WorldWideScience

Sample records for brain aging deciphering

  1. Successful brain aging: plasticity, environmental enrichment, and lifestyle

    OpenAIRE

    Mora, Francisco

    2013-01-01

    Aging is a physiological process that can develop without the appearance of concurrent diseases. However, very frequently, older people suffer from memory loss and an accelerated cognitive decline. Studies of the neurobiology of aging are beginning to decipher the mechanisms underlying not only the physiology of aging of the brain but also the mechanisms that make people more vulnerable to cognitive dysfunction and neurodegenerative diseases. Today we know that the aging brain retains a consi...

  2. Cognition and brain functional aging

    Directory of Open Access Journals (Sweden)

    Hui-jie LI

    2014-03-01

    Full Text Available China has the largest population of elderly adults. Meanwhile, it is one of the countries showing fastest aging speed in the world. Aging processing is always companied with a series of brain structural and functional changes, which result in the decline of processing speed, working memory, long-term memory and executive function, etc. The studies based on functional magnetic resonance imaging (fMRI found certain aging effects on brain function activation, spontaneous activity and functional connectivity in old people. However, few studies have explored the brain functional curve during the aging process while most previous studies explored the differences in the brain function between young people and old people. Delineation of the human brain functional aging curve will promote the understanding of brain aging mechanisms and support the normal aging monitoring and early detection of abnormal aging changes. doi: 10.3969/j.issn.1672-6731.2014.03.005

  3. Brain aging and therapeutic interventions

    DEFF Research Database (Denmark)

    This book brings together most up-to-date information on different aspects of brain aging and on the strategies for intervention and therapy of age-related brain disorders. It includes 18 chapters by leading researchers, and each chapter is a comprehensive and critical review of the topic...

  4. Neurogenesis in the aging brain

    Directory of Open Access Journals (Sweden)

    Veronica Galvan

    2007-01-01

    Full Text Available Veronica Galvan, Kunlin JinBuck Institute for Age Research, 8001 Redwood Blvd. Novato, CA, USAAbstract: Neurogenesis, or the birth of new neural cells, was thought to occur only in the developing nervous system and a fixed neuronal population in the adult brain was believed to be necessary to maintain the functional stability of adult brain circuitry. However, recent studies have demonstrated that neurogenesis does indeed continue into and throughout adult life in discrete regions of the central nervous systems (CNS of all mammals, including humans. Although neurogenesis may contribute to the ability of the adult brain to function normally and be induced in response to cerebral diseases for self-repair, this nevertheless declines with advancing age. Understanding the basic biology of neural stem cells and the molecular and cellular regulation mechanisms of neurogenesis in young and aged brain will allow us to modulate cell replacement processes in the adult brain for the maintenance of healthy brain tissues and for repair of disease states in the elderly.Keywords: neurogenesis, aging, brain, neural stem cells, subgranular zone, subventricular zone

  5. Nutrients, Microglia Aging, and Brain Aging

    OpenAIRE

    Zhou Wu; Janchun Yu; Aiqin Zhu; Hiroshi Nakanishi

    2016-01-01

    As the life expectancy continues to increase, the cognitive decline associated with Alzheimer’s disease (AD) becomes a big major issue in the world. After cellular activation upon systemic inflammation, microglia, the resident immune cells in the brain, start to release proinflammatory mediators to trigger neuroinflammation. We have found that chronic systemic inflammatory challenges induce differential age-dependent microglial responses, which are in line with the impairment of learning and ...

  6. NIH Conference. Brain imaging: aging and dementia

    International Nuclear Information System (INIS)

    The brain imaging techniques of positron emission tomography using [18F]-fluoro-2-deoxy-D-glucose, and computed tomography, together with neuropsychological tests, were used to examine overall brain function and anatomy in three study populations: healthy men at different ages, patients with presumptive Alzheimer's disease, and adults with Down's syndrome. Brain glucose use did not differ with age, whereas an age-related decrement in gray matter volume was found on computed tomographic assessment in healthy subjects. Memory deficits were found to precede significant reductions in brain glucose utilization in mild to moderate Alzheimer's dementia. Furthermore, differences between language and visuoconstructive impairments in patients with mild to moderate Alzheimer's disease were related to hemispheric asymmetry of brain metabolism. Brain glucose utilization was found to be significantly elevated in young adults with Down's syndrome, compared with controls. The importance of establishing strict criteria for selecting control subjects and patients is explained in relation to the findings

  7. NMDA receptor function, memory, and brain aging

    OpenAIRE

    Newcomer, John W.; Farber, Nuri B.; Olney, John W.

    2000-01-01

    An increasing level of N-methyl-D-aspartate (NMDA) receptor hypofunction within the brain is associated with memory and learning impairments, with psychosis, and ultimately with excitotoxic brain injury. As the brain ages, the NMDA receptor system becomes progressively hypofunctional, contributing to decreases in memory and learning performance. In those individuals destined to develop Alzheimer's disease, other abnormalities (eg, amyloidopathy and oxidative stress) interact to increase the N...

  8. Cardiovascular and hemodynamic contribution to brain aging

    NARCIS (Netherlands)

    Sabayan, Behnam

    2014-01-01

    In summary, chapter 1 of this thesis provides a background on the demographic, biologic and cardiovascular aspects of brain aging. Chapter 2 shows that higher blood pressure is associated with lower cognitive decline in very old age. Findings of Chapter 3 indicate that higher blood pressure is assoc

  9. Cognitive functioning of the aging brain

    OpenAIRE

    Tam, Man-kin, Helena; 譚敏堅

    2013-01-01

    This thesis contains two studies which examined the cognitive functioning of the aging brain. Specifically, age-related changes in processing speed and its remediation via cognitive training were studied. In study 1, younger adults (n = 34) and older adults (n = 39) were recruited to investigate the age-related differences in the relationships between processing speed and general cognitive status (GCS). Their performance in GCS (as measured by The Montreal Cognitive Assessment, Hong Kong Vers...

  10. Metabolic drift in the aging brain.

    Science.gov (United States)

    Ivanisevic, Julijana; Stauch, Kelly L; Petrascheck, Michael; Benton, H Paul; Epstein, Adrian A; Fang, Mingliang; Gorantla, Santhi; Tran, Minerva; Hoang, Linh; Kurczy, Michael E; Boska, Michael D; Gendelman, Howard E; Fox, Howard S; Siuzdak, Gary

    2016-05-01

    Brain function is highly dependent upon controlled energy metabolism whose loss heralds cognitive impairments. This is particularly notable in the aged individuals and in age-related neurodegenerative diseases. However, how metabolic homeostasis is disrupted in the aging brain is still poorly understood. Here we performed global, metabolomic and proteomic analyses across different anatomical regions of mouse brain at different stages of its adult lifespan. Interestingly, while severe proteomic imbalance was absent, global-untargeted metabolomics revealed an energymetabolic drift or significant imbalance in core metabolite levels in aged mouse brains. Metabolic imbalance was characterized by compromised cellular energy status (NAD decline, increased AMP/ATP, purine/pyrimidine accumulation) and significantly altered oxidative phosphorylation and nucleotide biosynthesis and degradation. The central energy metabolic drift suggests a failure of the cellular machinery to restore metabostasis (metabolite homeostasis) in the aged brain and therefore an inability to respond properly to external stimuli, likely driving the alterations in signaling activity and thus in neuronal function and communication. PMID:27182841

  11. Susceptibility to calcium dysregulation during brain aging

    Directory of Open Access Journals (Sweden)

    Ashok Kumar

    2009-11-01

    Full Text Available Calcium (Ca2+ is a highly versatile intracellular signaling molecule that is essential for regulating a variety of cellular and physiological processes ranging from fertilization to programmed cell death. Research has provided ample evidence that brain aging is associated with altered Ca2+ homeostasis. Much of the work has focused on the hippocampus, a brain region critically involved in learning and memory, which is particularly susceptible to dysfunction during senescence. The current review takes a broader perspective, assessing age-related changes in Ca2+ sources, Ca2+ sequestration, and Ca2+ binding proteins throughout the nervous system. The nature of altered Ca2+ homeostasis is cell specific and may represent a deficit or a compensatory mechanism, producing complex patterns of impaired cellular function. Incorporating the knowledge of the complexity of age-related alterations in Ca2+ homeostasis will positively shape the development of highly effective therapeutics to treat brain disorders.

  12. Light-sensitive brain pathways and aging.

    Science.gov (United States)

    Daneault, V; Dumont, M; Massé, É; Vandewalle, G; Carrier, J

    2016-03-15

    Notwithstanding its effects on the classical visual system allowing image formation, light acts upon several non-image-forming (NIF) functions including body temperature, hormonal secretions, sleep-wake cycle, alertness, and cognitive performance. Studies have shown that NIF functions are maximally sensitive to blue wavelengths (460-480 nm), in comparison to longer light wavelengths. Higher blue light sensitivity has been reported for melatonin suppression, pupillary constriction, vigilance, and performance improvement but also for modulation of cognitive brain functions. Studies investigating acute stimulating effects of light on brain activity during the execution of cognitive tasks have suggested that brain activations progress from subcortical regions involved in alertness, such as the thalamus, the hypothalamus, and the brainstem, before reaching cortical regions associated with the ongoing task. In the course of aging, lower blue light sensitivity of some NIF functions has been reported. Here, we first describe neural pathways underlying effects of light on NIF functions and we discuss eye and cerebral mechanisms associated with aging which may affect NIF light sensitivity. Thereafter, we report results of investigations on pupillary constriction and cognitive brain sensitivity to light in the course of aging. Whereas the impact of light on cognitive brain responses appears to decrease substantially, pupillary constriction seems to remain more intact over the lifespan. Altogether, these results demonstrate that aging research should take into account the diversity of the pathways underlying the effects of light on specific NIF functions which may explain their differences in light sensitivity.

  13. The Impact of Traumatic Brain Injury on the Aging Brain.

    Science.gov (United States)

    Young, Jacob S; Hobbs, Jonathan G; Bailes, Julian E

    2016-09-01

    Traumatic brain injury (TBI) has come to the forefront of both the scientific and popular culture. Specifically, sports-related concussions or mild TBI (mTBI) has become the center of scientific scrutiny with a large amount of research focusing on the long-term sequela of this type of injury. As the populace continues to age, the impact of TBI on the aging brain will become clearer. Currently, reports have come to light that link TBI to neurodegenerative disorders such as Alzheimer's and Parkinson's diseases, as well as certain psychiatric diseases. Whether these associations are causations, however, is yet to be determined. Other long-term sequelae, such as chronic traumatic encephalopathy (CTE), appear to be associated with repetitive injuries. Going forward, as we gain better understanding of the pathophysiological process involved in TBI and subclinical head traumas, and individual traits that influence susceptibility to neurocognitive diseases, a clearer, more comprehensive understanding of the connection between brain injury and resultant disease processes in the aging brain will become evident. PMID:27432348

  14. Functional interrelationship of brain aging and delirium.

    Science.gov (United States)

    Rapazzini, Piero

    2016-02-01

    Theories on the development of delirium are complementary rather than competing and they may relate to each other. Here, we highlight that similar alterations in functional brain connectivity underlie both the observed age-related deficits and episodes of delirium. The default mode network (DMN) is a group of brain regions showing a greater level of activity at rest than during attention-based tasks. These regions include the posteromedial-anteromedial cortices and temporoparietal junctions. Evidence suggests that awareness is subserved through higher order neurons associated with the DMN. By using functional MRI disruption of DMN, connectivity and weaker task-induced deactivations of these regions are observed both in age-related cognitive impairment and during episodes of delirium. We can assume that an acute up-regulation of inhibitory tone within the brain acts to further disrupt network connectivity in vulnerable patients, who are predisposed by a reduced baseline connectivity, and triggers the delirium.

  15. Brain plasticity, memory, and aging: a discussion

    Energy Technology Data Exchange (ETDEWEB)

    Bennett, E.L.; Rosenzweig, M.R.

    1977-12-01

    It is generally assumed that memory faculties decline with age. A discussion of the relationship of memory and aging and the possibility of retarding the potential decline is hampered by the fact that no satisfactory explanation of memory is available in either molecular or anatomical terms. However, this lack of description of memory does not mean that there is a lack of suggested mechanisms for long-term memory storage. Present theories of memory usually include first, neurophysiological or electrical events, followed by a series of chemical events which ultimately lead to long-lasting anatomical changes in the brain. Evidence is increasing for the biochemical and anatomical plasticity of the nervous system and its importance in the normal functioning of the brain. Modification of this plasticity may be an important factor in senescence. This discussion reports experiments which indicate that protein synthesis and anatomical changes may be involved in long-term memory storage. Environmental influences can produce quantitative differences in brain anatomy and in behavior. In experimental animals, enriched environments lead to more complex anatomical patterns than do colony or impoverished environments. This raises fundamental questions about the adequacy of the isolated animal which is frequently being used as a model for aging research. A more important applied question is the role of social and intellectual stimulation in influencing aging of the human brain.

  16. Sirtuins: from Metabolic Regulation to Brain Aging

    Directory of Open Access Journals (Sweden)

    Wenzhen eDuan

    2013-07-01

    Full Text Available Brain aging is characterized by progressive loss of neurophysiological functions that is often accompanied by age-associated neurodegeneration. Calorie restriction has been linked to extension of lifespan and reduction of the risk of neurodegenerative diseases in experimental model systems. Several signaling pathways have been indicated to underlie the beneficial effects of calorie restriction, among which the sirtuin family has been suggested to play a central role. In mammals, it has been established that sirtuins regulate physiological responses to metabolism and stress, two key factors that affect the process of aging. Sirtuins represent a promising new class of conserved deacetylases that play an important role in regulating metabolism and aging. This review focuses on current understanding of the relation between metabolic pathways involving sirtuins and the brain aging process, with focus on SIRT1 and SIRT3. Identification of therapeutic agents capable of modulating the expression and/or activity of sirtuins is expected to provide promising strategies for ameliorating neurodegeneration. Future investigations regarding the concerted interplay of the different sirtuins will help us understand more about the aging process, and potentially lead to the development of therapeutic approaches for the treatment of age-related neurodegenerative diseases and promotion of successful aging.

  17. Poststroke Cell Therapy of the Aged Brain

    Directory of Open Access Journals (Sweden)

    Aurel Popa-Wagner

    2015-01-01

    Full Text Available During aging, many neurodegenerative disorders are associated with reduced neurogenesis and a decline in the proliferation of stem/progenitor cells. The development of the stem cell (SC, the regenerative therapy field, gained tremendous expectations in the diseases that suffer from the lack of treatment options. Stem cell based therapy is a promising approach to promote neuroregeneration after brain injury and can be potentiated when combined with supportive pharmacological drug treatment, especially in the aged. However, the mechanism of action for a particular grafted cell type, the optimal delivery route, doses, or time window of administration after lesion is still under debate. Today, it is proved that these protections are most likely due to modulatory mechanisms rather than the expected cell replacement. Our group proved that important differences appear in the aged brain compared with young one, that is, the accelerated progression of ischemic area, or the delayed initiation of neurological recovery. In this light, these age-related aspects should be carefully evaluated in the clinical translation of neurorestorative therapies. This review is focused on the current perspectives and suitable sources of stem cells (SCs, mechanisms of action, and the most efficient delivery routes in neurorestoration therapies in the poststroke aged environment.

  18. Executive dysfunction, brain aging, and political leadership.

    Science.gov (United States)

    Fisher, Mark; Franklin, David L; Post, Jerrold M

    2014-01-01

    Decision-making is an essential component of executive function, and a critical skill of political leadership. Neuroanatomic localization studies have established the prefrontal cortex as the critical brain site for executive function. In addition to the prefrontal cortex, white matter tracts as well as subcortical brain structures are crucial for optimal executive function. Executive function shows a significant decline beginning at age 60, and this is associated with age-related atrophy of prefrontal cortex, cerebral white matter disease, and cerebral microbleeds. Notably, age-related decline in executive function appears to be a relatively selective cognitive deterioration, generally sparing language and memory function. While an individual may appear to be functioning normally with regard to relatively obvious cognitive functions such as language and memory, that same individual may lack the capacity to integrate these cognitive functions to achieve normal decision-making. From a historical perspective, global decline in cognitive function of political leaders has been alternatively described as a catastrophic event, a slowly progressive deterioration, or a relatively episodic phenomenon. Selective loss of executive function in political leaders is less appreciated, but increased utilization of highly sensitive brain imaging techniques will likely bring greater appreciation to this phenomenon. Former Israeli Prime Minister Ariel Sharon was an example of a political leader with a well-described neurodegenerative condition (cerebral amyloid angiopathy) that creates a neuropathological substrate for executive dysfunction. Based on the known neuroanatomical and neuropathological changes that occur with aging, we should probably assume that a significant proportion of political leaders over the age of 65 have impairment of executive function. PMID:25901887

  19. Brain Aging in the Oldest-Old

    Directory of Open Access Journals (Sweden)

    A. von Gunten

    2010-01-01

    Full Text Available Nonagenarians and centenarians represent a quickly growing age group worldwide. In parallel, the prevalence of dementia increases substantially, but how to define dementia in this oldest-old age segment remains unclear. Although the idea that the risk of Alzheimer's disease (AD decreases after age 90 has now been questioned, the oldest-old still represent a population relatively resistant to degenerative brain processes. Brain aging is characterised by the formation of neurofibrillary tangles (NFTs and senile plaques (SPs as well as neuronal and synaptic loss in both cognitively intact individuals and patients with AD. In nondemented cases NFTs are usually restricted to the hippocampal formation, whereas the progressive involvement of the association areas in the temporal neocortex parallels the development of overt clinical signs of dementia. In contrast, there is little correlation between the quantitative distribution of SP and AD severity. The pattern of lesion distribution and neuronal loss changes in extreme aging relative to the younger-old. In contrast to younger cases where dementia is mainly related to severe NFT formation within adjacent components of the medial and inferior aspects of the temporal cortex, oldest-old individuals display a preferential involvement of the anterior part of the CA1 field of the hippocampus whereas the inferior temporal and frontal association areas are relatively spared. This pattern suggests that both the extent of NFT development in the hippocampus as well as a displacement of subregional NFT distribution within the Cornu ammonis (CA fields may be key determinants of dementia in the very old. Cortical association areas are relatively preserved. The progression of NFT formation across increasing cognitive impairment was significantly slower in nonagenarians and centenarians compared to younger cases in the CA1 field and entorhinal cortex. The total amount of amyloid and the neuronal loss in these regions

  20. Social support, stress and the aging brain.

    Science.gov (United States)

    Sherman, Stephanie M; Cheng, Yen-Pi; Fingerman, Karen L; Schnyer, David M

    2016-07-01

    Social support benefits health and well-being in older individuals, however the mechanism remains poorly understood. One proposal, the stress-buffering hypothesis states social support 'buffers' the effects of stress on health. Alternatively, the main effect hypothesis suggests social support independently promotes health. We examined the combined association of social support and stress on the aging brain. Forty healthy older adults completed stress questionnaires, a social network interview and structural MRI to investigate the amygdala-medial prefrontal cortex circuitry, which is implicated in social and emotional processing and negatively affected by stress. Social support was positively correlated with right medial prefrontal cortical thickness while amygdala volume was negatively associated with social support and positively related to stress. We examined whether the association between social support and amygdala volume varied across stress level. Stress and social support uniquely contribute to amygdala volume, which is consistent with the health benefits of social support being independent of stress. PMID:26060327

  1. The Influence of the Brain on Overpopulation, Ageing and Dependency.

    Science.gov (United States)

    Cape, Ronald D. T.

    1989-01-01

    With time, an increasing number in the world population is becoming old, and changes in the aging brain mean that a significant proportion of the aged are likely to be dependent on others. The devotion of resources to research into the aging brain could bring benefits far outweighing the investment. (Author/CW)

  2. Effects of smoking on brain aging, 1

    International Nuclear Information System (INIS)

    The chronic effects of smoking on regional cerebral blood flow (CBF), and on serum lipids and lipoprotein levels in neurologically normal subjects from 25 to 85 years old were studied. CBF was studied by the 133-Xenon inhalation method and gray matter flow was calculated following the method of Obrist et al. A hundred and twentyfive subjects who had no abnormalities in neurological examinations nor in CT scan, were divided into two groups smokers (48) and non-smokers (77). Those who had a smoking index (Number of cigarettes/day) x (years of smoking history)>200 were designated as smokers. The mean smoking index of smokers was 697. sixty-five of the 77 subjects in the non-smoking group had never smoked, and the mean smoking index of non-smokers was 16. Increased reduction of CBF with advancing age was clearly observed. In the male, CBF was significantly lower in smokers than in non-smokers (mean CBF 15% lower in smokers, p<0.001). Compared to non-smokers, CBF in smokers was found to be significantly lower than the expected age matched value. Serum high density lipoprotein cholesterol values in smokers were significantly lower, and total cholesterol levels significantly higher than in non-smokers. We concluded that smoking chronically reduced CBF. Age dependent decrease of CBF was deteriorated by chronic smoking. Then, chronic smoking was suggested to be a risk factor for brain aging. Decrease of CBF in smokers was probably due to advanced atherosclerosis which produces vascular narrowing and raised resistance in cerebral blood vessels. (author)

  3. Neuroimaging studies of the aging HIV-1-infected brain

    OpenAIRE

    Holt, John L.; Kraft-Terry, Stephanie D.; Chang, Linda

    2012-01-01

    Highly active antiretroviral therapy (HAART) has increased life expectancy among HIV-infected individuals, and by 2015, at least half of all HIV-infected individuals will be over 50 years of age. Neurodegenerative processes associated with aging may be facilitated by HIV-1 infection, resulting in premature brain aging. This review will highlight brain abnormalities in HIV patients in the setting of aging, focusing on recent neuroimaging studies of the structural, physiological, functional and...

  4. Parameters of glucose metabolism and the aging brain

    DEFF Research Database (Denmark)

    Akintola, Abimbola A; van den Berg, Annette; Altmann-Schneider, Irmhild;

    2015-01-01

    Given the concurrent, escalating epidemic of diabetes mellitus and neurodegenerative diseases, two age-related disorders, we aimed to understand the relation between parameters of glucose metabolism and indices of pathology in the aging brain. From the Leiden Longevity Study, 132 participants (mean...... different parameters of glucose metabolism (impairment of which is characteristic of diabetes mellitus) and brain aging....... age 66 years) underwent a 2-h oral glucose tolerance test to assess glucose tolerance (fasted and area under the curve (AUC) glucose), insulin sensitivity (fasted and AUC insulin and homeostatic model assessment of insulin sensitivity (HOMA-IS)) and insulin secretion (insulinogenic index). 3-T brain...

  5. Visceral adipose tissue inflammation is associated with age-related brain changes and ischemic brain damage in aged mice.

    Science.gov (United States)

    Shin, Jin A; Jeong, Sae Im; Kim, Minsuk; Yoon, Joo Chun; Kim, Hee-Sun; Park, Eun-Mi

    2015-11-01

    Visceral adipose tissue is accumulated with aging. An increase in visceral fat accompanied by low-grade inflammation is associated with several adult-onset diseases. However, the effects of visceral adipose tissue inflammation on the normal and ischemic brains of aged are not clearly defined. To examine the role of visceral adipose tissue inflammation, we evaluated inflammatory cytokines in the serum, visceral adipose tissue, and brain as well as blood-brain barrier (BBB) permeability in aged male mice (20 months) underwent sham or visceral fat removal surgery compared with the young mice (2.5 months). Additionally, ischemic brain injury was compared in young and aged mice with sham and visceral fat removal surgery. Interleukin (IL)-1β, IL-6, and tumor necrosis factor-α levels in examined organs were increased in aged mice compared with the young mice, and these levels were reduced in the mice with visceral fat removal. Increased BBB permeability with reduced expression of tight junction proteins in aged sham mice were also decreased in mice with visceral fat removal. After focal ischemic injury, aged mice with visceral fat removal showed a reduction in infarct volumes, BBB permeability, and levels of proinflammatory cytokines in the ischemic brain compared with sham mice, although the neurological outcomes were not significantly improved. In addition, further upregulated visceral adipose tissue inflammation in response to ischemic brain injury was attenuated in mice with visceral fat removal. These results suggest that visceral adipose tissue inflammation is associated with age-related changes in the brain and contributes to the ischemic brain damage in the aged mice. We suggest that visceral adiposity should be considered as a factor affecting brain health and ischemic brain damage in the aged population. PMID:26184082

  6. Visceral adipose tissue inflammation is associated with age-related brain changes and ischemic brain damage in aged mice.

    Science.gov (United States)

    Shin, Jin A; Jeong, Sae Im; Kim, Minsuk; Yoon, Joo Chun; Kim, Hee-Sun; Park, Eun-Mi

    2015-11-01

    Visceral adipose tissue is accumulated with aging. An increase in visceral fat accompanied by low-grade inflammation is associated with several adult-onset diseases. However, the effects of visceral adipose tissue inflammation on the normal and ischemic brains of aged are not clearly defined. To examine the role of visceral adipose tissue inflammation, we evaluated inflammatory cytokines in the serum, visceral adipose tissue, and brain as well as blood-brain barrier (BBB) permeability in aged male mice (20 months) underwent sham or visceral fat removal surgery compared with the young mice (2.5 months). Additionally, ischemic brain injury was compared in young and aged mice with sham and visceral fat removal surgery. Interleukin (IL)-1β, IL-6, and tumor necrosis factor-α levels in examined organs were increased in aged mice compared with the young mice, and these levels were reduced in the mice with visceral fat removal. Increased BBB permeability with reduced expression of tight junction proteins in aged sham mice were also decreased in mice with visceral fat removal. After focal ischemic injury, aged mice with visceral fat removal showed a reduction in infarct volumes, BBB permeability, and levels of proinflammatory cytokines in the ischemic brain compared with sham mice, although the neurological outcomes were not significantly improved. In addition, further upregulated visceral adipose tissue inflammation in response to ischemic brain injury was attenuated in mice with visceral fat removal. These results suggest that visceral adipose tissue inflammation is associated with age-related changes in the brain and contributes to the ischemic brain damage in the aged mice. We suggest that visceral adiposity should be considered as a factor affecting brain health and ischemic brain damage in the aged population.

  7. A longitudinal study of brain volume changes in normal aging

    International Nuclear Information System (INIS)

    Purpose: To evaluate the effect of normal aging on brain volumes and examine the effects of age and sex on the rates of changes in global and regional brain volumes. Methods: A total of 199 normal subjects (65 females and 134 males, mean age = 56.4 ± 9.9 years, age range = 38.1–82.9 years) were included in this study. Each subject was scanned twice, at an interval of about 2 years (range = 1.5–2.3 years). Two-time-point percentage brain volume change (PBVC) was estimated with SIENA 2.6. Results: The mean annualized PBVC was −0.23%/y. Analysis of covariance (ANCOVA) for annual brain volume changes revealed a main effect of age. There was no main effect of sex, nor was there a sex-by-age interaction. Voxel-wise analysis revealed a negative correlation between age and edge displacement values mainly in the periventricular region. Conclusions: The results of our study indicate that brain atrophy accelerates with increasing age and that there is no gender difference in the rate of brain atrophy

  8. Accelerated brain aging in schizophrenia : A longitudinal pattern recognition study

    NARCIS (Netherlands)

    Schnack, Hugo G.; Van Haren, Neeltje E M; Nieuwenhuis, Mireille; Pol, Hilleke E Hulshoff; Cahn, Wiepke; Kahn, René S.

    2016-01-01

    OBJECTIVE: Despite the multitude of longitudinal neuroimaging studies that have been published, a basic question on the progressive brain loss in schizophrenia remains unaddressed: Does it reflect accelerated aging of the brain, or is it caused by a fundamentally different process? The authors used

  9. Modeling the brain morphology distribution in the general aging population

    Science.gov (United States)

    Huizinga, W.; Poot, D. H. J.; Roshchupkin, G.; Bron, E. E.; Ikram, M. A.; Vernooij, M. W.; Rueckert, D.; Niessen, W. J.; Klein, S.

    2016-03-01

    Both normal aging and neurodegenerative diseases such as Alzheimer's disease cause morphological changes of the brain. To better distinguish between normal and abnormal cases, it is necessary to model changes in brain morphology owing to normal aging. To this end, we developed a method for analyzing and visualizing these changes for the entire brain morphology distribution in the general aging population. The method is applied to 1000 subjects from a large population imaging study in the elderly, from which 900 were used to train the model and 100 were used for testing. The results of the 100 test subjects show that the model generalizes to subjects outside the model population. Smooth percentile curves showing the brain morphology changes as a function of age and spatiotemporal atlases derived from the model population are publicly available via an interactive web application at agingbrain.bigr.nl.

  10. Statistical Approaches for the Study of Cognitive and Brain Aging

    Science.gov (United States)

    Chen, Huaihou; Zhao, Bingxin; Cao, Guanqun; Proges, Eric C.; O'Shea, Andrew; Woods, Adam J.; Cohen, Ronald A.

    2016-01-01

    Neuroimaging studies of cognitive and brain aging often yield massive datasets that create many analytic and statistical challenges. In this paper, we discuss and address several limitations in the existing work. (1) Linear models are often used to model the age effects on neuroimaging markers, which may be inadequate in capturing the potential nonlinear age effects. (2) Marginal correlations are often used in brain network analysis, which are not efficient in characterizing a complex brain network. (3) Due to the challenge of high-dimensionality, only a small subset of the regional neuroimaging markers is considered in a prediction model, which could miss important regional markers. To overcome those obstacles, we introduce several advanced statistical methods for analyzing data from cognitive and brain aging studies. Specifically, we introduce semiparametric models for modeling age effects, graphical models for brain network analysis, and penalized regression methods for selecting the most important markers in predicting cognitive outcomes. We illustrate these methods using the healthy aging data from the Active Brain Study. PMID:27486400

  11. Brain Damage in School Age Children.

    Science.gov (United States)

    Haywood, H. Carl, Ed.

    The product of a professional workshop, 10 papers discuss brain damage. An introduction to clinical neuropsychology is presented by H. Carl Haywood. A section on neurological foundations includes papers on the organization of the central nervous system by Jack T. Tapp and Lance L. Simpson, on epilepsy by Angela T. Folsom, and on organic language…

  12. Ageing and diabetes: implications for brain function

    NARCIS (Netherlands)

    Gispen, W.H.; Biessels, G.J.; Heide, L.P. van der; Kamal, A.; Bleys, R.L.A.W.

    2002-01-01

    Diabetes mellitus is associated with moderate cognitive deficits and neurophysiological and structural changes in the brain, a condition that may be referred to as diabetic encephalopathy. Diabetes increases the risk of dementia, particularly in the elderly. The emerging view is that the diabetic br

  13. Nutritional Cognitive Neuroscience: Innovations for Healthy Brain Aging

    Directory of Open Access Journals (Sweden)

    Marta Karolina Zamroziewicz

    2016-06-01

    Full Text Available Nutritional cognitive neuroscience is an emerging interdisciplinary field of research that seeks to understand nutrition’s impact on cognition and brain health across the life span. Research in this burgeoning field demonstrates that many aspects of nutrition – from entire diets to specific nutrients – affect brain structure and function, and therefore have profound implications for understanding the nature of healthy brain aging. The aim of this Focused Review is to examine recent advances in nutritional cognitive neuroscience, with an emphasis on methods that enable discovery of nutrient biomarkers that predict healthy brain aging. We propose an integrative framework that calls for the synthesis of research in nutritional epidemiology and cognitive neuroscience, incorporating: (i methods for the precise characterization of nutritional health based on the analysis of nutrient biomarker patterns, along with (ii modern indices of brain health derived from high-resolution magnetic resonance imaging. By integrating cutting-edge techniques from nutritional epidemiology and cognitive neuroscience, nutritional cognitive neuroscience will continue to advance our understanding of the beneficial effects of nutrition on the aging brain and establish effective nutritional interventions to promote healthy brain aging.

  14. Emotion and Aging: Evidence from Brain and Behavior

    Directory of Open Access Journals (Sweden)

    Natalie eEbner

    2014-09-01

    Full Text Available Emotions play a central role in every human life from the moment we are born until we die. They prepare the body for action, highlight what should be noticed and remembered, and guide decisions and actions. As emotions are central to daily functioning, it is important to understand how aging affects perception, memory, experience, as well as regulation of emotions. The Frontiers research topic Emotion and Aging: Evidence from Brain and Behavior takes a step into uncovering emotional aging considering both brain and behavioral processes. The contributions featured in this issue adopt innovative theoretical perspectives and use novel methodological approaches to target a variety of topics that can be categorized into three overarching questions: How do cognition and emotion interact in aging in brain and behavior? What are behavioral and brain-related moderators of emotional aging? Does emotion-regulatory success as reflected in brain and behavior change with age? In this perspective paper we discuss theoretical innovation, methodological approach, and scientific advancement of the thirteen papers in the context of the broader literature on emotional aging. We conclude by reflecting on topics untouched and future directions to take.

