after 14 days (R+ML). Controls were collected at corresponding times. The objectives were 1) to learn whether hair cell ribbon synapses counts would be higher in tissues collected in space than in tissues collected postflight during or after readaptation to Earth's gravity; and 2) to compare results with those of SLS-1. Maculas were fixed by immersion, micro-dissected, dehydrated and prepared for ultrastructural study by usual methods. Synapses were counted in 100 serial sections 150 nm thick and were located to specific hair cells in montages of every 7th section. Counts were analyzed for statistical significance using analysis of variance. Results in maculas of IF dissected rats, one 13 day control (IFC), and one R + 0 rat have been analyzed. Study of an R+ML macula is nearly completed. For type I cells, IF mean is 2.3 +/-1.6; IFC mean is 1.6 +/-1.0; R+O mean is 2.3 +/- 1.6. For type II cells, IF mean is 11.4 +/- 17.1; IFC mean is 5.5 +/-3.5; R+O mean is 10.1 +/- 7.4. The difference between IF and IFC means for type I cells is statistically significant (p less than 0.0464). For type It cells, IF compared to IFC means, p less than 0.0003; and for IFC to R+O means, p less than 0.0139. Shifts toward spheres (p less than 0.0001) and pairs (p less than 0.0139) were significant in type II cells of IF rats. The results are largely replicating findings from SLS-1 and indicate that spaceflight affects synaptic number, form and distribution, particularly in type II hair cells. The increases in synaptic number and in sphere-like ribbons are interpreted to improve synaptic efficacy, to help return afferent discharges to a more normal state. Findings indicate that a great capacity for synaptic plasticity exists in mammalian gravity sensors, and that this plasticity is more dominant in the local circuitry. The

  3. Is static friction affected by aging and amount of elastomeric ligatures in orthodontic sliding mechanics? An in-vitro investigation.

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    Lo Giudice, A; Portelli, M; Militi, A; Spinuzza, P; Bellocchio, A M; Nucera, R; Marcolina, M; Ghilardi, G; Manuelli, M; Lucchese, A

    2018-03-15

    In straight-wire mechanics, friction can significantly influence the forces expressed by wires. The aim of this study is to assess whether the aging and the sum of elastomeric ligatures affect the static friction during orthodontic space closure. A 0.017x 0.025-in SS was drawn throughout a 3-bracket experimental model and engaged with elastomeric ligatures. Before performing the test, the ligatures were soaked in artificial saliva for 48 hours (Group 1), 2 weeks (Group 2) and 4 weeks (Group 3); brand-new ligatures were also tested as control group (Group 4). The resistance to sliding (RS) was recorded at 3 different numerical configurations of ligatures using a customized testing machine and tests were repeated for ten times. Data of RS were statistically analysed by using two way analysis of variance (ANOVA) and Tukey’s multiple comparison tests. RS was found to increase systematically when more elastomeric ligatures were included in the wire engaging system. At two weeks of immersion in artificial saliva elastomeric ligatures showed the lowest values of RS while they became significantly more frictional after immersion for 4 weeks. The results of this study showed that in multi-bracket orthodontic therapy, the RS increases with the number of elastomeric ligatures involved for arch-wire engagement. Differently from the frictional behavior of elastomeric modules, the aging of these ligatures does not influence their incremental effect of frictional forces.

  4. Factors affecting exclusive breastfeeding of healthy babies aged zero to four months: a community-based study of Turkish women.

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    Karaçam, Zekiye

    2008-02-01

    The purpose of this study was to determine the factors that affect exclusive breastfeeding of healthy babies aged 0-4 months. Both the World Health Organization (WHO) and UNICEF recommend feeding babies of 0-6 months exclusively with breast milk and starting complementary foods after the sixth month. In Turkey, however, a vast majority of babies 1-5 months of age (89.4%) are given complementary foods. This cross-sectional study was conducted in central Ankara province, with a sampling of 514 individuals who were selected using the convenience sampling method. Of the 514 mothers who participated in my research, 260 (50.6%) were found to be feeding their babies exclusively with breast milk; 77 (15.0%), with breast milk + water; 87 (16.9%), with breast milk + baby formula; 70 (13.6%), with breast milk + baby formula + other foods; and 20 (3.9%), baby formula + other foods. Based on multivariate logistic regression analysis results, the mother's employment [odds ratio (OR) = 0.488; 95% confidence interval (CI) = 0.288-0.827) considerably reduced the incidence of complementary foods, while frequent crying of the baby (OR = 1.687; 95% CI = 1.125-2.530) significantly increased the use of supplementary foods in infant nutrition. This study concluded that frequent crying of the baby increases the likelihood of giving the baby complementary foods. Midwives and nurses can encourage exclusive breastfeeding behaviour by providing individual education and counselling to women whose babies cry frequently. Exclusive breastfeeding of babies aged 0-6 months is crucial for the development and growth of the baby and instrumental in reducing infant morbidities and mortalities. One factor that increases the likelihood of provision of complementary foods is frequent crying of the baby. Midwives and nurses can encourage exclusive breastfeeding behaviour by providing individual education and counselling to women whose babies cry frequently.

  5. F42. CHONDROTIN-6 SULFATE CLUSTERS: ASSOCIATION OF SYNAPTIC DOMAINS AND REGULATION OF SYNAPTIC PLASTICITY DURING FEAR LEARNING

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    Chelini, Gabriele; Berciu, Cristina; Pilobello, Kanoelani; Peter, Durning; Rachel, Jenkins; Kahn, Moazzzam; Ramikie, Teniel; Subramanian, Siva; Ressler, Kerry; Pantazopoulos, Charalampos; Berretta, Sabina

    2018-01-01

    Abstract Background Emerging evidence from our group and others has brought the brain extracellular matrix (ECM) to the forefront of investigations on brain disorders. Our group has shown that organized perisynaptic ECM aggregates, i.e. perineuronal nets (PNNs) are decreased in several brain regions in people with schizophrenia (SZ) and bipolar disorder (BD). PNNs were detected by their expression of specific chondroitin sulfate proteoglycans (CSPGs), main components of the ECM, thought to play a key role in synaptic regulation during development and adulthood. Our studies have also shown that glial cells expressing CSPGs are altered in these disorders, suggesting a link between glial cell and PNN abnormalities. Finally, we have recently shown that novel CSPG structures, bearing a distinct CS-6 sulfation pattern and named CS-6 glial clusters, are decreased in the amygdala of people with SZ and BD. The morphology and function of CS-6 glial clusters is not currently known, but evidence from rodents and on the role of CSPGs in regulating synaptic functions strongly suggest that they may affect synaptic plasticity. We tested this hypothesis using a combination of human postmortem and rodent brain studies. Methods High Resolution electron microscopy was used to investigate the ultrastructural organization of CS-6 glia clusters. A transgenic mouse model expressing green fluorescent protein in a subset of excitatory pyramidal neurons was used to investigate dendritic spines association with CS-6 glia clusters. Mice were exposed to a single session of auditory fear conditioning for a total of 15 minutes. Animals were euthanized 4 hours after behavioral test. Multiplex immunocytochemistry was used to visualize CS-6 clusters. Results In human tissue, we show that CS-6 glia clusters are widespread in several brain regions, including the amygdala, entorhinal cortex, thalamus and hippocampus. Ultrastructural results show that CS-6 glia clusters are formed by CS-6 accumulations

  6. Identification of a mouse synaptic glycoprotein gene in cultured neurons.

    Science.gov (United States)

    Yu, Albert Cheung-Hoi; Sun, Chun Xiao; Li, Qiang; Liu, Hua Dong; Wang, Chen Ran; Zhao, Guo Ping; Jin, Meilei; Lau, Lok Ting; Fung, Yin-Wan Wendy; Liu, Shuang

    2005-10-01

    Neuronal differentiation and aging are known to involve many genes, which may also be differentially expressed during these developmental processes. From primary cultured cerebral cortical neurons, we have previously identified various differentially expressed gene transcripts from cultured cortical neurons using the technique of arbitrarily primed PCR (RAP-PCR). Among these transcripts, clone 0-2 was found to have high homology to rat and human synaptic glycoprotein. By in silico analysis using an EST database and the FACTURA software, the full-length sequence of 0-2 was assembled and the clone was named as mouse synaptic glycoprotein homolog 2 (mSC2). DNA sequencing revealed transcript size of mSC2 being smaller than the human and rat homologs. RT-PCR indicated that mSC2 was expressed differentially at various culture days. The mSC2 gene was located in various tissues with higher expression in brain, lung, and liver. Functions of mSC2 in neurons and other tissues remain elusive and will require more investigation.

  7. Age

    Science.gov (United States)

    ... adults? How can you reduce anesthesia risks in older patients? Age Age may bring wisdom but it also brings ... Ask your physician to conduct a pre-surgery cognitive test — an assessment of your mental function. The physician can use the results as a ...

  8. Age-related P-glycoprotein expression in the intestine and affecting the pharmacokinetics of orally administered enrofloxacin in broilers.

    Science.gov (United States)

    Guo, Mengjie; Bughio, Shamsuddin; Sun, Yong; Zhang, Yu; Dong, Lingling; Dai, Xiaohua; Wang, Liping

    2013-01-01

    Bioavailability is the most important factor for the efficacy of any drug and it is determined by P- glycoprotein (P-gp) expression. Confirmation of P-gp expression during ontogeny is needed for understanding the differences in therapeutic efficacy of any drug in juvenile and adult animals. In this study, Abcb1 mRNA levels in the liver and intestine of broilers during ontogeny were analysed by RT qPCR. Cellular distribution of P-gp was detected by immunohistochemstry. Age-related differences of enrofloxacin pharmacokinetics were also studied. It was found that broilers aged 4 week-old expressed significantly (P0.05) age-related difference in the duodenum. Furthermore, the highest and lowest levels of Abcb1 mRNA expression were observed in the jejunum, and duodenum, respectively. P-gp immunoreactivity was detected on the apical surface of the enterocytes and in the bile canalicular membranes of the hepatocytes. Pharmacokinetic analysis revealed that the 8 week-old broilers, when orally administrated enrofloxacin, exhibited significantly higher Cmax (1.97 vs. 0.98 μg • ml(-1), P=0.009), AUC(14.54 vs. 9.35 μg • ml(-1) • h, P=0.005) and Ka (1.38 vs. 0.43 h(-1), P=0.032), as well as lower Tpeak (1.78 vs. 3.28 h, P=0.048) and T1/2 ka (0.6 vs. 1.64 h, P=0.012) than the 4 week-old broilers. The bioavailability of enrofloxacin in 8 week-old broilers was increased by 15.9%, compared with that in 4 week-old birds. Interestingly, combining verapamil, a P-gp modulator, significantly improved pharmacokinetic behaviour of enrofloxacin in all birds. The results indicate juvenile broilers had a higher expression of P-gp in the intestine, affecting the pharmacokinetics and reducing the bioavailability of oral enrofloxacin in broilers. On the basis of our results, it is recommended that alternative dose regimes are necessary for different ages of broilers for effective therapy.

  9. Ultrafast Synaptic Events in a Chalcogenide Memristor

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    Li, Yi; Zhong, Yingpeng; Xu, Lei; Zhang, Jinjian; Xu, Xiaohua; Sun, Huajun; Miao, Xiangshui

    2013-04-01

    Compact and power-efficient plastic electronic synapses are of fundamental importance to overcoming the bottlenecks of developing a neuromorphic chip. Memristor is a strong contender among the various electronic synapses in existence today. However, the speeds of synaptic events are relatively slow in most attempts at emulating synapses due to the material-related mechanism. Here we revealed the intrinsic memristance of stoichiometric crystalline Ge2Sb2Te5 that originates from the charge trapping and releasing by the defects. The device resistance states, representing synaptic weights, were precisely modulated by 30 ns potentiating/depressing electrical pulses. We demonstrated four spike-timing-dependent plasticity (STDP) forms by applying programmed pre- and postsynaptic spiking pulse pairs in different time windows ranging from 50 ms down to 500 ns, the latter of which is 105 times faster than the speed of STDP in human brain. This study provides new opportunities for building ultrafast neuromorphic computing systems and surpassing Von Neumann architecture.

  10. Fragile X mental retardation protein regulates trans-synaptic signaling in Drosophila

    Directory of Open Access Journals (Sweden)

    Samuel H. Friedman

    2013-11-01

    Fragile X syndrome (FXS, the most common inherited determinant of intellectual disability and autism spectrum disorders, is caused by loss of the fragile X mental retardation 1 (FMR1 gene product (FMRP, an mRNA-binding translational repressor. A number of conserved FMRP targets have been identified in the well-characterized Drosophila FXS disease model, but FMRP is highly pleiotropic in function and the full spectrum of FMRP targets has yet to be revealed. In this study, screens for upregulated neural proteins in Drosophila fmr1 (dfmr1 null mutants reveal strong elevation of two synaptic heparan sulfate proteoglycans (HSPGs: GPI-anchored glypican Dally-like protein (Dlp and transmembrane Syndecan (Sdc. Our recent work has shown that Dlp and Sdc act as co-receptors regulating extracellular ligands upstream of intracellular signal transduction in multiple trans-synaptic pathways that drive synaptogenesis. Consistently, dfmr1 null synapses exhibit altered WNT signaling, with changes in both Wingless (Wg ligand abundance and downstream Frizzled-2 (Fz2 receptor C-terminal nuclear import. Similarly, a parallel anterograde signaling ligand, Jelly belly (Jeb, and downstream ERK phosphorylation (dpERK are depressed at dfmr1 null synapses. In contrast, the retrograde BMP ligand Glass bottom boat (Gbb and downstream signaling via phosphorylation of the transcription factor MAD (pMAD seem not to be affected. To determine whether HSPG upregulation is causative for synaptogenic defects, HSPGs were genetically reduced to control levels in the dfmr1 null background. HSPG correction restored both (1 Wg and Jeb trans-synaptic signaling, and (2 synaptic architecture and transmission strength back to wild-type levels. Taken together, these data suggest that FMRP negatively regulates HSPG co-receptors controlling trans-synaptic signaling during synaptogenesis, and that loss of this regulation causes synaptic structure and function defects characterizing the FXS disease state.

  11. Presynaptic inhibition of GABAergic synaptic transmission by adenosine in mouse hypothalamic hypocretin neurons.

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    Xia, J X; Xiong, J X; Wang, H K; Duan, S M; Ye, J N; Hu, Z A

    2012-01-10

    Hypocretin neurons in the lateral hypothalamus, a new wakefulness-promoting center, have been recently regarded as an important target involved in endogenous adenosine-regulating sleep homeostasis. The GABAergic synaptic transmissions are the main inhibitory afferents to hypocretin neurons, which play an important role in the regulation of excitability of these neurons. The inhibitory effect of adenosine, a homeostatic sleep-promoting factor, on the excitatory glutamatergic synaptic transmissions in hypocretin neurons has been well documented, whether adenosine also modulates these inhibitory GABAergic synaptic transmissions in these neurons has not been investigated. In this study, the effect of adenosine on inhibitory postsynaptic currents (IPSCs) in hypocretin neurons was examined by using perforated patch-clamp recordings in the acute hypothalamic slices. The findings demonstrated that adenosine suppressed the amplitude of evoked IPSCs in a dose-dependent manner, which was completely abolished by 8-cyclopentyltheophylline (CPT), a selective antagonist of adenosine A1 receptor but not adenosine A2 receptor antagonist 3,7-dimethyl-1-(2-propynyl) xanthine. A presynaptic origin was suggested as following: adenosine increased paired-pulse ratio as well as reduced GABAergic miniature IPSC frequency without affecting the miniature IPSC amplitude. Further findings demonstrated that when the frequency of electrical stimulation was raised to 10 Hz, but not 1 Hz, a time-dependent depression of evoked IPSC amplitude was detected in hypocretin neurons, which could be partially blocked by CPT. However, under a higher frequency at 100 Hz stimulation, CPT had no action on the depressed GABAergic synaptic transmission induced by such tetanic stimulation in these hypocretin neurons. These results suggest that endogenous adenosine generated under certain stronger activities of synaptic transmissions exerts an inhibitory effect on GABAergic synaptic transmission in hypocretin

  12. Synaptic neurotransmission depression in ventral tegmental dopamine neurons and cannabinoid-associated addictive learning.

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    Liu, Zhiqiang; Han, Jing; Jia, Lintao; Maillet, Jean-Christian; Bai, Guang; Xu, Lin; Jia, Zhengping; Zheng, Qiaohua; Zhang, Wandong; Monette, Robert; Merali, Zul; Zhu, Zhou; Wang, Wei; Ren, Wei; Zhang, Xia

    2010-12-20

    Drug addiction is an association of compulsive drug use with long-term associative learning/memory. Multiple forms of learning/memory are primarily subserved by activity- or experience-dependent synaptic long-term potentiation (LTP) and long-term depression (LTD). Recent studies suggest LTP expression in locally activated glutamate synapses onto dopamine neurons (local Glu-DA synapses) of the midbrain ventral tegmental area (VTA) following a single or chronic exposure to many drugs of abuse, whereas a single exposure to cannabinoid did not significantly affect synaptic plasticity at these synapses. It is unknown whether chronic exposure of cannabis (marijuana or cannabinoids), the most commonly used illicit drug worldwide, induce LTP or LTD at these synapses. More importantly, whether such alterations in VTA synaptic plasticity causatively contribute to drug addictive behavior has not previously been addressed. Here we show in rats that chronic cannabinoid exposure activates VTA cannabinoid CB1 receptors to induce transient neurotransmission depression at VTA local Glu-DA synapses through activation of NMDA receptors and subsequent endocytosis of AMPA receptor GluR2 subunits. A GluR2-derived peptide blocks cannabinoid-induced VTA synaptic depression and conditioned place preference, i.e., learning to associate drug exposure with environmental cues. These data not only provide the first evidence, to our knowledge, that NMDA receptor-dependent synaptic depression at VTA dopamine circuitry requires GluR2 endocytosis, but also suggest an essential contribution of such synaptic depression to cannabinoid-associated addictive learning, in addition to pointing to novel pharmacological strategies for the treatment of cannabis addiction.

  13. Synaptic neurotransmission depression in ventral tegmental dopamine neurons and cannabinoid-associated addictive learning.

    Directory of Open Access Journals (Sweden)

    Zhiqiang Liu

    2010-12-01

    Full Text Available Drug addiction is an association of compulsive drug use with long-term associative learning/memory. Multiple forms of learning/memory are primarily subserved by activity- or experience-dependent synaptic long-term potentiation (LTP and long-term depression (LTD. Recent studies suggest LTP expression in locally activated glutamate synapses onto dopamine neurons (local Glu-DA synapses of the midbrain ventral tegmental area (VTA following a single or chronic exposure to many drugs of abuse, whereas a single exposure to cannabinoid did not significantly affect synaptic plasticity at these synapses. It is unknown whether chronic exposure of cannabis (marijuana or cannabinoids, the most commonly used illicit drug worldwide, induce LTP or LTD at these synapses. More importantly, whether such alterations in VTA synaptic plasticity causatively contribute to drug addictive behavior has not previously been addressed. Here we show in rats that chronic cannabinoid exposure activates VTA cannabinoid CB1 receptors to induce transient neurotransmission depression at VTA local Glu-DA synapses through activation of NMDA receptors and subsequent endocytosis of AMPA receptor GluR2 subunits. A GluR2-derived peptide blocks cannabinoid-induced VTA synaptic depression and conditioned place preference, i.e., learning to associate drug exposure with environmental cues. These data not only provide the first evidence, to our knowledge, that NMDA receptor-dependent synaptic depression at VTA dopamine circuitry requires GluR2 endocytosis, but also suggest an essential contribution of such synaptic depression to cannabinoid-associated addictive learning, in addition to pointing to novel pharmacological strategies for the treatment of cannabis addiction.