  15. Do brain image databanks support understanding of normal ageing brain structure? A systematic review

    Energy Technology Data Exchange (ETDEWEB)

    Dickie, David Alexander; Job, Dominic E.; Wardlaw, Joanna M. [University of Edinburgh, Division of Clinical Neurosciences, Western General Hospital, Brain Research Imaging Centre (BRIC), Edinburgh (United Kingdom); Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE), Edinburgh (United Kingdom); Poole, Ian [Toshiba Medical Visualisation Systems Europe, Ltd., Edinburgh (United Kingdom); Ahearn, Trevor S.; Staff, Roger T.; Murray, Alison D. [University of Aberdeen, Aberdeen Biomedical Imaging Centre, Aberdeen (United Kingdom); Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE), Edinburgh (United Kingdom)

    2012-07-15

    To document accessible magnetic resonance (MR) brain images, metadata and statistical results from normal older subjects that may be used to improve diagnoses of dementia. We systematically reviewed published brain image databanks (print literature and Internet) concerned with normal ageing brain structure. From nine eligible databanks, there appeared to be 944 normal subjects aged {>=}60 years. However, many subjects were in more than one databank and not all were fully representative of normal ageing clinical characteristics. Therefore, there were approximately 343 subjects aged {>=}60 years with metadata representative of normal ageing, but only 98 subjects were openly accessible. No databank had the range of MR image sequences, e.g. T2*, fluid-attenuated inversion recovery (FLAIR), required to effectively characterise the features of brain ageing. No databank supported random subject retrieval; therefore, manual selection bias and errors may occur in studies that use these subjects as controls. Finally, no databank stored results from statistical analyses of its brain image and metadata that may be validated with analyses of further data. Brain image databanks require open access, more subjects, metadata, MR image sequences, searchability and statistical results to improve understanding of normal ageing brain structure and diagnoses of dementia. (orig.)

  16. Influence of age on brain edema formation, secondary brain damage and inflammatory response after brain trauma in mice.

    Directory of Open Access Journals (Sweden)

    Ralph Timaru-Kast

    Full Text Available After traumatic brain injury (TBI elderly patients suffer from higher mortality rate and worse functional outcome compared to young patients. However, experimental TBI research is primarily performed in young animals. Aim of the present study was to clarify whether age affects functional outcome, neuroinflammation and secondary brain damage after brain trauma in mice. Young (2 months and old (21 months male C57Bl6N mice were anesthetized and subjected to a controlled cortical impact injury (CCI on the right parietal cortex. Animals of both ages were randomly assigned to 15 min, 24 h, and 72 h survival. At the end of the observation periods, contusion volume, brain water content, neurologic function, cerebral and systemic inflammation (CD3+ T cell migration, inflammatory cytokine expression in brain and lung, blood differential cell count were determined. Old animals showed worse neurological function 72 h after CCI and a high mortality rate (19.2% compared to young (0%. This did not correlate with histopathological damage, as contusion volumes were equal in both age groups. Although a more pronounced brain edema formation was detected in old mice 24 hours after TBI, lack of correlation between brain water content and neurological deficit indicated that brain edema formation is not solely responsible for age-dependent differences in neurological outcome. Brains of old naïve mice were about 8% smaller compared to young naïve brains, suggesting age-related brain atrophy with possible decline in plasticity. Onset of cerebral inflammation started earlier and primarily ipsilateral to damage in old mice, whereas in young mice inflammation was delayed and present in both hemispheres with a characteristic T cell migration pattern. Pulmonary interleukin 1β expression was up-regulated after cerebral injury only in young, not aged mice. The results therefore indicate that old animals are prone to functional deficits and strong ipsilateral cerebral

  17. Fertility, aging and the brain neuroendocrinological studies in female rats

    NARCIS (Netherlands)

    Franke, A.N.

    2003-01-01

    It is well known that fertility decreases in female mammals with advancing age. In women this decrease already starts around the age of 30 and shows a large variation between individuals. The aim of this thesis was to elucidate changes in the reproductive system, especially in the brain, that may un

  18. Berry Fruit Supplementation in the Aging Brain

    Science.gov (United States)

    The onset of age-related neurodegenerative diseases such as Alzheimer’s or Parkinson’s Disease, superimposed on a declining nervous system, could exacerbate the motor and cognitive behavioral deficits that normally occur in senescence. In cases of severe deficits in memory or motor function, hospit...

  19. In vivo calcium imaging of the aging and diseased brain

    Energy Technology Data Exchange (ETDEWEB)

    Eichhoff, Gerhard; Busche, Marc A.; Garaschuk, Olga [Technical University of Munich, Institute of Neuroscience, Munich (Germany)

    2008-03-15

    Over the last decade, in vivo calcium imaging became a powerful tool for studying brain function. With the use of two-photon microscopy and modern labelling techniques, it allows functional studies of individual living cells, their processes and their interactions within neuronal networks. In vivo calcium imaging is even more important for studying the aged brain, which is hard to investigate in situ due to the fragility of neuronal tissue. In this article, we give a brief overview of the techniques applicable to image aged rodent brain at cellular resolution. We use multicolor imaging to visualize specific cell types (neurons, astrocytes, microglia) as well as the autofluorescence of the ''aging pigment'' lipofuscin. Further, we illustrate an approach for simultaneous imaging of cortical cells and senile plaques in mouse models of Alzheimer's disease. (orig.)

  20. The dopaminergic system in the aging brain of Drosophila

    Directory of Open Access Journals (Sweden)

    Katherine E White

    2010-12-01

    Full Text Available Drosophila models of Parkinson’s disease are characterised by two principal phenotypes: the specific loss of dopaminergic neurons in the aging brain and defects in motor behavior. However, an age-related analysis of these baseline parameters in wildtype Drosophila is lacking. Here we analysed the dopaminergic system and motor behavior in aging Drosophila. Dopaminergic neurons in the adult brain can be grouped into bilateral symmetric clusters, each comprising a stereotypical number of cells. Analysis of TH>mCD8::GFP and cell type-specific MARCM clones revealed that dopaminergic neurons show cluster-specific, stereotypical projection patterns with terminal arborization in target regions that represent distinct functional areas of the adult brain. Target areas include the mushroom bodies, involved in memory formation and motivation, and the central complex, involved in the control of motor behavior, indicating that similar to the mammalian brain, dopaminergic neurons in the fly brain are involved in the regulation of specific behaviors. Behavioral analysis revealed that Drosophila show an age-related decline in startle-induced locomotion and negative geotaxis. Motion tracking however, revealed that walking activity and exploration behavior, but not centrophobism increase at late stages of life. Analysis of TH>Dcr2, mCD8::GFP revealed a specific effect of Dcr2 expression on walking activity but not on exploratory or centrophobic behavior, indicating that the siRNA pathway may modulate distinct dopaminergic behaviors in Drosophila. Moreover, dopaminergic neurons were maintained between early- and late life, as quantified by TH>mCD8::GFP and anti-TH labelling, indicating that adult onset, age-related degeneration of dopaminergic neurons does not occur in the aging brain of Drosophila. Taken together, our data establish baseline parameters in Drosophila for the study of Parkinson’s disease as well as other disorders affecting dopaminergic neurons

  1. Estimating brain age using high-resolution pattern recognition: Younger brains in long-term meditation practitioners.

    Science.gov (United States)

    Luders, Eileen; Cherbuin, Nicolas; Gaser, Christian

    2016-07-01

    Normal aging is known to be accompanied by loss of brain substance. The present study was designed to examine whether the practice of meditation is associated with a reduced brain age. Specific focus was directed at age fifty and beyond, as mid-life is a time when aging processes are known to become more prominent. We applied a recently developed machine learning algorithm trained to identify anatomical correlates of age in the brain translating those into one single score: the BrainAGE index (in years). Using this validated approach based on high-dimensional pattern recognition, we re-analyzed a large sample of 50 long-term meditators and 50 control subjects estimating and comparing their brain ages. We observed that, at age fifty, brains of meditators were estimated to be 7.5years younger than those of controls. In addition, we examined if the brain age estimates change with increasing age. While brain age estimates varied only little in controls, significant changes were detected in meditators: for every additional year over fifty, meditators' brains were estimated to be an additional 1month and 22days younger than their chronological age. Altogether, these findings seem to suggest that meditation is beneficial for brain preservation, effectively protecting against age-related atrophy with a consistently slower rate of brain aging throughout life. PMID:27079530

  2. Deciphering orogenic evolution

    OpenAIRE

    Rolland, Yan; Lardeaux, Jean-Marc; Jolivet, Laurent

    2012-01-01

    Deciphering orogenic evolution requires the integration of a growing number of geological and geophysical techniques on various spatial and temporal scales. Contrasting visions of mountain building and lithospheric deformation have been proposed in recent years. These models depend on the respective roles assigned to the mantle, the crust or the sediments. This article summarizes the contents of the Special Issue dedicated to 'Geodynamics and Orogenesis' following the 'Réunion previous termde...

  3. A brain network processing the age of faces.

    Directory of Open Access Journals (Sweden)

    György A Homola

    Full Text Available Age is one of the most salient aspects in faces and of fundamental cognitive and social relevance. Although face processing has been studied extensively, brain regions responsive to age have yet to be localized. Using evocative face morphs and fMRI, we segregate two areas extending beyond the previously established face-sensitive core network, centered on the inferior temporal sulci and angular gyri bilaterally, both of which process changes of facial age. By means of probabilistic tractography, we compare their patterns of functional activation and structural connectivity. The ventral portion of Wernicke's understudied perpendicular association fasciculus is shown to interconnect the two areas, and activation within these clusters is related to the probability of fiber connectivity between them. In addition, post-hoc age-rating competence is found to be associated with high response magnitudes in the left angular gyrus. Our results provide the first evidence that facial age has a distinct representation pattern in the posterior human brain. We propose that particular face-sensitive nodes interact with additional object-unselective quantification modules to obtain individual estimates of facial age. This brain network processing the age of faces differs from the cortical areas that have previously been linked to less developmental but instantly changeable face aspects. Our probabilistic method of associating activations with connectivity patterns reveals an exemplary link that can be used to further study, assess and quantify structure-function relationships.

  4. Intrinsic brain connectivity related to age in young and middle aged adults.

    Directory of Open Access Journals (Sweden)

    Michelle Hampson

    Full Text Available Age-related variations in resting state connectivity of the human brain were examined from young adulthood through middle age. A voxel-based network measure, degree, was used to assess age-related differences in tissue connectivity throughout the brain. Increases in connectivity with age were found in paralimbic cortical and subcortical regions. Decreases in connectivity were found in cortical regions, including visual areas and the default mode network. These findings differ from those of recent developmental studies examining earlier growth trajectories, and are consistent with known changes in cognitive function and emotional processing during mature aging. The results support and extend previous findings that relied on a priori definitions of regions of interest for their analyses. This approach of applying a voxel-based measure to examine the functional connectivity of individual tissue elements over time, without the need for a priori region of interest definitions, provides an important new tool in brain science.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Alpha oscillatory correlates of motor inhibition in the aged brain

    Directory of Open Access Journals (Sweden)

    Marlene eBoenstrup

    2015-10-01

    Full Text Available Exerting inhibitory control is a cognitive ability mediated by functions known to decline with age. The goal of this study is to add to the mechanistic understanding of cortical inhibition during motor control in aged brains. Based on behavioral findings of impaired inhibitory control with age we hypothesized that elderly will show a reduced or a lack of EEG alpha-power increase during tasks that require motor inhibition. Since inhibitory control over movements has been shown to rely on prior motor memory formation, we investigated cortical inhibitory processes at two points in time - early after learning and after an overnight consolidation phase and hypothesized an overnight increase of inhibitory capacities. Young and elderly participants acquired a complex finger movement sequence and in each experimental session brain activity during execution and inhibition of the sequence was recorded with multi-channel EEG. We assessed cortical processes of sustained inhibition by means of task-induced changes of alpha oscillatory power. During inhibition of the learned movement, young participants showed a significant alpha power increase at the sensorimotor cortices whereas elderly did not. Interestingly, for both groups, the overnight consolidation phase improved up-regulation of alpha power during sustained inhibition. This points to deficits in the generation and enhancement of local inhibitory mechanisms at the sensorimotor cortices in aged brains. However, the alpha power increase in both groups implies neuroplastic changes that strengthen the network of alpha power generation over time in young as well as elderly brains.

  7. Brain-Based Teaching in the Digital Age

    Science.gov (United States)

    Sprenger, Marilee

    2010-01-01

    In the digital age, your students have the ways, means, and speed to gather any information they want. But they need your guidance more than ever. Discover how digital technology is actually changing your students' brains. Learn why this creates new obstacles for teachers, but also opens up potential new pathways for learning. You will understand…

  8. Aging and Gene Expression in the Primate Brain

    Energy Technology Data Exchange (ETDEWEB)

    Fraser, Hunter B.; Khaitovich, Philipp; Plotkin, Joshua B.; Paabo, Svante; Eisen, Michael B.

    2005-02-18

    It is well established that gene expression levels in many organisms change during the aging process, and the advent of DNA microarrays has allowed genome-wide patterns of transcriptional changes associated with aging to be studied in both model organisms and various human tissues. Understanding the effects of aging on gene expression in the human brain is of particular interest, because of its relation to both normal and pathological neurodegeneration. Here we show that human cerebral cortex, human cerebellum, and chimpanzee cortex each undergo different patterns of age-related gene expression alterations. In humans, many more genes undergo consistent expression changes in the cortex than in the cerebellum; in chimpanzees, many genes change expression with age in cortex, but the pattern of changes in expression bears almost no resemblance to that of human cortex. These results demonstrate the diversity of aging patterns present within the human brain, as well as how rapidly genome-wide patterns of aging can evolve between species; they may also have implications for the oxidative free radical theory of aging, and help to improve our understanding of human neurodegenerative diseases.

  9. Aging and gene expression in the primate brain.

    Directory of Open Access Journals (Sweden)

    2005-09-01

    Full Text Available It is well established that gene expression levels in many organisms change during the aging process, and the advent of DNA microarrays has allowed genome-wide patterns of transcriptional changes associated with aging to be studied in both model organisms and various human tissues. Understanding the effects of aging on gene expression in the human brain is of particular interest, because of its relation to both normal and pathological neurodegeneration. Here we show that human cerebral cortex, human cerebellum, and chimpanzee cortex each undergo different patterns of age-related gene expression alterations. In humans, many more genes undergo consistent expression changes in the cortex than in the cerebellum; in chimpanzees, many genes change expression with age in cortex, but the pattern of changes in expression bears almost no resemblance to that of human cortex. These results demonstrate the diversity of aging patterns present within the human brain, as well as how rapidly genome-wide patterns of aging can evolve between species; they may also have implications for the oxidative free radical theory of aging, and help to improve our understanding of human neurodegenerative diseases.

  10. Age-dependent complex noise fluctuations in the brain

    International Nuclear Information System (INIS)

    We investigated the parameters of colored noise in EEG data of 17 722 professional drivers aged 18–70. The whole study is based upon experiments showing that biological neural networks may operate in the vicinity of the critical point and that the balance between excitation and inhibition in the human brain is important for the transfer of information. This paper is devoted to the study of EEG power spectrum which can be described best by a power function with 1/fλ distribution and colored noise corresponding to the critical point in the EEG signal has the value of λ = 1 (purple noise). The slow accumulation of energy and its quick release is a universal property of the 1/f distribution. The physiological mechanism causing energy dissipation in the brain seems to depend on the number and strength of the connections between clusters of neurons. With ageing, the number of connections between the neurons decreases. Learning ability and intellectual performance also decrease. Therefore, age-related changes in the λ coefficient can be anticipated. We found that absolute values of λ coefficients decrease significantly with increasing age. Deviations from this rule are related to age-dependent slowing of the dominant frequency in the alpha band. Age-dependent change in the parameter and colored noise may be indicative of age-related changes in the self-organization of brain activity. Results obtained include (i) the age-dependent decrease of the absolute values of the average λ coefficient with the regression coefficient 0.005 1/year, (ii) distribution of λ value changes related to EEG frequency bands and to localization of electrodes on the scalp, and (iii) relation of age-dependent changes of colored noise and EEG energy in separate frequency bands. (paper)

  11. Brain energy metabolism and blood flow differences in healthy aging

    DEFF Research Database (Denmark)

    Aanerud, Joel; Borghammer, Per; Chakravarty, M Mallar;

    2012-01-01

    Cerebral metabolic rate of oxygen consumption (CMRO(2)), cerebral blood flow (CBF), and oxygen extraction fraction (OEF) are important indices of healthy aging of the brain. Although a frequent topic of study, changes of CBF and CMRO(2) during normal aging are still controversial, as some authors...... years. The magnitudes of CMRO(2) and CBF declined in large parts of the cerebral cortex, including association areas, but the primary motor and sensory areas were relatively spared. We found significant increases of OEF in frontal and parietal cortices, excluding primary motor and somatosensory regions......, and in the temporal cortex. Because of the inverse relation between OEF and capillary oxygen tension, increased OEF can compromise oxygen delivery to neurons, with possible perturbation of energy turnover. The results establish a possible mechanism of progression from healthy to unhealthy brain aging, as the regions...

  12. Resveratrol attenuates peripheral and brain inflammation and reduces ischemic brain injury in aged female mice.

    Science.gov (United States)

    Jeong, Sae Im; Shin, Jin A; Cho, Sunghee; Kim, Hye Won; Lee, Ji Yoon; Kang, Jihee Lee; Park, Eun-Mi

    2016-08-01

    Resveratrol is known to improve metabolic dysfunction associated with obesity. Visceral obesity is a sign of aging and is considered a risk factor for ischemic stroke. In this study, we investigated the effects of resveratrol on inflammation in visceral adipose tissue and the brain and its effects on ischemic brain injury in aged female mice. Mice treated with resveratrol (0.1 mg/kg, p.o.) for 10 days showed reduced levels of interleukin-1β and tumor necrosis factor-α, as well as a reduction in the size of adipocytes in visceral adipose tissue. Resveratrol also reduced interleukin-1β and tumor necrosis factor-α protein levels and immunoglobulin G extravasation in the brain. Mice treated with resveratrol demonstrated smaller infarct size, improved neurological function, and blunted peripheral inflammation at 3 days postischemic stroke. These results showed that resveratrol counteracted inflammation in visceral adipose tissue and in the brain and reduced stroke-induced brain injury and peripheral inflammation in aged female mice. Therefore, resveratrol administration can be a valuable strategy for the prevention of age-associated and disease-provoked inflammation in postmenopausal women. PMID:27318135

  13. Indestructible plastic: the neuroscience of the new aging brain.

    Science.gov (United States)

    Holman, Constance; de Villers-Sidani, Etienne

    2014-01-01

    In recent years, research on experience-dependent plasticity has provided valuable insight on adaptation to environmental input across the lifespan, and advances in understanding the minute cellular changes underlying the brain's capacity for self-reorganization have opened exciting new possibilities for treating illness and injury. Ongoing work in this line of inquiry has also come to deeply influence another field: cognitive neuroscience of the normal aging. This complex process, once considered inevitable or beyond the reach of treatment, has been transformed into an arena of intense investigation and strategic intervention. However, important questions remain about this characterization of the aging brain, and the assumptions it makes about the social, cultural, and biological space occupied by cognition in the older individual and body. The following paper will provide a critical examination of the move from basic experiments on the neurophysiology of experience-dependent plasticity to the growing market for (and public conception of) cognitive aging as a medicalized space for intervention by neuroscience-backed technologies. Entangled with changing concepts of normality, pathology, and self-preservation, we will argue that this new understanding, led by personalized cognitive training strategies, is approaching a point where interdisciplinary research is crucial to provide a holistic and nuanced understanding of the aging process. This new outlook will allow us to move forward in a space where our knowledge, like our new conception of the brain, is never static. PMID:24782746

  14. NSAIDs may protect against age-related brain atrophy

    Directory of Open Access Journals (Sweden)

    Barbara B Bendlin

    2010-09-01

    Full Text Available The use of non-steroidal anti-inflammatory drugs (NSAIDs in humans is associated with brain differences including decreased number of activated microglia. In animals, NSAIDs are associated with reduced microglia, decreased amyloid burden, and neuronal preservation. Several studies suggest NSAIDs protect brain regions affected in the earliest stages of AD, including hippocampal and parahippocampal regions. In this cross-sectional study, we examined the protective effect of NSAID use on gray matter volume in a group of middle-aged and older NSAID users (n = 25 compared to non-user controls (n = 50. All participants underwent neuropsychological testing and T1-weighted magnetic resonance imaging. Non-user controls showed smaller volume in portions of the left hippocampus compared to NSAID users. Age-related loss of volume differed between groups, with controls showing greater medial temporal lobe volume loss with age compared to NSAID users. These results should be considered preliminary, but support previous reports that NSAIDs may modulate age-related loss of brain volume.

  15. Male brain ages faster: the age and gender dependence of subcortical volumes.

    Science.gov (United States)

    Király, András; Szabó, Nikoletta; Tóth, Eszter; Csete, Gergő; Faragó, Péter; Kocsis, Krisztián; Must, Anita; Vécsei, László; Kincses, Zsigmond Tamás

    2016-09-01

    Effects of gender on grey matter (GM) volume differences in subcortical structures of the human brain have consistently been reported. Recent research evidence suggests that both gender and brain size influences volume distribution in subcortical areas independently. The goal of this study was to determine the effects of the interplay between brain size, gender and age contributing to volume differences of subcortical GM in the human brain. High-resolution T1-weighted images were acquired from 53 healthy males and 50 age-matched healthy females. Total GM volume was determined using voxel-based morphometry. We used model-based subcortical segmentation analysis to measure the volume of subcortical nuclei. Main effects of gender, brain volume and aging on subcortical structures were examined using multivariate analysis of variance. No significant difference was found in total brain volume between the two genders after correcting for total intracranial volume. Our analysis revealed significantly larger hippocampus volume for females. Additionally, GM volumes of the caudate nucleus, putamen and thalamus displayed a significant age-related decrease in males as compared to females. In contrast to this only the thalamic volume loss proved significant for females. Strikingly, GM volume decreases faster in males than in females emphasizing the interplay between aging and gender on subcortical structures. These findings might have important implications for the interpretation of the effects of unalterable factors (i.e. gender and age) in cross-sectional structural MRI studies. Furthermore, the volume distribution and changes of subcortical structures have been consistently related to several neuropsychiatric disorders (e.g. Parkinson's disease, attention deficit hyperactivity disorder, etc.). Understanding these changes might yield further insight in the course and prognosis of these disorders. PMID:26572143

  16. Neural Plastic Effects of Cognitive Training on Aging Brain

    OpenAIRE

    Leung, Natalie T. Y.; Tam, Helena M. K.; Leung W. Chu; Kwok, Timothy C. Y.; Felix Chan; Lam, Linda C. W.; Jean Woo; Lee, Tatia M. C.

    2015-01-01

    Increasing research has evidenced that our brain retains a capacity to change in response to experience until late adulthood. This implies that cognitive training can possibly ameliorate age-associated cognitive decline by inducing training-specific neural plastic changes at both neural and behavioral levels. This longitudinal study examined the behavioral effects of a systematic thirteen-week cognitive training program on attention and working memory of older adults who were at risk of cogni...

  17. NREM sleep oscillations and brain plasticity in aging

    OpenAIRE

    Stuart eFogel; Nicolas eMartin; Marjolaine eLafortune; Marc eBarakat; Karen eDebas; Samuel eLaventure; Véronique eLatreille; Jean-François eGagnon; Julien eDoyon; Julie eCarrier

    2012-01-01

    The human electroencephalogram (EEG) during non-rapid eye movement sleep (NREM) is characterized mainly by high-amplitude (> 75 µV), slow-frequency (< 4 Hz) waves (slow waves; SW) and sleep spindles (~11-15 Hz; > 0.25 s). These NREM oscillations play a crucial role in brain plasticity, and importantly, NREM sleep oscillations change considerably with aging. This review discusses the association between NREM sleep oscillations and cerebral plasticity as well as the functional imp...

  18. Lucid dreaming: an age-dependent brain dissociation.

    Science.gov (United States)

    Voss, Ursula; Frenzel, Clemens; Koppehele-Gossel, Judith; Hobson, Allan

    2012-12-01

    The current study focused on the distribution of lucid dreams in school children and young adults. The survey was conducted on a large sample of students aged 6-19 years. Questions distinguished between past and current experience with lucid dreams. Results suggest that lucid dreaming is quite pronounced in young children, its incidence rate drops at about age 16 years. Increased lucidity was found in those attending higher level compared with lower level schools. Taking methodological issues into account, we feel confident to propose a link between the natural occurrence of lucid dreaming and brain maturation.

  19. Increased self-diffusion of brain water in normal aging

    DEFF Research Database (Denmark)

    Gideon, P; Thomsen, C; Henriksen, O

    1994-01-01

    With magnetic resonance (MR) imaging, brain water self-diffusion was measured in 17 healthy volunteers 22-76 (mean, 44.6) years old. The calculated values for the apparent diffusion coefficients (ADCs) ranged from 0.58 x 10(-9) to 1.23 x 10(-9) m2/sec in cerebral white matter. A significant...... by an increase in the extracellular volume due to age-dependent neuronal degeneration or to changes in myelination. These findings have implications for future clinical investigations with diffusion MR imaging techniques in patients with neurologic diseases, and stress the importance of having an age...

  20. Lucid dreaming: an age-dependent brain dissociation.

    Science.gov (United States)

    Voss, Ursula; Frenzel, Clemens; Koppehele-Gossel, Judith; Hobson, Allan

    2012-12-01

    The current study focused on the distribution of lucid dreams in school children and young adults. The survey was conducted on a large sample of students aged 6-19 years. Questions distinguished between past and current experience with lucid dreams. Results suggest that lucid dreaming is quite pronounced in young children, its incidence rate drops at about age 16 years. Increased lucidity was found in those attending higher level compared with lower level schools. Taking methodological issues into account, we feel confident to propose a link between the natural occurrence of lucid dreaming and brain maturation. PMID:22639960

  1. Age-related hearing loss: ear and brain mechanisms.

    Science.gov (United States)

    Frisina, Robert D

    2009-07-01

    Loss of sensory function in the aged has serious consequences for economic productivity, quality of life, and healthcare costs in the billions each year. Understanding the neural and molecular bases will pave the way for biomedical interventions to prevent, slow, or reverse these conditions. This chapter summarizes new information regarding age changes in the auditory system involving both the ear (peripheral) and brain (central). A goal is to provide findings that have implications for understanding some common biological underpinnings that affect sensory systems, providing a basis for eventual interventions to improve overall sensory functioning, including the chemical senses.

  2. Brain Plasticity and Motor Practice in Cognitive Aging

    Directory of Open Access Journals (Sweden)

    Liuyang eCai

    2014-03-01

    Full Text Available For more than two decades, there have been extensive studies of experience-based neural plasticity exploring effective applications of brain plasticity for cognitive and motor development. Research suggests that human brains continuously undergo structural reorganization and functional changes in response to stimulations or training. From a developmental point of view, the assumption of lifespan brain plasticity has been extended to older adults in terms of the benefits of cognitive training and physical therapy. To summarize recent developments, first, we introduce the concept of neural plasticity from a developmental perspective. Secondly, we note that motor learning often refers to deliberate practice and the resulting performance enhancement and adaptability. We discuss the close interplay between neural plasticity, motor learning and cognitive aging. Thirdly, we review research on motor skill acquisition in older adults with, and without, impairments relative to aging-related cognitive decline. Finally, to enhance future research and application, we highlight the implications of neural plasticity in skills learning and cognitive rehabilitation for the aging population.

  3. Brain plasticity and motor practice in cognitive aging

    Science.gov (United States)

    Cai, Liuyang; Chan, John S. Y.; Yan, Jin H.; Peng, Kaiping

    2014-01-01

    For more than two decades, there have been extensive studies of experience-based neural plasticity exploring effective applications of brain plasticity for cognitive and motor development. Research suggests that human brains continuously undergo structural reorganization and functional changes in response to stimulations or training. From a developmental point of view, the assumption of lifespan brain plasticity has been extended to older adults in terms of the benefits of cognitive training and physical therapy. To summarize recent developments, first, we introduce the concept of neural plasticity from a developmental perspective. Secondly, we note that motor learning often refers to deliberate practice and the resulting performance enhancement and adaptability. We discuss the close interplay between neural plasticity, motor learning and cognitive aging. Thirdly, we review research on motor skill acquisition in older adults with, and without, impairments relative to aging-related cognitive decline. Finally, to enhance future research and application, we highlight the implications of neural plasticity in skills learning and cognitive rehabilitation for the aging population. PMID:24653695

  4. Auditory event-related brain potentials for an early discrimination between normal and pathological brain aging

    Institute of Scientific and Technical Information of China (English)

    Juliana Dushanova; Mario Christov

    2013-01-01

    The brain as a system with gradually decreasing resources maximizes its chances by reorganizing neural networks to ensure efficient performance. Auditory event-related potentials were recorded in 28 healthy volunteers comprising 14 young and 14 elderly subjects in auditory discrimination motor task (low frequency tone – right hand movement and high frequency tone – left hand movement). The amplitudes of the sensory event-related potential components (N1, P2) were more pronounced with increasing age for either tone and this effect for P2 amplitude was more pronounced in the frontal region. The latency relationship of N1 between the groups was tone-dependent, while that of P2 was tone-independent with a prominent delay in the elderly group over all brain regions. The amplitudes of the cognitive components (N2, P3) diminished with increasing age and the hemispheric asymmetry of N2 (but not for P3) reduced with increasing age. Prolonged N2 latency with increasing age was widespread for either tone while between-group difference in P3 latency was tone-dependent. High frequency tone stimulation and movement requirements lead to P3 delay in the elderly group. The amplitude difference of the sensory components between the age groups could be due to a general greater alertness, less expressed habituation, or decline in the ability to retreat attentional resources from the stimuli in the elderly group. With aging, a neural circuit reorganization of the brain activity affects the cognitive processes. The approach used in this study is useful for an early discrimination between normal and pathological brain aging for early treatment of cognitive alterations and dementia.

  5. Non-invasive brain stimulation of the aging brain: State of the art and future perspectives.

    Science.gov (United States)

    Tatti, Elisa; Rossi, Simone; Innocenti, Iglis; Rossi, Alessandro; Santarnecchi, Emiliano

    2016-08-01

    Favored by increased life expectancy and reduced birth rate, worldwide demography is rapidly shifting to older ages. The golden age of aging is not only an achievement but also a big challenge because of the load of the elderly on social and medical health care systems. Moreover, the impact of age-related decline of attention, memory, reasoning and executive functions on self-sufficiency emphasizes the need of interventions to maintain cognitive abilities at a useful degree in old age. Recently, neuroscientific research explored the chance to apply Non-Invasive Brain Stimulation (NiBS) techniques (as transcranial electrical and magnetic stimulation) to healthy aging population to preserve or enhance physiologically-declining cognitive functions. The present review will update and address the current state of the art on NiBS in healthy aging. Feasibility of NiBS techniques will be discussed in light of recent neuroimaging (either structural or functional) and neurophysiological models proposed to explain neural substrates of the physiologically aging brain. Further, the chance to design multidisciplinary interventions to maximize the efficacy of NiBS techniques will be introduced as a necessary future direction. PMID:27221544

  6. Indestructible plastic: The neuroscience of the new aging brain

    Directory of Open Access Journals (Sweden)

    Constance eHolman

    2014-04-01

    Full Text Available In recent years, research on experience-dependent plasticity has provided valuable insight on adaptation to environmental input across the lifespan, and advances in understanding the minute cellular changes underlying the brain’s capacity for self-reorganization have opened exciting new possibilities for treating illness and injury. Ongoing work in this line of inquiry has also come to deeply influence another field: the cognitive neuroscience of the normal aging. This complex process, once dubbed as inevitable or beyond the reach of treatment, has been transformed into an arena of intense investigation and strategic intervention. However, important questions remain about this characterization of the aging brain, and the assumptions it makes about the social, cultural, and biological space occupied by cognition in the older individual and body. The following paper will provide a critical examination of the move from basic experiments on the neurophysiology of experience-dependent plasticity to the growing market for (and public conception of cognitive aging as a medicalized space for intervention by neuroscience-backed technologies. Entangled with changing concepts of normality, pathology, and self-preservation, we will argue that this new understanding, led by personalized cognitive training strategies, is approaching a point where interdisciplinary research is crucial to provide a holistic and nuanced understanding of the aging process. This new outlook will allow us to move forward in a space where our knowledge, like our new conception of the brain, is never static.

  7. Reversal of glial and neurovascular markers of unhealthy brain aging by exercise in middle-aged female mice.

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    Caitlin S Latimer

    Full Text Available Healthy brain aging and cognitive function are promoted by exercise. The benefits of exercise are attributed to several mechanisms, many which highlight its neuroprotective role via actions that enhance neurogenesis, neuronal morphology and/or neurotrophin release. However, the brain is also composed of glial and vascular elements, and comparatively less is known regarding the effects of exercise on these components in the aging brain. Here, we show that aerobic exercise at mid-age decreased markers of unhealthy brain aging including astrocyte hypertrophy, a hallmark of brain aging. Middle-aged female mice were assigned to a sedentary group or provided a running wheel for six weeks. Exercise decreased hippocampal astrocyte and myelin markers of aging but increased VEGF, a marker of angiogenesis. Brain vascular casts revealed exercise-induced structural modifications associated with improved endothelial function in the periphery. Our results suggest that age-related astrocyte hypertrophy/reactivity and myelin dysregulation are aggravated by a sedentary lifestyle and accompanying reductions in vascular function. However, these effects appear reversible with exercise initiated at mid-age. As this period of the lifespan coincides with the appearance of multiple markers of brain aging, including initial signs of cognitive decline, it may represent a window of opportunity for intervention as the brain appears to still possess significant vascular plasticity. These results may also have particular implications for aging females who are more susceptible than males to certain risk factors which contribute to vascular aging.

  8. NREM sleep oscillations and brain plasticity in aging

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    Stuart eFogel

    2012-12-01

    Full Text Available The human electroencephalogram (EEG during non-rapid eye movement sleep (NREM is characterized mainly by high-amplitude (> 75 µV, slow-frequency (< 4 Hz waves (slow waves; SW and sleep spindles (~11-15 Hz; > 0.25 s. These NREM oscillations play a crucial role in brain plasticity, and importantly, NREM sleep oscillations change considerably with aging. This review discusses the association between NREM sleep oscillations and cerebral plasticity as well as the functional impact of age-related changes on NREM sleep oscillations. We propose that age-related reduction in sleep-dependent memory consolidation may be due in part to changes in NREM sleep oscillations.

  9. Brain computed tomography findings of aged schizophrenics; Comparison with healthy aged controls and aged schizophrenics with a history of psychosurgery

    Energy Technology Data Exchange (ETDEWEB)

    Oomori, Masao; Koshino, Yoshifumi; Murata, Tetsuhito; Murata, Ichirou; Tani, Kazuhiko; Horie, Tan; Isaki, Kiminori (Fukui Medical School, Matsuoka (Japan))

    1992-05-01

    Brain CT was performed in a total of 30 aged schizophrenic patients, consisting of 20 with no history of psychosurgery (lobotomy) and the other 10 lobotomized patients. The CT findings were compared with those from healthy aged persons. The group of schizophrenic patients had marked atrophy of the frontal lobe and dilatated Sylvian fissure as compared with the control group. There was no significant difference in ventricular factors between the two groups. These findings may have implications for the different mechanisms of the occurrence of atrophied brain surface and enlarged ventricle. The cerebral cortex involved in the occurrence of schizophrenia may be affected by aging-related cerebral atrophy, in addition to the morphological changes due to schizophrenia. Thus, schizophrenic cerebral atrophy was more noticeable than physiological aging-related atrophy. However, enlargement of the ventricle in the schizophrenic group progressed with aging in the same manner as that in the normal group. In comparing schizophrenic patients with or without a history of lobotomy, atrophy of the brain surface and enlargement of the ventricle were more marked in the lobotomized patients than the non-lobotomized patients. This confirmed that lobotomy, as well as surgical scar, is involved in the morphology of schizophrenic brain. (N.K.).

  10. Advanced BrainAGE in older adults with type 2 diabetes mellitus

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    Katja eFranke

    2013-12-01

    Full Text Available Aging alters brain structure and function and diabetes mellitus (DM may accelerate this process. This study investigated the effects of type 2 DM on individual brain aging as well as the relationships between individual brain aging, risk factors and functional measures. To differentiate a pattern of brain atrophy that deviates from normal brain aging, we used the novel BrainAGE approach, which determines the complex multidimensional aging pattern within the whole brain by applying established kernel regression methods to anatomical brain MRIs. The Brain Age Gap Estimation (i.e., BrainAGE score was then calculated as the difference between chronological age and estimated brain age. 185 subjects (98 with type 2 DM completed an MRI at 3T, laboratory and clinical assessments. Twenty-five subjects (12 with type 2 DM also completed a follow-up visit after 3.8 ± 1.5 years. The estimated brain age of DM subjects was 4.6 ± 7.2 years greater than their chronological age (p = 0.0001, whereas within the control group, estimated brain age was similar to chronological age. As compared to baseline, the average BrainAGE scores of DM subjects increased by 0.2 years per follow-up year (p = 0.034, whereas the BrainAGE scores of controls did not change between baseline and follow-up. At baseline, across all subjects, higher BrainAGE scores were associated with greater smoking and alcohol consumption, higher tumor necrosis factor (TNFα levels, lower verbal fluency scores and more severe depression. Within the DM group, higher BrainAGE scores were associated with longer diabetes duration (r = 0.31, p = 0.019 and increased fasting blood glucose levels (r = 0.34, p = 0.025. In conclusion, type 2 DM is independently associated with structural changes in the brain that reflect advanced aging. The BrainAGE approach may thus serve as a clinically relevant biomarker for the detection of abnormal patterns of brain aging associated with type 2 DM.

  11. Prognostic significance of age in traumatic brain injury

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    S S Dhandapani

    2012-01-01

    Full Text Available Background: Age is a strong prognostic factor following traumatic brain injury (TBI, with discrepancies defining the critical prognostic age threshold. This study was undertaken to determine the impact of various age thresholds on outcome after TBI. Materials and Methods : The ages of patients admitted with TBI were prospectively studied in relation to mode of injury, Glasgow coma score (GCS, CT category and surgical intervention. Mortality was assessed at 1 month, and neurological outcome was assessed at 6 months. Appropriate statistical analyzes (details in article were performed. Results: Of the total 244 patients enrolled, 144 patients had severe, 38 patients had moderate and 62 patients had mild TBI, respectively. Age had significant association with grade of injury, CT category and surgical intervention (P 59 years respectively (P 40 years in all subgroups, based on GCS and surgical intervention (P < 0.05. Conclusions : In patients with TBI, age demonstrates independent association with unfavorable outcome at 6 months, in stepwise manner centered on a threshold of 40 years.

  12. Age-related changes in brain structural covariance networks

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    Xinwei eLi

    2013-03-01

    Full Text Available Previous neuroimaging studies have suggested that cerebral changes over normal aging are not simply characterized by regional alterations, but rather by the reorganization of cortical connectivity patterns. The investigation of structural covariance networks (SCNs using voxel-based morphometry is an advanced approach to examining the pattern of covariance in gray matter volumes among different regions of the human cortex. To date, how the organization of critical SCNs change during normal aging remains largely unknown. In this study, we used an SCN mapping approach to investigate eight large-scale networks in 240 healthy participants aged 18–89 years. These participants were subdivided into young (18–23 years, middle aged (30–58 years, and older (61–89 years subjects. Eight seed regions were chosen from widely reported functional intrinsic connectivity networks. The voxels showing significant positive associations with these seed regions were used to describe the topological organization of an SCN. All of these networks exhibited non-linear patterns in their spatial extent that were associated with normal aging. These networks, except the primary motor network, had a distributed topology in young participants, a sharply localized topology in middle aged participants, and were relatively stable in older participants. The structural covariance derived using the primary motor cortex was limited to the ipsilateral motor regions in the young and older participants, but included contralateral homologous regions in the middle aged participants. In addition, there were significant between-group differences in the structural networks associated with language-related speech and semantics processing, executive control, and the default-mode network. Taken together, the results of this study demonstrate age-related changes in the topological organization of SCNs, and provide insights into normal aging of the human brain.

  13. Changes in intracellular calcium in brain cells of aged rats

    Institute of Scientific and Technical Information of China (English)

    Yu Li; Yunpeng Cao

    2008-01-01

    BACKGROUND: Studies have shown that voltage-dependent calcium influx, and enhancement of certain calcium-dependent processes in neurons, is related to aging. OBJECTIVE: To observe changes in intracellular calcium ([Ca2+]i) in neurons of aged rats, and to compare with young rats. DESIGN, TIME AND SETTING: A randomized control experiment of neurophysiology was performed at the Central Laboratory of School of Pharmaceutical Science, China Medical University from June to August 2004. MATERIALS: Ten male, healthy, Wistar rats, 19 months old, were selected for the aged group. Ten male, 3-month-old, Wistar rats were selected for the young control group. Fura-2/AM was provided by the Institute of Pharmaceutical Research of Chinese Academy of Medical Sciences, and the F-2000 fluorospectrophotometer was a product of Hitachi, Japan. METHODS: Fluorescence Fura-2 spectrophotometer was used to measure [Ca2+]i in acutely dissociated brain cells of aged and young rats. The concentration of extracellular potassium was controlled by adding different volumes of chloridated potassium solution of high concentration. MAIN OUTCOME MEASURES: [Ca2+]i in neurons of young and aged rats in the presence of 1 mmol/L extracellular calcium concentration and 0 mmol/L (resting state), 5, 10, 20, and 40 mmol/L extracellular potassium. Absolute increase of [Ca2+]i in neurons of young and aged rats when extraceUular potassium was 5,10,20, 40 mmol/L. RESULTS: In the presence of 1 mmol/L extracellular Ca2+ and 0 mmol/L (resting state), 5, 10, 20, and 40 mmol/L extracellular potassium, [Ca2+]i in the neurons of aged rats was significantly less than that in young rats (P 0.05). CONCLUSION: The overload of [Ca2+]i in neurons of aged rats is greater than that of young rats under the same circumstances.

  14. Oxidative stress, aging, and central nervous system disease in the canine model of human brain aging.

    Science.gov (United States)

    Head, Elizabeth; Rofina, Jaime; Zicker, Steven

    2008-01-01

    Decline in cognitive functions that accompany aging in dogs may have a biologic basis, and many of the disorders associated with aging in dogs may be mitigated through dietary modifications that incorporate specific nutraceuticals. Based on previous research and the results of laboratory and clinical studies, antioxidants may be one class of nutraceutical that provides benefits to aged dogs. Brains of aged dogs accumulate oxidative damage to proteins and lipids, which may lead to dysfunction of neuronal cells. The production of free radicals and lack of increase in compensatory antioxidant enzymes may lead to detrimental modifications to important macromolecules within neurons. Reducing oxidative damage through food ingredients rich in a broad spectrum of antioxidants significantly improves, or slows the decline of, learning and memory in aged dogs.

  15. Age sensitivity of behavioral tests and brain substrates of normal aging in mice.

    Science.gov (United States)

    Kennard, John A; Woodruff-Pak, Diana S

    2011-01-01

    Knowledge of age sensitivity, the capacity of a behavioral test to reliably detect age-related changes, has utility in the design of experiments to elucidate processes of normal aging. We review the application of these tests in studies of normal aging and compare and contrast the age sensitivity of the Barnes maze, eyeblink classical conditioning, fear conditioning, Morris water maze, and rotorod. These tests have all been implemented to assess normal age-related changes in learning and memory in rodents, which generalize in many cases to age-related changes in learning and memory in all mammals, including humans. Behavioral assessments are a valuable means to measure functional outcomes of neuroscientific studies of aging. Highlighted in this review are the attributes and limitations of these measures in mice in the context of age sensitivity and processes of brain aging. Attributes of these tests include reliability and validity as assessments of learning and memory, well-defined neural substrates, and sensitivity to neural and pharmacological manipulations and disruptions. These tests engage the hippocampus and/or the cerebellum, two structures centrally involved in learning and memory that undergo functional and anatomical changes in normal aging. A test that is less well represented in studies of normal aging, the context pre-exposure facilitation effect (CPFE) in fear conditioning, is described as a method to increase sensitivity of contextual fear conditioning to changes in the hippocampus. Recommendations for increasing the age sensitivity of all measures of normal aging in mice are included, as well as a discussion of the potential of the under-studied CPFE to advance understanding of subtle hippocampus-mediated phenomena.

  16. Age Sensitivity of Behavioral Tests and Brain Substrates of Normal Aging in Mice

    Directory of Open Access Journals (Sweden)

    John A. Kennard

    2011-05-01

    Full Text Available Knowledge of age sensitivity, the capacity of a behavioral test to reliably detect age-related changes, has utility in the design of experiments to elucidate processes of normal aging. We review the application of these tests in studies of normal aging and compare and contrast the age sensitivity of the Barnes maze, eyeblink classical conditioning, fear conditioning, Morris water maze and rotorod. These tests have all been implemented to assess normal age-related changes in learning and memory in rodents, which generalize in many cases to age-related changes in learning and memory in all mammals, including humans. Behavioral assessments are a valuable means to measure functional outcomes of neuroscientific studies of aging. Highlighted in this review are the attributes and limitations of these measures in mice in the context of age sensitivity and processes of brain aging. Attributes of these tests include reliability and validity as assessments of learning and memory, well-defined neural substrates, and sensitivity to neural and pharmacological manipulations and disruptions. These tests engage the hippocampus and/or the cerebellum, two structures centrally involved in learning and memory that undergo functional and anatomical changes in normal aging. A test that is less well represented in studies of normal aging, the context pre-exposure facilitation effect (CPFE in fear conditioning, is described as a method to increase sensitivity of contextual fear conditioning to changes in the hippocampus. Recommendations for increasing the age sensitivity of all measures of normal aging in mice are included, as well as a discussion of the potential of the under-studied CPFE to advance understanding of subtle hippocampus-mediated phenomena.

  17. Brain mitochondrial dysfunction in aging, neurodegeneration and Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Ana Navarro

    2010-09-01

    Full Text Available Brain senescence and neurodegeneration occur with a mitochondrial dysfunction characterized by impaired electron transfer and by oxidative damage. Brain mitochondria of old animals show decreased rates of electron transfer in complexes I and IV, decreased membrane potential, increased content of the oxidation products of phospholipids and proteins and increased size and fragility. This impairment, with complex I inactivation and oxidative damage, is named “complex I syndrome” and is recognized as characteristic of mammalian brain aging and of neurodegenerative diseases. Mitochondrial dysfunction is more marked in brain areas as rat hippocampus and frontal cortex, in human cortex in Parkinson’s disease and dementia with Lewy bodies, and in substantia nigra in Parkinson’s disease. The molecular mechanisms involved in complex I inactivation include the synergistic inactivations produced by ONOO- mediated reactions, by reactions with free radical intermediates of lipid peroxidation and by amine-aldehyde adduction reactions. The accumulation of oxidation products prompts the idea of antioxidant therapies. High doses of vitamin E produce a significant protection of complex I activity and mitochondrial function in rats and mice, and with improvement of neurological functions and increased median life span in mice. Mitochondria-targeted antioxidants, as the Skulachev cations covalently attached to vitamin E, ubiquinone and PBN and the SS tetrapeptides, are negatively charged and accumulate in mitochondria where they exert their antioxidant effects. Activation of the cellular mechanisms that regulate mitochondrial biogenesis is another potential therapeutic strategy, since the process generates organelles devoid of oxidation products and with full enzymatic activity and capacity for ATP production.

  18. The Effect of the APOE Genotype on Individual BrainAGE in Normal Aging, Mild Cognitive Impairment, and Alzheimer's Disease.

    Science.gov (United States)

    Löwe, Luise Christine; Gaser, Christian; Franke, Katja

    2016-01-01

    In our aging society, diseases in the elderly come more and more into focus. An important issue in research is Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD) with their causes, diagnosis, treatment, and disease prediction. We applied the Brain Age Gap Estimation (BrainAGE) method to examine the impact of the Apolipoprotein E (APOE) genotype on structural brain aging, utilizing longitudinal magnetic resonance image (MRI) data of 405 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We tested for differences in neuroanatomical aging between carrier and non-carrier of APOE ε4 within the diagnostic groups and for longitudinal changes in individual brain aging during about three years follow-up. We further examined whether a combination of BrainAGE and APOE status could improve prediction accuracy of conversion to AD in MCI patients. The influence of the APOE status on conversion from MCI to AD was analyzed within all allelic subgroups as well as for ε4 carriers and non-carriers. The BrainAGE scores differed significantly between normal controls, stable MCI (sMCI) and progressive MCI (pMCI) as well as AD patients. Differences in BrainAGE changing rates over time were observed for APOE ε4 carrier status as well as in the pMCI and AD groups. At baseline and during follow-up, BrainAGE scores correlated significantly with neuropsychological test scores in APOE ε4 carriers and non-carriers, especially in pMCI and AD patients. Prediction of conversion was most accurate using the BrainAGE score as compared to neuropsychological test scores, even when the patient's APOE status was unknown. For assessing the individual risk of coming down with AD as well as predicting conversion from MCI to AD, the BrainAGE method proves to be a useful and accurate tool even if the information of the patient's APOE status is missing. PMID:27410431

  19. Hemispherical dominance of glucose metabolic rate in the brain of the 'normal' ageing population

    NARCIS (Netherlands)

    Cutts, DA; Maguire, RP; Leenders, KL; Spyrou, NM

    2004-01-01

    In the 'normal' ageing brain a decrease in the cerebral metabolic rate has been determined across many brain regions. This study determines whether age differences would affect metabolic rates in regions and different hemispheres of the brain. The regional metabolic rate of glucose (rCMRGlu) was exa

  20. AGES in brain ageing: AGE-inhibitors as neuroprotective and anti-dementia drugs?

    Science.gov (United States)

    Dukic-Stefanovic, S; Schinzel, R; Riederer, P; Münch, G

    2001-01-01

    In Alzheimer's disease, age-related cellular changes such as compromised energy production and increased radical formation are worsened by the presence of AGEs as additional, AD specific stress factors. Intracellular AGEs (most likely derived from methylglyoxal) crosslink cytoskeletal proteins and render them insoluble. These aggregates inhibit cellular functions including transport processes and contribute to neuronal dysfunction and death. Extracellular AGEs, which accumulate in ageing tissue (but most prominently on long-lived protein deposits like the senile plaques) exert chronic oxidative stress on neurons. In addition, they activate glial cells to produce free radicals (superoxide and NO) and neurotoxic cytokines such as TNF-alpha. Drugs, which inhibit the formation of AGEs by specific chemical mechanisms (AGE-inhibitors), including aminoguanidine, carnosine, tenilsetam, OPB-9195 and pyridoxamine, attenuate the development of (AGE-mediated) diabetic complications. Assuming that 'carbonyl stress' contributes significantly to the progression of Alzheimer's disease, AGE-inhibitors might also become interesting novel therapeutic drugs for treatment of AD. PMID:11708614

  1. BrainAGE in Mild Cognitive Impaired Patients: Predicting the Conversion to Alzheimer's Disease.

    Directory of Open Access Journals (Sweden)

    Christian Gaser

    Full Text Available Alzheimer's disease (AD, the most common form of dementia, shares many aspects of abnormal brain aging. We present a novel magnetic resonance imaging (MRI-based biomarker that predicts the individual progression of mild cognitive impairment (MCI to AD on the basis of pathological brain aging patterns. By employing kernel regression methods, the expression of normal brain-aging patterns forms the basis to estimate the brain age of a given new subject. If the estimated age is higher than the chronological age, a positive brain age gap estimation (BrainAGE score indicates accelerated atrophy and is considered a risk factor for conversion to AD. Here, the BrainAGE framework was applied to predict the individual brain ages of 195 subjects with MCI at baseline, of which a total of 133 developed AD during 36 months of follow-up (corresponding to a pre-test probability of 68%. The ability of the BrainAGE framework to correctly identify MCI-converters was compared with the performance of commonly used cognitive scales, hippocampus volume, and state-of-the-art biomarkers derived from cerebrospinal fluid (CSF. With accuracy rates of up to 81%, BrainAGE outperformed all cognitive scales and CSF biomarkers in predicting conversion of MCI to AD within 3 years of follow-up. Each additional year in the BrainAGE score was associated with a 10% greater risk of developing AD (hazard rate: 1.10 [CI: 1.07-1.13]. Furthermore, the post-test probability was increased to 90% when using baseline BrainAGE scores to predict conversion to AD. The presented framework allows an accurate prediction even with multicenter data. Its fast and fully automated nature facilitates the integration into the clinical workflow. It can be exploited as a tool for screening as well as for monitoring treatment options.

  2. Prion protein accumulation in lipid rafts of mouse aging brain.

    Directory of Open Access Journals (Sweden)

    Federica Agostini

    Full Text Available The cellular form of the prion protein (PrP(C is a normal constituent of neuronal cell membranes. The protein misfolding causes rare neurodegenerative disorders known as transmissible spongiform encephalopathies or prion diseases. These maladies can be sporadic, genetic or infectious. Sporadic prion diseases are the most common form mainly affecting aging people. In this work, we investigate the biochemical environment in which sporadic prion diseases may develop, focusing our attention on the cell membrane of neurons in the aging brain. It is well established that with aging the ratio between the most abundant lipid components of rafts undergoes a major change: while cholesterol decreases, sphingomyelin content rises. Our results indicate that the aging process modifies the compartmentalization of PrP(C. In old mice, this change favors PrP(C accumulation in detergent-resistant membranes, particularly in hippocampi. To confirm the relationship between lipid content changes and PrP(C translocation into detergent-resistant membranes (DRMs, we looked at PrP(C compartmentalization in hippocampi from acid sphingomyelinase (ASM knockout (KO mice and synaptosomes enriched in sphingomyelin. In the presence of high sphingomyelin content, we observed a significant increase of PrP(C in DRMS. This process is not due to higher levels of total protein and it could, in turn, favor the onset of sporadic prion diseases during aging as it increases the PrP intermolecular contacts into lipid rafts. We observed that lowering sphingomyelin in scrapie-infected cells by using fumonisin B1 led to a 50% decrease in protease-resistant PrP formation. This may suggest an involvement of PrP lipid environment in prion formation and consequently it may play a role in the onset or development of sporadic forms of prion diseases.

  3. Aging and iron accumulation in the monkey brain

    International Nuclear Information System (INIS)

    Iron is deposited in the mammalian brain with a characteristic distribution, its amount increasing with aging. The relative abundance of iron in the globus pallidus, substantia nigra and putamen is thought to be responsible for the hypointensity of these nuclei on T2-weighted MR images, due to magnetic susceptibility effects. However, no quantitative correlation between iron content and hypointensity has been made to confirm this hypothesis. Two young (1-year-old) and two older (18-year-old) rhesus monkeys were studied with MR imaging at different field strengths (0.5, 1.5, 2.0 T). MR signal intensities from different anatomic structures were measured on T2-weighted coronal images (2,6000/80 [repetition time msec/echo time msec]). At completion of the MR studies, the monkeys were killed, coronal brain sections were stained for iron (Perls method), and optical densities of anatomic structures were measured. A quantitative correlation between the iron content and the signal intensity decrease was found on T2-weighted images in both deep and superficial cerebral structures. The detectability of magnetic susceptibility effects in a single structure is determined by the amount of iron present, with the threshold being inversely correlated to the strength of the magnetic field

  4. A Brain-Wide Study of Age-Related Changes in Functional Connectivity

    NARCIS (Netherlands)

    Geerligs, Linda; Renken, Remco J.; Saliasi, Emi; Maurits, Natasha M.; Lorist, Monicque M.

    2015-01-01

    Aging affects functional connectivity between brain areas, however, a complete picture of how aging affects integration of information within and between functional networks is missing. We used complex network measures, derived from a brain-wide graph, to provide a comprehensive overview of age-rela

  5. Age- and Brain Region-Specific Differences in Mitochondrial Bioenergetics in Brown Norway Rats

    Data.gov (United States)

    U.S. Environmental Protection Agency — Differences in various mitochondrial bioenergetics parameters in different brain regions in different age groups. This dataset is associated with the following...

  6. Age-related changes of normal adult brain structure: analysed with diffusion tensor imaging

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yun-ting; ZHANG Chun-yan; ZHANG Jing; LI Wei

    2005-01-01

    Background It is known that the brain structure changes with normal aging. The objective of this study was to quantify the anisotropy and average diffusion coefficient (DCavg) of the brain in normal adults to demonstrate the microstructure changes of brain with aging.Methods One hundred and six normal adults were examined with diffusion tensor imaging (DTI). The fractional anisotropy (FA), 1-volume ratio (1-VR), relative anisotropy (RA) and average diffusion coefficient (DCavg) of different anatomic sites of brain were measured, correlated with age and compared among three broad age groups.Results Except in lentiform nucleus, the anisotropy increased and DCavg decreased with aging. Both anisotropy and DCavg of lentiform nucleus increased with aging. The normal reference values of DTI parameters of normal Chinese adult in major anatomic sites were acquired. Conclusions DTI data obtained noninvasively can reflect the microstructural changes with aging. The normal reference values acquired can serve as reference standards in differentiation of brain white matter diseases.

  7. The Effect of Aging on Resting-State Brain Function: An fMRI Study

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    A. H. Batouli

    2009-11-01

    Full Text Available Background/Objective: Healthy aging may be accompanied by some types of cognitive impairment; moreover, normal aging may cause natural atrophy in the healthy human brain. The hypothesis of the healthy aging brain is the structural changes together with the functional impairment happening. The brain struggles to over-compensate for those functional age-related impairments to continue as a healthy brain in its functions. Our goal in this study was to evaluate the effects of aging on the resting-state activation network of the brain using the multi-session probabilistic independent component analysis algorithm (PICA. "nPatients and Methods: We compared the resting-state brain activities between two groups of healthy aged and young subjects, so we examined 30 right-handed subjects and finally 12 healthy aging and 11 controls were enrolled in the study. "nResults: Our results showed that during the resting-state, older brains benefit from larger areas of activation, while in young competent brains, higher activation occurs in terms of greater intensity. These results were obtained in prefrontal areas as regions with regard to memory function as well as the posterior cingulate cortex (PCC as parts of the default mode network. Meanwhile, we reached the same results after normalization of activation size with total brain volume. "nConclusion: The difference in activation patterns between the two groups shows the brain's endeavor to compensate the functional impairment.

  8. Associations between regional brain volumes at term-equivalent age and development at 2 years of age in preterm children

    International Nuclear Information System (INIS)

    Altered brain volumes and associations between volumes and developmental outcomes have been reported in prematurely born children. To assess which regional brain volumes are different in very low birth weight (VLBW) children without neurodevelopmental impairments ([NDI] cerebral palsy, hearing loss, blindness and significantly delayed cognitive performance) compared with VLBW children with NDI, and to evaluate the association between regional brain volumes at term-equivalent age and cognitive development and neurological performance at a corrected age of 2 years. The study group consisted of a regional cohort of 164 VLBW children, divided into one group of children without NDI (n = 148) and one group of children with NDI (n = 16). Brain (MRI) was performed at term-equivalent age, from which brain volumes were manually analysed. Cognitive development was assessed with the Bayley Scales of Infant Development II (BSID-II), and neurological performance with the Hammersmith Infant Neurological Examination at the corrected age of 2 years. The volumes of total brain tissue, cerebrum, frontal lobes, basal ganglia and thalami, and cerebellum were significantly smaller, and the volume of the ventricles significantly larger, in the children with NDI than in those without NDI. Even in children without NDI, a smaller cerebellar volume was significantly correlated with poor neurological performance at 2 years of corrected age. Volumetric analysis at brain MRI can provide an additional parameter for early prediction of outcome in VLBW children. (orig.)

  9. Associations between regional brain volumes at term-equivalent age and development at 2 years of age in preterm children

    Energy Technology Data Exchange (ETDEWEB)

    Lind, Annika [Turku University Hospital, Department of Pediatrics, Turku (Finland); Aabo Akademi University, Department of Psychology, Turku (Finland); Parkkola, Riitta [University of Turku and Turku University Hospital, Department of Radiology and Turku PET Center, PO Box 52, Turku (Finland); Lehtonen, Liisa; Maunu, Jonna; Lapinleimu, Helena [University of Turku and Turku University Hospital, Department of Pediatrics, Turku (Finland); Munck, Petriina [Turku University Hospital, Department of Pediatrics, Turku (Finland); University of Turku, Department of Psychology, Turku (Finland); Haataja, Leena [University of Turku and Turku University Hospital, Department of Pediatric Neurology, Turku (Finland)

    2011-08-15

    Altered brain volumes and associations between volumes and developmental outcomes have been reported in prematurely born children. To assess which regional brain volumes are different in very low birth weight (VLBW) children without neurodevelopmental impairments ([NDI] cerebral palsy, hearing loss, blindness and significantly delayed cognitive performance) compared with VLBW children with NDI, and to evaluate the association between regional brain volumes at term-equivalent age and cognitive development and neurological performance at a corrected age of 2 years. The study group consisted of a regional cohort of 164 VLBW children, divided into one group of children without NDI (n = 148) and one group of children with NDI (n = 16). Brain (MRI) was performed at term-equivalent age, from which brain volumes were manually analysed. Cognitive development was assessed with the Bayley Scales of Infant Development II (BSID-II), and neurological performance with the Hammersmith Infant Neurological Examination at the corrected age of 2 years. The volumes of total brain tissue, cerebrum, frontal lobes, basal ganglia and thalami, and cerebellum were significantly smaller, and the volume of the ventricles significantly larger, in the children with NDI than in those without NDI. Even in children without NDI, a smaller cerebellar volume was significantly correlated with poor neurological performance at 2 years of corrected age. Volumetric analysis at brain MRI can provide an additional parameter for early prediction of outcome in VLBW children. (orig.)

  10. Huntington's disease accelerates epigenetic aging of human brain and disrupts DNA methylation levels.

    Science.gov (United States)

    Horvath, Steve; Langfelder, Peter; Kwak, Seung; Aaronson, Jeff; Rosinski, Jim; Vogt, Thomas F; Eszes, Marika; Faull, Richard L M; Curtis, Maurice A; Waldvogel, Henry J; Choi, Oi-Wa; Tung, Spencer; Vinters, Harry V; Coppola, Giovanni; Yang, X William

    2016-07-01

    Age of Huntington's disease (HD) motoric onset is strongly related to the number of CAG trinucleotide repeats in the huntingtin gene, suggesting that biological tissue age plays an important role in disease etiology. Recently, a DNA methylation based biomarker of tissue age has been advanced as an epigenetic aging clock. We sought to inquire if HD is associated with an accelerated epigenetic age. DNA methylation data was generated for 475 brain samples from various brain regions of 26 HD cases and 39 controls. Overall, brain regions from HD cases exhibit a significant epigenetic age acceleration effect (p=0.0012). A multivariate model analysis suggests that HD status increases biological age by 3.2 years. Accelerated epigenetic age can be observed in specific brain regions (frontal lobe, parietal lobe, and cingulate gyrus). After excluding controls, we observe a negative correlation (r=-0.41, p=5.5×10-8) between HD gene CAG repeat length and the epigenetic age of HD brain samples. Using correlation network analysis, we identify 11 co-methylation modules with a significant association with HD status across 3 broad cortical regions. In conclusion, HD is associated with an accelerated epigenetic age of specific brain regions and more broadly with substantial changes in brain methylation levels. PMID:27479945

  11. Effects of tetrahydroxystilbene - glucoside on Animal Models of Dementia or Brain Aging

    Institute of Scientific and Technical Information of China (English)

    LinLi; JinChu; LiLiu; LingZhao; LanZhang

    2004-01-01

    Aim: To investigate the effects of 2, 3, 5, 4'-tetrahydroxystilbene-2-O-β-D-glucoside(TSG) from a Chinese Medicinal Herb polygonum multiflorum on dementia or brain aging. Methods. The brain aging model of mice was developed by s. c. injection of D-galactose (50mg/kg/day) for 60 days. The Alzheimer disease (AD) model of mice

  12. The brain response to peripheral insulin declines with age: a contribution of the blood-brain barrier?

    Directory of Open Access Journals (Sweden)

    Tina Sartorius

    Full Text Available It is a matter of debate whether impaired insulin action originates from a defect at the neural level or impaired transport of the hormone into the brain. In this study, we aimed to investigate the effect of aging on insulin concentrations in the periphery and the central nervous system as well as its impact on insulin-dependent brain activity.Insulin, glucose and albumin concentrations were determined in 160 paired human serum and cerebrospinal fluid (CSF samples. Additionally, insulin was applied in young and aged mice by subcutaneous injection or intracerebroventricularly to circumvent the blood-brain barrier. Insulin action and cortical activity were assessed by Western blotting and electrocorticography radiotelemetric measurements.In humans, CSF glucose and insulin concentrations were tightly correlated with the respective serum/plasma concentrations. The CSF/serum ratio for insulin was reduced in older subjects while the CSF/serum ratio for albumin increased with age like for most other proteins. Western blot analysis in murine whole brain lysates revealed impaired phosphorylation of AKT (P-AKT in aged mice following peripheral insulin stimulation whereas P-AKT was comparable to levels in young mice after intracerebroventricular insulin application. As readout for insulin action in the brain, insulin-mediated cortical brain activity instantly increased in young mice subcutaneously injected with insulin but was significantly reduced and delayed in aged mice during the treatment period. When insulin was applied intracerebroventricularly into aged animals, brain activity was readily improved.This study discloses age-dependent changes in insulin CSF/serum ratios in humans. In the elderly, cerebral insulin resistance might be partially attributed to an impaired transport of insulin into the central nervous system.

  13. BRAIN FUEL METABOLISM, AGING AND ALZHEIMER’S DISEASE

    OpenAIRE

    Cunnane, SC; NUGENT, S; Roy, M.; Courchesne-Loyer, A; Croteau, E; Tremblay, S.; Castellano, A.; Pifferi, F.; Bocti, C; Paquet, N; Begdouri, H; Bentourkia, M; Turcotte, E; M. Allard; Barberger-Gateau, P

    2010-01-01

    Lower brain glucose metabolism is present before the onset of clinically-measurable cognitive decline in two groups of people at risk of Alzheimer’s disease (AD) - carriers of apoE4, and in those with a maternal family history of AD. Supported by emerging evidence from in vitro and animal studies, these reports suggest that brain hypometabolism may precede and contribute to the neuropathological cascade leading cognitive decline in AD. The reason for brain hypometabolism is unclear but may in...

  14. Chronic vitamin C deficiency does not accelerate oxidative stress in ageing brains of guinea pigs

    DEFF Research Database (Denmark)

    Tveden-Nyborg, Pernille; Andersen, Stine Hasselholt; Miyashita, Namiyo;

    2012-01-01

    , a lack of vitamin C could be associated with an increase in redox imbalance in the ageing brain. The present study compared oxidative stress of ageing to that of a long-term non-scorbutic vitamin C deficiency in guinea pigs. Adults (3-9 months old) were compared to old (36-42 months old) animals during...... a six-month dietary intervention by assessing vitamin C transport and redox homeostasis in the brain. In contrast to our hypothesis, chronic vitamin C deficiency did not affect the measured markers of oxidative stress in the brains of adult and aged animals. However, aged animals generally showed...