  14. Synaptic Neurotransmission Depression in Ventral Tegmental Dopamine Neurons and Cannabinoid-Associated Addictive Learning

    Science.gov (United States)

    Liu, Zhiqiang; Han, Jing; Jia, Lintao; Maillet, Jean-Christian; Bai, Guang; Xu, Lin; Jia, Zhengping; Zheng, Qiaohua; Zhang, Wandong; Monette, Robert; Merali, Zul; Zhu, Zhou; Wang, Wei; Ren, Wei; Zhang, Xia

    2010-01-01

    Drug addiction is an association of compulsive drug use with long-term associative learning/memory. Multiple forms of learning/memory are primarily subserved by activity- or experience-dependent synaptic long-term potentiation (LTP) and long-term depression (LTD). Recent studies suggest LTP expression in locally activated glutamate synapses onto dopamine neurons (local Glu-DA synapses) of the midbrain ventral tegmental area (VTA) following a single or chronic exposure to many drugs of abuse, whereas a single exposure to cannabinoid did not significantly affect synaptic plasticity at these synapses. It is unknown whether chronic exposure of cannabis (marijuana or cannabinoids), the most commonly used illicit drug worldwide, induce LTP or LTD at these synapses. More importantly, whether such alterations in VTA synaptic plasticity causatively contribute to drug addictive behavior has not previously been addressed. Here we show in rats that chronic cannabinoid exposure activates VTA cannabinoid CB1 receptors to induce transient neurotransmission depression at VTA local Glu-DA synapses through activation of NMDA receptors and subsequent endocytosis of AMPA receptor GluR2 subunits. A GluR2-derived peptide blocks cannabinoid-induced VTA synaptic depression and conditioned place preference, i.e., learning to associate drug exposure with environmental cues. These data not only provide the first evidence, to our knowledge, that NMDA receptor-dependent synaptic depression at VTA dopamine circuitry requires GluR2 endocytosis, but also suggest an essential contribution of such synaptic depression to cannabinoid-associated addictive learning, in addition to pointing to novel pharmacological strategies for the treatment of cannabis addiction. PMID:21187978

  15. KV7 Channels Regulate Firing during Synaptic Integration in GABAergic Striatal Neurons

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    M. Belén Pérez-Ramírez

    2015-01-01

    Full Text Available Striatal projection neurons (SPNs process motor and cognitive information. Their activity is affected by Parkinson’s disease, in which dopamine concentration is decreased and acetylcholine concentration is increased. Acetylcholine activates muscarinic receptors in SPNs. Its main source is the cholinergic interneuron that responds with a briefer latency than SPNs during a cortical command. Therefore, an important question is whether muscarinic G-protein coupled receptors and their signaling cascades are fast enough to intervene during synaptic responses to regulate synaptic integration and firing. One of the most known voltage dependent channels regulated by muscarinic receptors is the KV7/KCNQ channel. It is not known whether these channels regulate the integration of suprathreshold corticostriatal responses. Here, we study the impact of cholinergic muscarinic modulation on the synaptic response of SPNs by regulating KV7 channels. We found that KV7 channels regulate corticostriatal synaptic integration and that this modulation occurs in the dendritic/spines compartment. In contrast, it is negligible in the somatic compartment. This modulation occurs on sub- and suprathreshold responses and lasts during the whole duration of the responses, hundreds of milliseconds, greatly altering SPNs firing properties. This modulation affected the behavior of the striatal microcircuit.

  16. X-linked retinoschisis: RS1 mutation severity and age affect the ERG phenotype in a cohort of 68 affected male subjects.

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    Bowles, Kristen; Cukras, Catherine; Turriff, Amy; Sergeev, Yuri; Vitale, Susan; Bush, Ronald A; Sieving, Paul A

    2011-11-29

    To assess the effect of age and RS1 mutation on the phenotype of X-linked retinoschisis (XLRS) subjects using the clinical electroretinogram (ERG) in a cross-sectional analysis. Sixty-eight XLRS males 4.5 to 55 years of age underwent genotyping, and the retinoschisis (RS1) mutations were classified as less severe (27 subjects) or more severe (41 subjects) based on the putative impact on the protein. ERG parameters of retinal function were analyzed by putative mutation severity with age as a continuous variable. The a-wave amplitude remained greater than the lower limit of normal (mean, -2 SD) for 72% of XLRS males and correlated with neither age nor mutation class. However, b-wave and b/a-ratio amplitudes were significantly lower in the more severe than in the less severe mutation groups and in older than in younger subjects. Subjects up to 10 years of age with more severe RS1 mutations had significantly greater b-wave amplitudes and faster a-wave trough implicit times than older subjects in this group. RS1 mutation putative severity and age both had significant effects on retinal function in XLRS only in the severe mutation group, as judged by ERG analysis of the b-wave amplitude and the b/a-ratio, whereas the a-wave amplitude remained normal in most. A new observation was that increasing age (limited to those aged 55 and younger) caused a significant delay in XLRS b-wave onset (i.e., a-wave implicit time), even for those who retained considerable b-wave amplitudes. The delayed b-wave onset suggested that dysfunction of the photoreceptor synapse or of bipolar cells increases with age of XLRS subjects.

  17. Lycopene from two food sources does not affect antioxidant or cholesterol status of middle-aged adults.

    Science.gov (United States)

    Collins, J K; Arjmandi, B H; Claypool, P L; Perkins-Veazie, P; Baker, R A; Clevidence, B A

    2004-09-15

    Epidemiological studies have reported associations between reduced cardiovascular disease and diets rich in tomato and/or lycopene. Intervention studies have shown that lycopene-containing foods may reduce cholesterol levels and lipid peroxidation, factors implicated in the initiation of cardiovascular disease. The objective of this study was to determine whether consumption of lycopene rich foods conferred cardiovascular protection to middle-aged adults as indicated by plasma lipid concentrations and measures of ex vivo antioxidants. Ten healthy men and women consumed a low lycopene diet with no added lycopene (control treatment) or supplemented with watermelon or tomato juice each containing 20 mg lycopene. Subjects consumed each treatment for three weeks in a crossover design. Plasma, collected weekly was analyzed for total cholesterol, high density lipoprotein cholesterol (HDL-C) and triglyceride concentrations and for the antioxidant biomarkers of malondialdehyde formation products (MDA), plasma glutathione peroxidase (GPX) and ferric reducing ability of plasma (FRAP). Data were analyzed using Proc Mixed Procedure and associations between antioxidant and lipid measures were identified by Pearson's product moment correlation analysis. Compared to the control diet, the lycopene-containing foods did not affect plasma lipid concentrations or antioxidant biomarkers. Women had higher total cholesterol, HDL-C and triglyceride concentrations than did the men. Total cholesterol was positively correlated to MDA and FRAP while HDL-C was positively correlated to MDA and GPX. GPX was negatively correlated to triglyceride concentration. The inclusion of watermelon or tomato juice containing 20 mg lycopene did not affect plasma lipid concentrations or antioxidant status of healthy subjects. However, plasma cholesterol levels impacted the results of MDA and FRAP antioxidant tests.

  18. Lycopene from two food sources does not affect antioxidant or cholesterol status of middle-aged adults

    Directory of Open Access Journals (Sweden)

    Baker RA

    2004-09-01

    Full Text Available Abstract Background Epidemiological studies have reported associations between reduced cardiovascular disease and diets rich in tomato and/or lycopene. Intervention studies have shown that lycopene-containing foods may reduce cholesterol levels and lipid peroxidation, factors implicated in the initiation of cardiovascular disease. The objective of this study was to determine whether consumption of lycopene rich foods conferred cardiovascular protection to middle-aged adults as indicated by plasma lipid concentrations and measures of ex vivo antioxidants. Methods Ten healthy men and women consumed a low lycopene diet with no added lycopene (control treatment or supplemented with watermelon or tomato juice each containing 20 mg lycopene. Subjects consumed each treatment for three weeks in a crossover design. Plasma, collected weekly was analyzed for total cholesterol, high density lipoprotein cholesterol (HDL-C and triglyceride concentrations and for the antioxidant biomarkers of malondialdehyde formation products (MDA, plasma glutathione peroxidase (GPX and ferric reducing ability of plasma (FRAP. Data were analyzed using Proc Mixed Procedure and associations between antioxidant and lipid measures were identified by Pearson's product moment correlation analysis. Results Compared to the control diet, the lycopene-containing foods did not affect plasma lipid concentrations or antioxidant biomarkers. Women had higher total cholesterol, HDL-C and triglyceride concentrations than did the men. Total cholesterol was positively correlated to MDA and FRAP while HDL-C was positively correlated to MDA and GPX. GPX was negatively correlated to triglyceride concentration. Conclusions The inclusion of watermelon or tomato juice containing 20 mg lycopene did not affect plasma lipid concentrations or antioxidant status of healthy subjects. However, plasma cholesterol levels impacted the results of MDA and FRAP antioxidant tests.

  19. How does age-related macular degeneration affect real-world visual ability and quality of life? A systematic review

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    Taylor, Deanna J; Hobby, Angharad E; Binns, Alison M; Crabb, David P

    2016-01-01

    Objectives To review systematically the evidence of age-related macular degeneration (AMD) affecting real-world visual ability and quality of life (QoL). To explore trends in specific topics within this body of the literature. Design Systematic review. Methods A systematic literature search was carried out using MEDLINE, EMBASE, CINAHL, PsycINFO, PsychARTICLES and Health and Psychosocial Instruments for articles published up to January 2015 for studies including people diagnosed with AMD, assessing real-world visual ability or QoL as an outcome. Two researchers screened studies for eligibility. Details of eligible studies including study design, characteristics of study population and outcomes measured were recorded in a data extraction table. All included studies underwent quality appraisal using the Mixed Methods Appraisal Tool 2011 Version (MMAT). Results From 5284 studies, 123 were eligible for inclusion. A range of approaches were identified, including performance-based methods, quantitative and qualitative patient-reported outcome measures (PROMs). AMD negatively affects tasks including mobility, face recognition, perception of scenes, computer use, meal preparation, shopping, cleaning, watching TV, reading, driving and, in some cases, self-care. There is evidence for higher rates of depression among people with AMD than among community dwelling elderly. A number of adaptation strategies have been associated with AMD of varying duration. Much of the research fails to report the type of AMD studied (59% of included studies) or the duration of disease in participants (74%). Of those that do report type studied, the breakdown is as follows: wet AMD 20%, dry AMD 4% and both types 17%. Conclusions There are many publications highlighting the negative effects of AMD in various domains of life. Future research should focus on delivering some of this research knowledge into patient management and clinical trials and differentiating between the types of AMD. PMID

  20. Aging

    International Nuclear Information System (INIS)

    Sasaki, Hideo; Kodama, Kazunori; Yamada, Michiko

    1991-01-01

    The hypothesis that exposure to ionizing radiation accelerates the aging process has been actively investigated at ABCC-RERF since 1958, when longitudinal cohort studies of the Adult Health Study (AHS) and the Life Span Study (LSS) were initiated. In their 1975 overall review of aging studies related to the atomic bomb (A-bomb) survivors, Finch and Beebe concluded that while most studies had shown no correlation between aging and radiation exposure, they had not involved the large numbers of subjects required to provide strong evidence for or against the hypothesis. Extending LSS mortality data up to 1978 did not alter the earlier conclusion that any observed life-shortening was associated primarily with cancer induction rather than with any nonspecific cause. The results of aging studies conducted during the intervening 15 years using data from the same populations are reviewed in the present paper. Using clinical, epidemiological, and laboratory techniques, a broad spectrum of aging parameters have been studied, such as postmortem morphological changes, tests of functional capacity, physical tests and measurements, laboratory tests, tissue changes, and morbidity. With respect to the aging process, the overall results have not been consistent and are generally thought to show no relation to radiation exposure. Although some preliminary results suggest a possible radiation-induced increase in atherosclerotic diseases and acceleration of aging in the T-cell-related immune system, further study is necessary to confirm these findings. In the future, applying the latest gerontological study techniques to data collected from subjects exposed 45 years ago to A-bomb radiation at relatively young ages will present a new body of data relevant to the study of late radiation effects. (author) 103 refs

  1. Characterization and extraction of the synaptic apposition surface for synaptic geometry analysis

    Science.gov (United States)

    Morales, Juan; Rodríguez, Angel; Rodríguez, José-Rodrigo; DeFelipe, Javier; Merchán-Pérez, Angel

    2013-01-01

    Geometrical features of chemical synapses are relevant to their function. Two critical components of the synaptic junction are the active zone (AZ) and the postsynaptic density (PSD), as they are related to the probability of synaptic release and the number of postsynaptic receptors, respectively. Morphological studies of these structures are greatly facilitated by the use of recent electron microscopy techniques, such as combined focused ion beam milling and scanning electron microscopy (FIB/SEM), and software tools that permit reconstruction of large numbers of synapses in three dimensions. Since the AZ and the PSD are in close apposition and have a similar surface area, they can be represented by a single surface—the synaptic apposition surface (SAS). We have developed an efficient computational technique to automatically extract this surface from synaptic junctions that have previously been three-dimensionally reconstructed from actual tissue samples imaged by automated FIB/SEM. Given its relationship with the release probability and the number of postsynaptic receptors, the surface area of the SAS is a functionally relevant measure of the size of a synapse that can complement other geometrical features like the volume of the reconstructed synaptic junction, the equivalent ellipsoid size and the Feret's diameter. PMID:23847474

  2. Aging

    International Nuclear Information System (INIS)

    Finch, S.C.; Beebe, G.W.

    1975-01-01

    The hypothesis that ionizing radiation accelerates natural aging has been under investigation at the Atomic Bomb Casualty Commission since 1959. Postmortem observations of morphologic and chemical changes, tests of functional capacity, physical tests and measurements, clinical laboratory tests, tissue changes, morbidity, and mortality have all been examined by ABCC investigators interested in this hypothesis. These studies have been beset with conceptual difficulties centered on the definition and measurement of aging. An empirical approach early led to the calculation of an index of physiologic age as a linear combination of age-related tests of various organ systems. Most studies have been negative but have not involved the large numbers that might be required to provide strong evidence for or against the hypothesis. Mortality, however, has been examined on the basis of a large sample and over the period 1950-1972 had provided no support for the hypothesis of radiation-accelerated aging. Ionizing radiation dose, of course shorten human life, but its life-shortening effect appears to be the result of specific radiation-induced disease, especially neoplasms. The hypothesis is now much less attractive than it was 10-20 years ago but still has some value in stimulating research on aging. The experience of the A-bomb survivors provides an unusual opportunity for a definitive test of the hypothesis. (auth.)

  3. Different effects of bisphenol-A on memory behavior and synaptic modification in intact and estrogen-deprived female mice.

    Science.gov (United States)

    Xu, Xiaohong; Gu, Ting; Shen, Qiaoqiao

    2015-03-01

    Bisphenol-A (BPA) has the capability of interfering with the effects of estrogens on modulating brain function. The purpose of this study was to investigate the effects of BPA on memory and synaptic modification in the hippocampus of female mice under different levels of cycling estrogen. BPA exposure (40, 400 μg/kg/day) for 8 weeks did not affect spatial memory and passive avoidance task of gonadally intact mice but improved ovariectomy (Ovx)-induced memory impairment, whereas co-exposure of BPA with estradiol benzoate (EB) diminished the rescue effect of EB on memory behavior of Ovx mice. The results of morphometric measurement showed that BPA positively modified the synaptic interface structure and increased the synaptic density of CA1 pyramidal cell in the hippocampus of Ovx females, but inhibited the enhancement of EB on synaptic modification and synaptogenesis of Ovx mice. Furthermore, BPA up-regulated synaptic proteins synapsin I and PSD-95 and NMDA receptor NR2B but inhibited EB-induced increase in PSD-95 and NR2B in the hippocampus of Ovx mice. These results suggest that BPA interfered with normal hormonal regulation in synaptic plasticity and memory of female mice as a potent estrogen mimetic and as a disruptor of estrogen under various concentrations of cycling estrogen. © 2014 International Society for Neurochemistry.

  4. Effects of dopamine and glutamate on synaptic plasticity: a computational modeling approach for drug abuse as comorbidity in mood disorders.

    Science.gov (United States)

    Qi, Z; Kikuchi, S; Tretter, F; Voit, E O

    2011-05-01

    Major depressive disorder (MDD) affects about 16% of the general population and is a leading cause of death in the United States and around the world. Aggravating the situation is the fact that "drug use disorders" are highly comorbid in MDD patients, and VICE VERSA. Drug use and MDD share a common component, the dopamine system, which is critical in many motivation and reward processes, as well as in the regulation of stress responses in MDD. A potentiating mechanism in drug use disorders appears to be synaptic plasticity, which is regulated by dopamine transmission. In this article, we describe a computational model of the synaptic plasticity of GABAergic medium spiny neurons in the nucleus accumbens, which is critical in the reward system. The model accounts for effects of both dopamine and glutamate transmission. Model simulations show that GABAergic medium spiny neurons tend to respond to dopamine stimuli with synaptic potentiation and to glutamate signals with synaptic depression. Concurrent dopamine and glutamate signals cause various types of synaptic plasticity, depending on input scenarios. Interestingly, the model shows that a single 0.5 mg/kg dose of amphetamine can cause synaptic potentiation for over 2 h, a phenomenon that makes synaptic plasticity of medium spiny neurons behave quasi as a bistable system. The model also identifies mechanisms that could potentially be critical to correcting modifications of synaptic plasticity caused by drugs in MDD patients. An example is the feedback loop between protein kinase A, phosphodiesterase, and the second messenger cAMP in the postsynapse. Since reward mechanisms activated by psychostimulants could be crucial in establishing addiction comorbidity in patients with MDD, this model might become an aid for identifying and targeting specific modules within the reward system and lead to a better understanding and potential treatment of comorbid drug use disorders in MDD. © Georg Thieme Verlag KG Stuttgart · New

  5. Reexamining age, race, site, and thermometer type as variables affecting temperature measurement in adults – A comparison study

    Directory of Open Access Journals (Sweden)

    Smith Linda S

    2003-06-01

    Full Text Available Abstract Background As a result of the recent international vigilance regarding disease assessment, accurate measurement of body temperature has become increasingly important. Yet, trusted low-tech, portable mercury glass thermometers are no longer available. Thus, comparing accuracy of mercury-free thermometers with mercury devices is essential. Study purposes were 1 to examine age, race, site as variables affecting temperature measurement in adults, and 2 to compare clinical accuracy of low-tech Galinstan-in-glass device to mercury-in-glass at oral, axillary, groin, and rectal sites in adults. Methods Setting 176 bed accredited healthcare facility, rural northwest US Participants Convenience sample (N = 120 of hospitalized persons ≥ 18 years old. Instruments Temperatures (°F measured at oral, skin (simultaneous, immediately followed by rectal sites with four each mercury-glass (BD and Galinstan-glass (Geratherm thermometers; 10 minute dwell times. Results Participants averaged 61.6 years (SD 17.9, 188 pounds (SD 55.3; 61% female; race: 85% White, 8.3% Native Am., 4.2% Hispanic, 1.7 % Asian, 0.8% Black. For both mercury and Galinstan-glass thermometers, within-subject temperature readings were highest rectally; followed by oral, then skin sites. Galinstan assessments demonstrated rectal sites 0.91°F > oral and ≅ 1.3°F > skin sites. Devices strongly correlated between and across sites. Site difference scores between devices showed greatest variability at skin sites; least at rectal site. 95% confidence intervals of difference scores by site (°F: oral (0.142 – 0.265, axilla (0.167 – 0.339, groin (0.037 – 0.321, and rectal (-0.111 – 0.111. Race correlated with age, temperature readings each site and device. Conclusion Temperature readings varied by age, race. Mercury readings correlated with Galinstan thermometer readings at all sites. Site mean differences between devices were considered clinically insignificant. Still considered

  6. NINJ2 SNP may affect the onset age of first-ever ischemic stroke without increasing silent cerebrovascular lesions

    Directory of Open Access Journals (Sweden)

    Kim Dong-Eog

    2012-03-01

    Full Text Available Abstract Background To investigate if single nucleotide polymorphisms on chromosome 12p13 and within 11 kb of the gene NINJ2 would be associated with earlier-onset (vs. late-onset first-ever ischemic stroke and increase silent cerebrovascular lesions prior to the manifestation of the stroke. Methods We prospectively enrolled 164 patients (67.6 ± 12.9 years, 92 men admitted with first-ever ischemic strokes. All patients underwent genotyping of rs11833579 and rs12425791 as well as systemic investigations including magnetic resonance (MR imaging and other vascular workup. Stroke-related MR lesions were registered on a brain-template-set using a custom-built software package 'Image_QNA': high-signal-intensity ischemic lesions on diffusion, T2-weighted, or fluid attenuation inversion recovery (FLAIR MR images, and low signal intensity hemorrhagic lesions on gradient-echo MR images. Results The rs11833579 A/A or G/A genotype was independently associated with the first-ever ischemic stroke before the age 59 vs. 59 or over, after adjusting for cardiovascular risk factors and prior medication of antiplatelet or anticoagulant drugs, increasing the risk by about 2.5 fold. In the quantitative MR lesion maps from age-sex matched subgroups (n = 124 or 126, there was no difference between the patients with the rs11833579 A/A or G/A genotype and those with the G/G genotype. Unexpectedly, the extent of leukoaraiosis on FLAIR-MR images tended to be smaller in the corona radiata and centrum semiovale of the patients with the rs12425791 A/A or G/A genotype than in those with the G/G genotype (P = 0.052. Neither the rs11833579 nor the rs12425791 genotype significantly affected initial stroke severity; however the latter was associated with relatively low modified Rankin scale scores at 1 year after stroke. Conclusions The rs11833579 A/A or G/A genotype may bring forward the onset age of first-ever ischemic stroke without increasing silent cerebrovascular lesions

  7. Myostatin-like proteins regulate synaptic function and neuronal morphology.

    Science.gov (United States)

    Augustin, Hrvoje; McGourty, Kieran; Steinert, Joern R; Cochemé, Helena M; Adcott, Jennifer; Cabecinha, Melissa; Vincent, Alec; Halff, Els F; Kittler, Josef T; Boucrot, Emmanuel; Partridge, Linda

    2017-07-01

    Growth factors of the TGFβ superfamily play key roles in regulating neuronal and muscle function. Myostatin (or GDF8) and GDF11 are potent negative regulators of skeletal muscle mass. However, expression of myostatin and its cognate receptors in other tissues, including brain and peripheral nerves, suggests a potential wider biological role. Here, we show that Myoglianin (MYO), the Drosophila homolog of myostatin and GDF11, regulates not only body weight and muscle size, but also inhibits neuromuscular synapse strength and composition in a Smad2-dependent manner. Both myostatin and GDF11 affected synapse formation in isolated rat cortical neuron cultures, suggesting an effect on synaptogenesis beyond neuromuscular junctions. We also show that MYO acts in vivo to inhibit synaptic transmission between neurons in the escape response neural circuit of adult flies. Thus, these anti-myogenic proteins act as important inhibitors of synapse function and neuronal growth. © 2017. Published by The Company of Biologists Ltd.