  15. CT ASSESSMENT OF BRAIN VENTRICULAR SIZE BASED ON AGE AND SEX: A STUDY OF 112 CASES

    Directory of Open Access Journals (Sweden)

    Vinoo

    2013-12-01

    Full Text Available CT being the primary modality of choice in many centers for the diagnosis of brain pathology, normal brain ventricular size measurem ents is an important parameter for the diagnosis of conditions like hydrocephalus, age related atrophic changes and also other brain pathologies producing ventriculomegaly. It is also important for knowing the normal upper and lower limits of the brain ven tricular system in the different age groups, and in both sexes so as to diagnose brain pathology.The ventricular system of the brain undergoes changes with aging and varies with gender.Our study consists of 48 female, and 64 male patients. Apart from the v entricular measurements, two ratios and two indices were also calculated – which included the right and left Evan’s ratio, CM index, and ventricular size inde

  16. HRT and its effect on normal ageing of the brain and dementia

    Science.gov (United States)

    Compton, Jacqueline; van Amelsvoort, Therese; Murphy, Declan

    2001-01-01

    There are significant gender differences in human brain disease. For example, females are significantly more likely to suffer from Alzheimer's disease (AD) than men (even after correcting for differences in life expectancy), and females on hormone replacement therapy (HRT) are significantly less likely to suffer from Alzheimer's disease than women who do not take HRT. However the neurobiological basis to these differences in clinical brain disease were unknown until relatively recently. In this review we will discuss results of studies that show; (i) gender differences in human brain disease are most likely to be explained by gender differences in brain development and ageing; (ii) sex steroids have a significant effect on the brain; (iii) sex steroids are crucial to the development and ageing of brain regions affected in age-related brain diseases (for example AD); (iv) sex steroids interact with neuronal networks and chemical systems at many different levels; (v) sex steroids affect cognitive function in elderly women. Thus, the current literature supports the hypothesis that sex steroids can modulate brain ageing, and this provides a neurobiological explanation for the significantly higher prevalence of AD in females who do not take HRT, and may lead to new treatment approaches for age-related brain disease including AD. PMID:11736875

  17. Structural and functional rejuvenation of the aged brain by an approved anti-asthmatic drug

    OpenAIRE

    Marschallinger, J.; I. Schäffner; B. Klein(Ghent University, Ghent, Belgium); R. Gelfert; F.J. Rivera; S. Illes; L. Grassner; Janssen, M.; P. Rotheneichner; C. Schmuckermair; R. Coras; M. Boccazzi; M. Chishty; F.B. Lagler; M. Renic

    2015-01-01

    As human life expectancy has improved rapidly in industrialized societies, age-related cognitive impairment presents an increasing challenge. Targeting histopathological processes that correlate with age-related cognitive declines, such as neuroinflammation, low levels of neurogenesis, disrupted blood–brain barrier and altered neuronal activity, might lead to structural and functional rejuvenation of the aged brain. Here we show that a 6-week treatment of young (4 months) and old (20 months) ...

  18. Carnosine reverses the aging-induced down regulation of brain regional serotonergic system.

    Science.gov (United States)

    Banerjee, Soumyabrata; Ghosh, Tushar K; Poddar, Mrinal K

    2015-12-01

    The purpose of the present investigation was to study the role of carnosine, an endogenous dipeptide biomolecule, on brain regional (cerebral cortex, hippocampus, hypothalamus and pons-medulla) serotonergic system during aging. Results showed an aging-induced brain region specific significant (a) increase in Trp (except cerebral cortex) and their 5-HIAA steady state level with an increase in their 5-HIAA accumulation and declination, (b) decrease in their both 5-HT steady state level and 5-HT accumulation (except cerebral cortex). A significant decrease in brain regional 5-HT/Trp ratio (except cerebral cortex) and increase in 5-HIAA/5-HT ratio were also observed during aging. Carnosine at lower dosages (0.5-1.0μg/Kg/day, i.t. for 21 consecutive days) didn't produce any significant response in any of the brain regions, but higher dosages (2.0-2.5μg/Kg/day, i.t. for 21 consecutive days) showed a significant response on those aging-induced brain regional serotonergic parameters. The treatment with carnosine (2.0μg/Kg/day, i.t. for 21 consecutive days), attenuated these brain regional aging-induced serotonergic parameters and restored towards their basal levels that observed in 4 months young control rats. These results suggest that carnosine attenuates and restores the aging-induced brain regional down regulation of serotonergic system towards that observed in young rats' brain regions. PMID:26364584

  19. Linking pathways in the developing and aging brain with neurodegeneration

    NARCIS (Netherlands)

    G.G. Kovacs; H. Adle-Biassett; I. Milenkovic; S. Cipriani; J. van Scheppingen; E. Aronica

    2014-01-01

    The molecular and cellular mechanisms, which coordinate the critical stages of brain development to reach a normal structural organization with appropriate networks, are progressively being elucidated. Experimental and clinical studies provide evidence of the occurrence of developmental alterations

  20. Age-related changes in glutathione and glutathione-related enzymes in rat brain

    OpenAIRE

    Zhu, Yuangui; Carvey, Paul M.; Ling, Zaodung

    2006-01-01

    The most reliable and robust risk factor for some neurodegenerative diseases is aging. It has been proposed that processes of aging are associated with the generation of reactive oxygen species and a disturbance of glutathione homeostasis in the brain. Yet, aged animals have rarely been used to model the diseases that are considered to be age-related such as Parkinson's or Alzheimer's disease. This suggests that the results from these studies would be more valuable if aged animals were used. ...

  1. White matter hyperintensities and imaging patterns of brain ageing in the general population.

    Science.gov (United States)

    Habes, Mohamad; Erus, Guray; Toledo, Jon B; Zhang, Tianhao; Bryan, Nick; Launer, Lenore J; Rosseel, Yves; Janowitz, Deborah; Doshi, Jimit; Van der Auwera, Sandra; von Sarnowski, Bettina; Hegenscheid, Katrin; Hosten, Norbert; Homuth, Georg; Völzke, Henry; Schminke, Ulf; Hoffmann, Wolfgang; Grabe, Hans J; Davatzikos, Christos

    2016-04-01

    White matter hyperintensities are associated with increased risk of dementia and cognitive decline. The current study investigates the relationship between white matter hyperintensities burden and patterns of brain atrophy associated with brain ageing and Alzheimer's disease in a large populatison-based sample (n = 2367) encompassing a wide age range (20-90 years), from the Study of Health in Pomerania. We quantified white matter hyperintensities using automated segmentation and summarized atrophy patterns using machine learning methods resulting in two indices: the SPARE-BA index (capturing age-related brain atrophy), and the SPARE-AD index (previously developed to capture patterns of atrophy found in patients with Alzheimer's disease). A characteristic pattern of age-related accumulation of white matter hyperintensities in both periventricular and deep white matter areas was found. Individuals with high white matter hyperintensities burden showed significantly (P brain regions typically affected by ageing and Alzheimer's disease dementia. To investigate a possibly causal role of white matter hyperintensities, structural equation modelling was used to quantify the effect of Framingham cardiovascular disease risk score and white matter hyperintensities burden on SPARE-BA, revealing a statistically significant (P brain atrophy found in beyond-normal brain ageing in the general population. White matter hyperintensities also contribute to brain atrophy patterns in regions related to Alzheimer's disease dementia, in agreement with their known additive role to the likelihood of dementia. Preventive strategies reducing the odds to develop cardiovascular disease and white matter hyperintensities could decrease the incidence or delay the onset of dementia.

  2. Parameterization of the Age-Dependent Whole Brain Apparent Diffusion Coefficient Histogram

    Directory of Open Access Journals (Sweden)

    Uwe Klose

    2015-01-01

    Full Text Available Purpose. The distribution of apparent diffusion coefficient (ADC values in the brain can be used to characterize age effects and pathological changes of the brain tissue. The aim of this study was the parameterization of the whole brain ADC histogram by an advanced model with influence of age considered. Methods. Whole brain ADC histograms were calculated for all data and for seven age groups between 10 and 80 years. Modeling of the histograms was performed for two parts of the histogram separately: the brain tissue part was modeled by two Gaussian curves, while the remaining part was fitted by the sum of a Gaussian curve, a biexponential decay, and a straight line. Results. A consistent fitting of the histograms of all age groups was possible with the proposed model. Conclusions. This study confirms the strong dependence of the whole brain ADC histograms on the age of the examined subjects. The proposed model can be used to characterize changes of the whole brain ADC histogram in certain diseases under consideration of age effects.

  3. The levels of soluble versus insoluble brain Abeta distinguish Alzheimer's disease from normal and pathologic aging.

    Science.gov (United States)

    Wang, J; Dickson, D W; Trojanowski, J Q; Lee, V M

    1999-08-01

    The abundance and solubility of Abeta peptides are critical determinants of amyloidosis in Alzheimer's disease (AD). Hence, we compared levels of total soluble, insoluble, and total Abeta1-40 and Abeta1-42 in AD brains with those in age-matched normal and pathologic aging brains using a sandwich enzyme-linked immunosorbent assay (ELISA). Since the measurement of Abeta1-40 and Abeta1-42 depends critically on the specificity of the monoclonal antibodies used in the sandwich ELISA, we first demonstrated that each assay is specific for Abeta1-40 or Abeta1-42 and the levels of these peptides are not affected by the amyloid precursor protein in the brain extracts. Thus, this sandwich ELISA enabled us to show that the average levels of total cortical soluble and insoluble Abeta1-40 and Abeta1-42 were highest in AD, lowest in normal aging, and intermediate in pathologic aging. Remarkably, the average levels of insoluble Abeta1-40 were increased 20-fold while the average levels of insoluble Abeta1-42 were increased only 2-fold in the AD brains compared to pathologic aging brains. Further, the soluble pools of Abeta1-40 and Abeta1-42 were the largest fractions of total Abeta in the normal brain (i.e., 50 and 23%, respectively), but they were the smallest in the AD brain (i.e., 2.7 and 0.7%, respectively) and intermediate (i.e., 8 and 0.8%, respectively) in pathologic aging brains. Thus, our data suggest that pathologic aging is a transition state between normal aging and AD. More importantly, our findings imply that a progressive shift of brain Abeta1-40 and Abeta1-42 from soluble to insoluble pools and a profound increase in the levels of insoluble Abeta1-40 plays mechanistic roles in the onset and/or progression of AD.

  4. Gender-specific impact of personal health parameters on individual brain aging in cognitively unimpaired elderly subjects

    Directory of Open Access Journals (Sweden)

    Katja eFranke

    2014-05-01

    Full Text Available Aging alters brain structure and function. Personal health markers and modifiable lifestyle factors are related to individual brain aging as well as to the risk of developing Alzheimer’s disease (AD. This study uses a novel magnetic resonance imaging (MRI-based biomarker to assess the effects of 17 health markers on individual brain aging in cognitively unimpaired elderly subjects. By employing kernel regression methods, the expression of normal brain-aging patterns forms the basis to estimate the brain age of a given new subject. If the estimated age is higher than the chronological age, a positive brain age gap estimation (BrainAGE score indicates accelerated atrophy and is considered a risk factor for developing AD. Within this cross-sectional, multi-center study 228 cognitively unimpaired elderly subjects (118 males completed an MRI at 1.5T, physiological and blood parameter assessments. The multivariate regression model combining all measured parameters was capable of explaining 39% of BrainAGE variance in males (p < 0.001 and 32% in females (p < 0.01. Furthermore, markers of the metabolic syndrome as well as markers of liver and kidney functions were profoundly related to BrainAGE scores in males (p < 0.05. In females, markers of liver and kidney functions as well as supply of vitamin B12 were significantly related to BrainAGE (p < 0.05. In conclusion, in cognitively unimpaired elderly subjects several clinical markers of poor health were associated with subtle structural changes in the brain that reflect accelerated aging, whereas protective effects on brain aging were observed for markers of good health. Additionally, the relations between individual brain aging and miscellaneous health markers show gender-specific patterns. The BrainAGE approach may thus serve as a clinically relevant biomarker for the detection of subtly abnormal patterns of brain aging probably preceding cognitive decline and development of AD.

  5. The Impact of MicroRNAs on Brain Aging and Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Stephan P. Persengiev

    2012-01-01

    Full Text Available The molecular instructions that govern gene expression regulation are encoded in the genome and ultimately determine the morphology and functional specifications of the human brain. As a consequence, changes in gene expression levels might be directly related to the functional decline associated with brain aging. Small noncoding RNAs, including miRNAs, comprise a group of regulatory molecules that modulate the expression of hundred of genes which play important roles in brain metabolism. Recent comparative studies in humans and nonhuman primates revealed that miRNAs regulate multiple pathways and interconnected signaling cascades that are the basis for the cognitive decline and neurodegenerative disorders during aging. Identifying the roles of miRNAs and their target genes in model organisms combined with system-level studies of the brain would provide more comprehensive understanding of the molecular basis of brain deterioration during the aging process.

  6. Diet and Age Interactions with Regards to Cholesterol Regulation and Brain Pathogenesis

    Directory of Open Access Journals (Sweden)

    Romina M. Uranga

    2010-01-01

    Full Text Available Cholesterol is an essential molecule for brain homeostasis; yet, hypercholesterolemia and its numerous complications are believed to play a role in promoting multiple aspects of brain pathogenesis. An ever increasing number of individuals in modern Western Society are regularly consuming diets high in fat which promote the development of hypercholesterolemia. Additionally, modern societies are becoming increasingly aged, causing a collision between increased hypercholesterolemia and increased aging, which will likely lead to the development of increased pathological conditions due to hypercholesterolemia, thereby promoting deleterious neurochemical and behavioral changes in the brain. Lastly, while beneficial in controlling cholesterol levels, the long-term use of statins itself may potentially promote adverse effects on brain homeostasis, although specifics on this remain largely unknown. This review will focus on linking the current understanding of diet-induced hypercholesterolemia (as well as statin use to the development of oxidative stress, neurochemical alterations, and cognitive disturbances in the aging brain.

  7. Association of structural global brain network properties with intelligence in normal aging.

    Directory of Open Access Journals (Sweden)

    Florian U Fischer

    Full Text Available Higher general intelligence attenuates age-associated cognitive decline and the risk of dementia. Thus, intelligence has been associated with cognitive reserve or resilience in normal aging. Neurophysiologically, intelligence is considered as a complex capacity that is dependent on a global cognitive network rather than isolated brain areas. An association of structural as well as functional brain network characteristics with intelligence has already been reported in young adults. We investigated the relationship between global structural brain network properties, general intelligence and age in a group of 43 cognitively healthy elderly, age 60-85 years. Individuals were assessed cross-sectionally using Wechsler Adult Intelligence Scale-Revised (WAIS-R and diffusion-tensor imaging. Structural brain networks were reconstructed individually using deterministic tractography, global network properties (global efficiency, mean shortest path length, and clustering coefficient were determined by graph theory and correlated to intelligence scores within both age groups. Network properties were significantly correlated to age, whereas no significant correlation to WAIS-R was observed. However, in a subgroup of 15 individuals aged 75 and above, the network properties were significantly correlated to WAIS-R. Our findings suggest that general intelligence and global properties of structural brain networks may not be generally associated in cognitively healthy elderly. However, we provide first evidence of an association between global structural brain network properties and general intelligence in advanced elderly. Intelligence might be affected by age-associated network deterioration only if a certain threshold of structural degeneration is exceeded. Thus, age-associated brain structural changes seem to be partially compensated by the network and the range of this compensation might be a surrogate of cognitive reserve or brain resilience.

  8. Novel microRNAs differentially expressed during aging in the mouse brain.

    Directory of Open Access Journals (Sweden)

    Sachi Inukai

    Full Text Available MicroRNAs (miRNAs are endogenous small RNA molecules that regulate gene expression post-transcriptionally. Work in Caenorhabditis elegans has shown that specific miRNAs function in lifespan regulation and in a variety of age-associated pathways, but the roles of miRNAs in the aging of vertebrates are not well understood. We examined the expression of small RNAs in whole brains of young and old mice by deep sequencing and report here on the expression of 558 known miRNAs and identification of 41 novel miRNAs. Of these miRNAs, 75 known and 18 novel miRNAs exhibit greater than 2.0-fold expression changes. The majority of expressed miRNAs in our study decline in relative abundance in the aged brain, in agreement with trends observed in other miRNA studies in aging tissues and organisms. Target prediction analysis suggests that many of our novel aging-associated miRNAs target genes in the insulin signaling pathway, a central node of aging-associated genetic networks. These novel miRNAs may thereby regulate aging-related functions in the brain. Since many mouse miRNAs are conserved in humans, the aging-affected brain miRNAs we report here may represent novel regulatory genes that also function during aging in the human brain.

  9. Microglial cell dysregulation in brain aging and neurodegeneration

    OpenAIRE

    von Bernhardi, Rommy; Eugenín-von Bernhardi, Laura; Eugenín, Jaime

    2015-01-01

    Aging is the main risk factor for neurodegenerative diseases. In aging, microglia undergoes phenotypic changes compatible with their activation. Glial activation can lead to neuroinflammation, which is increasingly accepted as part of the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease (AD). We hypothesize that in aging, aberrant microglia activation leads to a deleterious environment and neurodegeneration. In aged mice, microglia exhibit an increased expression of c...

  10. A longitudinal study of structural brain network changes with normal aging

    Directory of Open Access Journals (Sweden)

    Kai eWu

    2013-04-01

    Full Text Available The aim of this study was to investigate age-related changes in the topological organization of structural brain networks by applying a longitudinal design over 6 years. Structural brain networks were derived from measurements of regional gray matter volume and were constructed in age-specific groups from baseline and follow-up scans. The structural brain networks showed economical small-world properties, providing high global and local efficiency for parallel information processing at low connection costs. In the analysis of the global network properties, the local and global efficiency of the baseline scan were significantly lower compared to the follow-up scan. Moreover, the annual rate of changes in local and global efficiency showed a positive and negative quadratic correlation with the baseline age, respectively; both curvilinear correlations peaked at approximately the age of 50. In the analysis of the regional nodal properties, significant negative correlations between the annual rate of changes in nodal strength and the baseline age were found in the brain regions primarily involved in the visual and motor/ control systems, whereas significant positive quadratic correlations were found in the brain regions predominately associated with the default-mode, attention, and memory systems. The results of the longitudinal study are consistent with the findings of our previous cross-sectional study: the structural brain networks develop into a fast distribution from young to middle age (approximately 50 years old and eventually became a fast localization in the old age. Our findings elucidate the network topology of structural brain networks and its longitudinal changes, thus enhancing the understanding of the underlying physiology of normal aging in the human brain.

  11. Mechanisms of Brain Aging Regulation by Insulin: Implications for Neurodegeneration in Late-Onset Alzheimer's Disease

    OpenAIRE

    Schuh, Artur F.; Rieder, Carlos M.; Rizzi, Liara; Chaves, Márcia; Roriz-Cruz, Matheus

    2011-01-01

    Insulin and IGF seem to be important players in modulating brain aging. Neurons share more similarities with islet cells than any other human cell type. Insulin and insulin receptors are diffusely found in the brain, especially so in the hippocampus. Caloric restriction decreases insulin resistance, and it is the only proven mechanism to expand lifespan. Conversely, insulin resistance increases with age, obesity, and sedentarism, all of which have been shown to be risk factors for late-onset ...

  12. Age- and brain-region-specific effects of dietary vitamin K on myelin sulfatides

    OpenAIRE

    Crivello, Natalia A.; Casseus, Sherley L.; Peterson, James W.; Smith, Donald E.; Sarah L. Booth

    2010-01-01

    Dysregulation of myelin sulfatides is a risk factor for cognitive decline with age. Vitamin K is present in high concentrations in the brain and has been implicated in the regulation of sulfatide metabolism. Our objective was to investigate the age-related interrelation between dietary vitamin K and sulfatides in myelin fractions isolated from the brain regions of Fischer 344 male rats fed one of two dietary forms of vitamin K: phylloquinone or its hydrogenated form, dihydrophylloquinone for ...

  13. Age-Related Shifts in Brain Activity Dynamics during Task Switching

    OpenAIRE

    Jimura, Koji; Braver, Todd S.

    2009-01-01

    Cognitive aging studies have suggested that older adults show declines in both sustained and transient cognitive control processes. However, previous neuroimaging studies have primarily focused on age-related change in the magnitude, but not temporal dynamics, of brain activity. The present study compared brain activity dynamics in healthy old and young adults during task switching. A mixed blocked/event-related functional magnetic resonance imaging design enabled separation of transient and ...

  14. Studying variability in human brain aging in a population-based German cohort – Rationale and design of 1000BRAINS

    Directory of Open Access Journals (Sweden)

    Svenja eCaspers

    2014-07-01

    Full Text Available The ongoing 1000 brains study (1000BRAINS is an epidemiological and neuroscientific investigation of structural and functional variability in the human brain during aging. The two recruitment sources are the 10-year follow-up cohort of the German Heinz Nixdorf Recall (HNR Study, and the HNR MultiGeneration Study cohort, which comprises spouses and offspring of HNR subjects. The HNR is a longitudinal epidemiological investigation of cardiovascular risk factors, with a comprehensive collection of clinical, laboratory, socioeconomic, and environmental data from population-based subjects aged 45-75 years on inclusion. HNR subjects underwent detailed assessments in 2000, 2006, and 2011, and completed annual postal questionnaires on health status. 1000BRAINS accesses these HNR data and applies a separate protocol comprising: neuropsychological tests of attention, memory, executive functions & language; examination of motor skills; ratings of personality, life quality, mood & daily activities; analysis of laboratory and genetic data; and state-of-the-art magnetic resonance imaging (MRI, 3 Tesla of the brain. The latter includes (i 3D-T1- and 3D-T2-weighted scans for structural analyses and myelin mapping; (ii three diffusion imaging sequences optimized for diffusion tensor imaging, high-angular resolution diffusion imaging for detailed fibre tracking and for diffusion kurtosis imaging; (iii resting-state and task-based functional MRI; and (iv fluid-attenuated inversion recovery and MR angiography for the detection of vascular lesions and the mapping of white matter lesions. The unique design of 1000BRAINS allows: (i comprehensive investigation of various influences including genetics, environment and health status on variability in brain structure and function during aging; and (ii identification of the impact of selected influencing factors on specific cognitive subsystems and their anatomical correlates.

  15. Studying variability in human brain aging in a population-based German cohort-rationale and design of 1000BRAINS.

    Science.gov (United States)

    Caspers, Svenja; Moebus, Susanne; Lux, Silke; Pundt, Noreen; Schütz, Holger; Mühleisen, Thomas W; Gras, Vincent; Eickhoff, Simon B; Romanzetti, Sandro; Stöcker, Tony; Stirnberg, Rüdiger; Kirlangic, Mehmet E; Minnerop, Martina; Pieperhoff, Peter; Mödder, Ulrich; Das, Samir; Evans, Alan C; Jöckel, Karl-Heinz; Erbel, Raimund; Cichon, Sven; Nöthen, Markus M; Sturma, Dieter; Bauer, Andreas; Jon Shah, N; Zilles, Karl; Amunts, Katrin

    2014-01-01

    The ongoing 1000 brains study (1000BRAINS) is an epidemiological and neuroscientific investigation of structural and functional variability in the human brain during aging. The two recruitment sources are the 10-year follow-up cohort of the German Heinz Nixdorf Recall (HNR) Study, and the HNR MultiGeneration Study cohort, which comprises spouses and offspring of HNR subjects. The HNR is a longitudinal epidemiological investigation of cardiovascular risk factors, with a comprehensive collection of clinical, laboratory, socioeconomic, and environmental data from population-based subjects aged 45-75 years on inclusion. HNR subjects underwent detailed assessments in 2000, 2006, and 2011, and completed annual postal questionnaires on health status. 1000BRAINS accesses these HNR data and applies a separate protocol comprising: neuropsychological tests of attention, memory, executive functions and language; examination of motor skills; ratings of personality, life quality, mood and daily activities; analysis of laboratory and genetic data; and state-of-the-art magnetic resonance imaging (MRI, 3 Tesla) of the brain. The latter includes (i) 3D-T1- and 3D-T2-weighted scans for structural analyses and myelin mapping; (ii) three diffusion imaging sequences optimized for diffusion tensor imaging, high-angular resolution diffusion imaging for detailed fiber tracking and for diffusion kurtosis imaging; (iii) resting-state and task-based functional MRI; and (iv) fluid-attenuated inversion recovery and MR angiography for the detection of vascular lesions and the mapping of white matter lesions. The unique design of 1000BRAINS allows: (i) comprehensive investigation of various influences including genetics, environment and health status on variability in brain structure and function during aging; and (ii) identification of the impact of selected influencing factors on specific cognitive subsystems and their anatomical correlates. PMID:25071558

  16. Decipher

    CERN Multimedia

    2002-01-01

    Review of a new fiction work by Stel Pavlou whose starting point is the lifecycle of the sun and the implications for human civilization. The story invokes the use of the CERN accelerator to analyze a special type of crystal found in Antartica which may hold the key to the legend of the city of Atlantis (1/2 page).

  17. Age-specific MRI brain and head templates for healthy adults from twenty through eighty-nine years of age

    Directory of Open Access Journals (Sweden)

    Paul T Fillmore

    2015-04-01

    Full Text Available This study created and tested a database of adult, age-specific MRI brain and head templates. The participants included healthy adults from 20 through 89 years of age. The templates were done in 5-year, 10-year, and multi-year intervals from 20 through 89 years, and consist of average T1W for the head and brain, and segmenting priors for GM, WM, and CSF. It was found that age-appropriate templates provided less biased tissue classification estimates than age-inappropriate reference data and reference data based on young adult templates. This database is available for use by other investigators and clinicians for their MRI studies, as well as other types of neuroimaging and electrophysiological research (http://jerlab.psych.sc.edu/NeurodevelopmentalMRIDatabase/.

  18. Brain volumetric changes and cognitive ageing during the eighth decade of life.

    Science.gov (United States)

    Ritchie, Stuart J; Dickie, David Alexander; Cox, Simon R; Valdes Hernandez, Maria Del C; Corley, Janie; Royle, Natalie A; Pattie, Alison; Aribisala, Benjamin S; Redmond, Paul; Muñoz Maniega, Susana; Taylor, Adele M; Sibbett, Ruth; Gow, Alan J; Starr, John M; Bastin, Mark E; Wardlaw, Joanna M; Deary, Ian J

    2015-12-01

    Later-life changes in brain tissue volumes--decreases in the volume of healthy grey and white matter and increases in the volume of white matter hyperintensities (WMH)--are strong candidates to explain some of the variation in ageing-related cognitive decline. We assessed fluid intelligence, memory, processing speed, and brain volumes (from structural MRI) at mean age 73 years, and at mean age 76 in a narrow-age sample of older individuals (n = 657 with brain volumetric data at the initial wave, n = 465 at follow-up). We used latent variable modeling to extract error-free cognitive levels and slopes. Initial levels of cognitive ability were predictive of subsequent brain tissue volume changes. Initial brain volumes were not predictive of subsequent cognitive changes. Brain volume changes, especially increases in WMH, were associated with declines in each of the cognitive abilities. All statistically significant results were modest in size (absolute r-values ranged from 0.114 to 0.334). These results build a comprehensive picture of macrostructural brain volume changes and declines in important cognitive faculties during the eighth decade of life.

  19. Exercise as an intervention for the age-related decline in brain metabolic support

    Directory of Open Access Journals (Sweden)

    Brenda J Anderson

    2010-08-01

    Full Text Available To identify interventions for brain aging, we must first identify the processes in which we hope to intervene. Brain aging is a period of decreasing functional capacity and increasing vulnerability, which reflect a reduction in morphological organization and perhaps degeneration. Since life is ultimately dependent upon the ability to maintain cellular organization through metabolism, this review explores evidence for a decline in neural metabolic support during aging, which includes a reduction in whole brain cerebral blood flow, and cellular metabolic capacity. Capillary density may also decrease with age, although the results are less clear. Exercise may be a highly effective intervention for brain aging, because it improves the cardiovascular system as a whole, and increases regional capillary density and neuronal metabolic capacity. Although the evidence is strongest for motor regions, more work may yield additional evidence for exercise-related improvement in metabolic support in non-motor regions. The protective effects of exercise may be specific to brain region and the type of insult. For example, exercise protects striatal cells from ischemia, but it produces mixed results after hippocampal seizures. Exercise can improve metabolic support and bioenergetic capacity in adult animals, but it remains to be determined whether it has similar effects in aging animals. What is clear is that exercise can influence the multiple levels of support necessary for maintaining optimal neuronal function, which is unique among proposed interventions for aging.

  20. Recent Developments in Understanding Brain Aging: Implications for Alzheimer's Disease and Vascular Cognitive Impairment.

    Science.gov (United States)

    Deak, Ferenc; Freeman, Willard M; Ungvari, Zoltan; Csiszar, Anna; Sonntag, William E

    2016-01-01

    As the population of the Western world is aging, there is increasing awareness of age-related impairments in cognitive function and a rising interest in finding novel approaches to preserve cerebral health. A special collection of articles in The Journals of Gerontology: Biological Sciences and Medical Sciences brings together information of different aspects of brain aging, from latest developments in the field of neurodegenerative disorders to cerebral microvascular mechanisms of cognitive decline. It is emphasized that although the cellular changes that occur within aging neurons have been widely studied, more research is required as new signaling pathways are discovered that can potentially protect cells. New avenues for research targeting cellular senescence, epigenetics, and endocrine mechanisms of brain aging are also discussed. Based on the current literature it is clear that understanding brain aging and reducing risk for neurological disease with age requires searching for mechanisms and treatment options beyond the age-related changes in neuronal function. Thus, comprehensive approaches need to be developed that address the multiple, interrelated mechanisms of brain aging. Attention is brought to the importance of maintenance of cerebromicrovascular health, restoring neuroendocrine balance, and the pressing need for funding more innovative research into the interactions of neuronal, neuroendocrine, inflammatory and microvascular mechanisms of cognitive impairment, and Alzheimer's disease. PMID:26590911

  1. Contribution of brain atrophy on CT and aging to intelligence level

    International Nuclear Information System (INIS)

    Decrased intellectual functions due to senility have been much discussed in connection with aging or brain atophy alternatively. But this change should be analysed under multifactorial basis. Furthermore, variations between individuals should be taken into account in dealing with an advanced age group. In these regards, the author performed multivariate analysis on intellectual changes, aging and brain arophy demonstrated on brain CT. Clonological study was also performed to reveal the individual variations. The objects were consisted of 72 people, including the patients of more than 65 years of age who were hospitalized to a geriatrics hospital because of senile dementia, and, as a control group residents in a home for the aged nearby the hospital. Average age was 75.4 years old. Intellectual level was measured through Hasegawa's dementia rating scale. Ventricular enlargement was measured on brain CT to determine the severity of brain atrophy. These two factors and age were processed with multivariate analysis. And clonological study was made to the deviation of intellectual level vs. the change of ventricular enlargement. As the result, firstly, this simple analysing model was able to reveal some aspcts of the deteriolating phenomena of intellectual leve through double factorial basis, i.e. brain atrophy on CT and age. Secondly, the group showing greater changes in the brain atrophy on CT, which included one case with rapid deteriolation in dementia scale of more than 10 points, was distributed mainly around full marks or zero point in dementia scale. This result postulates that the range of the dementia scale should be expanded upwrds as well as downwards for the better explanation of the relation between intellectual deteriolation and above mentioned two factors. (author)

  2. Study of cerebral metabolism of glucose in normal human brain correlated with age

    International Nuclear Information System (INIS)

    Full text: The objective was to determine whether cerebral metabolism in various regions of the brain differs with advancing age by using 18F-FDG PET instrument and SPM software. Materials and Methods We reviewed clinical information of 295 healthy normal samples who were examined by a whole body GE Discovery LS PET-CT instrument in our center from Aug. 2004 to Dec. 2005.They (with the age ranging from 21 to 88; mean age+/-SD: 49.77+/-13.51) were selected with: (i)absence of clear focal brain lesions (epilepsy.cerebrovascular diseases etc);(ii) absence of metabolic diseases, such as hyperthyroidism, hypothyroidism and diabetes;(iii) absence of psychiatric disorders and abuse of drugs and alcohol. They were sub grouped into six groups with the interval of 10 years old starting from 21, and the gender, educational background and serum glucose were matched. All subgroups were compared to the control group of 31-40 years old (84 samples; mean age+/-SD: 37.15+/-2.63). All samples were injected with 18F-FDG (5.55MBq/kg), 45-60 minutes later, their brains were scanned for 10min. Pixel-by-pixel t-statistic analysis was applied to all brain images using the Statistical parametric mapping (SPM2) .The hypometabolic areas (p < 0. 01 or p<0.001, uncorrected) were identified in the Stereotaxic coordinate human brain atlas and three-dimensional localized by MNI Space utility (MSU) software. Results:Relative hypometabolic brain areas detected are mainly in the cortical structures such as bilateral prefrontal cortex, superior temporal gyrus(BA22), parietal cortex (inferior parietal lobule and precuneus(BA40, insula(BA13)), parahippocampal gyrus and amygdala (p<0.01).It is especially apparent in the prefrontal cortex (BA9)and sensory-motor cortex(BA5, 7) (p<0.001), while basal ganglia and cerebellum remained metabolically unchanged with advancing age. Conclusions Regional cerebral metabolism of glucose shows a descent tendency with aging, especially in the prefrontal cortex (BA9)and

  3. Brain SERT Expression of Male Rats Is Reduced by Aging and Increased by Testosterone Restitution

    Directory of Open Access Journals (Sweden)

    José Jaime Herrera-Pérez

    2013-01-01

    Full Text Available In preclinical and clinical studies aging has been associated with a deteriorated response to antidepressant treatment. We hypothesize that such impairment is explained by an age-related decrease in brain serotonin transporter (SERT expression associated with low testosterone (T levels. The objectives of this study were to establish (1 if brain SERT expression is reduced by aging and (2 if the SERT expression in middle-aged rats is increased by T-restitution. Intact young rats (3–5 months and gonad-intact middle-aged rats with or without T-restitution were used. The identification of the brain SERT expression was done by immunofluorescence in prefrontal cortex, lateral septum, hippocampus, and raphe nuclei. An age-dependent reduction of SERT expression was observed in all brain regions examined, while T-restitution recovered the SERT expression only in the dorsal raphe of middle-aged rats. This last action seems relevant since dorsal raphe plays an important role in the antidepressant action of selective serotonin reuptake inhibitors. All data suggest that this mechanism accounts for the T-replacement usefulness to improve the response to antidepressants in the aged population.