  8. Communication, support and psychosocial work environment affecting psychological distress among working women aged 20 to 39 years in Japan.

    Science.gov (United States)

    Honda, Ayumi; Date, Yutaka; Abe, Yasuyo; Aoyagi, Kiyoshi; Honda, Sumihisa

    2016-01-01

    When compared with their older counterparts, younger women are more likely to have depressive symptoms because they more often experience interrupted work history and a heavy childrearing burden. The purposes of the present study were 1) to investigate the possible association of psychosocial work environment with psychological distress and 2) to examine the way by which communication and support in the workplace affect to psychological distress among young women. We studied 198 women aged 20 to 39 yr in a cross-sectional study. The Kessler Scale-10 (K10 Scale) was used to examine psychological distress. In employees who experienced interpersonal conflict, those who had little or no conversations with their supervisor and/or co-workers had a significantly increased risk of psychological distress (OR, 4.2), and those who received little or no support from their supervisor and/or co-workers had a significantly increased risk of psychological distress (OR, 3.8) compared to those who had more frequent communication and received more support. Harmonious communication in the workplace can help prevent psychological distress among employees, which in turn may enable them to be satisfied with their work.

  9. Activity Induces Fmr1-Sensitive Synaptic Capture of Anterograde Circulating Neuropeptide Vesicles.

    Science.gov (United States)

    Cavolo, Samantha L; Bulgari, Dinara; Deitcher, David L; Levitan, Edwin S

    2016-11-16

    Synaptic neuropeptide and neurotrophin stores are maintained by constitutive bidirectional capture of dense-core vesicles (DCVs) as they circulate in and out of the nerve terminal. Activity increases DCV capture to rapidly replenish synaptic neuropeptide stores following release. However, it is not known whether this is due to enhanced bidirectional capture. Here experiments at the Drosophila neuromuscular junction, where DCVs contain neuropeptides and a bone morphogenic protein, show that activity-dependent replenishment of synaptic neuropeptides following release is evident after inhibiting the retrograde transport with the dynactin disruptor mycalolide B or photobleaching DCVs entering a synaptic bouton by retrograde transport. In contrast, photobleaching anterograde transport vesicles entering a bouton inhibits neuropeptide replenishment after activity. Furthermore, tracking of individual DCVs moving through boutons shows that activity selectively increases capture of DCVs undergoing anterograde transport. Finally, upregulating fragile X mental retardation 1 protein (Fmr1, also called FMRP) acts independently of futsch/MAP-1B to abolish activity-dependent, but not constitutive, capture. Fmr1 also reduces presynaptic neuropeptide stores without affecting activity-independent delivery and evoked release. Therefore, presynaptic motoneuron neuropeptide storage is increased by a vesicle capture mechanism that is distinguished from constitutive bidirectional capture by activity dependence, anterograde selectivity, and Fmr1 sensitivity. These results show that activity recruits a separate mechanism than used at rest to stimulate additional synaptic capture of DCVs for future release of neuropeptides and neurotrophins. Synaptic release of neuropeptides and neurotrophins depends on presynaptic accumulation of dense-core vesicles (DCVs). At rest, DCVs are captured bidirectionally as they circulate through Drosophila motoneuron terminals by anterograde and retrograde

  10. Disruption of an Evolutionarily Novel Synaptic Expression Pattern in Autism

    Science.gov (United States)

    Jiang, Xi; Hu, Haiyang; Guijarro, Patricia; Mitchell, Amanda; Ely, John J.; Sherwood, Chet C.; Hof, Patrick R.; Qiu, Zilong; Pääbo, Svante; Akbarian, Schahram; Khaitovich, Philipp

    2016-01-01

    Cognitive defects in autism spectrum disorder (ASD) include socialization and communication: key behavioral capacities that separate humans from other species. Here, we analyze gene expression in the prefrontal cortex of 63 autism patients and control individuals, as well as 62 chimpanzees and macaques, from natal to adult age. We show that among all aberrant expression changes seen in ASD brains, a single aberrant expression pattern overrepresented in genes involved synaptic-related pathways is enriched in nucleotide variants linked to autism. Furthermore, only this pattern contains an excess of developmental expression features unique to humans, thus resulting in the disruption of human-specific developmental programs in autism. Several members of the early growth response (EGR) transcription factor family can be implicated in regulation of this aberrant developmental change. Our study draws a connection between the genetic risk architecture of autism and molecular features of cortical development unique to humans. PMID:27685936

  11. Disruption of an Evolutionarily Novel Synaptic Expression Pattern in Autism.

    Directory of Open Access Journals (Sweden)

    Xiling Liu

    2016-09-01

    Full Text Available Cognitive defects in autism spectrum disorder (ASD include socialization and communication: key behavioral capacities that separate humans from other species. Here, we analyze gene expression in the prefrontal cortex of 63 autism patients and control individuals, as well as 62 chimpanzees and macaques, from natal to adult age. We show that among all aberrant expression changes seen in ASD brains, a single aberrant expression pattern overrepresented in genes involved synaptic-related pathways is enriched in nucleotide variants linked to autism. Furthermore, only this pattern contains an excess of developmental expression features unique to humans, thus resulting in the disruption of human-specific developmental programs in autism. Several members of the early growth response (EGR transcription factor family can be implicated in regulation of this aberrant developmental change. Our study draws a connection between the genetic risk architecture of autism and molecular features of cortical development unique to humans.

  12. Mechanisms of glycine release, which build up synaptic and extrasynaptic glycine levels: the role of synaptic and non-synaptic glycine transporters.

    Science.gov (United States)

    Harsing, Laszlo G; Matyus, Peter

    2013-04-01

    Glycine is an amino acid neurotransmitter that is involved in both inhibitory and excitatory neurochemical transmission in the central nervous system. The role of glycine in excitatory neurotransmission is related to its coagonist action at glutamatergic N-methyl-D-aspartate receptors. The glycine levels in the synaptic cleft rise many times higher during synaptic activation assuring that glycine spills over into the extrasynaptic space. Another possible origin of extrasynaptic glycine is the efflux of glycine occurring from astrocytes associated with glutamatergic synapses. The release of glycine from neuronal or glial origins exhibits several differences compared to that of biogenic amines or other amino acid neurotransmitters. These differences appear in an external Ca(2+)- and temperature-dependent manner, conferring unique characteristics on glycine as a neurotransmitter. Glycine transporter type-1 at synapses may exhibit neural and glial forms and plays a role in controlling synaptic glycine levels and the spill over rate of glycine from the synaptic cleft into the extrasynaptic biophase. Non-synaptic glycine transporter type-1 regulates extrasynaptic glycine concentrations, either increasing or decreasing them depending on the reverse or normal mode operation of the carrier molecule. While we can, at best, only estimate synaptic glycine levels at rest and during synaptic activation, glycine concentrations are readily measurable via brain microdialysis technique applied in the extrasynaptic space. The non-synaptic N-methyl-D-aspartate receptor may obtain glycine for activation following its spill over from highly active synapses or from its release mediated by the reverse operation of non-synaptic glycine transporter-1. The sensitivity of non-synaptic N-methyl-D-aspartate receptors to glutamate and glycine is many times higher than that of synaptic N-methyl-D-aspartate receptors making the former type of receptor the primary target for drug action. Synaptic

  13. A cell adhesion molecule mimetic, FGL peptide, induces alterations in synapse and dendritic spine structure in the dentate gyrus of aged rats: a three-dimensional ultrastructural study

    DEFF Research Database (Denmark)

    Popov, Victor I; Medvedev, Nikolay I; Kraev, Igor V

    2008-01-01

    pits. Three-dimensional analysis showed a significant decrease in both post-synaptic density and apposition zone curvature of mushroom spines following FGL treatment, whereas for thin spines the convexity of the apposition zone increased. These data indicate that FGL induces large changes in the fine...... 100 serial ultrathin sections. FGL affected neither hippocampal volume nor spine or synaptic density in the middle molecular layer of the dentate gyrus. However, it increased the ratio of mushroom to thin spines, number of multivesicular bodies and also increased the frequency of appearance of coated...... structure of synapses and dendritic spines in hippocampus of aged rats, complementing data showing its effect on cognitive processes....

  14. Synaptic control of local translation: the plot thickens with new characters.

    Science.gov (United States)

    Thomas, María Gabriela; Pascual, Malena Lucía; Maschi, Darío; Luchelli, Luciana; Boccaccio, Graciela Lidia

    2014-06-01

    The production of proteins from mRNAs localized at the synapse ultimately controls the strength of synaptic transmission, thereby affecting behavior and cognitive functions. The regulated transcription, processing, and transport of mRNAs provide dynamic control of the dendritic transcriptome, which includes thousands of messengers encoding multiple cellular functions. Translation is locally modulated by synaptic activity through a complex network of RNA-binding proteins (RBPs) and various types of non-coding RNAs (ncRNAs) including BC-RNAs, microRNAs, piwi-interacting RNAs, and small interference RNAs. The RBPs FMRP and CPEB play a well-established role in synaptic translation, and additional regulatory factors are emerging. The mRNA repressors Smaug, Nanos, and Pumilio define a novel pathway for local translational control that affects dendritic branching and spines in both flies and mammals. Recent findings support a role for processing bodies and related synaptic mRNA-silencing foci (SyAS-foci) in the modulation of synaptic plasticity and memory formation. The SyAS-foci respond to different stimuli with changes in their integrity thus enabling regulated mRNA release followed by translation. CPEB, Pumilio, TDP-43, and FUS/TLS form multimers through low-complexity regions related to prion domains or polyQ expansions. The oligomerization of these repressor RBPs is mechanistically linked to the aggregation of abnormal proteins commonly associated with neurodegeneration. Here, we summarize the current knowledge on how specificity in mRNA translation is achieved through the concerted action of multiple pathways that involve regulatory ncRNAs and RBPs, the modification of translation factors, and mRNA-silencing foci dynamics.

  15. Synaptic Contacts Enhance Cell-to-Cell Tau Pathology Propagation

    Directory of Open Access Journals (Sweden)

    Sara Calafate

    2015-05-01

    Full Text Available Accumulation of insoluble Tau protein aggregates and stereotypical propagation of Tau pathology through the brain are common hallmarks of tauopathies, including Alzheimer’s disease (AD. Propagation of Tau pathology appears to occur along connected neurons, but whether synaptic contacts between neurons are facilitating propagation has not been demonstrated. Using quantitative in vitro models, we demonstrate that, in parallel to non-synaptic mechanisms, synapses, but not merely the close distance between the cells, enhance the propagation of Tau pathology between acceptor hippocampal neurons and Tau donor cells. Similarly, in an artificial neuronal network using microfluidic devices, synapses and synaptic activity are promoting neuronal Tau pathology propagation in parallel to the non-synaptic mechanisms. Our work indicates that the physical presence of synaptic contacts between neurons facilitate Tau pathology propagation. These findings can have implications for synaptic repair therapies, which may turn out to have adverse effects by promoting propagation of Tau pathology.

  16. Attractor neural networks with resource-efficient synaptic connectivity

    Science.gov (United States)

    Pehlevan, Cengiz; Sengupta, Anirvan

    Memories are thought to be stored in the attractor states of recurrent neural networks. Here we explore how resource constraints interplay with memory storage function to shape synaptic connectivity of attractor networks. We propose that given a set of memories, in the form of population activity patterns, the neural circuit choses a synaptic connectivity configuration that minimizes a resource usage cost. We argue that the total synaptic weight (l1-norm) in the network measures the resource cost because synaptic weight is correlated with synaptic volume, which is a limited resource, and is proportional to neurotransmitter release and post-synaptic current, both of which cost energy. Using numerical simulations and replica theory, we characterize optimal connectivity profiles in resource-efficient attractor networks. Our theory explains several experimental observations on cortical connectivity profiles, 1) connectivity is sparse, because synapses are costly, 2) bidirectional connections are overrepresented and 3) are stronger, because attractor states need strong recurrence.

  17. Spike timing-dependent plasticity as the origin of the formation of clustered synaptic efficacy engrams

    Directory of Open Access Journals (Sweden)

    Nicolangelo L Iannella

    2010-07-01

    Full Text Available Synapse location, dendritic active properties and synaptic plasticity are all known to play some role in shaping the different input streams impinging onto a neuron. It remains unclear however, how the magnitude and spatial distribution of synaptic efficacies emerge from this interplay. Here, we investigate this interplay using a biophysically detailed neuron model of a reconstructed layer 2/3 pyramidal cell and spike timing-dependent plasticity (STDP. Specifically, we focus on the issue of how the efficacy of synapses contributed by different input streams are spatially represented in dendrites after STDP learning. We construct a simple feed forward network where a detailed model neuron receives synaptic inputs independently from multiple yet equally sized groups of afferent fibres with correlated activity, mimicking the spike activity from different neuronal populations encoding, for example, different sensory modalities. Interestingly, ensuing STDP learning, we observe that for all afferent groups, STDP leads to synaptic efficacies arranged into spatially segregated clusters effectively partitioning the dendritic tree. These segregated clusters possess a characteristic global organisation in space, where they form a tessellation in which each group dominates mutually exclusive regions of the dendrite.Put simply, the dendritic imprint from different input streams left after STDP learning effectively forms what we term a dendritic efficacy mosaic. Furthermore, we show how variations of the inputs and STDP rule affect such an organization. Our model suggests that STDP may be an important mechanism for creating a clustered plasticity engram, which shapes how different input streams are spatially represented in dendrite.

  18. The Roles of Protein Expression in Synaptic Plasticity and Memory Consolidation

    Directory of Open Access Journals (Sweden)

    Tali eRosenberg

    2014-11-01

    Full Text Available The amount and availability of proteins are regulated by their synthesis, degradation, and transport. These processes can specifically, locally, and temporally regulate a protein or a population of proteins, thus affecting numerous biological processes in health and disease states. Accordingly, malfunction in the processes of protein turnover and localization underlies different neuronal diseases. However, as early as a century ago, it was recognized that there is a specific need for normal macromolecular synthesis in a specific fragment of the learning process, memory consolidation, which takes place minutes to hours following acquisition. Memory consolidation is the process by which fragile short-term memory is converted into stable long-term memory. It is accepted today that synaptic plasticity is a cellular mechanism of learning and memory processes. Interestingly, similar molecular mechanisms subserve both memory and synaptic plasticity consolidation. In this review, we survey the current view on the connection between memory consolidation processes and proteostasis, i.e., maintaining the protein contents at the neuron and the synapse. In addition, we describe the technical obstacles and possible new methods to determine neuronal proteostasis of synaptic function and better explain the process of memory and synaptic plasticity consolidation.

  19. Lavandula angustifolia extract improves deteriorated synaptic plasticity in an animal model of Alzheimer’s disease

    Science.gov (United States)

    Soheili, Masoud; Tavirani, Mostafa Rezaei; Salami, Mahmoud

    2015-01-01

    Objective(s): Neurodegenerative Alzheimer’s disease (AD) is associated with profound deficits in synaptic transmission and synaptic plasticity. Long-term potentiation (LTP), an experimental form of synaptic plasticity, is intensively examined in hippocampus. In this study we evaluated the effect of aqueous extract of lavender (Lavandula angustifolia) on induction of LTP in the CA1 area of hippocampus. In response to stimulation of the Schaffer collaterals the baseline or tetanized field extracellular postsynaptic potentials (fEPSPs) were recorded in the CA1 area. Materials and Methods: The electrophysiological recordings were carried out in four groups of rats; two control groups including the vehicle (CON) and lavender (CE) treated rats and two Alzheimeric groups including the vehicle (ALZ) and lavender (AE) treated animals. Results: The extract inefficiently affected the baseline responses in the four testing groups. While the fEPSPs displayed a considerable LTP in the CON animals, no potentiation was evident in the tetanized responses in the ALZ rats. The herbal medicine effectively restored LTP in the AE group and further potentiated fEPSPs in the CE group. Conclusion: The positive effect of the lavender extract on the plasticity of synaptic transmission supports its previously reported behavioral effects on improvement of impaired spatial memory in the Alzheimeric animals. PMID:26949505

  20. Lavandula angustifolia extract improves deteriorated synaptic plasticity in an animal model of Alzheimer's disease.

    Science.gov (United States)

    Soheili, Masoud; Tavirani, Mostafa Rezaei; Salami, Mahmoud

    2015-11-01

    Neurodegenerative Alzheimer's disease (AD) is associated with profound deficits in synaptic transmission and synaptic plasticity. Long-term potentiation (LTP), an experimental form of synaptic plasticity, is intensively examined in hippocampus. In this study we evaluated the effect of aqueous extract of lavender (Lavandula angustifolia) on induction of LTP in the CA1 area of hippocampus. In response to stimulation of the Schaffer collaterals the baseline or tetanized field extracellular postsynaptic potentials (fEPSPs) were recorded in the CA1 area. The electrophysiological recordings were carried out in four groups of rats; two control groups including the vehicle (CON) and lavender (CE) treated rats and two Alzheimeric groups including the vehicle (ALZ) and lavender (AE) treated animals. The extract inefficiently affected the baseline responses in the four testing groups. While the fEPSPs displayed a considerable LTP in the CON animals, no potentiation was evident in the tetanized responses in the ALZ rats. The herbal medicine effectively restored LTP in the AE group and further potentiated fEPSPs in the CE group. The positive effect of the lavender extract on the plasticity of synaptic transmission supports its previously reported behavioral effects on improvement of impaired spatial memory in the Alzheimeric animals.

  1. Lavandula angustifolia extract improves deteriorated synaptic plasticity in an animal model of Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Masoud Soheili

    2015-11-01

    Full Text Available Objective(s:Neurodegenerative Alzheimer’s disease (AD is associated with profound deficits in synaptic transmission and synaptic plasticity. Long-term potentiation (LTP, an experimental form of synaptic plasticity, is intensively examined in hippocampus. In this study we evaluated the effect of aqueous extract of lavender (Lavandula angustifolia on induction of LTP in the CA1 area of hippocampus. In response to stimulation of the Schaffer collaterals the baseline or tetanized field extracellular postsynaptic potentials (fEPSPs were recorded in the CA1 area. Materials and Methods: The electrophysiological recordings were carried out in four groups of rats; two control groups including the vehicle (CON and lavender (CE treated rats and two Alzheimeric groups including the vehicle (ALZ and lavender (AE treated animals. Results: The extract inefficiently affected the baseline responses in the four testing groups. While the fEPSPs displayed a considerable LTP in the CON animals, no potentiation was evident in the tetanized responses in the ALZ rats. The herbal medicine effectively restored LTP in the AE group and further potentiated fEPSPs in the CE group. Conclusion:The positive effect of the lavender extract on the plasticity of synaptic transmission supports its previously reported behavioral effects on improvement of impaired spatial memory in the Alzheimeric animals.

  2. DREAM (Downstream Regulatory Element Antagonist Modulator contributes to synaptic depression and contextual fear memory

    Directory of Open Access Journals (Sweden)

    Wu Long-Jun

    2010-01-01

    Full Text Available Abstract The downstream regulatory element antagonist modulator (DREAM, a multifunctional Ca2+-binding protein, binds specifically to DNA and several nucleoproteins regulating gene expression and with proteins outside the nucleus to regulate membrane excitability or calcium homeostasis. DREAM is highly expressed in the central nervous system including the hippocampus and cortex; however, the roles of DREAM in hippocampal synaptic transmission and plasticity have not been investigated. Taking advantage of transgenic mice overexpressing a Ca2+-insensitive DREAM mutant (TgDREAM, we used integrative methods including electrophysiology, biochemistry, immunostaining, and behavior tests to study the function of DREAM in synaptic transmission, long-term plasticity and fear memory in hippocampal CA1 region. We found that NMDA receptor but not AMPA receptor-mediated current was decreased in TgDREAM mice. Moreover, synaptic plasticity, such as long-term depression (LTD but not long-term potentiation (LTP, was impaired in TgDREAM mice. Biochemical experiments found that DREAM interacts with PSD-95 and may inhibit NMDA receptor function through this interaction. Contextual fear memory was significantly impaired in TgDREAM mice. By contrast, sensory responses to noxious stimuli were not affected. Our results demonstrate that DREAM plays a novel role in postsynaptic modulation of the NMDA receptor, and contributes to synaptic plasticity and behavioral memory.

  3. Defective Glycinergic Synaptic Transmission in Zebrafish Motility Mutants

    OpenAIRE

    Hirata, Hiromi; Carta, Eloisa; Yamanaka, Iori; Harvey, Robert J.; Kuwada, John Y.

    2010-01-01

    Glycine is a major inhibitory neurotransmitter in the spinal cord and brainstem. Recently, in vivo analysis of glycinergic synaptic transmission has been pursued in zebrafish using molecular genetics. An ENU mutagenesis screen identified two behavioral mutants that are defective in glycinergic synaptic transmission. Zebrafish bandoneon (beo) mutants have a defect in glrbb, one of the duplicated glycine receptor (GlyR) β subunit genes. These mutants exhibit a loss of glycinergic synaptic ...

  4. The flavonoid baicalein rescues synaptic plasticity and memory deficits in a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Gu, Xun-Hu; Xu, Li-Jun; Liu, Zhi-Qiang; Wei, Bo; Yang, Yuan-Jian; Xu, Guo-Gang; Yin, Xiao-Ping; Wang, Wei

    2016-09-15

    Increasing evidence suggests that disruptions of synaptic functions correlate with the severity of cognitive deficit in Alzheimer's disease (AD). Our previous study demonstrated that baicalein enhances long-term potentiation (LTP) in acute rat hippocampal slices and improves hippocampus-dependent contextual fear conditioning in rats. Given that baicalein possess various biological activities, especially its effects on synaptic plasticity and cognitive function, we examined the effect of baicalein on synaptic function both in vitro and in vivo in AD model. The effect of baicalein on Aβ42 oligomer impaired LTP was investigated by electrophysiological methods. Baicalein was administered orally via drinking water to the APP/PS1 mice and sex- and age-matched wild-type mice. Treatment started at 5 months of age and mice were assessed for cognition and AD-like pathology at 7-month-old. Cognition was analyzed by Morris water maze test, fear conditioning test, and novel object recognition test. Changes in hippocampal 12/15 Lipoxygenase (12/15LO) and glycogen synthase kinase 3β (GSK3β) activity, Aβ production, tau phosphorylation, synaptic plasticity, and dendritic spine density were evaluated. Baicalein prevented Aβ-induced impairments in hippocampal LTP through activation of serine threonine Kinase (Akt) phosphorylation. Long-term oral administration of baicalein inhibited 12/15LO and GSK3β activity, reduced β-secretase enzyme (BACE1), decreased the concentration of total Aβ, and prevented phosphorylation of tau in APP/PS1 mice. Meanwhile, baicalein restored spine number, synaptic plasticity, and memory deficits. Our results strengthen the potential of the flavonoid baicalein as a novel and promising oral bioactive therapeutic agent that prevents memory deficits in AD. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Statistical mechanics of attractor neural network models with synaptic depression

    International Nuclear Information System (INIS)

    Igarashi, Yasuhiko; Oizumi, Masafumi; Otsubo, Yosuke; Nagata, Kenji; Okada, Masato

    2009-01-01

    Synaptic depression is known to control gain for presynaptic inputs. Since cortical neurons receive thousands of presynaptic inputs, and their outputs are fed into thousands of other neurons, the synaptic depression should influence macroscopic properties of neural networks. We employ simple neural network models to explore the macroscopic effects of synaptic depression. Systems with the synaptic depression cannot be analyzed due to asymmetry of connections with the conventional equilibrium statistical-mechanical approach. Thus, we first propose a microscopic dynamical mean field theory. Next, we derive macroscopic steady state equations and discuss the stabilities of steady states for various types of neural network models.

  6. Experimental Implementation of a Biometric Laser Synaptic Sensor

    Directory of Open Access Journals (Sweden)

    Alexander N. Pisarchik

    2013-12-01

    Full Text Available We fabricate a biometric laser fiber synaptic sensor to transmit information from one neuron cell to the other by an optical way. The optical synapse is constructed on the base of an erbium-doped fiber laser, whose pumped diode current is driven by a pre-synaptic FitzHugh–Nagumo electronic neuron, and the laser output controls a post-synaptic FitzHugh–Nagumo electronic neuron. The implemented laser synapse displays very rich dynamics, including fixed points, periodic orbits with different frequency-locking ratios and chaos. These regimes can be beneficial for efficient biorobotics, where behavioral flexibility subserved by synaptic connectivity is a challenge.

  7. A pivotal role of GSK-3 in synaptic plasticity

    Directory of Open Access Journals (Sweden)

    Clarrisa A Bradley

    2012-02-01

    Full Text Available Glycogen synthase kinase-3 (GSK-3 has many cellular functions. Recent evidence suggests that it plays a key role in certain types of synaptic plasticity, in particular a form of long-term depression (LTD that is induced by the synaptic activation of N-methyl-D-aspartate (NMDA receptors. In the present article we summarise what is currently known concerning the roles of GSK-3 in synaptic plasticity at both glutamatergic and GABAergic synapses. We summarise its role in cognition and speculate on how alterations in the synaptic functioning of GSK-3 may be a major factor in certain neurodegenerative disorders.

  8. TrkB and PKMζ regulate synaptic localization of PSD-95 in developing cortex

    Science.gov (United States)

    Yoshii, Akira; Murata, Yasunobu; Kim, Jihye; Zhang, Chao; Shokat, Kevan M.; Constantine-Paton, Martha

    2011-01-01

    Post-synaptic density 95 (PSD-95), the major scaffold at excitatory synapses, is critical for synapse maturation and learning. In rodents, eye opening, the onset of pattern vision, triggers a rapid movement of PSD-95 from visual neuron somata to synapses. We previously showed that the PI3 kinase-Akt pathway downstream of BDNF/TrkB signaling stimulates synaptic delivery of PSD-95 via vesicular transport. However, vesicular transport requires PSD-95 palmitoylation to attach it to a lipid membrane. Also PSD-95 insertion at synapses is known to require this lipid modification. Here, we show that BDNF/TrkB signaling is also necessary for PSD-95 palmitoylation and its transport to synapses in mouse visual cortical layer 2/3 neurons. However, palmitoylation of PSD-95 requires the activation of another pathway downstream of BDNF/TrkB, namely signaling through PLCγ and the brain-specific PKC variant PKMζ. We find that PKMζ selectively regulates phosphorylation of the palmitoylation enzyme ZDHHC8. Inhibition of PKMζ results in a reduction of synaptic PSD-95 accumulation in vivo, which can be rescued by over-expression ZDHHC8. Therefore, TrkB and PKMζ, two critical regulators of synaptic plasticity, facilitate PSD-95 targeting to synapses. These results also indicate that palmitoylation can be regulated by a trophic factor. Our findings have implications for neurodevelopmental disorders as well as ageing brains. PMID:21849550

  9. proBDNF Negatively Regulates Neuronal Remodeling, Synaptic Transmission, and Synaptic Plasticity in Hippocampus

    Directory of Open Access Journals (Sweden)

    Jianmin Yang

    2014-05-01

    Full Text Available Experience-dependent plasticity shapes postnatal development of neural circuits, but the mechanisms that refine dendritic arbors, remodel spines, and impair synaptic activity are poorly understood. Mature brain-derived neurotrophic factor (BDNF modulates neuronal morphology and synaptic plasticity, including long-term potentiation (LTP via TrkB activation. BDNF is initially translated as proBDNF, which binds p75NTR. In vitro, recombinant proBDNF modulates neuronal structure and alters hippocampal long-term plasticity, but the actions of endogenously expressed proBDNF are unclear. Therefore, we generated a cleavage-resistant probdnf knockin mouse. Our results demonstrate that proBDNF negatively regulates hippocampal dendritic complexity and spine density through p75NTR. Hippocampal slices from probdnf mice exhibit depressed synaptic transmission, impaired LTP, and enhanced long-term depression (LTD in area CA1. These results suggest that proBDNF acts in vivo as a biologically active factor that regulates hippocampal structure, synaptic transmission, and plasticity, effects that are distinct from those of mature BDNF.

  10. Adiponectin modulates synaptic plasticity in hippocampal dentate gyrus.

    Science.gov (United States)

    Pousti, Farideh; Ahmadi, Ramesh; Mirahmadi, Fatemeh; Hosseinmardi, Narges; Rohampour, Kambiz

    2018-01-01

    Recent studies have suggested the involvement of some metabolic hormones in memory formation and synaptic plasticity. Insulin dysfunction is known as an essential process in the pathogenesis of sporadic Alzheimer's disease (AD). In this study we examined whether adiponectin (ADN), as an insulin-sensitizing adipokine, could affect hippocampal synaptic plasticity. Field potential recordings were performed on intracerebroventricular (icv) cannulated urethane anesthetized rats. After baseline recording from dentate gyrus (DG) and 10min prior to high/low frequency stimulation (HFS/LFS), 10μl icv ADN (600nm) were injected. The slope of field excitatory postsynaptic potentials (fEPSP) and the amplitude of population spikes (PS) were recorded in response to perforanth path (PP) stimulation. Paired pulse stimuli and ADN injection without any stimulation protocols were also evaluated. Application of ADN before HFS increased PS amplitude recorded in DG significantly (P≤0.05) in comparison to HFS only group. ADN suppressed the potency of LFS to induce long-term depression (LTD), causing a significant difference between fEPSP slope (P≤0.05) and PS amplitude (P≤0.01) between ADN+LFS and ADN group. Paired pulse stimuli applied at 20ms intervals showed more paired pulse facilitation (PPF), when applied after ADN (P≤0.05). ADN induced a chemical long-term potentiation (LTP) in which fEPSP slope and PS amplitude increased significantly (P≤0.01 and P≤0.05, respectively). It is concluded that ADN is able to potentiate the HFS-induced LTP and suppress LFS-induced LTD. ADN caused a chemical LTP, when applied without any tetanic protocol. ADN may enhance the presynaptic release probability. Copyright © 2017. Published by Elsevier B.V.

  11. The Roles of Cortical Slow Waves in Synaptic Plasticity and Memory Consolidation

    OpenAIRE

    Miyamoto, Daisuke; Hirai, Daichi; Murayama, Masanori

    2017-01-01

    Sleep plays important roles in sensory and motor memory consolidation. Sleep oscillations, reflecting neural population activity, involve the reactivation of learning-related neurons and regulate synaptic strength and, thereby affect memory consolidation. Among sleep oscillations, slow waves (0.5–4 Hz) are closely associated with memory consolidation. For example, slow-wave power is regulated in an experience-dependent manner and correlates with acquired memory. Furthermore, manipulating slow...

  12. Synaptic Democracy and Vesicular Transport in Axons

    Science.gov (United States)

    Bressloff, Paul C.; Levien, Ethan

    2015-04-01

    Synaptic democracy concerns the general problem of how regions of an axon or dendrite far from the cell body (soma) of a neuron can play an effective role in neuronal function. For example, stimulated synapses far from the soma are unlikely to influence the firing of a neuron unless some sort of active dendritic processing occurs. Analogously, the motor-driven transport of newly synthesized proteins from the soma to presynaptic targets along the axon tends to favor the delivery of resources to proximal synapses. Both of these phenomena reflect fundamental limitations of transport processes based on a localized source. In this Letter, we show that a more democratic distribution of proteins along an axon can be achieved by making the transport process less efficient. This involves two components: bidirectional or "stop-and-go" motor transport (which can be modeled in terms of advection-diffusion), and reversible interactions between motor-cargo complexes and synaptic targets. Both of these features have recently been observed experimentally. Our model suggests that, just as in human societies, there needs to be a balance between "efficiency" and "equality".

  13. The influence of age on the associations between HR practices and both affective commitment and job satisfaction: A meta-analysis

    OpenAIRE

    Kooij, T.A.M.; Jansen, P.G.W.; Dikkers, J.S.E.; de Lange, A.H.

    2010-01-01

    Research on the association between high commitment Human Resource (HR) practices and work-related outcomes at the individual level rarely focuses on age differences. To fill this knowledge gap, a meta-analysis has been conducted to examine how the relationships between the availability of high commitment HR practices, as perceived by employees, and affective commitment and job satisfaction change with age. Drawing on Selection, Optimization, and Compensation (SOC) theory and on Regulatory Fo...

  14. Effects of decreased inhibition on synaptic plasticity and dendritic morphology in the juvenile prefrontal cortex

    Directory of Open Access Journals (Sweden)

    Xanthippi Konstantoudaki

    2014-03-01

    , we tested whether synaptic plasticity properties of intra-cortical layer II synapses are affected. In adult control mice, tetanic stimulation results in long-term potentiation that lasts at least 50 min (Konstantoudaki et al, 2013. In control mice of the age tested in this study (PD 20-30, LTP could not be induced with the same stimulation. However, we find that Rac1 KO mice do express long-term potentiation. We next studied the dendritic morphology of layer II neurons in the prefrontal cortex, in an effort to identify the mechanism by which Rac1 KO mice exhibit LTP, while the control mice of the same age do not. For this, we stained mouse brains of Rac1 KO and Rac1 heterozygous mice with the Golgi-Cox method. We analyzed the number of secondary apical dendrites, their thickness, as well as the number of spines. We find that the dendrites of pyramidal neurons of Rac1 KO mice have decreased thickness and increased number of spines compared to pyramidal neurons from Rac1 heterozygous mice. These findings could also provide a mechanistic explanation for the presence of LTP in Rac1 KO mice. In conclusion, we find that decreased inhibition during development alters the morphological and functional characteristics of pyramidal neurons in layer II prefrontal cortex of mice. These alterations could provide a cellular substrate for emotional and cognitive dysfunctions present in these mice (Konstantoudaki et al, 2012.

  15. Aggregation of polyQ proteins is increased upon yeast aging and affected by Sir2 and Hsf1: novel quantitative biochemical and microscopic assays.

    Directory of Open Access Journals (Sweden)

    Aviv Cohen

    Full Text Available Aging-related neurodegenerative disorders, such as Parkinson's, Alzheimer's and Huntington's diseases, are characterized by accumulation of protein aggregates in distinct neuronal cells that eventually die. In Huntington's disease, the protein huntingtin forms aggregates, and the age of disease onset is inversely correlated to the length of the protein's poly-glutamine tract. Using quantitative assays to estimate microscopically and capture biochemically protein aggregates, here we study in Saccharomyces cerevisiae aging-related aggregation of GFP-tagged, huntingtin-derived proteins with different polyQ lengths. We find that the short 25Q protein never aggregates whereas the long 103Q version always aggregates. However, the mid-size 47Q protein is soluble in young logarithmically growing yeast but aggregates as the yeast cells enter the stationary phase and age, allowing us to plot an "aggregation timeline". This aging-dependent aggregation was associated with increased cytotoxicity. We also show that two aging-related genes, SIR2 and HSF1, affect aggregation of the polyQ proteins. In Δsir2 strain the aging-dependent aggregation of the 47Q protein is aggravated, while overexpression of the transcription factor Hsf1 attenuates aggregation. Thus, the mid-size 47Q protein and our quantitative aggregation assays provide valuable tools to unravel the roles of genes and environmental conditions that affect aging-related aggregation.

  16. Adult Age Differences in Dual Information Processes: Implications for the Role of Affective and Deliberative Processes in Older Adults' Decision Making.

    Science.gov (United States)

    Peters, Ellen; Hess, Thomas M; Västfjäll, Daniel; Auman, Corinne

    2007-03-01

    Age differences in affective/experiential and deliberative processes have important theoretical implications for judgment and decision theory and important pragmatic implications for older-adult decision making. Age-related declines in the efficiency of deliberative processes predict poorer-quality decisions as we age. However, age-related adaptive processes, including motivated selectivity in the use of deliberative capacity, an increased focus on emotional goals, and greater experience, predict better or worse decisions for older adults depending on the situation. The aim of the current review is to examine adult age differences in affective and deliberative information processes in order to understand their potential impact on judgments and decisions. We review evidence for the role of these dual processes in judgment and decision making and then review two representative life-span perspectives (based on aging-related changes to cognitive or motivational processes) on the interplay between these processes. We present relevant predictions for older-adult decisions and make note of contradictions and gaps that currently exist in the literature. Finally, we review the sparse evidence about age differences in decision making and how theories and findings regarding dual processes could be applied to decision theory and decision aiding. In particular, we focus on prospect theory (Kahneman & Tversky, 1979) and how prospect theory and theories regarding age differences in information processing can inform one another. © 2007 Association for Psychological Science.

  17. Affective Responses to Acute Exercise in Elderly Impaired Males: The Moderating Effects of Self-Efficacy and Age.

    Science.gov (United States)

    McAuley, Edward; And Others

    1995-01-01

    Examined relationships between perceptions of personal efficacy and affective responsibility to acute exercise in elderly male inpatients and outpatients at a Veterans Administration Medical Center. A significant change in feelings of fatigue was revealed over time but exercise effects on affect were shown to be moderated by perceptions of…

  18. Synaptogenesis in visual cortex of normal and preterm monkeys: evidence for intrinsic regulation of synaptic overproduction.

    OpenAIRE

    Bourgeois, J P; Jastreboff, P J; Rakic, P

    1989-01-01

    We used quantitative electron microscopy to determine the effect of precocious visual experience on the time course, magnitude, and pattern of perinatal synaptic overproduction in the primary visual cortex of the rhesus monkey. Fetuses were delivered by caesarean section 3 weeks before term, exposed to normal light intensity and day/night cycles, and killed within the first postnatal month, together with age-matched controls that were delivered at term. We found that premature visual stimulat...