  4. Polychlorinated biphenyls in adipose tissue, liver, and brain from nine stillborns of varying gestational ages

    NARCIS (Netherlands)

    Huisman, M; Muskiet, FAJ; Van Der Paauw, CG; Essed, CE; Boersma, ER

    1998-01-01

    We analyzed polychlorinated biphenyls (PCBs) in s.c. adipose tissue, liver, and brain of nine fetuses who died in utero. Their median (range) gestational ages and birth weights were 34 (17-40) wk and 2050 (162-3225) g. Three fetuses were small for gestational age. The levels of PCB congener nos. 118

  5. Sex differences in metabolic aging of the brain: insights into female susceptibility to Alzheimer's disease.

    Science.gov (United States)

    Zhao, Liqin; Mao, Zisu; Woody, Sarah K; Brinton, Roberta D

    2016-06-01

    Despite recent advances in the understanding of clinical aspects of sex differences in Alzheimer's disease (AD), the underlying mechanisms, for instance, how sex modifies AD risk and why the female brain is more susceptible to AD, are not clear. The purpose of this study is to elucidate sex disparities in brain aging profiles focusing on 2 major areas-energy and amyloid metabolism-that are most significantly affected in preclinical development of AD. Total RNA isolated from hippocampal tissues of both female and male 129/C57BL/6 mice at ages of 6, 9, 12, or 15 months were comparatively analyzed by custom-designed Taqman low-density arrays for quantitative real-time polymerase chain reaction detection of a total of 182 genes involved in a broad spectrum of biological processes modulating energy production and amyloid homeostasis. Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains. In female brains, 44.2% of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation. In contrast, in male brains, only 5.4% of genes were significantly altered at this age transition. Subsequent changes in female brains were at a much smaller magnitude, including 10.9% from 9 months to 12 months and 6.1% from 12 months to 15 months. In male brains, most changes occurred from 12 months to 15 months and the majority were upregulated. Furthermore, gene network analysis revealed that clusterin appeared to serve as a link between the overall decreased bioenergetic metabolism and increased amyloid dyshomeostasis associated with the earliest transition in female brains. Together, results from this study indicate that: (1) female and male brains follow profoundly dissimilar trajectories as they age; (2) female brains undergo age-related changes much earlier than male brains; (3) early changes in female brains signal the onset of a hypometabolic phenotype at risk for AD. These

  6. Language in the aging brain: the network dynamics of cognitive decline and preservation.

    Science.gov (United States)

    Shafto, Meredith A; Tyler, Lorraine K

    2014-10-31

    Language is a crucial and complex lifelong faculty, underpinned by dynamic interactions within and between specialized brain networks. Whereas normal aging impairs specific aspects of language production, most core language processes are robust to brain aging. We review recent behavioral and neuroimaging evidence showing that language systems remain largely stable across the life span and that both younger and older adults depend on dynamic neural responses to linguistic demands. Although some aspects of network dynamics change with age, there is no consistent evidence that core language processes are underpinned by different neural networks in younger and older adults.

  7. Cognitive and brain function in adults with Type 1 diabetes mellitus : is there evidence of accelerated ageing?

    OpenAIRE

    Johnston, Harriet N.

    2013-01-01

    The physical complications of Type 1 diabetes mellitus (T1DM) have been understood as an accelerated ageing process (Morley, 2008). Do people with T1DM also experience accelerated cognitive and brain ageing? Using findings from research of the normal cognitive and brain ageing process and conceptualized in theories of the functional brain changes in cognitive ageing, a combination of cognitive testing and functional magnetic resonance imaging (fMRI) techniques were used to evaluate evidence o...

  8. Age-Related Decline in Brain Resources Modulates Genetic Effects on Cognitive Functioning

    Science.gov (United States)

    Lindenberger, Ulman; Nagel, Irene E.; Chicherio, Christian; Li, Shu-Chen; Heekeren, Hauke R.; Bäckman, Lars

    2008-01-01

    Individual differences in cognitive performance increase from early to late adulthood, likely reflecting influences of a multitude of factors. We hypothesize that losses in neurochemical and anatomical brain resources in normal aging modulate the effects of common genetic variations on cognitive functioning. Our hypothesis is based on the assumption that the function relating brain resources to cognition is nonlinear, so that genetic differences exert increasingly large effects on cognition as resources recede from high to medium levels in the course of aging. Direct empirical support for this hypothesis comes from a study by Nagel et al. (2008), who reported that the effects of the Catechol-O-Methyltransferase (COMT) gene on cognitive performance are magnified in old age and interacted with the Brain-Derived Neurotrophic Factor (BDNF) gene. We conclude that common genetic polymorphisms contribute to the increasing heterogeneity of cognitive functioning in old age. Extensions of the hypothesis to other polymorphisms are discussed. (150 of 150 words) PMID:19225597

  9. Age-related decline in brain resources modulates genetic effects on cognitive functioning

    Directory of Open Access Journals (Sweden)

    Ulman Lindenberger

    2008-12-01

    Full Text Available Individual differences in cognitive performance increase from early to late adulthood, likely reflecting influences of a multitude of factors. We hypothesize that losses in neurochemical and anatomical brain resources in normal aging modulate the effects of common genetic variations on cognitive functioning. Our hypothesis is based on the assumption that the function relating brain resources to cognition is nonlinear, so that genetic differences exert increasingly large effects on cognition as resources recede from high to medium levels in the course of aging.Direct empirical support for this hypothesis comes from a study by Nagel et al. (2008, who reported that the effects of the Catechol-O-Methyltransferase (COMT gene on cognitive performance are magnified in old age and interacted with the Brain-Derived Neurotrophic Factor (BDNF gene. We conclude that common genetic polymorphisms contribute to the increasing heterogeneity of cognitive functioning in old age. Extensions of the hypothesis to other polymorphisms are discussed.

  10. Age-related changes in kynurenic acid production in rat brain

    DEFF Research Database (Denmark)

    Gramsbergen, J B; Schmidt, W; Turski, W A;

    1992-01-01

    -dependent increase of KYNA concentration in brain tissue, suggest an enhanced KYNA tone in the aged brain. Together with the reported decline in cerebral excitatory amino acid receptor densities with age, increased production of KYNA may play a role in cognitive and memory dysfunction in old animals....... investigated in tissue slices and was found to be significantly enhanced in the cortex and hippocampus of old animals. The effect of depolarizing agents or sodium replacement was virtually identical in tissues from young and old rats. These data, which are in excellent agreement with reports on an age...... months of age in all five brain regions examined. No changes were observed in the liver. The changes were particularly pronounced in the cortex and in the striatum where enzyme activity increased three-fold during the period studied. KYNA production from its bioprecursor L-kynurenine was also...

  11. Exercise enhances memory consolidation in the aging brain

    Directory of Open Access Journals (Sweden)

    Shikha eSnigdha

    2014-02-01

    Full Text Available Exercise has been shown to reduce age-related losses in cognitive function including learning and memory, but the mechanisms underlying this effect remain poorly understood. Memory formation occurs in stages that include an initial acquisition phase, an intermediate labile phase, and then a process of consolidation which leads to long term memory formation. An effective way to examine the mechanism by which exercise improves memory is to introduce the intervention (exercise, post-acquisition, making it possible to selectively examine memory storage and consolidation. Accordingly we evaluated the effects of post-trial exercise (10 minutes on a treadmill on memory consolidation in aged canines both right after, an hour after, and twenty-four hours after acute exercise training in concurrent discrimination, object location memory (OLM and novel object recognition (NOR tasks. Our study shows that post-trial exercise facilitates memory function by improving memory consolidation in aged animals in a time-dependent manner. The improvements were significant at twenty-four hour post exercise and not right after or one hour after exercise. Aged animals were also tested following chronic exercise (10 min/day for 14 consecutive days on OLM or till criterion were reached (for reversal learning task. We found improvements from a chronic exercise design in both the object location and reversal learning tasks. Our studies suggest that mechanisms to improve overall consolidation and cognitive function remain accessible even with progressing age and can be re-engaged by both acute and chronic exercise.

  12. White matter hyperintensities and imaging patterns of brain ageing in the general population.

    Science.gov (United States)

    Habes, Mohamad; Erus, Guray; Toledo, Jon B; Zhang, Tianhao; Bryan, Nick; Launer, Lenore J; Rosseel, Yves; Janowitz, Deborah; Doshi, Jimit; Van der Auwera, Sandra; von Sarnowski, Bettina; Hegenscheid, Katrin; Hosten, Norbert; Homuth, Georg; Völzke, Henry; Schminke, Ulf; Hoffmann, Wolfgang; Grabe, Hans J; Davatzikos, Christos

    2016-04-01

    White matter hyperintensities are associated with increased risk of dementia and cognitive decline. The current study investigates the relationship between white matter hyperintensities burden and patterns of brain atrophy associated with brain ageing and Alzheimer's disease in a large populatison-based sample (n = 2367) encompassing a wide age range (20-90 years), from the Study of Health in Pomerania. We quantified white matter hyperintensities using automated segmentation and summarized atrophy patterns using machine learning methods resulting in two indices: the SPARE-BA index (capturing age-related brain atrophy), and the SPARE-AD index (previously developed to capture patterns of atrophy found in patients with Alzheimer's disease). A characteristic pattern of age-related accumulation of white matter hyperintensities in both periventricular and deep white matter areas was found. Individuals with high white matter hyperintensities burden showed significantly (P brain regions typically affected by ageing and Alzheimer's disease dementia. To investigate a possibly causal role of white matter hyperintensities, structural equation modelling was used to quantify the effect of Framingham cardiovascular disease risk score and white matter hyperintensities burden on SPARE-BA, revealing a statistically significant (P learning memory test. No significant association was present with the APOE genotype. These results support the hypothesis that white matter hyperintensities contribute to patterns of brain atrophy found in beyond-normal brain ageing in the general population. White matter hyperintensities also contribute to brain atrophy patterns in regions related to Alzheimer's disease dementia, in agreement with their known additive role to the likelihood of dementia. Preventive strategies reducing the odds to develop cardiovascular disease and white matter hyperintensities could decrease the incidence or delay the onset of dementia. PMID:26912649

  13. Brain tumors in children and adolescents: cognitive and psychological disorders at different ages.

    Science.gov (United States)

    Poggi, Geraldina; Liscio, Mariarosaria; Galbiati, Susanna; Adduci, Annarita; Massimino, Maura; Gandola, Lorenza; Spreafico, Filippo; Clerici, Carlo Alfredo; Fossati-Bellani, Franca; Sommovigo, Michela; Castelli, Enrico

    2005-05-01

    Cognitive and psychological disorders are among the most frequently observed sequelae in brain tumor survivors. The goal of this work was to verify the presence of these disorders in a group of children and adolescents diagnosed with brain tumor before age 18 years, differentiate these disorders according to age of assessment, identify correlations between the two types of impairments and define possible associations between these impairments and clinical variables. The study involved 76 patients diagnosed with brain tumor before age 18 years. Three age groups were formed, and all the patients received a standardized battery of age-matched cognitive and psychological tests. According to our findings, all three groups present with cognitive and psychological-behavioral disorders. Their frequency varies according to age of onset and is strongly associated to time since diagnosis. The performance intelligence quotient (PIQ) was more impaired than the verbal intelligence quotient (VIQ). Internalizing problems, withdrawal and social problems were the most frequent psychological disorders. Correlations were found between cognitive impairment and the onset of the main psychological and behavioral disorders. These findings are relevant as they point out the long-term outcome of brain tumor survivors. Hence, the recommendation to diversify psychological interventions and rehabilitation plans according to the patients' age.

  14. Brain Infarction and Hemorrhage in Young and Middle-aged Adults

    OpenAIRE

    Lacy, Joseph R.; Filley, Christopher M.; Earnest, Michael P.; Graff-Radford, Neill R

    1984-01-01

    Of 131 young (17 to 44 years) and middle-aged (45 to 55 years) adults who had brain infarction or hemorrhage, the most common etiologic factors were rheumatic heart disease, migraine and oral contraceptive use among the younger group. In contrast, atherosclerotic, hypertensive and diabetes-associated cerebrovascular were the most common causes in the middle-aged group. Patients who have a stroke before age 45 should have prompt, complete laboratory and radiologic testing to define a possible ...

  15. Fitness, but not physical activity, is related to functional integrity of brain networks associated with aging.

    Science.gov (United States)

    Voss, Michelle W; Weng, Timothy B; Burzynska, Agnieszka Z; Wong, Chelsea N; Cooke, Gillian E; Clark, Rachel; Fanning, Jason; Awick, Elizabeth; Gothe, Neha P; Olson, Erin A; McAuley, Edward; Kramer, Arthur F

    2016-05-01

    Greater physical activity and cardiorespiratory fitness are associated with reduced age-related cognitive decline and lower risk for dementia. However, significant gaps remain in the understanding of how physical activity and fitness protect the brain from adverse effects of brain aging. The primary goal of the current study was to empirically evaluate the independent relationships between physical activity and fitness with functional brain health among healthy older adults, as measured by the functional connectivity of cognitively and clinically relevant resting state networks. To build context for fitness and physical activity associations in older adults, we first demonstrate that young adults have greater within-network functional connectivity across a broad range of cortical association networks. Based on these results and previous research, we predicted that individual differences in fitness and physical activity would be most strongly associated with functional integrity of the networks most sensitive to aging. Consistent with this prediction, and extending on previous research, we showed that cardiorespiratory fitness has a positive relationship with functional connectivity of several cortical networks associated with age-related decline, and effects were strongest in the default mode network (DMN). Furthermore, our results suggest that the positive association of fitness with brain function can occur independent of habitual physical activity. Overall, our findings provide further support that cardiorespiratory fitness is an important factor in moderating the adverse effects of aging on cognitively and clinically relevant functional brain networks.

  16. NOX Activity in Brain Aging: Exacerbation by High Fat Diet

    OpenAIRE

    Bruce-Keller, Annadora J.; White, Christy L.; Gupta, Sunita; Knight, Alecia G.; Pistell, Paul J.; Ingram, Donald K.; Morrison, Christopher D.; Keller, Jeffrey N.

    2010-01-01

    This study describes how age and high fat diet affect the profile of NADPH oxidase (NOX). Specifically, NOX activity and subunit expression were evaluated in the frontal cerebral cortex of 7-, 16-, and 24-month old mice following a 4-month exposure to either Western diet (WD, 41% calories from fat) or very high fat lard diet (VHFD, 60% calories from fat). Data reveal a significant effect of age in on NOX activity, and show that NOX activity was only increased by VHFD, and only in 24-month old...

  17. Exceptional Brain Aging in a Rural Population-Based Cohort

    Science.gov (United States)

    Kaye, Jeffrey; Michael, Yvonne; Calvert, James; Leahy, Marjorie; Crawford, Debbie; Kramer, Patricia

    2009-01-01

    Context: The 2000 US Census identified 50,454 Americans over the age of 100. Increased longevity is only of benefit if accompanied by maintenance of independence and quality of life. Little is known about the prevalence of dementia and other disabling conditions among rural centenarians although this information is important to clinicians caring…

  18. Flexible Connectivity in the Aging Brain Revealed by Task Modulations

    NARCIS (Netherlands)

    Geerligs, Linda; Saliasi, Emi; Renken, Remco J.; Maurits, Natasha M.; Lorist, Monicque M.

    2014-01-01

    Recent studies have shown that aging has a large impact on connectivity within and between functional networks. An open question is whether elderly still have the flexibility to adapt functional network connectivity (FNC) to the demands of the task at hand. To study this, we collected fMRI data in y

  19. Caloric restriction: beneficial effects on brain aging and Alzheimer's disease.

    Science.gov (United States)

    Van Cauwenberghe, Caroline; Vandendriessche, Charysse; Libert, Claude; Vandenbroucke, Roosmarijn E

    2016-08-01

    Dietary interventions such as caloric restriction (CR) extend lifespan and health span. Recent data from animal and human studies indicate that CR slows down the aging process, benefits general health, and improves memory performance. Caloric restriction also retards and slows down the progression of different age-related diseases, such as Alzheimer's disease. However, the specific molecular basis of these effects remains unclear. A better understanding of the pathways underlying these effects could pave the way to novel preventive or therapeutic strategies. In this review, we will discuss the mechanisms and effects of CR on aging and Alzheimer's disease. A potential alternative to CR as a lifestyle modification is the use of CR mimetics. These compounds mimic the biochemical and functional effects of CR without the need to reduce energy intake. We discuss the effect of two of the most investigated mimetics, resveratrol and rapamycin, on aging and their potential as Alzheimer's disease therapeutics. However, additional research will be needed to determine the safety, efficacy, and usability of CR and its mimetics before a general recommendation can be proposed to implement them. PMID:27240590

  20. Aging aggravates ischemic stroke-induced brain damage in mice with chronic peripheral infection.

    Science.gov (United States)

    Dhungana, Hiramani; Malm, Tarja; Denes, Adam; Valonen, Piia; Wojciechowski, Sara; Magga, Johanna; Savchenko, Ekaterina; Humphreys, Neil; Grencis, Richard; Rothwell, Nancy; Koistinaho, Jari

    2013-10-01

    Ischemic stroke is confounded by conditions such as atherosclerosis, diabetes, and infection, all of which alter peripheral inflammatory processes with concomitant impact on stroke outcome. The majority of the stroke patients are elderly, but the impact of interactions between aging and inflammation on stroke remains unknown. We thus investigated the influence of age on the outcome of stroke in animals predisposed to systemic chronic infection. Th1-polarized chronic systemic infection was induced in 18-22 month and 4-month-old C57BL/6j mice by administration of Trichuris muris (gut parasite). One month after infection, mice underwent permanent middle cerebral artery occlusion and infarct size, brain gliosis, and brain and plasma cytokine profiles were analyzed. Chronic infection increased the infarct size in aged but not in young mice at 24 h. Aged, ischemic mice showed altered plasma and brain cytokine responses, while the lesion size correlated with plasma prestroke levels of RANTES. Moreover, the old, infected mice exhibited significantly increased neutrophil recruitment and upregulation of both plasma interleukin-17α and tumor necrosis factor-α levels. Neither age nor infection status alone or in combination altered the ischemia-induced brain microgliosis. Our results show that chronic peripheral infection in aged animals renders the brain more vulnerable to ischemic insults, possibly by increasing the invasion of neutrophils and altering the inflammation status in the blood and brain. Understanding the interactions between age and infections is crucial for developing a better therapeutic regimen for ischemic stroke and when modeling it as a disease of the elderly.

  1. Maintaining Brain Health by Monitoring Inflammatory Processes: a Mechanism to Promote Successful Aging

    OpenAIRE

    Rosano, Caterina; Marsland, Anna L.; Gianaros, Peter J.

    2011-01-01

    Maintaining brain health promotes successful aging. The main determinants of brain health are the preservation of cognitive function and remaining free from structural and metabolic abnormalities, including loss of neuronal synapses, atrophy, small vessel disease and focal amyloid deposits visible by neuroimaging. Promising studies indicate that these determinants are to some extent modifiable, even among adults seventy years and older. Converging animal and human evidence further suggests th...

  2. Combined age- and trauma-related proteomic changes in rat neocortex: a basis for brain vulnerability

    OpenAIRE

    Mehan, Neal D.; Strauss, Kenneth I

    2011-01-01

    This proteomic study investigates the widely observed clinical phenomenon, that after comparable brain injuries, geriatric patients fare worse and recover less cognitive and neurologic function than younger victims. Utilizing a rat traumatic brain injury model, sham surgery or a neocortical contusion was induced in 3 age groups. Geriatric (21 months) rats performed worse on behavioral measures than young adults (12–16 weeks) and juveniles (5– 6 weeks). Motor coordination and certain cognitive...

  3. Hot Topics in Research: Preventive Neuroradiology in Brain Aging and Cognitive Decline

    OpenAIRE

    Raji, Cyrus A.; Eyre, Harris; Wei, Sindy H.; Bredesen, Dale; Moylan, Steven; Law, Meng; Small, Gary; Thompson, Paul; Friedlander, Robert; Silverman, Dan H.; Baune, Bernhard T.; Hoang, Thu-Anh; Salamon, Noriko; Toga, Arthur; Vernooij, Meike W

    2015-01-01

    Preventive neuroradiology is a new concept supported by a growing literature. The main rationale of preventive neuroradiology is the application of multi-modal brain imaging towards early and subclinical detection of brain disease and subsequent preventive actions through identification of modifiable risk factors. An insightful example of this is in the area of age-related cognitive decline, mild cognitive impairment and dementia with potentially modifiable risk factors such as obesity, diet,...

  4. Effects of Long-Term Mindfulness Meditation on Brain's White Matter Microstructure and its Aging

    OpenAIRE

    Davide eLaneri; Verena eSchuster; Bruno eDietsche; Andreas eJansen; Ulrich eOtt; Jens eSommer

    2016-01-01

    Although research on the effects of mindfulness meditation (MM) is increasing, still very little has been done to address its influence on the white matter (WM) of the brain. We hypothesized that the practice of MM might affect the WM microstructure adjacent to five brain regions of interest associated with mindfulness. Diffusion tensor imaging was employed on samples of meditators and non-meditators (n=64) in order to investigate the effects of MM on group difference and aging. Tract-Based S...

  5. Association of Metabolic Dysregulation With Volumetric Brain Magnetic Resonance Imaging and Cognitive Markers of Subclinical Brain Aging in Middle-Aged Adults

    OpenAIRE

    Beiser, Alexa S; Au, Rhoda; Himali, Jayandra J.; Debette, Stephanie; DeCarli, Charles; Vasan, Ramachandran S.; Wolf, Philip A.; Seshadri, Sudha; Tan, Zaldy S.; Fox, Caroline

    2011-01-01

    Objective: Diabetic and prediabtic states, including insulin resistance, fasting hyperglycemia, and hyperinsulinemia, are associated with metabolic dysregulation. These components have been individually linked to increased risks of cognitive decline and Alzheimer’s disease. We aimed to comprehensively relate all of the components of metabolic dysregulation to cognitive function and brain magnetic resonance imaging (MRI) in middle-aged adults. Research Design and Methods: Framingham Offspring ...

  6. Carnosine and taurine treatments diminished brain oxidative stress and apoptosis in D-galactose aging model.

    Science.gov (United States)

    Aydın, A Fatih; Çoban, Jale; Doğan-Ekici, Işın; Betül-Kalaz, Esra; Doğru-Abbasoğlu, Semra; Uysal, Müjdat

    2016-04-01

    D-galactose (GAL) has been used as an animal model for brain aging and antiaging studies. GAL stimulates oxidative stress in several tissues including brain. Carnosine (CAR; β-alanil-L-histidine) and taurine (TAU; 2-aminoethanesulfonic acid) exhibit antioxidant properties. CAR and TAU have anti-aging and neuroprotective effects. We investigated the effect of CAR and TAU supplementations on oxidative stress and brain damage in GAL-treated rats. Rats received GAL (300 mg/kg; s.c.; 5 days per week) alone or together with CAR (250 mg/kg/daily; i.p.; 5 days per week) or TAU (2.5% w/w; in rat chow) for 2 months. Brain malondialdehyde (MDA), protein carbonyl (PC) and glutathione (GSH) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione transferase (GST) and acetylcholinesterase (AChE) activities were determined. Expressions of B cell lymphoma-2 (Bcl-2), Bax and caspase-3 were also evaluated in the brains by immunohistochemistry. GAL treatment increased brain MDA and PC levels and AChE activities. It decreased significantly brain GSH levels, SOD and GSH-Px but not GST activities. GAL treatment caused histopathological changes and increased apoptosis. CAR and TAU significantly reduced brain AChE activities, MDA and PC levels and elevated GSH levels in GAL-treated rats. CAR, but not TAU, significantly increased low activities of SOD and GSH-Px. Both CAR and TAU diminished apoptosis and ameliorated histopathological findings in the brain of GAL-treated rats. Our results indicate that CAR and TAU may be effective to prevent the development of oxidative stress, apoptosis and histopathological deterioration in the brain of GAL-treated rats. PMID:26518192

  7. Effect of high-intensity exercise on aged mouse brain mitochondria, neurogenesis, and inflammation

    OpenAIRE

    Lezi, E; Burns, Jeffrey M.; Swerdlow, Russell H.

    2014-01-01

    In aged mice we assessed how intensive exercise affects brain bioenergetics, inflammation, and neurogenesis-relevant parameters. After 8 weeks of a supra-lactate threshold treadmill exercise intervention, 21-month old C57BL/6 mice showed increased brain PGC-1α protein, mTOR and phospho-mTOR protein, citrate synthase mRNA, and mtDNA copy number. Hippocampal VEGF-A gene expression trended higher, and a positive correlation between VEGF-A and PRC mRNA levels was observed. Brain DCX, BDNF, TNF-α,...

  8. Measurement of brain atrophy of aging using x-ray computed tomography

    International Nuclear Information System (INIS)

    We measured brain volume of 1,045 subjects with no brain damage using x-ray computed tomography and investigated brain atrophy of aging. Severity of brain atrophy was estimated by brain atrophy index (BAI): BAI (%)=100 (%)x(cerebrospinal fluid space volume/cranial cavity volume). Atrophy of the brain began with statistical significance in the forties in both sexes. In males 40-49 years of age the mean BAI was 1.0% greater (p<0.001) and the S.D. of BAI was 1.1% greater (p<0.001) than those in their thirties. In females of 40-49 years the mean BAI was 0.5% greater (p<0.001) than that in their thirties, but there was no statistical significance between the two S.D.'s of both decades. The BAI increased exponentially with the increasing age from thirties in both sexes. Correlation coefficients were 0.702 (p< 0.001, n=471) in males and 0.721 (p<0.001, n=480) in females. From the regression coefficients it was calculated that the BAI was doubled in 19.4 years in males and 17.4 years in females after thirties. (author)

  9. White Matter Lipids as a Ketogenic Fuel Supply in Aging Female Brain: Implications for Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Lauren P. Klosinski

    2015-12-01

    Full Text Available White matter degeneration is a pathological hallmark of neurodegenerative diseases including Alzheimer's. Age remains the greatest risk factor for Alzheimer's and the prevalence of age-related late onset Alzheimer's is greatest in females. We investigated mechanisms underlying white matter degeneration in an animal model consistent with the sex at greatest Alzheimer's risk. Results of these analyses demonstrated decline in mitochondrial respiration, increased mitochondrial hydrogen peroxide production and cytosolic-phospholipase-A2 sphingomyelinase pathway activation during female brain aging. Electron microscopic and lipidomic analyses confirmed myelin degeneration. An increase in fatty acids and mitochondrial fatty acid metabolism machinery was coincident with a rise in brain ketone bodies and decline in plasma ketone bodies. This mechanistic pathway and its chronologically phased activation, links mitochondrial dysfunction early in aging with later age development of white matter degeneration. The catabolism of myelin lipids to generate ketone bodies can be viewed as a systems level adaptive response to address brain fuel and energy demand. Elucidation of the initiating factors and the mechanistic pathway leading to white matter catabolism in the aging female brain provides potential therapeutic targets to prevent and treat demyelinating diseases such as Alzheimer's and multiple sclerosis. Targeting stages of disease and associated mechanisms will be critical.

  10. White Matter Lipids as a Ketogenic Fuel Supply in Aging Female Brain: Implications for Alzheimer's Disease.

    Science.gov (United States)

    Klosinski, Lauren P; Yao, Jia; Yin, Fei; Fonteh, Alfred N; Harrington, Michael G; Christensen, Trace A; Trushina, Eugenia; Brinton, Roberta Diaz

    2015-12-01

    White matter degeneration is a pathological hallmark of neurodegenerative diseases including Alzheimer's. Age remains the greatest risk factor for Alzheimer's and the prevalence of age-related late onset Alzheimer's is greatest in females. We investigated mechanisms underlying white matter degeneration in an animal model consistent with the sex at greatest Alzheimer's risk. Results of these analyses demonstrated decline in mitochondrial respiration, increased mitochondrial hydrogen peroxide production and cytosolic-phospholipase-A2 sphingomyelinase pathway activation during female brain aging. Electron microscopic and lipidomic analyses confirmed myelin degeneration. An increase in fatty acids and mitochondrial fatty acid metabolism machinery was coincident with a rise in brain ketone bodies and decline in plasma ketone bodies. This mechanistic pathway and its chronologically phased activation, links mitochondrial dysfunction early in aging with later age development of white matter degeneration. The catabolism of myelin lipids to generate ketone bodies can be viewed as a systems level adaptive response to address brain fuel and energy demand. Elucidation of the initiating factors and the mechanistic pathway leading to white matter catabolism in the aging female brain provides potential therapeutic targets to prevent and treat demyelinating diseases such as Alzheimer's and multiple sclerosis. Targeting stages of disease and associated mechanisms will be critical. PMID:26844268

  11. Fluid intelligence and brain functional organization in aging yoga and meditation practitioners.

    Science.gov (United States)

    Gard, Tim; Taquet, Maxime; Dixit, Rohan; Hölzel, Britta K; de Montjoye, Yves-Alexandre; Brach, Narayan; Salat, David H; Dickerson, Bradford C; Gray, Jeremy R; Lazar, Sara W

    2014-01-01

    Numerous studies have documented the normal age-related decline of neural structure, function, and cognitive performance. Preliminary evidence suggests that meditation may reduce decline in specific cognitive domains and in brain structure. Here we extended this research by investigating the relation between age and fluid intelligence and resting state brain functional network architecture using graph theory, in middle-aged yoga and meditation practitioners, and matched controls. Fluid intelligence declined slower in yoga practitioners and meditators combined than in controls. Resting state functional networks of yoga practitioners and meditators combined were more integrated and more resilient to damage than those of controls. Furthermore, mindfulness was positively correlated with fluid intelligence, resilience, and global network efficiency. These findings reveal the possibility to increase resilience and to slow the decline of fluid intelligence and brain functional architecture and suggest that mindfulness plays a mechanistic role in this preservation.

  12. Fluid intelligence and brain functional organization in aging yoga and meditation practitioners

    Directory of Open Access Journals (Sweden)

    Tim eGard

    2014-04-01

    Full Text Available Numerous studies have documented the normal age-related decline of neural structure, function, and cognitive performance. Preliminary evidence suggests that meditation may reduce decline in specific cognitive domains and in brain structure. Here we extended this research by investigating the relation between age and fluid intelligence and resting state brain functional network architecture using graph theory, in middle-aged yoga and meditation practitioners, and matched controls. Fluid intelligence declined slower in yoga practitioners and meditators combined than in controls. Resting state functional networks of yoga practitioners and meditators combined were more integrated and more resilient to damage than those of controls. Furthermore, mindfulness was positively correlated with fluid intelligence, resilience, and global network efficiency. These findings reveal the possibility to increase resilience and to slow the decline of fluid intelligence and brain functional architecture and suggest that mindfulness plays a mechanistic role in this preservation.

  13. Exercise enhances memory consolidation in the aging brain

    OpenAIRE

    Shikha Snigdha; Christina de Rivera

    2014-01-01

    Exercise has been shown to reduce age-related losses in cognitive function including learning and memory, but the mechanisms underlying this effect remain poorly understood. Memory formation occurs in stages that include an initial acquisition phase, an intermediate labile phase, and then a process of consolidation which leads to long term memory formation. An effective way to examine the mechanism by which exercise improves memory is to introduce the intervention (exercise), post-acquisition...

  14. Indestructible plastic: the neuroscience of the new aging brain

    OpenAIRE

    Constance Holman; Etienne de Villers-Sidani

    2014-01-01

    In recent years, research on experience-dependent plasticity has provided valuable insight on adaptation to environmental input across the lifespan, and advances in understanding the minute cellular changes underlying the brain’s capacity for self-reorganization have opened exciting new possibilities for treating illness and injury. Ongoing work in this line of inquiry has also come to deeply influence another field: the cognitive neuroscience of the normal aging. This complex process, once d...

  15. Practice-Oriented Retest Learning as the Basic Form of Cognitive Plasticity of the Aging Brain

    Directory of Open Access Journals (Sweden)

    Lixia Yang

    2011-01-01

    Full Text Available It has been well documented that aging is associated with declines in a variety of cognitive functions. A growing body of research shows that the age-related cognitive declines are reversible through cognitive training programs, suggesting maintained cognitive plasticity of the aging brain. Retest learning represents a basic form of cognitive plasticity. It has been consistently demonstrated for adults in young-old and old-old ages. Accumulated research indicates that retest learning is effective, robust, endurable and could occur at a more conceptual level beyond item-specific memorization. Recent studies also demonstrate promisingly broader transfer effects from retest practice of activities involving complex executive functioning to other untrained tasks. The results shed light on the development of self-guided mental exercise programs to improve cognitive performance and efficiency of the aging brain. The relevant studies were reviewed, and the findings were discussed in light of their limitations, implications, and future directions.