  19. Contribution of the D-Serine-dependent pathway to the cellular mechanisms underlying cognitive aging

    Directory of Open Access Journals (Sweden)

    Emilie Rouaud

    2010-02-01

    Full Text Available An association between age-related memory impairments and changes in functional plasticity in the aging brain has been under intense study within the last decade. In this article, we show that an impaired activation of the strychnine-insensitive glycine site of N-Methyl-D-Aspartate receptors (NMDA-R by its agonist D-serine contributes to deficits of synaptic plasticity in the hippocampus of memory-impaired aged rats. Supplementation with exogenous D-serine prevents the age-related deficits of isolated NMDA-R-dependent synaptic potentials as well as those of theta-burst-induced long-term potentiation and synaptic depotentiation. Endogenous levels of D-serine are reduced in the hippocampus with aging, that correlates with a weaker expression of serine racemase synthesizing the amino acid. On the contrary, the affinity of D-serine binding to NMDA-R is not affected by aging. These results point to a critical role for the D-serine-dependent pathway in the functional alterations of the brain underlying memory impairment and provide key information in the search for new therapeutic strategies for the treatment of memory deficits in the elderly.

  20. Ethanol extract of the seed of Zizyphus jujuba var. spinosa potentiates hippocampal synaptic transmission through mitogen-activated protein kinase, adenylyl cyclase, and protein kinase A pathways.

    Science.gov (United States)

    Jo, So Yeon; Jung, In Ho; Yi, Jee Hyun; Choi, Tae Joon; Lee, Seungheon; Jung, Ji Wook; Yun, Jeanho; Lee, Young Choon; Ryu, Jong Hoon; Kim, Dong Hyun

    2017-03-22

    As the seed of Zizyphus jujuba var. spinosa (Bunge) Hu ex H.F. Chow (Rhamnaceae) has been used to sleep disturbances in traditional Chinese and Korean medicine, many previous studies have focused on its sedative effect. Recently, we reported the neuroprotective effect of the effect of Z. jujuba var. spinosa. However, its effects on synaptic function have not yet been studied. In this project, we examined the action of ethanol extract of the seed of Z. jujuba var. spinosa (DHP1401) on synaptic transmission in the hippocampus. To investigate the effects of DHP1401, field recordings were conducted using hippocampal slices (400µm). Object recognition test was introduced to examine whether DHP1401 affect normal recognition memory. DHP1401 (50μg/ml) induced a significant increase in synaptic activity in Shaffer collateral pathway in a concentration-dependent manner. This increase of synaptic responses was blocked by NBQX, a broad spectrum α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist, but not IEM-1460, a Ca 2+ -permeable AMPAR blocker. Moreover, U0126, a mitogen-activated protein kinase inhibitor, SQ22536, an adenylyl cyclase inhibitor, and PKI, a protein kinase A inhibitor, blocked DHP1401-induced increase in synaptic transmission. Finally, DHP1401 facilitated object recognition memory. These results suggest that DHP1401 increase synaptic transmission through increase of synaptic AMPAR transmission via MAPK, AC and PAK. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  1. Age as an Affective Factor in Influencing Public Speaking Anxiety of English Language Learners at Omar Al-Mukhtar University

    Science.gov (United States)

    Gaibani, Ahmed; Elmenfi, Fadil

    2016-01-01

    The study is to show how age factor can influence public speaking anxiety among English Language Learners at Omar Al-Mukhtar University. To indicate the influence of age factor a questionnaire was distributed to the participants of the study. As well as correlation was also undertaken to the data collected to investigate the influence of age…

  2. A presynaptic role for PKA in synaptic tagging and memory.

    Science.gov (United States)

    Park, Alan Jung; Havekes, Robbert; Choi, Jennifer Hk; Luczak, Vince; Nie, Ting; Huang, Ted; Abel, Ted

    2014-10-01

    Protein kinase A (PKA) and other signaling molecules are spatially restricted within neurons by A-kinase anchoring proteins (AKAPs). Although studies on compartmentalized PKA signaling have focused on postsynaptic mechanisms, presynaptically anchored PKA may contribute to synaptic plasticity and memory because PKA also regulates presynaptic transmitter release. Here, we examine this issue using genetic and pharmacological application of Ht31, a PKA anchoring disrupting peptide. At the hippocampal Schaffer collateral CA3-CA1 synapse, Ht31 treatment elicits a rapid decay of synaptic responses to repetitive stimuli, indicating a fast depletion of the readily releasable pool of synaptic vesicles. The interaction between PKA and proteins involved in producing this pool of synaptic vesicles is supported by biochemical assays showing that synaptic vesicle protein 2 (SV2), Rim1, and SNAP25 are components of a complex that interacts with cAMP. Moreover, acute treatment with Ht31 reduces the levels of SV2. Finally, experiments with transgenic mouse lines, which express Ht31 in excitatory neurons at the Schaffer collateral CA3-CA1 synapse, highlight a requirement for presynaptically anchored PKA in pathway-specific synaptic tagging and long-term contextual fear memory. These results suggest that a presynaptically compartmentalized PKA is critical for synaptic plasticity and memory by regulating the readily releasable pool of synaptic vesicles. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Glutamatergic synaptic plasticity in the mesocorticolimbic system in addiction

    Directory of Open Access Journals (Sweden)

    Aile evan Huijstee

    2015-01-01

    Full Text Available Addictive drugs remodel the brain’s reward circuitry, the mesocorticolimbic dopamine system, by inducing widespread adaptations of glutamatergic synapses. This drug-induced synaptic plasticity is thought to contribute to both the development and the persistence of addiction. This review highlights the synaptic modifications that are induced by in vivo exposure to addictive drugs and describes how these drug-induced synaptic changes may contribute to the different components of addictive behaviour, such as compulsive drug use despite negative consequences and relapse. Initially, exposure to an addictive drug induces synaptic changes in the ventral tegmental area (VTA. This drug-induced synaptic potentiation in the VTA subsequently triggers synaptic changes in downstream areas of the mesocorticolimbic system, such as the nucleus accumbens (NAc and the prefrontal cortex (PFC, with further drug exposure. These glutamatergic synaptic alterations are then thought to mediate many of the behavioural symptoms that characterize addiction. The later stages of glutamatergic synaptic plasticity in the NAc and in particular in the PFC play a role in maintaining addiction and drive relapse to drug-taking induced by drug-associated cues. Remodelling of PFC glutamatergic circuits can persist into adulthood, causing a lasting vulnerability to relapse. We will discuss how these neurobiological changes produced by drugs of abuse may provide novel targets for potential treatment strategies for addiction.

  4. Synaptogenic proteins and synaptic organizers: "many hands make light work".

    Science.gov (United States)

    Brose, Nils

    2009-03-12

    Synaptogenesis is thought to be mediated by cell adhesion proteins, which induce the initial contact between an axon and its target cell and subsequently recruit and organize the presynaptic and postsynaptic protein machinery required for synaptic transmission. A new study by Linhoff and colleagues in this issue of Neuron identifies adhesion proteins of the LRRTM family as novel synaptic organizers.

  5. Synaptic Tagging, Evaluation of Memories, and the Distal Reward Problem

    Science.gov (United States)

    Papper, Marc; Kempter, Richard; Leibold, Christian

    2011-01-01

    Long-term synaptic plasticity exhibits distinct phases. The synaptic tagging hypothesis suggests an early phase in which synapses are prepared, or "tagged," for protein capture, and a late phase in which those proteins are integrated into the synapses to achieve memory consolidation. The synapse specificity of the tags is consistent with…

  6. Glutamatergic synaptic plasticity in the mesocorticolimbic system in addiction

    Science.gov (United States)

    van Huijstee, Aile N.; Mansvelder, Huibert D.

    2015-01-01

    Addictive drugs remodel the brain’s reward circuitry, the mesocorticolimbic dopamine (DA) system, by inducing widespread adaptations of glutamatergic synapses. This drug-induced synaptic plasticity is thought to contribute to both the development and the persistence of addiction. This review highlights the synaptic modifications that are induced by in vivo exposure to addictive drugs and describes how these drug-induced synaptic changes may contribute to the different components of addictive behavior, such as compulsive drug use despite negative consequences and relapse. Initially, exposure to an addictive drug induces synaptic changes in the ventral tegmental area (VTA). This drug-induced synaptic potentiation in the VTA subsequently triggers synaptic changes in downstream areas of the mesocorticolimbic system, such as the nucleus accumbens (NAc) and the prefrontal cortex (PFC), with further drug exposure. These glutamatergic synaptic alterations are then thought to mediate many of the behavioral symptoms that characterize addiction. The later stages of glutamatergic synaptic plasticity in the NAc and in particular in the PFC play a role in maintaining addiction and drive relapse to drug-taking induced by drug-associated cues. Remodeling of PFC glutamatergic circuits can persist into adulthood, causing a lasting vulnerability to relapse. We will discuss how these neurobiological changes produced by drugs of abuse may provide novel targets for potential treatment strategies for addiction. PMID:25653591

  7. Modulation of synaptic plasticity by stress hormone associates with plastic alteration of synaptic NMDA receptor in the adult hippocampus.

    Directory of Open Access Journals (Sweden)

    Yiu Chung Tse

    Full Text Available Stress exerts a profound impact on learning and memory, in part, through the actions of adrenal corticosterone (CORT on synaptic plasticity, a cellular model of learning and memory. Increasing findings suggest that CORT exerts its impact on synaptic plasticity by altering the functional properties of glutamate receptors, which include changes in the motility and function of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid subtype of glutamate receptor (AMPAR that are responsible for the expression of synaptic plasticity. Here we provide evidence that CORT could also regulate synaptic plasticity by modulating the function of synaptic N-methyl-D-aspartate receptors (NMDARs, which mediate the induction of synaptic plasticity. We found that stress level CORT applied to adult rat hippocampal slices potentiated evoked NMDAR-mediated synaptic responses within 30 min. Surprisingly, following this fast-onset change, we observed a slow-onset (>1 hour after termination of CORT exposure increase in synaptic expression of GluN2A-containing NMDARs. To investigate the consequences of the distinct fast- and slow-onset modulation of NMDARs for synaptic plasticity, we examined the formation of long-term potentiation (LTP and long-term depression (LTD within relevant time windows. Paralleling the increased NMDAR function, both LTP and LTD were facilitated during CORT treatment. However, 1-2 hours after CORT treatment when synaptic expression of GluN2A-containing NMDARs is increased, bidirectional plasticity was no longer facilitated. Our findings reveal the remarkable plasticity of NMDARs in the adult hippocampus in response to CORT. CORT-mediated slow-onset increase in GluN2A in hippocampal synapses could be a homeostatic mechanism to normalize synaptic plasticity following fast-onset stress-induced facilitation.

  8. A change in social activity affect cognitive function in middle-aged and older Koreans: analysis of a Korean longitudinal study on aging (2006-2012).

    Science.gov (United States)

    Choi, Young; Park, Sohee; Cho, Kyoung Hee; Chun, Sung-Youn; Park, Eun-Cheol

    2016-08-01

    To examine the association between a changes in social activity and cognitive function in Koreans aged 45 years or older. Data were obtained from 6076 participants aged 45 years and older included in the Korean Longitudinal Study of Aging (2006-2012). Cognitive function was measured using the mini-mental state examination-Korean version (MMSE-K). Participation in social activities was classified as "consistent participation," "consistent non-participation," "participation to non-participation," and "non-participation to participation." Linear mixed models were used to investigate the relationship between type of social activity (religious organizations, friendship organizations, leisure/culture/sports clubs, family or school reunion, volunteering work, and political organizations), and cognitive function. Individuals who reported "no participation to participation" (b = 0.778, p cognitive decline than those who reported "consistent non-participation" (p cognitive function and consistent participation in religious activities, friendship organizations, and family/school reunions was particularly strong (b = 0.325, p older persons) may help preserve cognitive function in individuals aged 45 years or older in Korea. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  9. MPTP-meditated hippocampal dopamine deprivation modulates synaptic transmission and activity-dependent synaptic plasticity

    International Nuclear Information System (INIS)

    Zhu Guoqi; Chen Ying; Huang Yuying; Li Qinglin; Behnisch, Thomas

    2011-01-01

    Parkinson's disease (PD)-like symptoms including learning deficits are inducible by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Therefore, it is possible that MPTP may disturb hippocampal memory processing by modulation of dopamine (DA)- and activity-dependent synaptic plasticity. We demonstrate here that intraperitoneal (i.p.) MPTP injection reduces the number of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra (SN) within 7 days. Subsequently, the TH expression level in SN and hippocampus and the amount of DA and its metabolite DOPAC in striatum and hippocampus decrease. DA depletion does not alter basal synaptic transmission and changes pair-pulse facilitation (PPF) of field excitatory postsynaptic potentials (fEPSPs) only at the 30 ms inter-pulse interval. In addition, the induction of long-term potentiation (LTP) is impaired whereas the duration of long-term depression (LTD) becomes prolonged. Since both LTP and LTD depend critically on activation of NMDA and DA receptors, we also tested the effect of DA depletion on NMDA receptor-mediated synaptic transmission. Seven days after MPTP injection, the NMDA receptor-mediated fEPSPs are decreased by about 23%. Blocking the NMDA receptor-mediated fEPSP does not mimic the MPTP-LTP. Only co-application of D1/D5 and NMDA receptor antagonists during tetanization resembled the time course of fEPSP potentiation as observed 7 days after i.p. MPTP injection. Together, our data demonstrate that MPTP-induced degeneration of DA neurons and the subsequent hippocampal DA depletion alter NMDA receptor-mediated synaptic transmission and activity-dependent synaptic plasticity. - Highlights: → I.p. MPTP-injection mediates death of dopaminergic neurons. → I.p. MPTP-injection depletes DA and DOPAC in striatum and hippocampus. → I.p. MPTP-injection does not alter basal synaptic transmission. → Reduction of LTP and enhancement of LTD after i.p. MPTP-injection. → Attenuation of NMDA-receptors mediated

  10. Aging affects both perceptual and lexical/semantic components of word stem priming: An event-related fMRI study

    NARCIS (Netherlands)

    Daselaar, S.M.; Veltman, D.J.; Rombouts, S.A.R.B.; Raaijmakers, J.G.; Jonker, C.

    2005-01-01

    In this event-related fMRI study, brain activity patterns were compared in extensive groups of young (N = 25) and older (N = 38) adults, while they were performing a word stem completion priming task. Based on behavioral findings, we tested the hypothesis that aging affects only the

  11. [Involvement of aquaporin-4 in synaptic plasticity, learning and memory].

    Science.gov (United States)

    Wu, Xin; Gao, Jian-Feng

    2017-06-25

    Aquaporin-4 (AQP-4) is the predominant water channel in the central nervous system (CNS) and primarily expressed in astrocytes. Astrocytes have been generally believed to play important roles in regulating synaptic plasticity and information processing. However, the role of AQP-4 in regulating synaptic plasticity, learning and memory, cognitive function is only beginning to be investigated. It is well known that synaptic plasticity is the prime candidate for mediating of learning and memory. Long term potentiation (LTP) and long term depression (LTD) are two forms of synaptic plasticity, and they share some but not all the properties and mechanisms. Hippocampus is a part of limbic system that is particularly important in regulation of learning and memory. This article is to review some research progresses of the function of AQP-4 in synaptic plasticity, learning and memory, and propose the possible role of AQP-4 as a new target in the treatment of cognitive dysfunction.

  12. Aging and cytomegalovirus (CMV) infection differentially and jointly affect distinct circulating T cell subsets in humans1

    Science.gov (United States)

    Wertheimer, Anne M.; Bennett, Michael S.; Park, Byung; Uhrlaub, Jennifer L.; Martinez, Carmine; Pulko, Vesna; Currier, Noreen L.; Nikolich-Zugich, Dragana; Kaye, Jeffrey; Nikolich-Zugich, Janko

    2014-01-01

    The impact of intrinsic aging upon human peripheral blood T-cell subsets remains incompletely quantified and understood. This impact must be distinguished from the influence of latent persistent microorganisms, particularly cytomegalovirus (CMV), which has been associated with age-related changes in the T cell pool. In a cross-sectional cohort of 152 CMV-negative individuals, aged 21–101 years, we found that aging correlated strictly to an absolute loss of naïve CD8, but not CD4, T cells, but, contrary to many reports, did not lead to an increase in memory T cell numbers. The loss of naïve CD8 T cells was not altered by CMV in 239 subjects (range 21–96 years) but the decline in CD4+ naïve cells showed significance in CMV+ individuals. These individuals also exhibited an absolute increase in the effector/effector memory CD4+ and CD8+ cells with age. That increase was seen mainly, if not exclusively, in older subjects with elevated anti-CMV Ab titers, suggesting that efficacy of viral control over time may determine the magnitude of CMV impact upon T cell memory, and perhaps upon immune defense. These findings provide important new insights into the age-related changes in the peripheral blood pool of older adults, demonstrating that aging and CMV exert both distinct and joint influence upon blood T cell homeostasis in humans. PMID:24501199

  13. Stochastic lattice model of synaptic membrane protein domains.

    Science.gov (United States)

    Li, Yiwei; Kahraman, Osman; Haselwandter, Christoph A

    2017-05-01

    Neurotransmitter receptor molecules, concentrated in synaptic membrane domains along with scaffolds and other kinds of proteins, are crucial for signal transmission across chemical synapses. In common with other membrane protein domains, synaptic domains are characterized by low protein copy numbers and protein crowding, with rapid stochastic turnover of individual molecules. We study here in detail a stochastic lattice model of the receptor-scaffold reaction-diffusion dynamics at synaptic domains that was found previously to capture, at the mean-field level, the self-assembly, stability, and characteristic size of synaptic domains observed in experiments. We show that our stochastic lattice model yields quantitative agreement with mean-field models of nonlinear diffusion in crowded membranes. Through a combination of analytic and numerical solutions of the master equation governing the reaction dynamics at synaptic domains, together with kinetic Monte Carlo simulations, we find substantial discrepancies between mean-field and stochastic models for the reaction dynamics at synaptic domains. Based on the reaction and diffusion properties of synaptic receptors and scaffolds suggested by previous experiments and mean-field calculations, we show that the stochastic reaction-diffusion dynamics of synaptic receptors and scaffolds provide a simple physical mechanism for collective fluctuations in synaptic domains, the molecular turnover observed at synaptic domains, key features of the observed single-molecule trajectories, and spatial heterogeneity in the effective rates at which receptors and scaffolds are recycled at the cell membrane. Our work sheds light on the physical mechanisms and principles linking the collective properties of membrane protein domains to the stochastic dynamics that rule their molecular components.

  14. Alteration of synaptic connectivity of oligodendrocyte precursor cells following demyelination

    Science.gov (United States)

    Sahel, Aurélia; Ortiz, Fernando C.; Kerninon, Christophe; Maldonado, Paloma P.; Angulo, María Cecilia; Nait-Oumesmar, Brahim

    2015-01-01

    Oligodendrocyte precursor cells (OPCs) are a major source of remyelinating oligodendrocytes in demyelinating diseases such as Multiple Sclerosis (MS). While OPCs are innervated by unmyelinated axons in the normal brain, the fate of such synaptic contacts after demyelination is still unclear. By combining electrophysiology and immunostainings in different transgenic mice expressing fluorescent reporters, we studied the synaptic innervation of OPCs in the model of lysolecithin (LPC)-induced demyelination of corpus callosum. Synaptic innervation of reactivated OPCs in the lesion was revealed by the presence of AMPA receptor-mediated synaptic currents, VGluT1+ axon-OPC contacts in 3D confocal reconstructions and synaptic junctions observed by electron microscopy. Moreover, 3D confocal reconstructions of VGluT1 and NG2 immunolabeling showed the existence of glutamatergic axon-OPC contacts in post-mortem MS lesions. Interestingly, patch-clamp recordings in LPC-induced lesions demonstrated a drastic decrease in spontaneous synaptic activity of OPCs early after demyelination that was not caused by an impaired conduction of compound action potentials. A reduction in synaptic connectivity was confirmed by the lack of VGluT1+ axon-OPC contacts in virtually all rapidly proliferating OPCs stained with EdU (50-ethynyl-20-deoxyuridine). At the end of the massive proliferation phase in lesions, the proportion of innervated OPCs rapidly recovers, although the frequency of spontaneous synaptic currents did not reach control levels. In conclusion, our results demonstrate that newly-generated OPCs do not receive synaptic inputs during their active proliferation after demyelination, but gain synapses during the remyelination process. Hence, glutamatergic synaptic inputs may contribute to inhibit OPC proliferation and might have a physiopathological relevance in demyelinating disorders. PMID:25852473

  15. Leucine-rich repeat-containing synaptic adhesion molecules as organizers of synaptic specificity and diversity.

    Science.gov (United States)

    Schroeder, Anna; de Wit, Joris

    2018-04-09

    The brain harbors billions of neurons that form distinct neural circuits with exquisite specificity. Specific patterns of connectivity between distinct neuronal cell types permit the transfer and computation of information. The molecular correlates that give rise to synaptic specificity are incompletely understood. Recent studies indicate that cell-surface molecules are important determinants of cell type identity and suggest that these are essential players in the specification of synaptic connectivity. Leucine-rich repeat (LRR)-containing adhesion molecules in particular have emerged as key organizers of excitatory and inhibitory synapses. Here, we discuss emerging evidence that LRR proteins regulate the assembly of specific connectivity patterns across neural circuits, and contribute to the diverse structural and functional properties of synapses, two key features that are critical for the proper formation and function of neural circuits.

  16. Vitex agnus-castus essential oil affects thyroid C cells and bone metabolism in middle-aged male rats

    OpenAIRE

    Pantelić Jasmina; Filipović B.; Šošić-Jurjević Branka; Ajdžanović V.; Trifunović Svetlana; Medigović Ivana; Milošević Verica

    2013-01-01

    Ageing in men is accompanied by an increased occurrence of osteoporosis, but traditional hormonal replacement therapy elevates the risk of developing endocrine cancer. Vitex agnus-castus L. (Vac) essential oil is commonly used as an alternative therapy for ageing symptoms in both men and women. It is known that calcitonin (CT), thyroid C cell hormone, inhibits bone resorption. The purpose of this experimental study was to investigate the influence of Vac es...

  17. Paternal Aging Affects Behavior in Pax6 Mutant Mice: A Gene/Environment Interaction in Understanding Neurodevelopmental Disorders.

    Science.gov (United States)

    Yoshizaki, Kaichi; Furuse, Tamio; Kimura, Ryuichi; Tucci, Valter; Kaneda, Hideki; Wakana, Shigeharu; Osumi, Noriko

    2016-01-01

    Neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention deficit and hyperactivity disorder (ADHD) have increased over the last few decades. These neurodevelopmental disorders are characterized by a complex etiology, which involves multiple genes and gene-environmental interactions. Various genes that control specific properties of neural development exert pivotal roles in the occurrence and severity of phenotypes associated with neurodevelopmental disorders. Moreover, paternal aging has been reported as one of the factors that contribute to the risk of ASD and ADHD. Here we report, for the first time, that paternal aging has profound effects on the onset of behavioral abnormalities in mice carrying a mutation of Pax6, a gene with neurodevelopmental regulatory functions. We adopted an in vitro fertilization approach to restrict the influence of additional factors. Comprehensive behavioral analyses were performed in Sey/+ mice (i.e., Pax6 mutant heterozygotes) born from in vitro fertilization of sperm taken from young or aged Sey/+ fathers. No body weight changes were found in the four groups, i.e., Sey/+ and wild type (WT) mice born to young or aged father. However, we found important differences in maternal separation-induced ultrasonic vocalizations of Sey/+ mice born from young father and in the level of hyperactivity of Sey/+ mice born from aged fathers in the open-field test, respectively, compared to WT littermates. Phenotypes of anxiety were observed in both genotypes born from aged fathers compared with those born from young fathers. No significant difference was found in social behavior and sensorimotor gating among the four groups. These results indicate that mice with a single genetic risk factor can develop different phenotypes depending on the paternal age. Our study advocates for serious considerations on the role of paternal aging in breeding strategies for animal studies.

  18. Paternal Aging Affects Behavior in Pax6 Mutant Mice: A Gene/Environment Interaction in Understanding Neurodevelopmental Disorders.

    Directory of Open Access Journals (Sweden)

    Kaichi Yoshizaki

    Full Text Available Neurodevelopmental disorders such as autism spectrum disorder (ASD and attention deficit and hyperactivity disorder (ADHD have increased over the last few decades. These neurodevelopmental disorders are characterized by a complex etiology, which involves multiple genes and gene-environmental interactions. Various genes that control specific properties of neural development exert pivotal roles in the occurrence and severity of phenotypes associated with neurodevelopmental disorders. Moreover, paternal aging has been reported as one of the factors that contribute to the risk of ASD and ADHD. Here we report, for the first time, that paternal aging has profound effects on the onset of behavioral abnormalities in mice carrying a mutation of Pax6, a gene with neurodevelopmental regulatory functions. We adopted an in vitro fertilization approach to restrict the influence of additional factors. Comprehensive behavioral analyses were performed in Sey/+ mice (i.e., Pax6 mutant heterozygotes born from in vitro fertilization of sperm taken from young or aged Sey/+ fathers. No body weight changes were found in the four groups, i.e., Sey/+ and wild type (WT mice born to young or aged father. However, we found important differences in maternal separation-induced ultrasonic vocalizations of Sey/+ mice born from young father and in the level of hyperactivity of Sey/+ mice born from aged fathers in the open-field test, respectively, compared to WT littermates. Phenotypes of anxiety were observed in both genotypes born from aged fathers compared with those born from young fathers. No significant difference was found in social behavior and sensorimotor gating among the four groups. These results indicate that mice with a single genetic risk factor can develop different phenotypes depending on the paternal age. Our study advocates for serious considerations on the role of paternal aging in breeding strategies for animal studies.

  19. Factors and Caregiver’s Behavior Affecting Inadequate Complementary Food of Infants Aged 6-12 Months in Naresuan University Hospital

    Directory of Open Access Journals (Sweden)

    Thitima Ngoenmak, M.D.

    2017-09-01

    Full Text Available Objective: Food plays an important role in infant nutrition. Hence, the various factors and behavior that affect the right choice of nutrition for infants aged 6-12 months by caregivers need to be investigated. The objectives were to study the associated factors and caregiver’s behavior affecting inadequate feeding of food to infants aged 6-12 months. Methods: This present work was a cross-sectional study in which 54 caregivers for infants were included. In this study, a survey was performed by using questionnaires for collecting data. The data were analyzed statistically in terms of percentage and mean and by using Chi-Square test (Fisher’s Exact Test and z-test. Results: It was found that most of the infants (79.6 % had normal weight. The age at the start of proper feeding was 5 months and 27 days old. The education level, age, occupation, and income of the caregivers were factors affecting the food choices for the infants at p< 0.05. Inappropriate feeding practices were as follows: feeding pre- masticated foods, liquid food feeding, drinking sweetened juice and soft drinks, eating sweets, and adding salt, sugar, monosodium glutamate and fish sauce to the infants’ food. The caregivers chose food by judging for age and FDA logo on product labels. Advertising did not affect their decision to purchase food. Moreover, occupation, education, and income of the caregivers were not associated with purchasing the right food for the baby. Conclusion: Occupation, income, age, and education level of the infant caregivers were associated with the food selection. The inappropriate feeding behaviors were still persisting.

  20. Ankyrins: Roles in synaptic biology and pathology.

    Science.gov (United States)

    Smith, Katharine R; Penzes, Peter

    2018-05-03

    Ankyrins are broadly expressed adaptors that organize diverse membrane proteins into specialized domains and link them to the sub-membranous cytoskeleton. In neurons, ankyrins are known to have essential roles in organizing the axon initial segment and nodes of Ranvier. However, recent studies have revealed novel functions for ankyrins at synapses, where they organize and stabilize neurotransmitter receptors, modulate dendritic spine morphology and control adhesion to the presynaptic site. Ankyrin genes have also been highly associated with a range of neurodevelopmental and psychiatric diseases, including bipolar disorder, schizophrenia and autism, which all demonstrate overlap in their genetics, mechanisms and phenotypes. This review discusses the novel synaptic functions of ankyrin proteins in neurons, and places these exciting findings in the context of ANK genes as key neuropsychiatric disorder risk-factors. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. Alzheimer's disease: synaptic dysfunction and Abeta

    LENUS (Irish Health Repository)

    Shankar, Ganesh M

    2009-11-23

    Abstract Synapse loss is an early and invariant feature of Alzheimer\\'s disease (AD) and there is a strong correlation between the extent of synapse loss and the severity of dementia. Accordingly, it has been proposed that synapse loss underlies the memory impairment evident in the early phase of AD and that since plasticity is important for neuronal viability, persistent disruption of plasticity may account for the frank cell loss typical of later phases of the disease. Extensive multi-disciplinary research has implicated the amyloid β-protein (Aβ) in the aetiology of AD and here we review the evidence that non-fibrillar soluble forms of Aβ are mediators of synaptic compromise. We also discuss the possible mechanisms of Aβ synaptotoxicity and potential targets for therapeutic intervention.

  2. Optogenetic acidification of synaptic vesicles and lysosomes.

    Science.gov (United States)

    Rost, Benjamin R; Schneider, Franziska; Grauel, M Katharina; Wozny, Christian; Bentz, Claudia; Blessing, Anja; Rosenmund, Tanja; Jentsch, Thomas J; Schmitz, Dietmar; Hegemann, Peter; Rosenmund, Christian

    2015-12-01

    Acidification is required for the function of many intracellular organelles, but methods to acutely manipulate their intraluminal pH have not been available. Here we present a targeting strategy to selectively express the light-driven proton pump Arch3 on synaptic vesicles. Our new tool, pHoenix, can functionally replace endogenous proton pumps, enabling optogenetic control of vesicular acidification and neurotransmitter accumulation. Under physiological conditions, glutamatergic vesicles are nearly full, as additional vesicle acidification with pHoenix only slightly increased the quantal size. By contrast, we found that incompletely filled vesicles exhibited a lower release probability than full vesicles, suggesting preferential exocytosis of vesicles with high transmitter content. Our subcellular targeting approach can be transferred to other organelles, as demonstrated for a pHoenix variant that allows light-activated acidification of lysosomes.

  3. An Analysis of Factors Affecting Mature Age Students' Academic Success in Undergraduate Nursing Programs: A Critical Literature Review.

    Science.gov (United States)

    Hayden, Lisa J; Jeong, Sarah Y; Norton, Carol A

    2016-01-01

    The population of mature age students entering university nursing programs has steadily increased in both Australia and worldwide. The objective of the literature review was to explore how mature age students perform academically and to analyse the factors associated with their academic performance in nursing programs. A literature search was conducted in the following databases: CINAHL, ProQuest, Medline, Cochrane, Mosby's Index, Joanna Briggs Institute (JBI), and Scopus. Twenty-six (26) research papers published between 2000 and 2014 have met the selection criteria of this review. The key themes identified include; 1) ambiguity in definition of mature age and academic success, 2) age and academic success, 3) intrinsic factors (life experiences, emotional intelligence, and motivation and volition), and 4) extrinsic factors (peer, academic and family support; and learning style, components of the modules and mode of delivery). Current literature provides evidence that mature age nursing students perform at a higher level within the methodological issues discussed in this paper. Future research is warranted to advance the understanding of the complex relationship between extrinsic and intrinsic factors of mature age students and their academic success in higher education. Nursing educators will benefit from novel evidence, ideas and opportunities to explore and implement in nursing education.

  4. Inhibition of DNA Methylation Impairs Synaptic Plasticity during an Early Time Window in Rats

    Directory of Open Access Journals (Sweden)

    Pablo Muñoz

    2016-01-01

    Full Text Available Although the importance of DNA methylation-dependent gene expression to neuronal plasticity is well established, the dynamics of methylation and demethylation during the induction and expression of synaptic plasticity have not been explored. Here, we combined electrophysiological, pharmacological, molecular, and immunohistochemical approaches to examine the contribution of DNA methylation and the phosphorylation of Methyl-CpG-binding protein 2 (MeCP2 to synaptic plasticity. We found that, at twenty minutes after theta burst stimulation (TBS, the DNA methylation inhibitor 5-aza-2-deoxycytidine (5AZA impaired hippocampal long-term potentiation (LTP. Surprisingly, after two hours of TBS, when LTP had become a transcription-dependent process, 5AZA treatment had no effect. By comparing these results to those in naive slices, we found that, at two hours after TBS, an intergenic region of the RLN gene was hypomethylated and that the phosphorylation of residue S80 of MeCP2 was decreased, while the phosphorylation of residue S421 was increased. As expected, 5AZA affected only the methylation of the RLN gene and exerted no effect on MeCP2 phosphorylation patterns. In summary, our data suggest that tetanic stimulation induces critical changes in synaptic plasticity that affects both DNA methylation and the phosphorylation of MeCP2. These data also suggest that early alterations in DNA methylation are sufficient to impair the full expression of LTP.

  5. Inhibition of DNA Methylation Impairs Synaptic Plasticity during an Early Time Window in Rats.

    Science.gov (United States)

    Muñoz, Pablo; Estay, Carolina; Díaz, Paula; Elgueta, Claudio; Ardiles, Álvaro O; Lizana, Pablo A

    2016-01-01

    Although the importance of DNA methylation-dependent gene expression to neuronal plasticity is well established, the dynamics of methylation and demethylation during the induction and expression of synaptic plasticity have not been explored. Here, we combined electrophysiological, pharmacological, molecular, and immunohistochemical approaches to examine the contribution of DNA methylation and the phosphorylation of Methyl-CpG-binding protein 2 (MeCP2) to synaptic plasticity. We found that, at twenty minutes after theta burst stimulation (TBS), the DNA methylation inhibitor 5-aza-2-deoxycytidine (5AZA) impaired hippocampal long-term potentiation (LTP). Surprisingly, after two hours of TBS, when LTP had become a transcription-dependent process, 5AZA treatment had no effect. By comparing these results to those in naive slices, we found that, at two hours after TBS, an intergenic region of the RLN gene was hypomethylated and that the phosphorylation of residue S80 of MeCP2 was decreased, while the phosphorylation of residue S421 was increased. As expected, 5AZA affected only the methylation of the RLN gene and exerted no effect on MeCP2 phosphorylation patterns. In summary, our data suggest that tetanic stimulation induces critical changes in synaptic plasticity that affects both DNA methylation and the phosphorylation of MeCP2. These data also suggest that early alterations in DNA methylation are sufficient to impair the full expression of LTP.

  6. DPP6 Loss Impacts Hippocampal Synaptic Development and Induces Behavioral Impairments in Recognition, Learning and Memory

    Directory of Open Access Journals (Sweden)

    Lin Lin

    2018-03-01

    Full Text Available DPP6 is well known as an auxiliary subunit of Kv4-containing, A-type K+ channels which regulate dendritic excitability in hippocampal CA1 pyramidal neurons. We have recently reported, however, a novel role for DPP6 in regulating dendritic filopodia formation and stability, affecting synaptic development and function. These results are notable considering recent clinical findings associating DPP6 with neurodevelopmental and intellectual disorders. Here we assessed the behavioral consequences of DPP6 loss. We found that DPP6 knockout (DPP6-KO mice are impaired in hippocampus-dependent learning and memory. Results from the Morris water maze and T-maze tasks showed that DPP6-KO mice exhibit slower learning and reduced memory performance. DPP6 mouse brain weight is reduced throughout development compared with WT, and in vitro imaging results indicated that DPP6 loss affects synaptic structure and motility. Taken together, these results show impaired synaptic development along with spatial learning and memory deficiencies in DPP6-KO mice.

  7. Synaptic proteome changes in the superior frontal gyrus and occipital cortex of the alcoholic brain.

    Science.gov (United States)

    Etheridge, Naomi; Lewohl, Joanne M; Mayfield, R Dayne; Harris, R Adron; Dodd, Peter R

    2009-06-24

    Cognitive deficits and behavioral changes that result from chronic alcohol abuse are a consequence of neuropathological changes which alter signal transmission through the neural network. To focus on the changes that occur at the point of connection between the neural network cells, synaptosomal preparations from post-mortem human brain of six chronic alcoholics and six non-alcoholic controls were compared using 2D-DIGE. Functionally affected and spared regions (superior frontal gyrus, SFG, and occipital cortex, OC, respectively) were analyzed from both groups to further investigate the specific pathological response that alcoholism has on the brain. Forty-nine proteins were differentially regulated between the SFG of alcoholics and the SFG of controls and 94 proteins were regulated in the OC with an overlap of 23 proteins. Additionally, the SFG was compared to the OC within each group (alcoholics or controls) to identify region specific differences. A selection were identified by MALDI-TOF mass spectrometry revealing proteins involved in vesicle transport, metabolism, folding and trafficking, and signal transduction, all of which have the potential to influence synaptic activity. A number of proteins identified in this study have been previously related to alcoholism; however, the focus on synaptic proteins has also uncovered novel alcoholism-affected proteins. Further exploration of these proteins will illuminate the mechanisms altering synaptic plasticity, and thus neuronal signaling and response, in the alcoholic brain.

  8. Synaptic activity-related classical protein kinase C isoform localization in the adult rat neuromuscular synapse.

    Science.gov (United States)

    Besalduch, Núria; Tomàs, Marta; Santafé, Manel M; Garcia, Neus; Tomàs, Josep; Lanuza, Maria Angel

    2010-01-10

    Protein kinase C (PKC) is essential for signal transduction in a variety of cells, including neurons and myocytes, and is involved in both acetylcholine release and muscle fiber contraction. Here, we demonstrate that the increases in synaptic activity by nerve stimulation couple PKC to transmitter release in the rat neuromuscular junction and increase the level of alpha, betaI, and betaII isoforms in the membrane when muscle contraction follows the stimulation. The phosphorylation activity of these classical PKCs also increases. It seems that the muscle has to contract in order to maintain or increase classical PKCs in the membrane. We use immunohistochemistry to show that PKCalpha and PKCbetaI were located in the nerve terminals, whereas PKCalpha and PKCbetaII were located in the postsynaptic and the Schwann cells. Stimulation and contraction do not change these cellular distributions, but our results show that the localization of classical PKC isoforms in the membrane is affected by synaptic activity.