  16. Working memory in middle-aged males: age-related brain activation changes and cognitive fatigue effects.

    Science.gov (United States)

    Klaassen, Elissa B; Evers, Elisabeth A T; de Groot, Renate H M; Backes, Walter H; Veltman, Dick J; Jolles, Jelle

    2014-02-01

    We examined the effects of aging and cognitive fatigue on working memory (WM) related brain activation using functional magnetic resonance imaging. Age-related differences were investigated in 13 young and 16 middle-aged male school teachers. Cognitive fatigue was induced by sustained performance on cognitively demanding tasks (compared to a control condition). Results showed a main effect of age on left dorsolateral prefrontal and superior parietal cortex activation during WM encoding; greater activation was evident in middle-aged than young adults regardless of WM load or fatigue condition. An interaction effect was found in the dorsomedial prefrontal cortex (DMPFC); WM load-dependent activation was elevated in middle-aged compared to young in the control condition, but did not differ in the fatigue condition due to a reduction in activation in middle-aged in contrast to an increase in activation in the young group. These findings demonstrate age-related activation differences and differential effects of fatigue on activation in young and middle-aged adults.

  17. Effects of non-pharmacological or pharmacological interventions on cognition and brain plasticity of aging individuals

    Science.gov (United States)

    Pieramico, Valentina; Esposito, Roberto; Cesinaro, Stefano; Frazzini, Valerio; Sensi, Stefano L.

    2014-01-01

    Brain aging and aging-related neurodegenerative disorders are major health challenges faced by modern societies. Brain aging is associated with cognitive and functional decline and represents the favourable background for the onset and development of dementia. Brain aging is associated with early and subtle anatomo-functional physiological changes that often precede the appearance of clinical signs of cognitive decline. Neuroimaging approaches unveiled the functional correlates of these alterations and helped in the identification of therapeutic targets that can be potentially useful in counteracting age-dependent cognitive decline. A growing body of evidence supports the notion that cognitive stimulation and aerobic training can preserve and enhance operational skills in elderly individuals as well as reduce the incidence of dementia. This review aims at providing an extensive and critical overview of the most recent data that support the efficacy of non-pharmacological and pharmacological interventions aimed at enhancing cognition and brain plasticity in healthy elderly individuals as well as delaying the cognitive decline associated with dementia. PMID:25228860

  18. The effect of aging on brain barriers and the consequences for Alzheimer's disease development.

    Science.gov (United States)

    Gorlé, Nina; Van Cauwenberghe, Caroline; Libert, Claude; Vandenbroucke, Roosmarijn E

    2016-08-01

    Life expectancy has increased in most developed countries, which has led to an increase in the proportion of elderly people in the world's population. However, this increase in life expectancy is not accompanied by a lengthening of the health span since aging is characterized with progressive deterioration in cellular and organ functions. The brain is particularly vulnerable to disease, and this is reflected in the onset of age-related neurodegenerative diseases such as Alzheimer's disease. Research shows that dysfunction of two barriers in the central nervous system (CNS), the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier (BCSFB), plays an important role in the progression of these neurodegenerative diseases. The BBB is formed by the endothelial cells of the blood capillaries, whereas the BCSFB is formed by the epithelial cells of the choroid plexus (CP), both of which are affected during aging. Here, we give an overview of how these barriers undergo changes during aging and in Alzheimer's disease, thereby disturbing brain homeostasis. Studying these changes is needed in order to gain a better understanding of the mechanisms of aging at the brain barriers, which might lead to the development of new therapies to lengthen the health span (including mental health) and reduce the chances of developing Alzheimer's disease. PMID:27143113

  19. Aging Effects on Whole-Brain Functional Connectivity in Adults Free of Cognitive and Psychiatric Disorders.

    Science.gov (United States)

    Ferreira, Luiz Kobuti; Regina, Ana Carolina Brocanello; Kovacevic, Natasa; Martin, Maria da Graça Morais; Santos, Pedro Paim; Carneiro, Camila de Godoi; Kerr, Daniel Shikanai; Amaro, Edson; McIntosh, Anthony Randal; Busatto, Geraldo F

    2016-09-01

    Aging is associated with decreased resting-state functional connectivity (RSFC) within the default mode network (DMN), but most functional imaging studies have restricted the analysis to specific brain regions or networks, a strategy not appropriate to describe system-wide changes. Moreover, few investigations have employed operational psychiatric interviewing procedures to select participants; this is an important limitation since mental disorders are prevalent and underdiagnosed and can be associated with RSFC abnormalities. In this study, resting-state fMRI was acquired from 59 adults free of cognitive and psychiatric disorders according to standardized criteria and based on extensive neuropsychological and clinical assessments. We tested for associations between age and whole-brain RSFC using Partial Least Squares, a multivariate technique. We found that normal aging is not only characterized by decreased RSFC within the DMN but also by ubiquitous increases in internetwork positive correlations and focal internetwork losses of anticorrelations (involving mainly connections between the DMN and the attentional networks). Our results reinforce the notion that the aging brain undergoes a dedifferentiation processes with loss of functional diversity. These findings advance the characterization of healthy aging effects on RSFC and highlight the importance of adopting a broad, system-wide perspective to analyze brain connectivity.

  20. Effects of diet & behavioral enrichment on free fatty acids in the aged canine brain

    Science.gov (United States)

    Snigdha, Shikha; Astarita, Giuseppe; Piomelli, Daniele; Cotman, Carl W.

    2012-01-01

    Despite several recent studies suggesting that dysregulation of brain lipid metabolism might contribute to the mechanisms of aging and Alzheimer’s disease (AD), lipid metabolism has not been evaluated extensively in the aging brain. Here, we use a lipidomic approach to demonstrate that antioxidants plus mitochondrial cofactors treatment, either alone or in combination with behavioral enrichment, attenuates lipid abnormalities in the frontal cortices of aged canine in a manner correlated with cognitive scores. Our analyses revealed that the levels of free palmitoleic acid and nervonic acid were decreased in frontal cortices of aged dogs (n=5-6/group) treated with antioxidant compared to the control group. The monounsaturated/saturated fatty acid ratio, also known as ‘desaturation index’ - an ex-vivo indicator of stearoyl-CoA desaturase activity, was also reduced in the frontal cortex of dogs treated with antioxidants compared to control groups. Increased palmitoleic acid levels and desaturation index were positively correlated with increased reversal learning errors and decreased cognitive performance. In conclusion, our study indicates that the addition of antioxidants and mitochondrial cofactors to the regular diet alters the composition of free fatty acids in the aged brain. Together with data showing increased palmitoleic acid levels in AD patients, our data suggest that reducing palmitoleic acid levels and desaturation index in the brain may be associated with improved cognitive performance. PMID:22183056

  1. EEG Resting-State Brain Topological Reorganization as a Function of Age

    Directory of Open Access Journals (Sweden)

    Manuela Petti

    2016-01-01

    Full Text Available Resting state connectivity has been increasingly studied to investigate the effects of aging on the brain. A reduced organization in the communication between brain areas was demonstrated by combining a variety of different imaging technologies (fMRI, EEG, and MEG and graph theory. In this paper, we propose a methodology to get new insights into resting state connectivity and its variations with age, by combining advanced techniques of effective connectivity estimation, graph theoretical approach, and classification by SVM method. We analyzed high density EEG signals recorded at rest from 71 healthy subjects (age: 20–63 years. Weighted and directed connectivity was computed by means of Partial Directed Coherence based on a General Linear Kalman filter approach. To keep the information collected by the estimator, weighted and directed graph indices were extracted from the resulting networks. A relation between brain network properties and age of the subject was found, indicating a tendency of the network to randomly organize increasing with age. This result is also confirmed dividing the whole population into two subgroups according to the age (young and middle-aged adults: significant differences exist in terms of network organization measures. Classification of the subjects by means of such indices returns an accuracy greater than 80%.

  2. Aging Brain: Prevention of Oxidative Stress by Vitamin E and Exercise

    Directory of Open Access Journals (Sweden)

    Sambe Asha Devi

    2009-01-01

    Full Text Available With aging, the brain undergoes neuronal loss in many areas. Although the loss of cells in the cerebral cortex, in particular the frontal cortex, has been recognized with aging, the influence of synaptic losses has a larger impact on cognitive decline. Much of the recent research on animals, as well as humans, has been aimed at slowing the cognitive decline through enrichment, and it has been found that the key factors are antioxidants and exercise. Several reports support the concept that regular supplementation of vitamin E and physical activity from as early as middle age can slow the cognitive decline observed during the later years. A few studies have also suggested that exercise is analogous to acetylcholine esterase inhibitors that are also used extensively to treat cognitive impairment and dementia in Alzheimer's disease. In addition, reports also support that vitamin E and exercise may act synergistically to overcome free radical injury and oxidative stress in the aging brain.

  3. Taurine content in different brain structures during ageing: effect on hippocampal synaptic plasticity.

    Science.gov (United States)

    Suárez, Luz M; Muñoz, María-Dolores; Martín Del Río, Rafael; Solís, José M

    2016-05-01

    A reduction in taurine content accompanies the ageing process in many tissues. In fact, the decline of brain taurine levels has been associated with cognitive deficits whereas chronic administration of taurine seems to ameliorate age-related deficits such as memory acquisition and retention. In the present study, using rats of three age groups (young, adult and aged) we determined whether the content of taurine and other amino acids (glutamate, serine, glutamine, glycine, alanine and GABA) was altered during ageing in different brain areas (cerebellum, cortex and hippocampus) as well non-brain tissues (heart, kidney, liver and plasma). Moreover, using hippocampal slices we tested whether ageing affects synaptic function and plasticity. These parameters were also determined in aged rats fed with either taurine-devoid or taurine-supplemented diets. With age, we found heterogeneous changes in amino acid content depending on the amino acid type and the tissue. In the case of taurine, its content was reduced in the cerebellum of adult and aged rats, but it remained unchanged in the hippocampus, cortex, heart and liver. The synaptic response amplitude decreased in aged rats, although the late phase of long-term synaptic potentiation (late-LTP), a taurine-dependent process, was not altered. Our study highlights the stability of taurine content in the hippocampus during ageing regardless of whether taurine was present in the diet, which is consistent with the lack of changes detected in late-LTP. These results indicate that the beneficial effects of taurine supplementation might be independent of the replenishment of taurine stores. PMID:26803657

  4. The effects of age, sex, and hormones on emotional conflict-related brain response during adolescence.

    Science.gov (United States)

    Cservenka, Anita; Stroup, Madison L; Etkin, Amit; Nagel, Bonnie J

    2015-10-01

    While cognitive and emotional systems both undergo development during adolescence, few studies have explored top-down inhibitory control brain activity in the context of affective processing, critical to informing adolescent psychopathology. In this study, we used functional magnetic resonance imaging to examine brain response during an Emotional Conflict (EmC) Task across 10-15-year-old youth. During the EmC Task, participants indicated the emotion of facial expressions, while disregarding emotion-congruent and incongruent words printed across the faces. We examined the relationships of age, sex, and gonadal hormones with brain activity on Incongruent vs. Congruent trials. Age was negatively associated with middle frontal gyrus activity, controlling for performance and movement confounds. Sex differences were present in occipital and parietal cortices, and were driven by activation in females, and deactivation in males to Congruent trials. Testosterone was negatively related with frontal and striatal brain response in males, and cerebellar and precuneus response in females. Estradiol was negatively related with fronto-cerebellar, cingulate, and precuneus brain activity in males, and positively related with occipital response in females. To our knowledge, this is the first study reporting the effects of age, sex, and sex steroids during an emotion-cognition task in adolescents. Further research is needed to examine longitudinal development of emotion-cognition interactions and deviations in psychiatric disorders in adolescence.

  5. Physiological neuronal decline in healthy aging human brain - An in vivo study with MRI and short echo-time whole-brain (1)H MR spectroscopic imaging.

    Science.gov (United States)

    Ding, Xiao-Qi; Maudsley, Andrew A; Sabati, Mohammad; Sheriff, Sulaiman; Schmitz, Birte; Schütze, Martin; Bronzlik, Paul; Kahl, Kai G; Lanfermann, Heinrich

    2016-08-15

    Knowledge of physiological aging in healthy human brain is increasingly important for neuroscientific research and clinical diagnosis. To investigate neuronal decline in normal aging brain eighty-one healthy subjects aged between 20 and 70years were studied with MRI and whole-brain (1)H MR spectroscopic imaging. Concentrations of brain metabolites N-acetyl-aspartate (NAA), choline (Cho), total creatine (tCr), myo-inositol (mI), and glutamine+glutamate (Glx) in ratios to internal water, and the fractional volumes of brain tissue were estimated simultaneously in eight cerebral lobes and in cerebellum. Results demonstrated that an age-related decrease in gray matter volume was the largest contribution to changes in brain volume. Both lobar NAA and the fractional volume of gray matter (FVGM) decreased with age in all cerebral lobes, indicating that the decreased NAA was predominantly associated with decreased gray matter volume and neuronal density or metabolic activity. In cerebral white matter Cho, tCr, and mI increased with age in association with increased fractional volume, showing altered cellular membrane turn-over, energy metabolism, and glial activity in human aging white matter. In cerebellum tCr increased while brain tissue volume decreased with age, showing difference to cerebral aging. The observed age-related metabolic and microstructural variations suggest that physiological neuronal decline in aging human brain is associated with a reduction of gray matter volume and neuronal density, in combination with cellular aging in white matter indicated by microstructural alterations and altered energy metabolism in the cerebellum. PMID:27164326

  6. The effect of somatic disorders on brain aging and dementia : Findings from population studies

    OpenAIRE

    Atti, Anna Rita

    2009-01-01

    This doctoral thesis investigates the effect of somatic disorders on dementia, Alzheimer s disease (AD) and brain aging in late-life. The data for the studies are provided by the Kungsholmen Project (Studies I and II) and the Faenza Project (Studies III and IV). The Kungsholmen Project is a population-based longitudinal study on aging and dementia carried out on 75+ years old people, living in Stockholm, Sweden. The Faenza Project is a cross-sectional population-based study ...

  7. Aging Brain: Prevention of Oxidative Stress by Vitamin E and Exercise

    OpenAIRE

    Sambe Asha Devi

    2009-01-01

    With aging, the brain undergoes neuronal loss in many areas. Although the loss of cells in the cerebral cortex, in particular the frontal cortex, has been recognized with aging, the influence of synaptic losses has a larger impact on cognitive decline. Much of the recent research on animals, as well as humans, has been aimed at slowing the cognitive decline through enrichment, and it has been found that the key factors are antioxidants and exercise. Several reports support the concept that re...

  8. AED Treatment Through Different Ages: As Our Brains Change, Should Our Drug Choices Also?

    OpenAIRE

    French, Jacqueline A.; Staley, Brigid A.

    2012-01-01

    Patient age can impact selection of the optimal antiepileptic drug for a number of reasons. Changes in brain physiology from neonate to elderly, as well as changes in underlying etiologies of epilepsy, could potentially affect the ability of different drugs to control seizures. Unfortunately, much of this is speculative, as good studies demonstrating differences in efficacy across age ranges do not exist. Beyond the issue of efficacy, certain drugs may be more or less appropriate at different...

  9. Neuroinflammation in the Aging Down Syndrome Brain; Lessons from Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Donna M. Wilcock

    2012-01-01

    Full Text Available Down syndrome (DS is the most genetic cause of mental retardation and is caused by the triplication of chromosome 21. In addition to the disabilities caused early in life, DS is also noted as causing Alzheimer's-disease-like pathological changes in the brain, leading to 50–70% of DS patients showing dementia by 60–70 years of age. Inflammation is a complex process that has a key role to play in the pathogenesis of Alzheimer's disease. There is relatively little understood about inflammation in the DS brain and how the genetics of DS may alter this inflammatory response and change the course of disease in the DS brain. The goal of this review is to highlight our current understanding of inflammation in Alzheimer's disease and predict how inflammation may affect the pathology of the DS brain based on this information and the known genetic changes that occur due to triplication of chromosome 21.

  10. Neurogenetic effects on cognition in aging brains: A window of opportunity for intervention?

    Directory of Open Access Journals (Sweden)

    Ivar Reinvang

    2010-11-01

    Full Text Available Knowledge of genetic influences on cognitive aging can constrain and guide interventions aimed at limiting age-related cognitive decline in older adults. Progress in understanding the neural basis of cognitive aging also requires a better understanding of the neurogenetics of cognition. This selective review article describes studies aimed at deriving specific neurogenetic information from three parallel and interrelated phenotype based approaches: psychometric constructs, cognitive neuroscience based processing measures, and brain imaging morphometric data. Developments in newer genetic analysis tools, including genome wide association, are also described. In particular, we focus on models for establishing genotype-phenotype associations within an explanatory framework linking molecular, brain, and cognitive levels of analysis. Such multiple-phenotype approaches indicate that individual variation in genes central to maintaining synaptic integrity, neurotransmitter function, and synaptic plasticity are important in affecting age-related changes in brain structure and cognition. Investigating phenotypes at multiple levels is recommended as a means to advance understanding of the neural impact of genetic variants relevant to cognitive aging. Further knowledge regarding the mechanisms of interaction between genetic and preventative procedures will in turn help in understanding the ameliorative effect of various experiential and lifestyle factors on age-related cognitive decline.

  11. New neurons in aging brains: molecular control by small non-coding RNAs.

    NARCIS (Netherlands)

    M. Schouten; M.R. Buijink; P.J. Lucassen; C.P. Fitzsimons

    2012-01-01

    Adult neurogenesis generates functional neurons from neural stem cells present in specific brain regions. It is largely confined to two main regions: the subventricular zone of the lateral ventricle, and the subgranular zone of the dentate gyrus (DG), in the hippocampus. With age, the function of th

  12. Watching TV news as a memory task -- brain activation and age effects

    Directory of Open Access Journals (Sweden)

    Frings Lars

    2010-08-01

    Full Text Available Abstract Background Neuroimaging studies which investigate brain activity underlying declarative memory processes typically use artificial, unimodal laboratory stimuli. In contrast, we developed a paradigm which much more closely approximates real-life situations of information encoding. Methods In this study, we tested whether ecologically valid stimuli - clips of a TV news show - are apt to assess memory-related fMRI activation in healthy participants across a wide age range (22-70 years. We contrasted brain responses during natural stimulation (TV news video clips with a control condition (scrambled versions of the same clips with reversed audio tracks. After scanning, free recall performance was assessed. Results The memory task evoked robust activation of a left-lateralized network, including primarily lateral temporal cortex, frontal cortex, as well as the left hippocampus. Further analyses revealed that - when controlling for performance effects - older age was associated with greater activation of left temporal and right frontal cortex. Conclusion We demonstrate the feasibility of assessing brain activity underlying declarative memory using a natural stimulation paradigm with high ecological validity. The preliminary result of greater brain activation with increasing age might reflect an attempt to compensate for decreasing episodic memory capacity associated with aging.

  13. Exercise and the Aging Brain. (The 1982 C. H. McCloy Research Lecture)

    Science.gov (United States)

    Spirduso, Waneen W.

    1983-01-01

    Exercise may postpone the deterioration in response speed that generally appears in the motor system of the aging by maintaining the nigrostriatal dopaminergic system in the brain. Exercise may also ameliorate symptoms of Parkinson's disease. Results of laboratory studies involving animals and rats are reported. (Author/PP)

  14. Aging brain from a network science perspective: something to be positive about?

    Directory of Open Access Journals (Sweden)

    Michelle W Voss

    Full Text Available To better understand age differences in brain function and behavior, the current study applied network science to model functional interactions between brain regions. We observed a shift in network topology whereby for older adults subcortical and cerebellar structures overlapping with the Salience network had more connectivity to the rest of the brain, coupled with fragmentation of large-scale cortical networks such as the Default and Fronto-Parietal networks. Additionally, greater integration of the dorsal medial thalamus and red nucleus in the Salience network was associated with greater satisfaction with life for older adults, which is consistent with theoretical predictions of age-related increases in emotion regulation that are thought to help maintain well-being and life satisfaction in late adulthood. In regard to cognitive abilities, greater ventral medial prefrontal cortex coherence with its topological neighbors in the Default Network was associated with faster processing speed. Results suggest that large-scale organizing properties of the brain differ with normal aging, and this perspective may offer novel insight into understanding age-related differences in cognitive function and well-being.

  15. Calcium antagonists decrease capillary wall damage in aging hypertensive rat brain

    NARCIS (Netherlands)

    Farkas, E.; de Jong, G.I.; Apro, E.; Keuker, J.I.H.; Luiten, P.G.M.

    2001-01-01

    Chronic hypertension during aging is a serious threat to the cerebral vasculature. The larger brain arteries can react to hypertension with an abnormal wall thickening, a loss of elasticity and a narrowed lumen. However, little is known about the hypertension-induced alterations of cerebral capillar

  16. Age-related changes in brain support cells: Implications for stroke severity.

    Science.gov (United States)

    Sohrabji, Farida; Bake, Shameena; Lewis, Danielle K

    2013-10-01

    Stroke is one of the leading causes of adult disability and the fourth leading cause of mortality in the US. Stroke disproportionately occurs among the elderly, where the disease is more likely to be fatal or lead to long-term supportive care. Animal models, where the ischemic insult can be controlled more precisely, also confirm that aged animals sustain more severe strokes as compared to young animals. Furthermore, the neuroprotection usually seen in younger females when compared to young males is not observed in older females. The preclinical literature thus provides a valuable resource for understanding why the aging brain is more susceptible to severe infarction. In this review, we discuss the hypothesis that stroke severity in the aging brain may be associated with reduced functional capacity of critical support cells. Specifically, we focus on astrocytes, that are critical for detoxification of the brain microenvironment and endothelial cells, which play a crucial role in maintaining the blood brain barrier. In view of the sex difference in stroke severity, this review also discusses studies of middle-aged acyclic females as well as the effects of the estrogen on astrocytes and endothelial cells.

  17. Keep Your Brain Fit! A Psychoeducational Training Program for Healthy Cognitive Aging: A Feasibility Study

    Science.gov (United States)

    Reijnders, Jennifer; van Heugten, Caroline; van Boxtel, Martin

    2015-01-01

    A psychoeducational face-to-face training program (Keep Your Brain Fit!) was developed to support the working population in coping with age-related cognitive changes and taking proactive preventive measures to maintain cognitive health. A feasibility study was conducted to test the training program presented in a workshop format. Participants…

  18. An in vivo study on brain microstructure in biological and chronological ageing

    DEFF Research Database (Denmark)

    Altmann-Schneider, Irmhild; de Craen, Anton J M; van den Berg-Huysmans, Annette A;

    2015-01-01

    phenotype of familial longevity. Moreover, we aimed to describe cerebral ageing effects on MTI parameters in an elderly cohort. All subjects were included from the Leiden Longevity Study and underwent 3 Tesla MTI of the brain. In total, 183 offspring of nonagenarian siblings, who are enriched for familial...

  19. Discovering novel microRNAs and age-related nonlinear changes in rat brains using deep sequencing.

    Science.gov (United States)

    Yin, Lanxuan; Sun, Yubai; Wu, Jinfeng; Yan, Siyu; Deng, Zhenglu; Wang, Jun; Liao, Shenke; Yin, Dazhong; Li, Guolin

    2015-02-01

    Elucidating the molecular mechanisms of brain aging remains a significant challenge for biogerontologists. The discovery of gene regulation by microRNAs (miRNAs) has added a new dimension for examining this process; however, the full complement of miRNAs involved in brain aging is still not known. In this study, miRNA profiles of young, adult, and old rats were obtained to evaluate molecular changes during aging. High-throughput deep sequencing revealed 547 known and 171 candidate novel miRNAs that were differentially expressed among groups. Unexpectedly, miRNA expression did not decline progressively with advancing age; moreover, genes targeted by age-associated miRNAs were predicted to be involved in biological processes linked to aging and neurodegenerative diseases. These findings provide novel insight into the molecular mechanisms underlying brain aging and a resource for future studies on age-related brain disorders.

  20. Aging-induced changes in brain regional serotonin receptor binding: Effect of Carnosine.

    Science.gov (United States)

    Banerjee, S; Poddar, M K

    2016-04-01

    Monoamine neurotransmitter, serotonin (5-HT) has its own specific receptors in both pre- and post-synapse. In the present study the role of carnosine on aging-induced changes of [(3)H]-5-HT receptor binding in different brain regions in a rat model was studied. The results showed that during aging (18 and 24 months) the [(3)H]-5-HT receptor binding was reduced in hippocampus, hypothalamus and pons-medulla with a decrease in their both Bmax and KD but in cerebral cortex the [(3)H]-5-HT binding was increased with the increase of its only Bmax. The aging-induced changes in [(3)H]-5-HT receptor binding with carnosine (2.0 μg/kg/day, intrathecally, for 21 consecutive days) attenuated in (a) 24-month-aged rats irrespective of the brain regions with the attenuation of its Bmax except hypothalamus where both Bmax and KD were significantly attenuated, (b) hippocampus and hypothalamus of 18-month-aged rats with the attenuation of its Bmax, and restored toward the [(3)H]-5-HT receptor binding that observed in 4-month-young rats. The decrease in pons-medullary [(3)H]-5-HT binding including its Bmax of 18-month-aged rats was promoted with carnosine without any significant change in its cerebral cortex. The [(3)H]-5-HT receptor binding with the same dosages of carnosine in 4-month-young rats (a) increased in the cerebral cortex and hippocampus with the increase in their only Bmax whereas (b) decreased in hypothalamus and pons-medulla with a decrease in their both Bmax and KD. These results suggest that carnosine treatment may (a) play a preventive role in aging-induced brain region-specific changes in serotonergic activity (b) not be worthy in 4-month-young rats in relation to the brain regional serotonergic activity. PMID:26808776

  1. Associations between insulin action and integrity of brain microstructure differ with familial longevity and with age

    Directory of Open Access Journals (Sweden)

    Abimbola A. Akintola

    2015-05-01

    Full Text Available Impaired glucose metabolism and type 2 diabetes have been associated with cognitive decline, dementia, and with structural and functional brain features. However, it is unclear whether these associations differ in individuals that differ in familial longevity or age. Here, we investigated the association between parameters of glucose metabolism and microstructural brain integrity in offspring of long-lived families (offspring and controls; and age categories thereof. From the Leiden Longevity Study, 132 participants underwent oral glucose tolerance test to assess glycemia (fasted glucose and glucose area-under-the-curve (AUC, insulin resistance (fasted insulin, AUCinsulin, and homeostatic model assessment of insulin resistance (HOMA-IR, and pancreatic Beta cell secretory capacity (insulinogenic index. 3Tesla MRI and Magnetization Transfer (MT imaging MT-ratio peak-height was used to quantify differences in microstructural brain parenchymal tissue homogeneity that remain invisible on conventional MRI. Analyses were performed in offspring and age-matched controls, with and without stratification for age.In the full offspring group only, reduced peak-height in grey and white matter was inversely associated with AUCinsulin, fasted insulin, HOMA-IR and insulinogenic-index (all p65 years: in younger controls, significantly stronger inverse associations were observed between peak-height and fasted glucose, AUCglucose, fasted insulin, AUCinsulin and HOMA-IR in grey matter; and for AUCglucose, fasted insulin and HOMA-IR in white matter (all P-interaction<0.05. Although the strength of the associations tended to attenuate with age in the offspring group, the difference between age groups was not statistically significant. Thus, associations between impaired insulin action and reduced microstructural brain parenchymal tissue homogeneity were stronger in offspring compared to controls, and seemed to diminish with age.

  2. Brain network characterization of high-risk preterm-born school-age children.

    Science.gov (United States)

    Fischi-Gomez, Elda; Muñoz-Moreno, Emma; Vasung, Lana; Griffa, Alessandra; Borradori-Tolsa, Cristina; Monnier, Maryline; Lazeyras, François; Thiran, Jean-Philippe; Hüppi, Petra S

    2016-01-01

    Higher risk for long-term cognitive and behavioral impairments is one of the hallmarks of extreme prematurity (EP) and pregnancy-associated fetal adverse conditions such as intrauterine growth restriction (IUGR). While neurodevelopmental delay and abnormal brain function occur in the absence of overt brain lesions, these conditions have been recently associated with changes in microstructural brain development. Recent imaging studies indicate changes in brain connectivity, in particular involving the white matter fibers belonging to the cortico-basal ganglia-thalamic loop. Furthermore, EP and IUGR have been related to altered brain network architecture in childhood, with reduced network global capacity, global efficiency and average nodal strength. In this study, we used a connectome analysis to characterize the structural brain networks of these children, with a special focus on their topological organization. On one hand, we confirm the reduced averaged network node degree and strength due to EP and IUGR. On the other, the decomposition of the brain networks in an optimal set of clusters remained substantially different among groups, talking in favor of a different network community structure. However, and despite the different community structure, the brain networks of these high-risk school-age children maintained the typical small-world, rich-club and modularity characteristics in all cases. Thus, our results suggest that brain reorganizes after EP and IUGR, prioritizing a tight modular structure, to maintain the small-world, rich-club and modularity characteristics. By themselves, both extreme prematurity and IUGR bear a similar risk for neurocognitive and behavioral impairment, and the here defined modular network alterations confirm similar structural changes both by IUGR and EP at school age compared to control. Interestingly, the combination of both conditions (IUGR + EP) does not result in a worse outcome. In such cases, the alteration in network

  3. Brain network characterization of high-risk preterm-born school-age children

    Directory of Open Access Journals (Sweden)

    Elda Fischi-Gomez

    2016-01-01

    Full Text Available Higher risk for long-term cognitive and behavioral impairments is one of the hallmarks of extreme prematurity (EP and pregnancy-associated fetal adverse conditions such as intrauterine growth restriction (IUGR. While neurodevelopmental delay and abnormal brain function occur in the absence of overt brain lesions, these conditions have been recently associated with changes in microstructural brain development. Recent imaging studies indicate changes in brain connectivity, in particular involving the white matter fibers belonging to the cortico-basal ganglia-thalamic loop. Furthermore, EP and IUGR have been related to altered brain network architecture in childhood, with reduced network global capacity, global efficiency and average nodal strength. In this study, we used a connectome analysis to characterize the structural brain networks of these children, with a special focus on their topological organization. On one hand, we confirm the reduced averaged network node degree and strength due to EP and IUGR. On the other, the decomposition of the brain networks in an optimal set of clusters remained substantially different among groups, talking in favor of a different network community structure. However, and despite the different community structure, the brain networks of these high-risk school-age children maintained the typical small-world, rich-club and modularity characteristics in all cases. Thus, our results suggest that brain reorganizes after EP and IUGR, prioritizing a tight modular structure, to maintain the small-world, rich-club and modularity characteristics. By themselves, both extreme prematurity and IUGR bear a similar risk for neurocognitive and behavioral impairment, and the here defined modular network alterations confirm similar structural changes both by IUGR and EP at school age compared to control. Interestingly, the combination of both conditions (IUGR + EP does not result in a worse outcome. In such cases, the alteration

  4. Peripheral injection of human umbilical cord blood stimulates neurogenesis in the aged rat brain

    Directory of Open Access Journals (Sweden)

    Sanberg Paul R

    2008-02-01

    Full Text Available Abstract Background Neurogenesis continues to occur throughout life but dramatically decreases with increasing age. This decrease is mostly related to a decline in proliferative activity as a result of an impoverishment of the microenvironment of the aged brain, including a reduction in trophic factors and increased inflammation. Results We determined that human umbilical cord blood mononuclear cells (UCBMC given peripherally, by an intravenous injection, could rejuvenate the proliferative activity of the aged neural stem/progenitor cells. This increase in proliferation lasted for at least 15 days after the delivery of the UCBMC. Along with the increase in proliferation following UCBMC treatment, an increase in neurogenesis was also found in the aged animals. The increase in neurogenesis as a result of UCBMC treatment seemed to be due to a decrease in inflammation, as a decrease in the number of activated microglia was found and this decrease correlated with the increase in neurogenesis. Conclusion The results demonstrate that a single intravenous injection of UCBMC in aged rats can significantly improve the microenvironment of the aged hippocampus and rejuvenate the aged neural stem/progenitor cells. Our results raise the possibility of a peripherally administered cell therapy as an effective approach to improve the microenvironment of the aged brain.