  9. Dietary inulin intake and age can significantly affect intestinal absorption of calcium and magnesium in rats: a stable isotope approach

    Science.gov (United States)

    Coudray, Charles; Rambeau, Mathieu; Feillet-Coudray, Christine; Tressol, Jean Claude; Demigne, Christian; Gueux, Elyett; Mazur, Andrzej; Rayssiguier, Yves

    2005-01-01

    Background previous studies have shown that non-digestible inulin-type fructan intake can increase intestinal mineral absorption in both humans and animals. However, this stimulatory effect on intestinal absorption may depend on experimental conditions such as duration of fermentable fiber intake, mineral diet levels and animals' physiological status, in particular their age. Objectives the aim of this study was to determine the effect of inulin intake on Ca and Mg absorption in rats at different age stages. Methods eighty male Wistar rats of four different ages (2, 5, 10 and 20 months) were randomized into either a control group or a group receiving 3.75% inulin in their diet for 4 days and then 7.5% inulin for three weeks. The animals were fed fresh food and water ad libitum for the duration of the experiment. Intestinal absorption of Ca and Mg was determined by fecal monitoring using stable isotopic tracers. Ca and Mg status was also assessed. Results absorption of Ca and Mg was significantly lower in the aged rats (10 and 20 mo) than in the young and adult rat groups. As expected, inulin intake increased Ca and Mg absorption in all four rat groups. However, inulin had a numerically greater effect on Ca absorption in aged rats than in younger rats whereas its effect on Mg absorption remained similar across all four rat age groups. Conclusion the extent of the stimulatory effect of inulin on absorption of Ca may differ according to animal ages. Further studies are required to explore this effect over longer inulin intake periods, and to confirm these results in humans. PMID:16253138

  10. Spine Calcium Transients Induced by Synaptically-Evoked Action Potentials Can Predict Synapse Location and Establish Synaptic Democracy

    Science.gov (United States)

    Meredith, Rhiannon M.; van Ooyen, Arjen

    2012-01-01

    CA1 pyramidal neurons receive hundreds of synaptic inputs at different distances from the soma. Distance-dependent synaptic scaling enables distal and proximal synapses to influence the somatic membrane equally, a phenomenon called “synaptic democracy”. How this is established is unclear. The backpropagating action potential (BAP) is hypothesised to provide distance-dependent information to synapses, allowing synaptic strengths to scale accordingly. Experimental measurements show that a BAP evoked by current injection at the soma causes calcium currents in the apical shaft whose amplitudes decay with distance from the soma. However, in vivo action potentials are not induced by somatic current injection but by synaptic inputs along the dendrites, which creates a different excitable state of the dendrites. Due to technical limitations, it is not possible to study experimentally whether distance information can also be provided by synaptically-evoked BAPs. Therefore we adapted a realistic morphological and electrophysiological model to measure BAP-induced voltage and calcium signals in spines after Schaffer collateral synapse stimulation. We show that peak calcium concentration is highly correlated with soma-synapse distance under a number of physiologically-realistic suprathreshold stimulation regimes and for a range of dendritic morphologies. Peak calcium levels also predicted the attenuation of the EPSP across the dendritic tree. Furthermore, we show that peak calcium can be used to set up a synaptic democracy in a homeostatic manner, whereby synapses regulate their synaptic strength on the basis of the difference between peak calcium and a uniform target value. We conclude that information derived from synaptically-generated BAPs can indicate synapse location and can subsequently be utilised to implement a synaptic democracy. PMID:22719238

  11. Gingival Pigmentation Affected by Smoking among Different Age Groups: A Quantitative Analysis of Gingival Pigmentation Using Clinical Oral Photographs.

    Science.gov (United States)

    Kato, Tomotaka; Mizutani, Shinsuke; Takiuchi, Hiroya; Sugiyama, Seiichi; Hanioka, Takashi; Naito, Toru

    2017-08-04

    The presence of any age-related differences in gingival pigmentation associated with smoking, particularly in a young population, remains to be fully investigated. The purpose of this study was to determine the age-related differences in smoking gingival pigmentation. Gingival pigmentation was analyzed using the gingival melanosis record (GMR) and Hedin's classification with frontal oral photographs taken at 16 dental offices in Japan. Participants were categorized into 10-year age groups, and their baseline photographs were compared. In addition, to evaluate the effect of smoking cessation on gingival pigmentation, subjects were divided into a former smoker group (stopped smoking) and current smoker group. A total of 259 patients 19 to 79 years of age were analyzed. People in their 30s showed the most widespread gingival pigmentation. In addition, subjects in their 20s showed a weak effect of smoking cessation on gingival pigmentation. These findings suggested that the gingival pigmentation induced by smoking was more remarkable in young people than in middle-aged people. This information may be useful for anti-smoking education, especially among young populations with a high affinity for smoking.

  12. Polymorphic variants of neurotransmitter receptor genes may affect sexual function in aging males: data from the HALS study.

    Science.gov (United States)

    Jóźków, Paweł; Słowińska-Lisowska, Małgorzata; Łaczmański, Łukasz; Mędraś, Marek

    2013-01-01

    Human behavior is influenced by a number of brain neurotransmitters. Central dopamine, serotonin and melanocortin systems have special importance for male sexual function. We searched for associations between male aging symptoms and polymorphic sites of serotonin (5-HTR1B), melanocortin (MC4R) and dopamine (DRD2, DRD4) receptors. In a population-based sample, genotyping of 5-HTR1B (polymorphism: G861C), MC4R (polymorphisms: C-2745T, Val103Ile), DRD2 (polymorphism: C313T) and DRD4 (polymorphism: 48-bp VNTR) was performed in 387 healthy men. The Aging Males' Symptoms (AMS) scale was used to evaluate specific ailments of aging men. We analyzed answers to questions from the AMS scale. Five points of the questionnaire addressed sexual symptoms of the aging male: feeling of passing one's peak, decrease in beard growth, decrease in ability/frequency to perform sexually, decrease in the number of morning erections, and decrease in sexual desire/libido (lacking pleasure in sex, lacking desire for sexual intercourse). Relations between reported symptoms and variants of the polymorphic sites of the studied genes were assessed. After adjusting for confounding factors (education, arterial hypertension, physical activity, weight, waist circumference) an association between the sexual dimension of AMS and genetic variants of 5-HTR1B G861C (p = 0.04) was observed. Variability of neurotransmitter receptor genes may be associated with sexual symptoms of aging in men. Copyright © 2013 S. Karger AG, Basel.

  13. CASP-19 special section: how does chronic disease status affect CASP quality of life at older ages? Examining the WHO ICF disability domains as mediators of this relationship.

    Science.gov (United States)

    Sexton, E; King-Kallimanis, B L; Layte, R; Hickey, A

    2015-07-01

    The effect of chronic disease status on quality of life (QoL) has been well established. However, less is known about how chronic diseases affect QoL. This article examines impairment in three domains of the WHO International Classification of Functioning, Health and Disability (ICF) - body function, activity and participation, as well as affective well-being, - as potential mediators of the relationship between chronic disease and QoL. A cross-sectional sample (n = 4961) of the general Irish community-dwelling population aged 50+ years was obtained from the Irish Longitudinal Study of Ageing (TILDA). The CASP measure of QoL was examined as two dimensions - control/autonomy and self-realisation/pleasure. Structural equation modelling was used to test the direct and indirect effects of chronic disease on QoL, via variables capturing body function, activity, participation and positive affect. A factor analysis showed that indicators of body function and activity loaded onto a single overall physical impairment factor. This physical impairment factor fully mediated the effect of chronic disease on positive affect and QoL. The total effect of chronic disease on control/autonomy (-0.160) was primarily composed of an indirect effect via physical impairment (-0.86), and via physical impairment and positive affect (-0.45). The decomposition of effects on self-realisation/pleasure was similar, although the direct effect of physical impairment was weaker. The model fitted the data well (RMSEA = 0.02, TLI = 0.96, CFI = 0.96). Chronic disease affects QoL through increased deficits in physical body function and activity. This overall physical impairment affects QoL both directly and indirectly via reduced positive affect.

  14. Short communication: Changes in body temperature of calves up to 2 months of age as affected by time of day, age, and ambient temperature.

    Science.gov (United States)

    Hill, T M; Bateman, H G; Suarez-Mena, F X; Dennis, T S; Schlotterbeck, R L

    2016-11-01

    Extensive measurements of calf body temperature are limited in the literature. In this study, body temperatures were collected by taping a data logger to the skin over the tail vein opposing the rectum of Holstein calves between 4 and 60d of age during 3 different periods of the summer and fall. The summer period was separated into moderate (21-33°C average low to high) and hot (25-37°C) periods, whereas the fall exhibited cool (11-19°C) ambient temperatures. Tail temperatures were compared in a mixed model ANOVA using ambient temperature, age of calf, and time of day (10-min increments) as fixed effects and calf as a random effect. Measures within calf were modeled as repeated effects of type autoregressive 1. Calf temperature increased 0.0325°C (±0.00035) per 1°C increase in ambient temperature. Body temperature varied in a distinct, diurnal pattern with time of day, with body temperatures being lowest around 0800h and highest between 1700 and 2200h. During periods of hot weather, the highest calf temperature was later in the day (~2200h). Calf minimum, maximum, and average body temperatures were all higher in hot than in moderate periods and higher in moderate than in cool periods. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  15. Synaptic Remodeling in the Dentate Gyrus, CA3, CA1, Subiculum, and Entorhinal Cortex of Mice: Effects of Deprived Rearing and Voluntary Running

    Directory of Open Access Journals (Sweden)

    Andrea T. U. Schaefers

    2010-01-01

    Full Text Available Hippocampal cell proliferation is strongly increased and synaptic turnover decreased after rearing under social and physical deprivation in gerbils (Meriones unguiculatus. We examined if a similar epigenetic effect of rearing environment on adult neuroplastic responses can be found in mice (Mus musculus. We examined synaptic turnover rates in the dentate gyrus, CA3, CA1, subiculum, and entorhinal cortex. No direct effects of deprived rearing on rates of synaptic turnover were found in any of the studied regions. However, adult wheel running had the effect of leveling layer-specific differences in synaptic remodeling in the dentate gyrus, CA3, and CA1, but not in the entorhinal cortex and subiculum of animals of both rearing treatments. Epigenetic effects during juvenile development affected adult neural plasticity in mice, but seemed to be less pronounced than in gerbils.

  16. Loci Affecting Gamma-Glutamyl Transferase in Adults and Adolescents Show Age X SNP interaction and Cardiometabolic Disease Associations

    NARCIS (Netherlands)

    Middelberg, R.P.S.; Benyamin, B.; de Moor, M.H.M.; Warrington, N.M.; Gordon, S.; Henders, A.K.; Medland, S.E.; Nyholt, DR; de Geus, E.J.C.; Hottenga, J.J.; Willemsen, G.; Beilin, L.J.; Mori, T.A.; Wright, M.J.; Heath, A.C.; Madden, P.A.F.; Boomsma, D.I.; Pennell, C.E.; Montgomery, G.W.; Martin, N.G.; Whitfield, J.B.

    2012-01-01

    Serum gamma-glutamyl transferase (GGT) activity is a marker of liver disease which is also prospectively associated with the risk of all-cause mortality, cardiovascular disease, type 2 diabetes and cancers. We have discovered novel loci affecting GGT in a genome-wide association study (rs1497406 in

  17. Age Differences in Affective and Cardiovascular Responses to a Negative Social Interaction: The Role of Goals, Appraisals, and Emotion Regulation

    Science.gov (United States)

    Luong, Gloria; Charles, Susan T.

    2014-01-01

    Older adults often report less affective reactivity to interpersonal tensions than younger individuals, but few studies have directly investigated mechanisms explaining this effect. The current study examined whether older adults' differential endorsement of goals, appraisals, and emotion regulation strategies (i.e., conflict…

  18. Age affects the expression of maternal care and subsequent behavioural development of offspring in a precocial bird.

    Directory of Open Access Journals (Sweden)

    Florent Pittet

    Full Text Available Variations of breeding success with age have been studied largely in iteroparous species and particularly in birds: survival of offspring increases with parental age until senescence. Nevertheless, these results are from observations of free-living individuals and therefore, it remains impossible to determine whether these variations result from parental investment or efficiency or both, and whether these variations occur during the prenatal or the postnatal stage or during both. Our study aimed first, to determine whether age had an impact on the expression of maternal breeding care by comparing inexperienced female birds of two different ages, and second, to define how these potential differences impact chicks' growth and behavioural development. We made 22 2-month-old and 22 8-month-old female Japanese quail foster 1-day-old chicks. We observed their maternal behaviour until the chicks were 11 days old and then tested these chicks after separation from their mothers. Several behavioural tests estimated their fearfulness and their sociality. We observed first that a longer induction was required for young females to express maternal behaviour. Subsequently as many young females as elder females expressed maternal behaviour, but young females warmed chicks less, expressed less covering postures and rejected their chicks more. Chicks brooded by elder females presented higher growth rates and more fearfulness and sociality. Our results reveal that maternal investment increased with age independently of maternal experience, suggesting modification of hormone levels implied in maternal behaviour. Isolated effects of maternal experience should now be assessed in females of the same age. In addition, our results show, for first time in birds, that variations in maternal care directly induce important differences in the behavioural development of chicks. Finally, our results confirm that Japanese quail remains a great laboratory model of avian

  19. Hormonal status and age differentially affect tolerance to the disruptive effects of delta-9-tetrahydrocannabinol (Δ9-THC on learning in female rats

    Directory of Open Access Journals (Sweden)

    Peter J Winsauer

    2015-07-01

    Full Text Available The effects of hormone status and age on the development of tolerance to D9-THC were assessed in sham-operated (intact or ovariectomized (OVX female rats that received either intraperitoneal saline or 5.6 mg/kg of D9-THC daily from postnatal day (PD 75 to 180 (early adulthood onward or PD 35 to 140 (adolescence onward. During this time, the 4 groups for each age (i.e., intact/saline, intact/THC, OVX/saline, and OVX/THC were trained in a learning and performance procedure and dose-effect curves were established for D9-THC (0.56-56 mg/kg and the cannabinoid type-1 receptor (CB1R antagonist rimonabant (0.32-10 mg/kg. Despite the persistence of small rate-decreasing and error-increasing effects in intact and OVX females from both ages during chronic D9-THC, all of the D9-THC groups developed tolerance. However, the magnitude of tolerance, as well as the effect of hormone status, varied with the age at which chronic D9-THC was initiated. There was no evidence of dependence in any of the groups. Hippocampal protein expression of CB1R, AHA1 (a co-chaperone of CB1R and HSP90β (a molecular chaperone modulated by AHA-1 was affected more by OVX than chronic D9-THC; striatal protein expression was not consistently affected by either manipulation. Hippocampal BDNF expression varied with age, hormone status, and chronic treatment. Thus, hormonal status differentially affects the development of tolerance to the disruptive effects of delta-9-tetrahydrocannabinol (D9-THC on learning and performance behavior in adolescent, but not adult, female rats. These factors and their interactions also differentially affect cannabinoid signaling proteins in the hippocampus and striatum, and ultimately, neural plasticity.

  20. Creative Thinking of University Teachers in the Age of Intellectual Capital: Is It Affected by Personality Types and Traits?

    Science.gov (United States)

    AlFuqaha, Isam Najib; Tobasi, Adnan

    2015-01-01

    This article attempts to probe the level of creative thinking of teachers at Philadelphia University in Jordan, and to define its relation with several independent demographic variables, namely age, gender, duration of experience, specialization, and personality types and traits. To accomplish this purpose, three questionnaires are administered on…

  1. Psychosocial Adaptation to Visual Impairment and Its Relationship to Depressive Affect in Older Adults with Age-Related Macular Degeneration

    Science.gov (United States)

    Tolman, Jennifer; Hill, Robert D.; Kleinschmidt, Julia J.; Gregg, Charles H.

    2005-01-01

    Purpose: In this study we examined psychosocial adaptation to vision loss and its relationship to depressive symptomatology in legally blind older adults with age-related macular degeneration (ARMD). Design and Methods: The 144 study participants were outpatients of a large regional vision clinic that specializes in the diagnosis and treatment of…

  2. Perceptions of Retirement Affect Career Commitment: The Mediating Role of Retirement System Satisfaction for Two Teacher Age Groups

    Science.gov (United States)

    Smith, Justin L.; Conley, Sharon; You, Sukkyung

    2015-01-01

    This study investigated a sample of California elementary, intermediate, and high school employed teachers (N = 247) to assess the effects of retirement perceptions on career commitment among teachers who are in different age groupings. Using path analysis, the influence of five retirement perceptions variables was examined: concerns about…

  3. Do gender, disability, and morbidity affect aging rate in the LLFS? Application of indices of cumulative deficits

    DEFF Research Database (Denmark)

    Kulminski, Alexander M; Arbeev, Konstantin G; Christensen, Kaare

    2011-01-01

    of deficits. When a wider spectrum of health dimensions is considered these rates are better approximated by quadratic law. Exponential rates are more characteristic for more severe health dimensions. The aging rates are the same for males and females. Individuals who contracted major diseases and those who...

  4. Role NO in realization of disorders of reactivity of an aorta after affecting an low intensive ionizing radiation: age aspects

    International Nuclear Information System (INIS)

    Solov'eva, N.G.

    2008-01-01

    The ionizing radiation in a dose 1 Gy mediates depressing of vasodilatation functions of an endothelium against the background of discriminated variations of neurohumoral regulations of reactivity of an aorta for young and old rats. The radiation-induced modification of physiological function of endothelial NO executes the key role in these age variations. (authors)

  5. Leaf age affects the responses of foliar injury and gas exchange to tropospheric ozone in Prunus serotina seedlings

    Science.gov (United States)

    Jianwei Zhang; Marcus Schaub; Jonathan A. Ferdinand; John M. Skelly; Kim C. Steiner; James E. Savage

    2010-01-01

    We investigated the effect of leaf age on the response of net photosynthesis (A), stomatal conductance (gwv), foliar injury, and leaf nitrogen concentration (NL) to tropospheric ozone (O3) on Prunus serotina seedlings grown in open-plots (AA) and open-top...

  6. Regulation of hippocampal synaptic plasticity by the tyrosine kinase receptor, REK7/EphA5, and its ligand, AL-1/Ephrin-A5.

    Science.gov (United States)

    Gao, W Q; Shinsky, N; Armanini, M P; Moran, P; Zheng, J L; Mendoza-Ramirez, J L; Phillips, H S; Winslow, J W; Caras, I W

    1998-08-01

    The Eph-related tyrosine kinase receptor, REK7/EphA5, mediates the effects of AL-1/Ephrin-A5 and related ligands and is involved in the guidance of retinal, cortical, and hippocampal axons during development. The continued expression of REK7/EphA5 in the adult brain, in particular in areas associated with a high degree of synaptic plasticity such as the hippocampus, raises the question of its function in the mature nervous system. In this report we examined the role of REK7/EphA5 in synaptic remodeling by asking if agents that either block or activate REK7/EphA5 affect synaptic strength in hippocampal slices from adult mouse brain. We show that a REK7/EphA5 antagonist, soluble REK7/EphA5-IgG, impairs the induction of long-term potentiation (LTP) without affecting other synaptic parameters such as normal synaptic transmission or paired-pulse facilitation. In contrast, perfusion with AL-1/Ephrin-A5-IgG, an activator of REK7/EphA5, induces a sustained increase in normal synaptic transmission that partially mimics LTP. The sustained elevation of normal synaptic transmission could be attributable to a long-lasting binding of the AL-1/Ephrin-A5-IgG to the endogenous REK7/EphA5 receptor, as revealed by immunohistochemistry. Furthermore, maximal electrical induction of LTP occludes the potentiating effects of subsequent treatment with AL-1/Ephrin-A5-IgG. Taken together these results implicate REK7/EphA5 in the regulation of synaptic plasticity in the mature hippocampus and suggest that REK7/EphA5 activation is recruited in the LTP induced by tetanization. Copyright 1998 Academic Press.

  7. A Voltage Mode Memristor Bridge Synaptic Circuit with Memristor Emulators

    Directory of Open Access Journals (Sweden)

    Leon Chua

    2012-03-01

    Full Text Available A memristor bridge neural circuit which is able to perform signed synaptic weighting was proposed in our previous study, where the synaptic operation was verified via software simulation of the mathematical model of the HP memristor. This study is an extension of the previous work advancing toward the circuit implementation where the architecture of the memristor bridge synapse is built with memristor emulator circuits. In addition, a simple neural network which performs both synaptic weighting and summation is built by combining memristor emulators-based synapses and differential amplifier circuits. The feasibility of the memristor bridge neural circuit is verified via SPICE simulations.

  8. Biology of aging brain

    Directory of Open Access Journals (Sweden)

    Shankar S

    2010-10-01

    Full Text Available Normal aging of the nervous system is associated with some degree of decline in a number of cognitive functions. With the present day attempts to increase the life span, understanding the metabolic interactions and various mechanisms involved in normal neuronal aging continues to be a challenge. Loss of neurons is now recognized to be more modest than the initial estimates suggested and the loss only affected some of the specific neuroanatomical areas like hippocampus and prefrontal cortex. Individual neurons in addition show reduced size of dendritic and axonal arborization. Neurons have significant homeostatic control of the essential physiological functions like synaptic excitability, gene expression and metabolic regulation. Deviation in these normal events can have severe consequences as observed in aging and neurodegeneration. Based on experimental evidence, the evolution of aging is probably the result of altered metabolic triad: the mitochondria, reactive oxygen species and intracellular calcium homeostasis. Perturbations in the metabolic and functional state of this triad lead to a state of decreased homeostatic reserve, where the aged neurons still could maintain adequate function during normal activity. However, these neurons become vulnerable to the stress of excessive metabolic loads associated with spells of ischemia, trauma progressing to neuronal degeneration. Age-related neuronal dysfunction probably involves a host of subtle changes involving the synapses, receptors, neurotransmitters, cytological alterations, electrical transmission, leading to cognitive dysfunction. An exaggeration of it could be the clinical manifestation of dementia, with intraneuronal accumulation of protein aggregates deranging the metabolic state. This review deals with some of the structural, functional and metabolic features of aging nervous system and discusses briefly the functional consequences.

  9. Endothelial progenitor cells (EPCs) in ageing and age-related diseases: How currently available treatment modalities affect EPC biology, atherosclerosis, and cardiovascular outcomes.

    Science.gov (United States)

    Altabas, Velimir; Altabas, Karmela; Kirigin, Lora

    2016-10-01

    Endothelial progenitor cells (EPCs) are mononuclear cells that circulate in the blood and are derived from different tissues, expressing cell surface markers that are similar to mature endothelial cells. The discovery of EPCs has lead to new insights in vascular repair and atherosclerosis and also a new theory for ageing. EPCs from the bone marrow and some other organs aid in vascular repair by migrating to distant vessels where they differentiate into mature endothelial cells and replace old and injured endothelial cells. The ability of EPCs to repair vascular damage depends on their number and functionality. Currently marketed drugs used in a variety of diseases can modulate these characteristics. In this review, the effect of currently available treatment options for cardiovascular and metabolic disorders on EPC biology will be discussed. The various EPC-based therapies that will be discussed include lipid-lowering agents, antihypertensive agents, antidiabetic drugs, phosphodiesteraze inhibitors, hormones, as well as EPC capturing stents. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Entrepreneurs’ gender, age and education affecting their networks in private and public spheres: Denmark, Middle East and North Africa

    DEFF Research Database (Denmark)

    Ashourizadeh, Shayegheh; Schøtt, Thomas

    2013-01-01

    The purpose is to account for entrepreneurs’ networking in private and public spheres, as influenced by gender, age and education in the context of culture. The Global Entrepreneurship Monitor has surveyed 17,742 entrepreneurs’ networking for advice in Denmark and 14 countries representative of t....... Education influences networking in the way that networking in the public sphere is especially extensive among educated entrepreneurs.......The purpose is to account for entrepreneurs’ networking in private and public spheres, as influenced by gender, age and education in the context of culture. The Global Entrepreneurship Monitor has surveyed 17,742 entrepreneurs’ networking for advice in Denmark and 14 countries representative...... of the Middle East and North Africa. Analyses show that entrepreneurs are networking in the private sphere of family and friends, especially in traditional culture in Middle East and North Africa, and are networking in public spheres, especially in secular-rational culture in Denmark. Male entrepreneurs network...

  11. The Baby Boom As It Ages: How Has It Affected Patterns of Consumptions and Savings in the United States?

    OpenAIRE

    Diane Macunovich

    1999-01-01

    Using detailed estimates of personal consumption expenditures at the state level for 1900, 1929, 1970, and 1982 developed by Stanley Lebergott, this paper demonstrates that the passage of the Baby Boom from childhood through the teen years and into family formation would have caused market swings in patterns of aggregate consumption and savings in the United States during the past 50 years. The effect of age structure on personal consumption expenditures is estimated using population by singl...

  12. Do age and extended culture affect the architecture of the zona pellucida of human oocytes and embryos?

    Science.gov (United States)

    Kilani, Suha S; Cooke, Simon; Kan, Andrew K; Chapman, Michael G

    2006-02-01

    Advanced female age and extended in vitro culture have both been implicated in zona pellucida (ZP) hardening and thickening. This study aimed to determine the influence of (i) the woman's age and (ii) prolonged in vitro culture of embryos on ZP thickness and density using non-invasive polarized light (LC-PolScope) microscopy. ZP thickness and density (measured as retardance) were determined in oocytes, embryos and blastocysts in women undergoing intracytoplasmic sperm injection (ICSI) in two age groups (older, > 38 years; younger, vs 23.1 +/- 3.3 microm; p = 0.01) but ZP density was equal (2.8 +/- 0.7 nm). By day 2 of culture, embryos from the two groups had similar ZP thickness (22.2 +/- 2.2 microm vs 21.7 +/- 1.6 microm; p = 0.28) and density (2.9 +/- 0.7 nm vs 2.8 +/- 0.8 nm; p = 0.57). For the embryos cultured to blastocyst (older: n = 20; younger: n = 18) ZP thickness was similar in the two groups (19.2 +/- 2.7 microm vs 19.1 +/- 5.0 microm; p = 0.8) but thinner than on day 2. The older group had significantly denser ZP than the younger group (4.2 +/- 0.5 nm vs 3.3 +/- 1.0 nm, p vs 2.9 +/- 0.7 nm, p vs 2.8 +/- 0.8 nm, p = 0.013). It is concluded that there is little relationship between ZP thickness and its density as measured by polarized light microscopy. While ZP thickness decreases with extended embryo culturing, the density of the ZP increases. ZP density increases in both age groups with extended culture and, interestingly, more in embryos from older compared with younger women.

  13. Variation in term birthweight across European countries affects the prevalence of small for gestational age among very preterm infants

    DEFF Research Database (Denmark)

    Zeitlin, Jennifer; Bonamy, Anna-Karin Edstedt; Piedvache, Aurelie

    2017-01-01

    AIM: This study assessed the prevalence of small for gestational age (SGA) among very preterm (VPT) infants using national and European intrauterine references. METHODS: We generated country-specific and common European intrauterine growth references for 11 European countries, according to Gardosi...... with lower term birthweights (39.9%) - Portugal, Italy and France - and higher term birthweights, namely Denmark, the Netherlands, Sweden (28.9%; p third...

  14. Post-traumatic stress disorder amongst children aged 8–18 affected by the 2011 northern-Namibia floods

    Directory of Open Access Journals (Sweden)

    Simon Taukeni

    2016-01-01

    Full Text Available Extreme flooding in the northern parts of Namibia occurred in 2011, impacting many schoolgoing children in the region. The rationale for the current research is to assess post-traumatic stress disorder (PTSD on school children as a result of the floods. A self-administered Child Trauma Screening Questionnaire (CTSQ with closed-ended questions was administered to 480 children between the ages of eight and 18 years at their respective schools. The CTSQ consists of five items assessing re-experiencing and five items assessing hyper-arousal symptoms. The results show that 55.2% of learners aged 12 and below and 72.8% of learners aged 13 and above reported experiencing symptoms of trauma from the floods 2 years after the event. These percentages were quite high and are therefore a cause for concern. Given the magnitude of this problem, it is important for the government and other stakeholders to provide the necessary psychological and/or emotional support in the event of future floods or similar disasters.

  15. Vitex agnus-castus essential oil affects thyroid C cells and bone metabolism in middle-aged male rats

    Directory of Open Access Journals (Sweden)

    Pantelić Jasmina

    2013-01-01

    Full Text Available Ageing in men is accompanied by an increased occurrence of osteoporosis, but traditional hormonal replacement therapy elevates the risk of developing endocrine cancer. Vitex agnus-castus L. (Vac essential oil is commonly used as an alternative therapy for ageing symptoms in both men and women. It is known that calcitonin (CT, thyroid C cell hormone, inhibits bone resorption. The purpose of this experimental study was to investigate the influence of Vac essential oil administration on the immunohistomorphometric features of thyroid C cells and bone metabolism in 16-month-old male Wistar rats. The first group of animals (n=8 was treated subcutaneously (s.c. with 60 mg/kg of Vac essential oil once a day for 3 weeks. Control animals (n=8 received sterile olive oil s.c. by the same schedule. After Vac treatment significant increases (p<0.05 were found in the volume of C cells (by 10% and serum CT level (by 27% compared with the controls. Serum osteocalcin (OC and calcium (Ca2+ levels were 31% and 8% lower (p<0.05 respectively, in comparison with the control group. These are the first experimental results suggesting that Vac essential oil stimulates thyroid C cells activity and decreases bone turnover in middle-aged male rats. [Projekat Ministarstva nauke Republike Srbije, br. 173009

  16. Are age-related differences between young and older adults in an affective working memory test sensitive to the music effects?

    Science.gov (United States)

    Borella, Erika; Carretti, Barbara; Grassi, Massimo; Nucci, Massimo; Sciore, Roberta

    2014-01-01

    There are evidences showing that music can affect cognitive performance by improving our emotional state. The aim of the current study was to analyze whether age-related differences between young and older adults in a Working Memory (WM) Span test in which the stimuli to be recalled have a different valence (i.e., neutral, positive, or negative words), are sensitive to exposure to music. Because some previous studies showed that emotional words can sustain older adults' performance in WM, we examined whether listening to music could enhance the benefit of emotional material, with respect to neutral words, on WM performance decreasing the age-related difference between younger and older adults. In particular, the effect of two types of music (Mozart vs. Albinoni), which differ in tempo, arousal and mood induction, on age-related differences in an affective version of the Operation WM Span task was analyzed. Results showed no effect of music on the WM test regardless of the emotional content of the music (Mozart vs. Albinoni). However, a valence effect for the words in the WM task was found with a higher number of negative words recalled with respect to positive and neutral ones in both younger and older adults. When individual differences in terms of accuracy in the processing phase of the Operation Span task were considered, only younger low-performing participants were affected by the type music, with the Albinoni condition that lowered their performance with respect to the Mozart condition. Such a result suggests that individual differences in WM performance, at least when young adults are considered, could be affected by the type of music. Altogether, these findings suggest that complex span tasks, such as WM tasks, along with age-related differences are not sensitive to music effects.

  17. Are age-related differences between young and older adults in an affective working memory test sensitive to the music effects?

    OpenAIRE

    Borella, Erika; Carretti, Barbara; Grassi, Massimo; Nucci, Massimo; Sciore, Roberta

    2014-01-01

    There are evidences showing that music can affect cognitive performance by improving our emotional state. The aim of the current study was to analyze whether age-related differences between young and older adults in a Working Memory (WM) Span test in which the stimuli to be recalled have a different valence (i.e., neutral, positive, or negative words), are sensitive to exposure to music. Because some previous studies showed that emotional words can sustain older adults’ performance in WM, we ...

  18. Are Age-Related Differences Between Young and Older Adults in an Affective Working Memory Test Sensitive to the Music Effects?

    Directory of Open Access Journals (Sweden)

    Erika eBorella

    2014-11-01

    Full Text Available There are evidences showing that music can affect cognitive performance by improving our emotional state. The aim of the current study was to analyze whether age-related differences between young and older adults in a Working Memory (WM Span test in which the stimuli to be recalled have a different valence (i.e., neutral, positive, or negative words, are sensitive to exposure to music. Because some previous studies showed that emotional words can sustain older adults’ performance in WM, we examined whether listening to music could enhance the benefit of emotional material, with respect to neutral words, on WM performance decreasing the age-related difference between younger and older adults. In particular, the effect of two types of music (Mozart vs. Albinoni, which differ in tempo, arousal and mood induction, on age-related differences in an affective version of the Operation WM Span task were analyzed.Results showed no effect of music on the WM test regardless of the emotional content of the music (Mozart vs. Albinoni. However, as in previous studies, a valence effect for the words in the WM task was found with a higher number of negative words recalled with respect to positive and neutral ones in both younger and older adults. When individual differences, in terms of accuracy in the processing phase of the Operation Span task, were considered, only younger low-performing participants were affected by the type music, with the Albinoni condition that lowered their performance with respect to the Mozart condition. Such a result suggests that individual differences in WM performance, at least when young adults are considered, could be affected by the type of music.Altogether, these findings suggest that complex span tasks, such as WM tasks, along with age-related differences are less sensitive to music effects.

  19. Need Satisfaction Moderates the Association Between Physical Activity and Affective States in Adults Aged 50+: an Activity-Triggered Ambulatory Assessment.

    Science.gov (United States)

    Kanning, Martina; Hansen, Sylvia

    2017-02-01

    Substantial evidence shows that physical activities of daily living are positively correlated with affective states in middle-aged and older adults. However, people's physical activity decreases when they grow older, and conditions that enhance older individuals' physical activities of daily living are not well understood. This study investigated need satisfaction (competence, relatedness, and autonomy) and its moderating effect on the within-subject relation between physical activities of daily living and three dimensions of affective states (valence, energetic arousal, and calmness) based on an ambulatory assessment that used activity-triggered e-diaries. The physical activities of daily living of 68 adults aged 50+ (mean age = 60.1 ± 7.1) were measured objectively for three consecutive days, and need satisfaction and affective states were assessed as a function of the amount of physical activity during the preceding 10 min before the affect measurement (in activity-triggered e-diaries). Hierarchical multilevel analyses were performed. Need satisfaction was significantly and positively correlated with the three dimensions of affective states. Further, physical activities of daily living were significantly associated with energetic arousal and calmness, but not valence. However, when physical activities of daily living were more autonomously regulated, the association of physical activities of daily living and valence became significant and positive. The findings regarding the significant moderating effects of need satisfaction are crucial for interventions aiming to improve the health-enhancing effects of physical activity in adults aged 50+. Positive feelings owing to physical activities in daily living depend on the extent that psychological needs are satisfied.

  20. Synaptic, transcriptional and chromatin genes disrupted in autism.

    Science.gov (United States)

    De Rubeis, Silvia; He, Xin; Goldberg, Arthur P; Poultney, Christopher S; Samocha, Kaitlin; Cicek, A Erucment; Kou, Yan; Liu, Li; Fromer, Menachem; Walker, Susan; Singh, Tarinder; Klei, Lambertus; Kosmicki, Jack; Shih-Chen, Fu; Aleksic, Branko; Biscaldi, Monica; Bolton, Patrick F; Brownfeld, Jessica M; Cai, Jinlu; Campbell, Nicholas G; Carracedo, Angel; Chahrour, Maria H; Chiocchetti, Andreas G; Coon, Hilary; Crawford, Emily L; Curran, Sarah R; Dawson, Geraldine; Duketis, Eftichia; Fernandez, Bridget A; Gallagher, Louise; Geller, Evan; Guter, Stephen J; Hill, R Sean; Ionita-Laza, Juliana; Jimenz Gonzalez, Patricia; Kilpinen, Helena; Klauck, Sabine M; Kolevzon, Alexander; Lee, Irene; Lei, Irene; Lei, Jing; Lehtimäki, Terho; Lin, Chiao-Feng; Ma'ayan, Avi; Marshall, Christian R; McInnes, Alison L; Neale, Benjamin; Owen, Michael J; Ozaki, Noriio; Parellada, Mara; Parr, Jeremy R; Purcell, Shaun; Puura, Kaija; Rajagopalan, Deepthi; Rehnström, Karola; Reichenberg, Abraham; Sabo, Aniko; Sachse, Michael; Sanders, Stephan J; Schafer, Chad; Schulte-Rüther, Martin; Skuse, David; Stevens, Christine; Szatmari, Peter; Tammimies, Kristiina; Valladares, Otto; Voran, Annette; Li-San, Wang; Weiss, Lauren A; Willsey, A Jeremy; Yu, Timothy W; Yuen, Ryan K C; Cook, Edwin H; Freitag, Christine M; Gill, Michael; Hultman, Christina M; Lehner, Thomas; Palotie, Aaarno; Schellenberg, Gerard D; Sklar, Pamela; State, Matthew W; Sutcliffe, James S; Walsh, Christiopher A; Scherer, Stephen W; Zwick, Michael E; Barett, Jeffrey C; Cutler, David J; Roeder, Kathryn; Devlin, Bernie; Daly, Mark J; Buxbaum, Joseph D

    2014-11-13

    The genetic architecture of autism spectrum disorder involves the interplay of common and rare variants and their impact on hundreds of genes. Using exome sequencing, here we show that analysis of rare coding variation in 3,871 autism cases and 9,937 ancestry-matched or parental controls implicates 22 autosomal genes at a false discovery rate (FDR) < 0.05, plus a set of 107 autosomal genes strongly enriched for those likely to affect risk (FDR < 0.30). These 107 genes, which show unusual evolutionary constraint against mutations, incur de novo loss-of-function mutations in over 5% of autistic subjects. Many of the genes implicated encode proteins for synaptic formation, transcriptional regulation and chromatin-remodelling pathways. These include voltage-gated ion channels regulating the propagation of action potentials, pacemaking and excitability-transcription coupling, as well as histone-modifying enzymes and chromatin remodellers-most prominently those that mediate post-translational lysine methylation/demethylation modifications of histones.

  1. Endocannabinoid System and Synaptic Plasticity: Implications for Emotional Responses

    Directory of Open Access Journals (Sweden)

    María-Paz Viveros

    2007-01-01

    Full Text Available The endocannabinoid system has been involved in the regulation of anxiety, and proposed as an inhibitory modulator of neuronal, behavioral and adrenocortical responses to stressful stimuli. Brain regions such as the amygdala, hippocampus and cortex, which are directly involved in the regulation of emotional behavior, contain high densities of cannabinoid CB1 receptors. Mutant mice lacking CB1 receptors show anxiogenic and depressive-like behaviors as well as an altered hypothalamus pituitary adrenal axis activity, whereas enhancement of endocannabinoid signaling produces anxiolytic and antidepressant-like effects. Genetic and pharmacological approaches also support an involvement of endocannabinoids in extinction of aversive memories. Thus, the endocannabinoid system appears to play a pivotal role in the regulation of emotional states. Endocannabinoids have emerged as mediators of short- and long- term synaptic plasticity in diverse brain structures. Despite the fact that most of the studies on this field have been performed using in vitro models, endocannabinoid-mediated plasticity might be considered as a plausible candidate underlying some of the diverse physiological functions of the endogenous cannabinoid system, including developmental, affective and cognitive processes. In this paper, we will focus on the functional relevance of endocannabinoid-mediated plasticity within the framework of emotional responses. Alterations of the endocannabinoid system may constitute an important factor in the aetiology of certain neuropsychiatric disorders, and, in turn, enhancers of endocannabinoid signaling could represent a potential therapeutical tool in the treatment of both anxiety and depressive symptoms.

  2. Distinct Functions of Endophilin Isoforms in Synaptic Vesicle Endocytosis

    Directory of Open Access Journals (Sweden)

    Jifeng Zhang

    2015-01-01

    Full Text Available Endophilin isoforms perform distinct characteristics in their interactions with N-type Ca2+ channels and dynamin. However, precise functional differences for the endophilin isoforms on synaptic vesicle (SV endocytosis remain unknown. By coupling RNA interference and electrophysiological recording techniques in cultured rat hippocampal neurons, we investigated the functional differences of three isoforms of endophilin in SV endocytosis. The results showed that the amplitude of normalized evoked excitatory postsynaptic currents in endophilin1 knockdown neurons decreased significantly for both single train and multiple train stimulations. Similar results were found using endophilin2 knockdown neurons, whereas endophilin3 siRNA exhibited no change compared with control neurons. Endophilin1 and endophilin2 affected SV endocytosis, but the effect of endophilin1 and endophilin2 double knockdown was not different from that of either knockdown alone. This result suggested that endophilin1 and endophilin2 functioned together but not independently during SV endocytosis. Taken together, our results indicate that SV endocytosis is sustained by endophilin1 and endophilin2 isoforms, but not by endophilin3, in primary cultured hippocampal neurons.

  3. Maternal Dexamethasone Exposure Alters Synaptic Inputs to Gonadotropin-Releasing Hormone Neurons in the Early Postnatal Rat

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    Wei Ling Lim

    2016-08-01

    Full Text Available Maternal dexamethasone (DEX; a glucocorticoid receptor agonist exposure delays pubertal onset and alters reproductive behaviour in the adult offspring. However, little is known whether maternal DEX exposure affects the offspring’s reproductive function by disrupting the gonadotropin-releasing hormone (GnRH neuronal function in the brain. Therefore, this study determined the exposure of maternal DEX on the GnRH neuronal spine development and synaptic cluster inputs to GnRH neurons using transgenic rats expressing enhanced green fluorescent protein (EGFP un