  5. Peripheral injection of human umbilical cord blood stimulates neurogenesis in the aged rat brain

    Science.gov (United States)

    Bachstetter, Adam D; Pabon, Mibel M; Cole, Michael J; Hudson, Charles E; Sanberg, Paul R; Willing, Alison E; Bickford, Paula C; Gemma, Carmelina

    2008-01-01

    Background Neurogenesis continues to occur throughout life but dramatically decreases with increasing age. This decrease is mostly related to a decline in proliferative activity as a result of an impoverishment of the microenvironment of the aged brain, including a reduction in trophic factors and increased inflammation. Results We determined that human umbilical cord blood mononuclear cells (UCBMC) given peripherally, by an intravenous injection, could rejuvenate the proliferative activity of the aged neural stem/progenitor cells. This increase in proliferation lasted for at least 15 days after the delivery of the UCBMC. Along with the increase in proliferation following UCBMC treatment, an increase in neurogenesis was also found in the aged animals. The increase in neurogenesis as a result of UCBMC treatment seemed to be due to a decrease in inflammation, as a decrease in the number of activated microglia was found and this decrease correlated with the increase in neurogenesis. Conclusion The results demonstrate that a single intravenous injection of UCBMC in aged rats can significantly improve the microenvironment of the aged hippocampus and rejuvenate the aged neural stem/progenitor cells. Our results raise the possibility of a peripherally administered cell therapy as an effective approach to improve the microenvironment of the aged brain. PMID:18275610

  6. Local amplification of glucocorticoids in the ageing brain and impaired spatial memory

    Directory of Open Access Journals (Sweden)

    Joyce L.W. Yau

    2012-08-01

    Full Text Available The hippocampus is a prime target for glucocorticoids (GCs and a brain structure particularly vulnerable to ageing. Prolonged exposure to excess GCs compromises hippocampal electrophysiology, structure and function. Blood GC levels tend to increase with ageing and correlate with impaired spatial memory in ageing rodents and humans. The magnitude of GC action within tissues depends not only on levels of steroid hormone that enter the cells from the periphery and the density of intracellular receptors but also on the local metabolism of GCs by 11ß-hydroxysteroid dehydrogenases (11ß-HSD. The predominant isozyme in the adult brain, 11ß-HSD1, locally regenerates active GCs from inert 11-keto forms thus amplifying GC levels within specific target cells including in the hippocampus and cortex. Ageing associates with elevated hippocampal and neocortical 11ß-HSD1 and impaired spatial learning while deficiency of 11ß-HSD1 in knockout mice prevents the emergence of cognitive decline with age. Furthermore, short-term pharmacological inhibition of 11ß-HSD1 in already aged mice reverses spatial memory impairments. Here, we review research findings that support a key role for GCs with special emphasis on their intracellular regulation by 11ß-HSD1 in the emergence of spatial memory deficits with ageing, and discuss the use of 11ß-HSD1 inhibitors as a promising novel treatment in ameliorating/improving age-related memory impairments.

  7. Neuroculture, active ageing and the 'older brain': problems, promises and prospects.

    Science.gov (United States)

    Williams, Simon J; Higgs, Paul; Katz, Stephen

    2012-01-01

    This article explores the characteristics of a newly emergent 'neuroculture' and its relationship to cultures of ageing; in particular, the social meanings associated with 'active ageing' and 'cognitive health' and the discourses and sciences around memory and the 'ageing brain'. The argument proposes a critical perspective on this relationship by looking at the shifting boundaries between standards of normality and abnormality, values of health and illness, practices of therapy and enhancement, and the lines demarcating Third Age (healthy, active and agentic) and Fourth Age (dependency, loss and decline) periods of ageing. Conclusions offer further reflections on the complex questions that arise regarding expectations, hopes and ethics in relation to the promises and perils of a neurocultural future.

  8. Cognitive function and brain structure after recurrent mild traumatic brain injuries in young-to-middle-aged adults

    Directory of Open Access Journals (Sweden)

    Jonathan eList

    2015-05-01

    Full Text Available Recurrent mild traumatic brain injuries (mTBIs are regarded as an independent risk factor for developing dementia in later life. We here aimed to evaluate associations between recurrent mTBIs, cognition, and grey matter volume and microstructure as revealed by structural magnetic resonance imaging (MRI in the chronic phase after mTBIs in young adulthood. We enrolled 20 young-to-middle-aged subjects, who reported two or more sports-related mTBIs, with the last mTBI>6 months prior to study enrolment (mTBI group, and 21 age-, sex- and education matched controls with no history of mTBI (control group. All participants received comprehensive neuropsychological testing, and high resolution T1-weighted and diffusion tensor MRI in order to assess cortical thickness (CT and microstructure, hippocampal volume, and ventricle size. Compared to the control group, subjects of the mTBI group presented with lower CT within the right temporal lobe and left insula using an a priori region of interest approach. Higher number of mTBIs was associated with lower CT in bilateral insula, right middle temporal gyrus and right entorhinal area. Our results suggest persistent detrimental effects of recurrent mTBIs on CT already in young-to-middle-aged adults. If additional structural deterioration occurs during aging, subtle neuropsychological decline may progress to clinically overt dementia earlier than in age-matched controls, a hypothesis to be assessed in future prospective trials.

  9. Cognitive function and brain structure after recurrent mild traumatic brain injuries in young-to-middle-aged adults

    Science.gov (United States)

    List, Jonathan; Ott, Stefanie; Bukowski, Martin; Lindenberg, Robert; Flöel, Agnes

    2015-01-01

    Recurrent mild traumatic brain injuries (mTBIs) are regarded as an independent risk factor for developing dementia in later life. We here aimed to evaluate associations between recurrent mTBIs, cognition, and gray matter volume and microstructure as revealed by structural magnetic resonance imaging (MRI) in the chronic phase after mTBIs in young adulthood. We enrolled 20 young-to-middle-aged subjects, who reported two or more sports-related mTBIs, with the last mTBI > 6 months prior to study enrolment (mTBI group), and 21 age-, sex- and education matched controls with no history of mTBI (control group). All participants received comprehensive neuropsychological testing, and high resolution T1-weighted and diffusion tensor MRI in order to assess cortical thickness (CT) and microstructure, hippocampal volume, and ventricle size. Compared to the control group, subjects of the mTBI group presented with lower CT within the right temporal lobe and left insula using an a priori region of interest approach. Higher number of mTBIs was associated with lower CT in bilateral insula, right middle temporal gyrus and right entorhinal area. Our results suggest persistent detrimental effects of recurrent mTBIs on CT already in young-to-middle-aged adults. If additional structural deterioration occurs during aging, subtle neuropsychological decline may progress to clinically overt dementia earlier than in age-matched controls, a hypothesis to be assessed in future prospective trials. PMID:26052275

  10. Age-related shifts in brain activity dynamics during task switching.

    Science.gov (United States)

    Jimura, Koji; Braver, Todd S

    2010-06-01

    Cognitive aging studies have suggested that older adults show declines in both sustained and transient cognitive control processes. However, previous neuroimaging studies have primarily focused on age-related change in the magnitude, but not temporal dynamics, of brain activity. The present study compared brain activity dynamics in healthy old and young adults during task switching. A mixed blocked/event-related functional magnetic resonance imaging design enabled separation of transient and sustained neural activity associated with cognitive control. Relative to young adults, older adults exhibited not only decreased sustained activity in the anterior prefrontal cortex (aPFC) during task-switching blocks but also increased transient activity on task-switch trials. Another pattern of age-related shift in dynamics was present in the lateral PFC (lPFC) and posterior parietal cortex (PPC), with younger adults showing a cue-related response during task-switch trials in lPFC and PPC, whereas older adults exhibited switch-related activation during the cue period in PPC only. In all 3 regions, these qualitatively distinct patterns of brain activity predicted qualitatively distinct patterns of behavioral performance across the 2 age groups. Together, these results suggest that older adults may shift from a proactive to reactive cognitive control strategy as a means of retaining relatively preserved behavioral performance in the face of age-related neurocognitive changes. PMID:19805420

  11. Sildenafil enhances neurogenesis and oligodendrogenesis in ischemic brain of middle-aged mouse.

    Directory of Open Access Journals (Sweden)

    Rui Lan Zhang

    Full Text Available Adult neural stem cells give rise to neurons, oligodendrocytes and astrocytes. Aging reduces neural stem cells. Using an inducible nestin-CreER(T2/R26R-yellow fluorescent protein (YFP mouse, we investigated the effect of Sildenafil, a phosphodiesterase type 5 (PDE5 inhibitor, on nestin lineage neural stem cells and their progeny in the ischemic brain of the middle-aged mouse. We showed that focal cerebral ischemia induced nestin lineage neural stem cells in the subventricular zone (SVZ of the lateral ventricles and nestin expressing NeuN positive neurons and adenomatous polyposis coli (APC positive mature oligodendrocytes in the ischemic striatum and corpus callosum in the aged mouse. Treatment of the ischemic middle-aged mouse with Sildenafil increased nestin expressing neural stem cells, mature neurons, and oligodendrocytes by 33, 75, and 30%, respectively, in the ischemic brain. These data indicate that Sildenafil amplifies nestin expressing neural stem cells and their neuronal and oligodendrocyte progeny in the ischemic brain of the middle-aged mouse.

  12. Distinct Brain and Behavioral Benefits from Cognitive vs. Physical Training: A Randomized Trial in Aging Adults.

    Science.gov (United States)

    Chapman, Sandra B; Aslan, Sina; Spence, Jeffrey S; Keebler, Molly W; DeFina, Laura F; Didehbani, Nyaz; Perez, Alison M; Lu, Hanzhang; D'Esposito, Mark

    2016-01-01

    Insidious declines in normal aging are well-established. Emerging evidence suggests that non-pharmacological interventions, specifically cognitive and physical training, may counter diminishing age-related cognitive and brain functions. This randomized trial compared effects of two training protocols: cognitive training (CT) vs. physical training (PT) on cognition and brain function in adults 56-75 years. Sedentary participants (N = 36) were randomized to either CT or PT group for 3 h/week over 12 weeks. They were assessed at baseline-, mid-, and post-training using neurocognitive, MRI, and physiological measures. The CT group improved on executive function whereas PT group's memory was enhanced. Uniquely deploying cerebral blood flow (CBF) and cerebral vascular reactivity (CVR) MRI, the CT cohort showed increased CBF within the prefrontal and middle/posterior cingulate cortex (PCC) without change to CVR compared to PT group. Improvements in complex abstraction were positively associated with increased resting CBF in dorsal anterior cingulate cortex (dACC). Exercisers with higher CBF in hippocampi bilaterally showed better immediate memory. The preliminary evidence indicates that increased cognitive and physical activity improves brain health in distinct ways. Reasoning training enhanced frontal networks shown to be integral to top-down cognitive control and brain resilience. Evidence of increased resting CBF without changes to CVR implicates increased neural health rather than improved vascular response. Exercise did not improve cerebrovascular response, although CBF increased in hippocampi of those with memory gains. Distinct benefits incentivize testing effectiveness of combined protocols to strengthen brain health. PMID:27462210

  13. Distinct Brain and Behavioral Benefits from Cognitive vs. Physical Training: A Randomized Trial in Aging Adults

    Science.gov (United States)

    Chapman, Sandra B.; Aslan, Sina; Spence, Jeffrey S.; Keebler, Molly W.; DeFina, Laura F.; Didehbani, Nyaz; Perez, Alison M.; Lu, Hanzhang; D'Esposito, Mark

    2016-01-01

    Insidious declines in normal aging are well-established. Emerging evidence suggests that non-pharmacological interventions, specifically cognitive and physical training, may counter diminishing age-related cognitive and brain functions. This randomized trial compared effects of two training protocols: cognitive training (CT) vs. physical training (PT) on cognition and brain function in adults 56–75 years. Sedentary participants (N = 36) were randomized to either CT or PT group for 3 h/week over 12 weeks. They were assessed at baseline-, mid-, and post-training using neurocognitive, MRI, and physiological measures. The CT group improved on executive function whereas PT group's memory was enhanced. Uniquely deploying cerebral blood flow (CBF) and cerebral vascular reactivity (CVR) MRI, the CT cohort showed increased CBF within the prefrontal and middle/posterior cingulate cortex (PCC) without change to CVR compared to PT group. Improvements in complex abstraction were positively associated with increased resting CBF in dorsal anterior cingulate cortex (dACC). Exercisers with higher CBF in hippocampi bilaterally showed better immediate memory. The preliminary evidence indicates that increased cognitive and physical activity improves brain health in distinct ways. Reasoning training enhanced frontal networks shown to be integral to top-down cognitive control and brain resilience. Evidence of increased resting CBF without changes to CVR implicates increased neural health rather than improved vascular response. Exercise did not improve cerebrovascular response, although CBF increased in hippocampi of those with memory gains. Distinct benefits incentivize testing effectiveness of combined protocols to strengthen brain health. PMID:27462210

  14. Impairments of astrocytes are involved in the D-galactose-induced brain aging

    International Nuclear Information System (INIS)

    Astrocyte dysfunction is implicated in course of various age-related neurodegenerative diseases. Chronic injection of D-galactose can cause a progressive deterioration in learning and memory capacity and serve as an animal model of aging. To investigate the involvement of astrocytes in this model, oxidative stress biomarkers, biochemical and pathological changes of astrocytes were examined in the hippocampus of the rats with six weeks of D-galactose injection. D-galactose-injected rats displayed impaired antioxidant systems, an increase in nitric oxide levels, and a decrease in reduced glutathione levels. Consistently, western blotting and immunostaining of glial fibrillary acidic protein showed extensive activation of astrocytes. Double-immunofluorescent staining further showed activated astrocytes highly expressed inducible nitric oxide synthase. Electron microscopy demonstrated the degeneration of astrocytes, especially in the aggregated area of synapse and brain microvessels. These findings indicate that impairments of astrocytes are involved in oxidative stress-induced brain aging by chronic injection of D-galactose

  15. Structural and functional rejuvenation of the aged brain by an approved anti-asthmatic drug.

    Science.gov (United States)

    Marschallinger, Julia; Schäffner, Iris; Klein, Barbara; Gelfert, Renate; Rivera, Francisco J; Illes, Sebastian; Grassner, Lukas; Janssen, Maximilian; Rotheneichner, Peter; Schmuckermair, Claudia; Coras, Roland; Boccazzi, Marta; Chishty, Mansoor; Lagler, Florian B; Renic, Marija; Bauer, Hans-Christian; Singewald, Nicolas; Blümcke, Ingmar; Bogdahn, Ulrich; Couillard-Despres, Sebastien; Lie, D Chichung; Abbracchio, Maria P; Aigner, Ludwig

    2015-10-27

    As human life expectancy has improved rapidly in industrialized societies, age-related cognitive impairment presents an increasing challenge. Targeting histopathological processes that correlate with age-related cognitive declines, such as neuroinflammation, low levels of neurogenesis, disrupted blood-brain barrier and altered neuronal activity, might lead to structural and functional rejuvenation of the aged brain. Here we show that a 6-week treatment of young (4 months) and old (20 months) rats with montelukast, a marketed anti-asthmatic drug antagonizing leukotriene receptors, reduces neuroinflammation, elevates hippocampal neurogenesis and improves learning and memory in old animals. By using gene knockdown and knockout approaches, we demonstrate that the effect is mediated through inhibition of the GPR17 receptor. This work illustrates that inhibition of leukotriene receptor signalling might represent a safe and druggable target to restore cognitive functions in old individuals and paves the way for future clinical translation of leukotriene receptor inhibition for the treatment of dementias.

  16. Classification of normal and pathological aging processes based on brain MRI morphology measures

    Science.gov (United States)

    Perez-Gonzalez, J. L.; Yanez-Suarez, O.; Medina-Bañuelos, V.

    2014-03-01

    Reported studies describing normal and abnormal aging based on anatomical MRI analysis do not consider morphological brain changes, but only volumetric measures to distinguish among these processes. This work presents a classification scheme, based both on size and shape features extracted from brain volumes, to determine different aging stages: healthy control (HC) adults, mild cognitive impairment (MCI), and Alzheimer's disease (AD). Three support vector machines were optimized and validated for the pair-wise separation of these three classes, using selected features from a set of 3D discrete compactness measures and normalized volumes of several global and local anatomical structures. Our analysis show classification rates of up to 98.3% between HC and AD; of 85% between HC and MCI and of 93.3% for MCI and AD separation. These results outperform those reported in the literature and demonstrate the viability of the proposed morphological indexes to classify different aging stages.

  17. Early Shifts of Brain Metabolism by Caloric Restriction Preserve White Matter Integrity and Long-Term Memory in Aging Mice

    OpenAIRE

    Janet eGuo; Vikas eBakshi; Ai-Ling eLin

    2015-01-01

    Preservation of brain integrity with age is highly associated with lifespan determination. Caloric restriction (CR) has been shown to increase longevity and healthspan in various species; however, its effects on preserving living brain functions in aging remain largely unexplored. In the study, we used multimodal, non-invasive neuroimaging (PET/MRI/MRS) to determine in vivo brain glucose metabolism, energy metabolites, and white matter structural integrity in young and old mice fed with eithe...

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

    Institute of Scientific and Technical Information of China (English)

    Zhan-chi Zhang; Feng Luan; Chun-yan Xie; Dan-dan Geng; Yan-yong Wang; Jun Ma

    2015-01-01

    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 deifcits in learning-im-paired mice. However, the mechanisms by which this treatment improves these deifcits during normal aging are still unknown. Therefore, the current study investigated the effects of tran-scranial 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, syn-aptophysin and growth-associated protein 43 (both synaptic markers), to determine the possible mechanisms by which transcranial magnetic stimulation regulates cognitive capacity. Transcra-nial 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 hippo-campus 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 reg-ulation. These responses may change the structural plasticity of the aging hippocampus, thereby improving cognitive function.

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

    Science.gov (United States)

    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. PMID:27103520

  20. Dietary and behavioral interventions protect against age related activation of caspase cascades in the canine brain.

    Directory of Open Access Journals (Sweden)

    Shikha Snigdha

    Full Text Available Lifestyle interventions such as diet, exercise, and cognitive training represent a quietly emerging revolution in the modern approach to counteracting age-related declines in brain health. Previous studies in our laboratory have shown that long-term dietary supplementation with antioxidants and mitochondrial cofactors (AOX or behavioral enrichment with social, cognitive, and exercise components (ENR, can effectively improve cognitive performance and reduce brain pathology of aged canines, including oxidative damage and Aβ accumulation. In this study, we build on and extend our previous findings by investigating if the interventions reduce caspase activation and ceramide accumulation in the aged frontal cortex, since caspase activation and ceramide accumulation are common convergence points for oxidative damage and Aβ, among other factors associated with the aged and AD brain. Aged beagles were placed into one of four treatment groups: CON--control environment/control diet, AOX--control environment/antioxidant diet, ENR--enriched environment/control diet, AOX/ENR--enriched environment/antioxidant diet for 2.8 years. Following behavioral testing, brains were removed and frontal cortices were analyzed to monitor levels of active caspase 3, active caspase 9 and their respective cleavage products such as tau and semaphorin7a, and ceramides. Our results show that levels of activated caspase-3 were reduced by ENR and AOX interventions with the largest reduction occurring with combined AOX/ENR group. Further, reductions in caspase-3 correlated with reduced errors in a reversal learning task, which depends on frontal cortex function. In addition, animals treated with an AOX arm showed reduced numbers of cells expressing active caspase 9 or its cleavage product semaphorin 7A, while ENR (but not AOX reduced ceramide levels. Overall, these data demonstrate that lifestyle interventions curtail activation of pro-degenerative pathways to improve cellular

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Dietary and behavioral interventions protect against age related activation of caspase cascades in the canine brain.

    Science.gov (United States)

    Snigdha, Shikha; Berchtold, Nicole; Astarita, Giuseppe; Saing, Tommy; Piomelli, Daniele; Cotman, Carl W

    2011-01-01

    Lifestyle interventions such as diet, exercise, and cognitive training represent a quietly emerging revolution in the modern approach to counteracting age-related declines in brain health. Previous studies in our laboratory have shown that long-term dietary supplementation with antioxidants and mitochondrial cofactors (AOX) or behavioral enrichment with social, cognitive, and exercise components (ENR), can effectively improve cognitive performance and reduce brain pathology of aged canines, including oxidative damage and Aβ accumulation. In this study, we build on and extend our previous findings by investigating if the interventions reduce caspase activation and ceramide accumulation in the aged frontal cortex, since caspase activation and ceramide accumulation are common convergence points for oxidative damage and Aβ, among other factors associated with the aged and AD brain. Aged beagles were placed into one of four treatment groups: CON--control environment/control diet, AOX--control environment/antioxidant diet, ENR--enriched environment/control diet, AOX/ENR--enriched environment/antioxidant diet for 2.8 years. Following behavioral testing, brains were removed and frontal cortices were analyzed to monitor levels of active caspase 3, active caspase 9 and their respective cleavage products such as tau and semaphorin7a, and ceramides. Our results show that levels of activated caspase-3 were reduced by ENR and AOX interventions with the largest reduction occurring with combined AOX/ENR group. Further, reductions in caspase-3 correlated with reduced errors in a reversal learning task, which depends on frontal cortex function. In addition, animals treated with an AOX arm showed reduced numbers of cells expressing active caspase 9 or its cleavage product semaphorin 7A, while ENR (but not AOX) reduced ceramide levels. Overall, these data demonstrate that lifestyle interventions curtail activation of pro-degenerative pathways to improve cellular health and are the

  3. Association of amyloid burden, brain atrophy and memory deficits in aged apolipoprotein ε4 mice.

    Science.gov (United States)

    Yin, Junxiang; Turner, Gregory H; Coons, Stephen W; Maalouf, Marwan; Reiman, Eric M; Shi, Jiong

    2014-03-01

    Apolipoprotein E ε4 allele (ApoE4) has been associated with increased risk of sporadic Alzheimer's disease (AD) and of conversion from mild cognitive impairment to AD. But the underlying mechanism of ApoE4 affecting brain atrophy and cognition is not fully understood. We investigated the effect of ApoE4 on amyloid beta (Aβ) protein burden and its correlation with the structure change of hippocampus and cortex, cognitive and behavioral changes in ApoE4 transgenic mice. Male ApoE4 transgenic mice and age-matched control mice at age 12 months and 24 months were tested in the Morris Water Maze (MWM). Brain volume changes (including whole brain, hippocampus, cortex, total ventricles and caudate putamen) were assessed by using small animal 7T-MRI. Aβ level was assessed by immunohistochemistry (IHC) and immunoprecipitation/western blot. In MWM, escape latency was longer and time spent in the target quadrant was shorter in aged ApoE4 mice (12- and 24-month-old), suggesting age- and ApoE4-dependent visuospatial deficits. Atrophy on MRI was prominent in the hippocampus (p=0.039) and cortex (p=0.013) of ApoE4 mice (24-month-old) as compared to age-matched control mice. IHC revealed elevated Aβ deposition in the hippocampus. Consistently, both soluble and insoluble Aβ aggregates were increased in aged ApoE4 mice. This increase was correlated inversely with hippocampal atrophy and cognitive deficits. These data give further evidence that ApoE4 plays an important role in brain atrophy and memory impairment by modulating amyloid production and deposition.

  4. Brain Food for Alzheimer-Free Ageing: Focus on Herbal Medicines.

    Science.gov (United States)

    Hügel, Helmut M

    2015-01-01

    Healthy brain aging and the problems of dementia and Alzheimer's disease (AD) are a global concern. Beyond 60 years of age, most, if not everyone, will experience a decline in cognitive skills, memory capacity and changes in brain structure. Longevity eventually leads to an accumulation of amyloid plaques and/or tau tangles, including some vascular dementia damage. Therefore, lifestyle choices are paramount to leading either a brain-derived or a brain-deprived life. The focus of this review is to critically examine the evidence, impact, influence and mechanisms of natural products as chemopreventive agents which induce therapeutic outcomes that modulate the aggregation process of beta-amyloid (Aβ), providing measureable cognitive benefits in the aging process. Plants can be considered as chemical factories that manufacture huge numbers of diverse bioactive substances, many of which have the potential to provide substantial neuroprotective benefits. Medicinal herbs and health food supplements have been widely used in Asia since over 2,000 years. The phytochemicals utilized in traditional Chinese medicine have demonstrated safety profiles for human consumption. Many herbs with anti-amyloidogenic activity, including those containing polyphenolic constituents such as green tea, turmeric, Salvia miltiorrhiza, and Panax ginseng, are presented. Also covered in this review are extracts from kitchen spices including cinnamon, ginger, rosemary, sage, salvia herbs, Chinese celery and many others some of which are commonly used in herbal combinations and represent highly promising therapeutic natural compounds against AD. A number of clinical trials conducted on herbs to counter dementia and AD are discussed.

  5. Brain protein oxidation in age-related neurodegenerative disorders that are associated with aggregated proteins.

    Science.gov (United States)

    Butterfield, D A; Kanski, J

    2001-07-15

    Protein oxidation, one of a number of brain biomarkers of oxidative stress, is increased in several age-related neurodegenerative disorders or animal models thereof, including Alzheimer's disease, Huntington's disease, prion disorders, such as Creutzfeld-Jakob disease, and alpha-synuclein disorders, such as Parkinson's disease and frontotemporal dementia. Each of these neurodegenerative disorders is associated with aggregated proteins in brain. However, the relationship among protein oxidation, protein aggregation, and neurodegeneration remain unclear. The current rapid progress in elucidation of mechanisms of protein oxidation in neuronal loss should provide further insight into the importance of free radical oxidative stress in these neurodegenerative disorders.

  6. The Indirect Effect of Age Group on Switch Costs via Gray Matter Volume and Task-Related Brain Activity

    Science.gov (United States)

    Steffener, Jason; Gazes, Yunglin; Habeck, Christian; Stern, Yaakov

    2016-01-01

    Healthy aging simultaneously affects brain structure, brain function, and cognition. These effects are often investigated in isolation ignoring any relationships between them. It is plausible that age related declines in cognitive performance are the result of age-related structural and functional changes. This straightforward idea is tested in within a conceptual research model of cognitive aging. The current study tested whether age-related declines in task-performance were explained by age-related differences in brain structure and brain function using a task-switching paradigm in 175 participants. Sixty-three young and 112 old participants underwent MRI scanning of brain structure and brain activation. The experimental task was an executive context dual task with switch costs in response time as the behavioral measure. A serial mediation model was applied voxel-wise throughout the brain testing all pathways between age group, gray matter volume, brain activation and increased switch costs, worsening performance. There were widespread age group differences in gray matter volume and brain activation. Switch costs also significantly differed by age group. There were brain regions demonstrating significant indirect effects of age group on switch costs via the pathway through gray matter volume and brain activation. These were in the bilateral precuneus, bilateral parietal cortex, the left precentral gyrus, cerebellum, fusiform, and occipital cortices. There were also significant indirect effects via the brain activation pathway after controlling for gray matter volume. These effects were in the cerebellum, occipital cortex, left precentral gyrus, bilateral supramarginal, bilateral parietal, precuneus, middle cingulate extending to medial superior frontal gyri and the left middle frontal gyri. There were no significant effects through the gray matter volume alone pathway. These results demonstrate that a large proportion of the age group effect on switch costs can

  7. Environment as 'Brain Training': A review of geographical and physical environmental influences on cognitive ageing.

    Science.gov (United States)

    Cassarino, Marica; Setti, Annalisa

    2015-09-01

    Global ageing demographics coupled with increased urbanisation pose major challenges to the provision of optimal living environments for older persons, particularly in relation to cognitive health. Although animal studies emphasize the benefits of enriched environments for cognition, and brain training interventions have shown that maintaining or improving cognitive vitality in older age is possible, our knowledge of the characteristics of our physical environment which are protective for cognitive ageing is lacking. The present review analyses different environmental characteristics (e.g. urban vs. rural settings, presence of green) in relation to cognitive performance in ageing. Studies of direct and indirect associations between physical environment and cognitive performance are reviewed in order to describe the evidence that our living contexts constitute a measurable factor in determining cognitive ageing. PMID:26144974

  8. Fetal functional brain age assessed from universal developmental indices obtained from neuro-vegetative activity patterns.

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    Dirk Hoyer

    Full Text Available Fetal brain development involves the development of the neuro-vegetative (autonomic control that is mediated by the autonomic nervous system (ANS. Disturbances of the fetal brain development have implications for diseases in later postnatal life. In that context, the fetal functional brain age can be altered. Universal principles of developmental biology applied to patterns of autonomic control may allow a functional age assessment. The work aims at the development of a fetal autonomic brain age score (fABAS based on heart rate patterns. We analysed n = 113 recordings in quiet sleep, n = 286 in active sleep, and n = 29 in active awakeness from normals. We estimated fABAS from magnetocardiographic recordings (21.4-40.3 weeks of gestation preclassified in quiet sleep (n = 113, 63 females and active sleep (n = 286, 145 females state by cross-validated multivariate linear regression models in a cross-sectional study. According to universal system developmental principles, we included indices that address increasing fluctuation range, increasing complexity, and pattern formation (skewness, power spectral ratio VLF/LF, pNN5. The resulting models constituted fABAS. fABAS explained 66/63% (coefficient of determination R(2 of training and validation set of the variance by age in quiet, while 51/50% in active sleep. By means of a logistic regression model using fluctuation range and fetal age, quiet and active sleep were automatically reclassified (94.3/93.1% correct classifications. We did not find relevant gender differences. We conclude that functional brain age can be assessed based on universal developmental indices obtained from autonomic control patterns. fABAS reflect normal complex functional brain maturation. The presented normative data are supplemented by an explorative study of 19 fetuses compromised by intrauterine growth restriction. We observed a shift in the state distribution towards active awakeness. The lower WGA

  9. Brain

    Science.gov (United States)

    ... will return after updating. Resources Archived Modules Updates Brain Cerebrum The cerebrum is the part of the ... the outside of the brain and spinal cord. Brain Stem The brain stem is the part of ...

  10. Childhood cognitive ability accounts for associations between cognitive ability and brain cortical thickness in old age.

    Science.gov (United States)

    Karama, S; Bastin, M E; Murray, C; Royle, N A; Penke, L; Muñoz Maniega, S; Gow, A J; Corley, J; Valdés Hernández, M del C; Lewis, J D; Rousseau, M-É; Lepage, C; Fonov, V; Collins, D L; Booth, T; Rioux, P; Sherif, T; Adalat, R; Starr, J M; Evans, A C; Wardlaw, J M; Deary, I J

    2014-05-01

    Associations between brain cortical tissue volume and cognitive function in old age are frequently interpreted as suggesting that preservation of cortical tissue is the foundation of successful cognitive aging. However, this association could also, in part, reflect a lifelong association between cognitive ability and cortical tissue. We analyzed data on 588 subjects from the Lothian Birth Cohort 1936 who had intelligence quotient (IQ) scores from the same cognitive test available at both 11 and 70 years of age as well as high-resolution brain magnetic resonance imaging data obtained at approximately 73 years of age. Cortical thickness was estimated at 81 924 sampling points across the cortex for each subject using an automated pipeline. Multiple regression was used to assess associations between cortical thickness and the IQ measures at 11 and 70 years. Childhood IQ accounted for more than two-third of the association between IQ at 70 years and cortical thickness measured at age 73 years. This warns against ascribing a causal interpretation to the association between cognitive ability and cortical tissue in old age based on assumptions about, and exclusive reference to, the aging process and any associated disease. Without early-life measures of cognitive ability, it would have been tempting to conclude that preservation of cortical thickness in old age is a foundation for successful cognitive aging when, instead, it is a lifelong association. This being said, results should not be construed as meaning that all studies on aging require direct measures of childhood IQ, but as suggesting that proxy measures of prior cognitive function can be useful to take into consideration.

  11. New neurons in aging brains: molecular control by small non-coding RNAs

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    Marijn eSchouten

    2012-02-01

    Full Text Available Adult neurogenesis is a process that continues in the adult and also aging brain. It generates functional neurons from neural stem cells present in specific brain regions. This phenomenon is largely confined to two main regions: the subventricular zone of the lateral ventricle, and the subgranular zone of the dentate gyrus, in the hippocampus. With age, the hippocampus and particularly the dentate gyrus are affected. For instance, adult neurogenesis is decreased with aging, in both the number of proliferating cells as well as their neuronal differentiation, while in parallel an age-associated decline in cognitive performance is often seen. Surprisingly, the synaptogenic potential of adult-born neurons appears unaffected by aging. Therefore, although proliferation, differentiation, survival and synaptogenesis of adult-born new neurons in the dentate gyrus are closely related to each other, they appear differentially regulated with aging. In this review we discuss the crucial role of a novel class of recently discovered regulators of gene expression, i.e. the small non-coding RNAs, in the development of adult neurogenesis from neural stem cells to functionally integrated neurons. In particular, a subgroup of the small non-coding RNAs, the microRNAs, fine-tune many events during adult neurogenesis progression. Moreover, multiple small non-coding RNAs are differentially expressed in the aged hippocampus. This makes small non-coding RNAs appealing candidates to orchestrate, and possibly correct or prevent, the functional alterations in adult neurogenesis and cognition associated with aging. Finally, we briefly summarize observations that link changes in circulating levels of steroid hormones with alterations in adult neurogenesis and subsequent vulnerability to psychopathology in advanced age, and discuss a possible role of microRNAs in stress-associated alterations in adult neurogenesis during aging.

  12. Positron emission tomography studies in the normal and abnormal ageing of human brain

    International Nuclear Information System (INIS)

    Until recently, the investigation of the neurophysiological correlates of normal and abnormal ageing of the human brain was limited by methodological constraints, as the technics available provided only a few parameters (e.g. electroencephalograms, cerebral blood flow) monitored in superficial brain structures in a grossly regional and poorly quantitative way. Lately several non invasive techniques have been developed which allow to investigate in vivo both quantitatively and on local basis a number of previously inaccessible important aspects of brain function. Among these techniques, such as single photon emission tomography imaging of computerized electric events, nuclear magnetic resonance, positron emission tomography stands out as the most powerful and promising method since it allows the in vivo measurement of biochemical and pharmacological parameters

  13. Brain FDG PET study of normal aging in Japanese: effect of atrophy correction

    International Nuclear Information System (INIS)

    The aim of this study was to investigate the effects of atrophy correction on the results of 18F-fluorodeoxyglucose positron emission tomography (FDG PET) in the context of normal aging. Before the human study was performed, a Hoffman 3D brain phantom experiment was carried out in order to validate a newly developed correction method for partial volume effects (PVEs). Brain FDG PET was then performed in 139 healthy Japanese volunteers (71 men, 68 women; age 24-81 years). PET images were corrected for PVEs using grey matter volume, which was segmented from co-registered magnetic resonance images and convoluted with the spatial resolution of the PET scanner. We investigated the correlation between advancing age and relative regional FDG activity, which was normalised to the global activity before and after PVE correction using Statistical Parametric Mapping 99. The PET image, when corrected for PVEs, provided more homogeneous tracer distribution in the whole phantom than in the original PET image. The human PET study of both sexes revealed significant negative correlations between age and relative FDG activity in the bilateral perisylvian and medial frontal areas before PVE correction. However, these negative correlations were largely resolved after PVE correction. Correction for PVEs was effective in our FDG PET study. The reduction in FDG uptake with advancing age that was detected by FDG PET without PVE correction could be accounted for largely by an age-related cerebral volume loss in the bilateral perisylvian and medial frontal areas. (orig.)

  14. Computed tomographic features of the feline brain change with advancing age?

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    Viviam R. Babicsak

    2015-12-01

    Full Text Available Abstract: A better understanding of normal or expected encephalic changes with increasing age in cats is needed as a growing number of these animals is attended in veterinary clinics, and imaging data referring to normal age-associated changes are extremely scarce in the literature. The objective of this study was to identify age-related changes in feline brain using CT imaging. Fifteen non-brachycephalic healthy cats with age between 1 to 6 years (adult group and others over 12 years (geriatric group were submitted to CT scan of the brain. Statistically significant differences were found between the groups for the ability to identify the left lateral ventricle and for falx cerebri calcification, both identified in a greater number of cats of the geriatric group. A significantly higher mean width of the third ventricle was also detected in geriatric animals. There were no statistically significant differences between lateral ventricular dimensions and encephalic parenchymal attenuation on pre and post-contrast CT phases. The results of the present study show an increase in the incidence of falx cerebri calcification and a third ventricular dilatation with advancing age in cats. Future researches using MRI scanners and a greater quantity of cats are needed in order to identify supplementary age-related changes.

  15. Shaping the aging brain: Role of auditory input patterns in the emergence of auditory cortical impairments

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    Brishna Soraya Kamal

    2013-09-01

    Full Text Available Age-related impairments in the primary auditory cortex (A1 include poor tuning selectivity, neural desynchronization and degraded responses to low-probability sounds. These changes have been largely attributed to reduced inhibition in the aged brain, and are thought to contribute to substantial hearing impairment in both humans and animals. Since many of these changes can be partially reversed with auditory training, it has been speculated that they might not be purely degenerative, but might rather represent negative plastic adjustments to noisy or distorted auditory signals reaching the brain. To test this hypothesis, we examined the impact of exposing young adult rats to 8 weeks of low-grade broadband noise on several aspects of A1 function and structure. We then characterized the same A1 elements in aging rats for comparison. We found that the impact of noise exposure on A1 tuning selectivity, temporal processing of auditory signal and responses to oddball tones was almost indistinguishable from the effect of natural aging. Moreover, noise exposure resulted in a reduction in the population of parvalbumin inhibitory interneurons and cortical myelin as previously documented in the aged group. Most of these changes reversed after returning the rats to a quiet environment. These results support the hypothesis that age-related changes in A1 have a strong activity-dependent component and indicate that the presence or absence of clear auditory input patterns might be a key factor in sustaining adult A1 function.

  16. Age-dependent changes in lipid peroxide levels in peripheral organs, but not in brain, in senescence-accelerated mice.

    Science.gov (United States)

    Matsugo, S; Kitagawa, T; Minami, S; Esashi, Y; Oomura, Y; Tokumaru, S; Kojo, S; Matsushima, K; Sasaki, K

    2000-01-01

    The tissue concentration of lipid peroxides was determined in the brain, heart, liver, lung and kidney of accelerated senescence-prone (SAMP-8) and -resistant (SAMR-1) mice at 3, 6 and 9 months of age by a method involving chemical derivatization and high performance liquid chromatography. The level of lipid peroxides in the brain did not show an age-dependent change, but at each age the brain level of lipid peroxides was significantly higher in SAMP-8 than in SAMR-1. In contrast, the lipid peroxide levels in the peripheral organs showed increases with aging in both strains, and they were significantly higher in SAMP-8 than in SAMR-1 at both 3 and 6 months of age (except at 3 months of age in the kidney). These results suggest that increased oxidative stress in the brain and peripheral organs is a cause of the senescence-related degeneration and impairments seen in SAMP-8. PMID:10643812

  17. Age-Related Loss of Brain Volume and T2 Relaxation Time in Youth With Type 1 Diabetes

    OpenAIRE

    Pell, Gaby S; Lin, Ashleigh; Wellard, R. Mark; Werther, George A.; Cameron, Fergus J.; Finch, Sue J.; Papoutsis, Jennifer; Northam, Elisabeth A.

    2012-01-01

    OBJECTIVE—2 Childhood-onset type 1 diabetes is associated with neurocognitive deficits, but there is limited evidence to date regarding associated neuroanatomical brain changes and their relationship to illness variables such as age at disease onset. This report examines age-related changes in volume and T2 relaxation time (a fundamental parameter of magnetic resonance imaging that reflects tissue health) across the whole brain. RESEARCH DESIGN AND METHODS— Type 1 diabetes, N = 79 (mean age 2...

  18. Problems of radiotherapy on the brain tumors in children less than two years of age

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    Miyagami, Mitsusuke; Tsubokawa, Takashi (Nihon Univ., Tokyo (Japan). School of Medicine); Nishimoto, Hiroshi; Ueno, Yuhichi

    1990-06-01

    Impaired growth and mental or developmental disturbance due to radiotherapy for 10 cases of brain tumors in the children ages less than 2 years old were evaluated. Six cases of brain tumor which did not involve the hypothalamic-pituitary axis, were followed more than 2 years after cranial or craniospinal irradiation. Four cases irradiated greater than 2900 rad to the whole brain all revealed markedly lower body heights than -2 SD of the medium. Growth impairment was found to be progressive over time, and markedly evident after 2 years following cranial or craniospinal radiotherapy. Somatomedin C in the blood was measured in 8 cases of brain tumors in childhood receiving radiotherapy. The measurement of Somatomedin C showed markedly low values measuring 0.19 to 0.54 U/ml (medium; 0.36 U/ml) in children having lower body height than -2 SD. Mental retardation or developmental disturbances were found in IQ or DQ tests in all of 5 infants or children younger than 2 years with brain tumors who got radiotherapy over 2900 rad to the whole brain. A case of craniopharyngioma, which had 5400 rad for tumor localization at the hypothalamus-pituitary axis and showed markedly low height, was given growth hormone and grew to normal height without distinct side effects. It was suggested that radiotherapy for brain tumors in infants or children should have special care in deciding the dose, field and time of radiation. If low height due to radiotherapy results, growth hormone therapy should be used for its treatment in childhood. (author).

  19. A review of cardiorespiratory fitness-related neuroplasticity in the aging brain

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    Scott M Hayes

    2013-07-01

    Full Text Available The literature examining the relationship between cardiorespiratory fitness and the brain in older adults has increased rapidly, with 30 of 34 studies published since 2008. Here we review cross-sectional and exercise intervention studies in older adults examining the relationship between cardiorespiratory fitness and brain structure and function, typically assessed using Magnetic Resonance Imaging (MRI. Studies of patients with Alzheimer’s disease are discussed when available. The structural MRI studies revealed a consistent positive relationship between cardiorespiratory fitness and brain volume in cortical regions including anterior cingulate, lateral prefrontal, and lateral parietal cortex. Support for a positive relationship between cardiorespiratory fitness and medial temporal lobe volume was less consistent, although evident when a region-of-interest approach was implemented. In fMRI studies, cardiorespiratory fitness in older adults was associated with activation in similar regions as those identified in the structural studies, including anterior cingulate, lateral prefrontal, and lateral parietal cortex, despite heterogeneity among the functional tasks implemented. This comprehensive review highlights the overlap in brain regions showing a positive relationship with cardiorespiratory fitness in both structural and functional imaging modalities. The findings suggest that aerobic exercise and cardiorespiratory fitness contribute to healthy brain aging, although additional studies in Alzheimer’s disease are needed.

  20. Exercise-related changes of networks in aging and mild cognitive impairment brain

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    Pei eHuang

    2016-03-01

    Full Text Available Aging and mild cognitive impairment are accompanied by decline of cognitive functions. Meanwhile, the most common form of dementia is Alzheimer’s disease, which is characterized by loss of memory and other intellectual abilities serious to make difficulties for patients in their daily life. Mild cognitive impairment is a transition period between normal aging and dementia, which has been used for early detection of emerging dementia. It converts to dementia with an annual rate of 5-15% as compared to normal aging with 1% rate. Small decreases in the conversion rate of mild cognitive impairment to Alzheimer’s disease might significantly reduce the prevalence of dementia. Thus, it is important to intervene at the preclinical stage. Since there are still no effective drugs to treat Alzheimer’s disease, non-drug intervention is crucial for the prevention and treatment of cognitive decline in aging and mild cognitive impairment populations. Previous studies have found some cognitive brain networks disrupted in aging and mild cognitive impairment population, and physical exercise could effectively remediate the function of these brain networks. Understanding the exercise-related mechanisms is crucial to design efficient and effective physical exercise programs for treatment/intervention of cognitive decline. In this review, we provide an overview of the neuroimaging studies on physical training in normal aging and mild cognitive impairment to identify the potential mechanisms underlying current physical training procedures. Studies of functional magnetic resonance imaging, electroencephalography, magnetoencephalography and positron emission tomography on brain networks were all included. Based on our review, the default mode network, fronto-parietal network and fronto-executive network are probably the three most valuable targets for efficiency evaluation of interventions.

  1. Brain volumetric and microstructural correlates of executive and motor performance in aged rhesus monkeys

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    Aadhavi eSridharan

    2012-11-01

    Full Text Available The aged rhesus macaque exhibits brain atrophy and behavioral deficits similar to normal aging in humans. Here we studied the association between cognitive and motor performance and anatomic and microstructural brain integrity measured with 3T magnetic resonance imaging in aged monkeys. About half of these animals were maintained on moderate calorie restriction, the only intervention shown to delay the aging process in lower animals. T1-weighted anatomic and diffusion tensor images were used to obtain gray matter volume, and fractional anisotropy and mean diffusivity, respectively. We tested the extent to which brain health indexed by gray matter volume, fractional anisotropy, and mean diffusivity were related to executive and motor function, and determined the effect of the dietary intervention on this relationship. We hypothesized that fewer errors on the executive function test and faster motor times would be correlated with higher volume, higher fractional anisotropy, and lower mean diffusivity in frontal areas that mediate executive function, and in motor, premotor, subcortical, and cerebellar areas underlying goal-directed motor behaviors. Higher error percentage on a cognitive conceptual shift task was significantly associated with lower gray matter volume in frontal and parietal cortices, and lower fractional anisotropy in major association fiber bundles. Similarly, slower performance time on the motor task was significantly correlated with lower volumetric measures in cortical, subcortical, and cerebellar areas and decreased fractional anisotropy in several major association fiber bundles. Notably, performance during the acquisition phase of the hardest level of the motor task was significantly associated with anterior mesial temporal lobe volume. Finally, these brain-behavior correlations for the motor task were attenuated in calorie restricted animals compared to controls, indicating a potential protective effect of the dietary

  2. Decreased Brain Levels of Vitamin B12 in Aging, Autism and Schizophrenia.

    Science.gov (United States)

    Zhang, Yiting; Hodgson, Nathaniel W; Trivedi, Malav S; Abdolmaleky, Hamid M; Fournier, Margot; Cuenod, Michel; Do, Kim Quang; Deth, Richard C

    2016-01-01

    Many studies indicate a crucial role for the vitamin B12 and folate-dependent enzyme methionine synthase (MS) in brain development and function, but vitamin B12 status in the brain across the lifespan has not been previously investigated. Vitamin B12 (cobalamin, Cbl) exists in multiple forms, including methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl), serving as cofactors for MS and methylmalonylCoA mutase, respectively. We measured levels of five Cbl species in postmortem human frontal cortex of 43 control subjects, from 19 weeks of fetal development through 80 years of age, and 12 autistic and 9 schizophrenic subjects. Total Cbl was significantly lower in older control subjects (> 60 yrs of age), primarily reflecting a >10-fold age-dependent decline in the level of MeCbl. Levels of inactive cyanocobalamin (CNCbl) were remarkably higher in fetal brain samples. In both autistic and schizophrenic subjects MeCbl and AdoCbl levels were more than 3-fold lower than age-matched controls. In autistic subjects lower MeCbl was associated with decreased MS activity and elevated levels of its substrate homocysteine (HCY). Low levels of the antioxidant glutathione (GSH) have been linked to both autism and schizophrenia, and both total Cbl and MeCbl levels were decreased in glutamate-cysteine ligase modulatory subunit knockout (GCLM-KO) mice, which exhibit low GSH levels. Thus our findings reveal a previously unrecognized decrease in brain vitamin B12 status across the lifespan that may reflect an adaptation to increasing antioxidant demand, while accelerated deficits due to GSH deficiency may contribute to neurodevelopmental and neuropsychiatric disorders.

  3. Dissociable circuits for visual shape learning in the young and aging human brain

    OpenAIRE

    Mayhew, Stephen D.; Kourtzi, Zoe

    2013-01-01

    Recognizing objects in cluttered scenes is vital for successful interactions in our complex environments. Learning is known to play a key role in facilitating performance in a wide range of perceptual skills not only in young but also older adults. However, the neural mechanisms that support our ability to improve visual form recognition with training in older age remain largely unknown. Here, we combine behavioral and fMRI measurements to identify the brain circuits involved in the learning ...

  4. Decreased Brain Levels of Vitamin B12 in Aging, Autism and Schizophrenia.

    Directory of Open Access Journals (Sweden)

    Yiting Zhang

    Full Text Available Many studies indicate a crucial role for the vitamin B12 and folate-dependent enzyme methionine synthase (MS in brain development and function, but vitamin B12 status in the brain across the lifespan has not been previously investigated. Vitamin B12 (cobalamin, Cbl exists in multiple forms, including methylcobalamin (MeCbl and adenosylcobalamin (AdoCbl, serving as cofactors for MS and methylmalonylCoA mutase, respectively. We measured levels of five Cbl species in postmortem human frontal cortex of 43 control subjects, from 19 weeks of fetal development through 80 years of age, and 12 autistic and 9 schizophrenic subjects. Total Cbl was significantly lower in older control subjects (> 60 yrs of age, primarily reflecting a >10-fold age-dependent decline in the level of MeCbl. Levels of inactive cyanocobalamin (CNCbl were remarkably higher in fetal brain samples. In both autistic and schizophrenic subjects MeCbl and AdoCbl levels were more than 3-fold lower than age-matched controls. In autistic subjects lower MeCbl was associated with decreased MS activity and elevated levels of its substrate homocysteine (HCY. Low levels of the antioxidant glutathione (GSH have been linked to both autism and schizophrenia, and both total Cbl and MeCbl levels were decreased in glutamate-cysteine ligase modulatory subunit knockout (GCLM-KO mice, which exhibit low GSH levels. Thus our findings reveal a previously unrecognized decrease in brain vitamin B12 status across the lifespan that may reflect an adaptation to increasing antioxidant demand, while accelerated deficits due to GSH deficiency may contribute to neurodevelopmental and neuropsychiatric disorders.

  5. Age-Dependent Effects of Haptoglobin Deletion in Neurobehavioral and Anatomical Outcomes Following Traumatic Brain Injury

    Science.gov (United States)

    Glushakov, Alexander V.; Arias, Rodrigo A.; Tolosano, Emanuela; Doré, Sylvain

    2016-01-01

    Cerebral hemorrhages are common features of traumatic brain injury (TBI) and their presence is associated with chronic disabilities. Recent clinical and experimental evidence suggests that haptoglobin (Hp), an endogenous hemoglobin-binding protein most abundant in blood plasma, is involved in the intrinsic molecular defensive mechanism, though its role in TBI is poorly understood. The aim of this study was to investigate the effects of Hp deletion on the anatomical and behavioral outcomes in the controlled cortical impact model using wildtype (WT) C57BL/6 mice and genetically modified mice lacking the Hp gene (Hp−∕−) in two age cohorts [2–4 mo-old (young adult) and 7–8 mo-old (older adult)]. The data obtained suggest age-dependent significant effects on behavioral and anatomical TBI outcomes and recovery from injury. Moreover, in the adult cohort, neurological deficits in Hp−∕− mice at 24 h were significantly improved compared to WT, whereas there were no significant differences in brain pathology between these genotypes. In contrast, in the older adult cohort, Hp−∕− mice had significantly larger lesion volumes compared to WT, but neurological deficits were not significantly different. Immunohistochemistry for ionized calcium-binding adapter molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP) revealed significant differences in microglial and astrocytic reactivity between Hp−∕− and WT in selected brain regions of the adult but not the older adult-aged cohort. In conclusion, the data obtained in the study provide clarification on the age-dependent aspects of the intrinsic defensive mechanisms involving Hp that might be involved in complex pathways differentially affecting acute brain trauma outcomes. PMID:27486583

  6. Effects of age and underlying brain dysfunction on the postictal state

    OpenAIRE

    Theodore, William H

    2010-01-01

    There is relatively little information on the underlying parameters that affect clinical features of the postictal period. Age-related physiological changes, including alterations in cerebral blood flow and metabolism, neurotransmitter function, and responses of the brain to seizure activity may affect postictal clinical phenomena. Some conclusions can be drawn. Elderly adults and children, particularly in the presence of diffuse cerebral dysfunction, may have more prolonged postictal confusi...

  7. Gut Microbiota: A Modulator of Brain Plasticity and Cognitive Function in Ageing

    Science.gov (United States)

    Leung, Katherine; Thuret, Sandrine

    2015-01-01

    Gut microbiota have recently been a topic of great interest in the field of microbiology, particularly their role in normal physiology and its influence on human health in disease. A large body of research has supported the presence of a pathway of communication between the gut and the brain, modulated by gut microbiota, giving rise to the term “microbiota-gut-brain” axis. It is now thought that, through this pathway, microbiota can affect behaviour and modulate brain plasticity and cognitive function in ageing. This review summarizes the evidence supporting the existence of such a connection and possible mechanisms of action whereby microbiota can influence the function of the central nervous system. Since normalisation of gut flora has been shown to prevent changes in behaviour, we further postulate on possible therapeutic targets to intervene with cognitive decline in ageing. The research poses various limitations, for example uncertainty about how this data translates to broad human populations. Nonetheless, the microbiota-gut-brain axis is an exciting field worthy of further investigation, particularly with regards to its implications on the ageing population.

  8. Gut Microbiota: A Modulator of Brain Plasticity and Cognitive Function in Ageing

    Directory of Open Access Journals (Sweden)

    Katherine Leung

    2015-09-01

    Full Text Available Gut microbiota have recently been a topic of great interest in the field of microbiology, particularly their role in normal physiology and its influence on human health in disease. A large body of research has supported the presence of a pathway of communication between the gut and the brain, modulated by gut microbiota, giving rise to the term “microbiota-gut-brain” axis. It is now thought that, through this pathway, microbiota can affect behaviour and modulate brain plasticity and cognitive function in ageing. This review summarizes the evidence supporting the existence of such a connection and possible mechanisms of action whereby microbiota can influence the function of the central nervous system. Since normalisation of gut flora has been shown to prevent changes in behaviour, we further postulate on possible therapeutic targets to intervene with cognitive decline in ageing. The research poses various limitations, for example uncertainty about how this data translates to broad human populations. Nonetheless, the microbiota-gut-brain axis is an exciting field worthy of further investigation, particularly with regards to its implications on the ageing population.

  9. Age of language learning shapes brain structure: a cortical thickness study of bilingual and monolingual individuals.

    Science.gov (United States)

    Klein, Denise; Mok, Kelvin; Chen, Jen-Kai; Watkins, Kate E

    2014-04-01

    We examined the effects of learning a second language (L2) on brain structure. Cortical thickness was measured in the MRI datasets of 22 monolinguals and 66 bilinguals. Some bilingual subjects had learned both languages simultaneously (0-3 years) while some had learned their L2 after achieving proficiency in their first language during either early (4-7 years) or late childhood (8-13 years). Later acquisition of L2 was associated with significantly thicker cortex in the left inferior frontal gyrus (IFG) and thinner cortex in the right IFG. These effects were seen in the group comparisons of monolinguals, simultaneous bilinguals and early and late bilinguals. Within the bilingual group, significant correlations between age of acquisition of L2 and cortical thickness were seen in the same regions: cortical thickness correlated with age of acquisition positively in the left IFG and negatively in the right IFG. Interestingly, the monolinguals and simultaneous bilinguals did not differ in cortical thickness in any region. Our results show that learning a second language after gaining proficiency in the first language modifies brain structure in an age-dependent manner whereas simultaneous acquisition of two languages has no additional effect on brain development. PMID:23819901

  10. Brain Aging and AD-Like Pathology in Streptozotocin-Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Jian-Qin Wang

    2014-01-01

    Full Text Available Objective. Numerous epidemiological studies have linked diabetes mellitus (DM with an increased risk of developing Alzheimer’s disease (AD. However, whether or not diabetic encephalopathy shows AD-like pathology remains unclear. Research Design and Methods. Forebrain and hippocampal volumes were measured using stereology in serial coronal sections of the brain in streptozotocin- (STZ- induced rats. Neurodegeneration in the frontal cortex, hypothalamus, and hippocampus was evaluated using Fluoro-Jade C (FJC. Aβ aggregation in the frontal cortex and hippocampus was tested using immunohistochemistry and ELISA. Dendritic spine density in the frontal cortex and hippocampus was measured using Golgi staining, and western blot was conducted to detect the levels of synaptophysin. Cognitive ability was evaluated through the Morris water maze and inhibitory avoidant box. Results. Rats are characterized by insulin deficiency accompanied with polydipsia, polyphagia, polyuria, and weight loss after STZ injection. The number of FJC-positive cells significantly increased in discrete brain regions of the diabetic rats compared with the age-matched control rats. Hippocampal atrophy, Aβ aggregation, and synapse loss were observed in the diabetic rats compared with the control rats. The learning and memory of the diabetic rats decreased compared with those of the age-matched control rats. Conclusions. Our results suggested that aberrant metabolism induced brain aging as characterized by AD-like pathologies.

  11. Age of language learning shapes brain structure: a cortical thickness study of bilingual and monolingual individuals.

    Science.gov (United States)

    Klein, Denise; Mok, Kelvin; Chen, Jen-Kai; Watkins, Kate E

    2014-04-01

    We examined the effects of learning a second language (L2) on brain structure. Cortical thickness was measured in the MRI datasets of 22 monolinguals and 66 bilinguals. Some bilingual subjects had learned both languages simultaneously (0-3 years) while some had learned their L2 after achieving proficiency in their first language during either early (4-7 years) or late childhood (8-13 years). Later acquisition of L2 was associated with significantly thicker cortex in the left inferior frontal gyrus (IFG) and thinner cortex in the right IFG. These effects were seen in the group comparisons of monolinguals, simultaneous bilinguals and early and late bilinguals. Within the bilingual group, significant correlations between age of acquisition of L2 and cortical thickness were seen in the same regions: cortical thickness correlated with age of acquisition positively in the left IFG and negatively in the right IFG. Interestingly, the monolinguals and simultaneous bilinguals did not differ in cortical thickness in any region. Our results show that learning a second language after gaining proficiency in the first language modifies brain structure in an age-dependent manner whereas simultaneous acquisition of two languages has no additional effect on brain development.

  12. Age-related degeneration of the fornix in the human brain: a diffusion tensor imaging study.

    Science.gov (United States)

    Jang, Sung Ho; Cho, Sang-Hyun; Chang, Min Cheol

    2011-02-01

    As a part of the Papez circuit, the fornix carries information on episodic memory. Several diffusion tensor imaging (DTI) studies have reported on changes in the fornix that occur with aging; however, these studies have been controversial. Using DTI, we attempted to investigate age-related changes of the fornix in the human brain. Sixty subjects (30 males, 30 females; mean age, 49.2 years; range, 20-78 years) were recruited. We categorized subjects into three groups, including young (20-39 years), middle-aged (40-59 years), and older (60-79 years) adults. DTIs were acquired using a sensitivity-encoding head coil on a 1.5 T. We divided the whole fornix into three parts (column, body, and crus) and constructed tractography for each part. We measured fractional anisotropy (FA), apparent diffusion coefficient (ADC), and tract number for each part of the fornix. In all three parts of the fornix, the FA value and tract number decreased, whereas ADC value increased with aging. In addition, a linear regression model was fitted to all three DTI parameters in each part of the fornix. Degenerative change of the fornix in the human brain appears to have occurred at a near constant rate from the 20s to the30s throughout the lifespan. PMID:21062216

  13. The Effect of the APOE Genotype on Individual BrainAGE in Normal Aging, Mild Cognitive Impairment, and Alzheimer’s Disease

    Science.gov (United States)

    Gaser, Christian; Franke, Katja

    2016-01-01

    In our aging society, diseases in the elderly come more and more into focus. An important issue in research is Mild Cognitive Impairment (MCI) and Alzheimer’s Disease (AD) with their causes, diagnosis, treatment, and disease prediction. We applied the Brain Age Gap Estimation (BrainAGE) method to examine the impact of the Apolipoprotein E (APOE) genotype on structural brain aging, utilizing longitudinal magnetic resonance image (MRI) data of 405 subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. We tested for differences in neuroanatomical aging between carrier and non-carrier of APOE ε4 within the diagnostic groups and for longitudinal changes in individual brain aging during about three years follow-up. We further examined whether a combination of BrainAGE and APOE status could improve prediction accuracy of conversion to AD in MCI patients. The influence of the APOE status on conversion from MCI to AD was analyzed within all allelic subgroups as well as for ε4 carriers and non-carriers. The BrainAGE scores differed significantly between normal controls, stable MCI (sMCI) and progressive MCI (pMCI) as well as AD patients. Differences in BrainAGE changing rates over time were observed for APOE ε4 carrier status as well as in the pMCI and AD groups. At baseline and during follow-up, BrainAGE scores correlated significantly with neuropsychological test scores in APOE ε4 carriers and non-carriers, especially in pMCI and AD patients. Prediction of conversion was most accurate using the BrainAGE score as compared to neuropsychological test scores, even when the patient’s APOE status was unknown. For assessing the individual risk of coming down with AD as well as predicting conversion from MCI to AD, the BrainAGE method proves to be a useful and accurate tool even if the information of the patient’s APOE status is missing. PMID:27410431

  14. Late-life brain volume: a life-course approach. The AGES-Reykjavik study.

    Science.gov (United States)

    Muller, Majon; Sigurdsson, Sigurdur; Kjartansson, Olafur; Gunnarsdottir, Ingibjorg; Thorsdottir, Inga; Harris, Tamara B; van Buchem, Mark; Gudnason, Vilmundur; Launer, Lenore J

    2016-05-01

    The "fetal-origins-of-adult-disease" hypothesis proposes that an unfavorable intrauterine environment, estimated from small birth size, may induce permanent changes in fetal organs, including the brain. These changes in combination with effects of (cardiovascular) exposures during adult life may condition the later risk of brain atrophy. We investigated the combined effect of small birth size and mid-life cardiovascular risk on late-life brain volumes. Archived birth records of weight and height were abstracted for 1348 participants of the age, gene/environment susceptibility-Reykjavik study (RS; 2002-2006) population-based cohort, who participated in the original cohort of the RS (baseline 1967). Mid-life cardiovascular risk factors (CVRF) were collected in the RS. As a part of the late-life age, gene/environment susceptibility-RS examination, a brain magnetic resonance imaging was acquired and from it, volumes of total brain, gray matter, white matter, and white matter lesions were estimated. Adjusting for intracranial volume, demographics, and education showed small birth size (low ponderal index [PI]) and increased mid-life cardiovascular risk had an additive effect on having smaller late-life brain volumes. Compared with the reference group (high PI/absence of mid-life CVRF), participants with lower PI/presence of mid-life CVRF (body mass index >25 kg/m(2), hypertension, diabetes, "ever smokers") had smaller total brain volume later in life; B (95% confidence interval) were -10.9 mL (-21.0 to -0.9), -10.9 mL (-20.4 to -1.4), -20.9 mL (-46.9 to 5.2), and -10.8 mL (-19.3 to -2.2), respectively. These results suggest that exposure to an unfavorable intrauterine environment contributes to the trajectory toward smaller brain volume, adding to the atrophy that may be associated with mid-life cardiovascular risk. PMID:27103521

  15. Non-injurious neonatal hypoxia confers resistance to brain senescence in aged male rats.

    Directory of Open Access Journals (Sweden)

    Nicolas Martin

    Full Text Available Whereas brief acute or intermittent episodes of hypoxia have been shown to exert a protective role in the central nervous system and to stimulate neurogenesis, other studies suggest that early hypoxia may constitute a risk factor that influences the future development of mental disorders. We therefore investigated the effects of a neonatal "conditioning-like" hypoxia (100% N₂, 5 min on the brain and the cognitive outcomes of rats until 720 days of age (physiologic senescence. We confirmed that such a short hypoxia led to brain neurogenesis within the ensuing weeks, along with reduced apoptosis in the hippocampus involving activation of Erk1/2 and repression of p38 and death-associated protein (DAP kinase. At 21 days of age, increased thicknesses and cell densities were recorded in various subregions, with strong synapsin activation. During aging, previous exposure to neonatal hypoxia was associated with enhanced memory retrieval scores specifically in males, better preservation of their brain integrity than controls, reduced age-related apoptosis, larger hippocampal cell layers, and higher expression of glutamatergic and GABAergic markers. These changes were accompanied with a marked expression of synapsin proteins, mainly of their phosphorylated active forms which constitute major players of synapse function and plasticity, and with increases of their key regulators, i.e. Erk1/2, the transcription factor EGR-1/Zif-268 and Src kinase. Moreover, the significantly higher interactions between PSD-95 scaffolding protein and NMDA receptors measured in the hippocampus of 720-day-old male animals strengthen the conclusion of increased synaptic functional activity and plasticity associated with neonatal hypoxia. Thus, early non-injurious hypoxia may trigger beneficial long term effects conferring higher resistance to senescence in aged male rats, with a better preservation of cognitive functions.

  16. Fetal autonomic brain age scores, segmented heart rate variability analysis, and traditional short term variability

    Directory of Open Access Journals (Sweden)

    Dirk eHoyer

    2014-11-01

    Full Text Available Disturbances of fetal autonomic brain development can be evaluated from fetal heart rate patterns reflecting the activity of the autonomic nervous system. Although heart rate pattern analysis from cardiotocographic (CTG recordings is established for fetal surveillance, temporal resolution is low. Fetal magnetocardiography (MCG, however, provides stable continuous recordings at a higher temporal resolution combined with a more precise heart rate variability (HRV analysis. A direct comparison of CTG and MCG based HRV analysis is pending. The aims of the present study are (i to compare the fetal maturation age predicting value of the MCG based fetal Autonomic Brain Age Score (fABAS approach with that of CTG based Dawes Redman methodology and (ii to elaborate fABAS methodology by segmentation according to fetal behavioral states and heart rate patterns. We investigated MCG recordings from 418 normal fetuses, aged between 21 and 40 weeks of gestation.In linear regression models we obtained an age predicting value of CTG compatible short term variability (STV of R2=0.200 (coefficient of determination in contrast to MCG/fABAS related multivariate models with R2=0.648 in 30 minute recordings, R2=0.610 in active sleep segments of 10 minutes, and R2=0.626 in quiet sleep segments of 10 minutes. Additionally segmented analysis under particular exclusion of accelerations and decelerations in quiet sleep resulted in a novel multivariate model with R2=0.706.According to our results, fMCG based fABAS may provide a promising tool for the estimation of fetal autonomic brain age. Beside other traditional and novel HRV indices as possible indicators of developmental disturbances, the establishment of a fABAS score normogram may represent a specific reference. The present results are intended to contribute to further exploration and validation using independent data sets and multicenter research structures.

  17. The Role of Insulin, Insulin Growth Factor, and Insulin-Degrading Enzyme in Brain Aging and Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Claude Messier

    2005-01-01

    Full Text Available Most brain insulin comes from the pancreas and is taken up by the brain by what appears to be a receptor-based carrier. Type 2 diabetes animal models associated with insulin resistance show reduced insulin brain uptake and content. Recent data point to changes in the insulin receptor cascade in obesity-related insulin resistance, suggesting that brain insulin receptors also become less sensitive to insulin, which could reduce synaptic plasticity. Insulin transport to the brain is reduced in aging and in some animal models of type 2 diabetes; brain insulin resistance may be present as well. Studies examining the effect of the hyperinsulinic clamp or intranasal insulin on cognitive function have found a small but consistent improvement in memory and changes in brain neuroelectric parameters in evoked brain potentials consistent with improved attention or memory processing. These effects appear to be due to raised brain insulin levels. Peripheral levels of Insulin Growth Factor-I (IGF-I are associated with glucose regulation and influence glucose disposal. There is some indication that reduced sensitivity to insulin or IGF-I in the brain, as observed in aging, obesity, and diabetes, decreases the clearance of Aβ amyloid. Such a decrease involves the insulin receptor cascade and can also increase amyloid toxicity. Insulin and IGF-I may modulate brain levels of insulin degrading enzyme, which would also lead to an accumulation of Aβ amyloid.

  18. Characterization of multiciliated ependymal cells that emerge in the neurogenic niche of the aged zebrafish brain.

    Science.gov (United States)

    Ogino, Takashi; Sawada, Masato; Takase, Hiroshi; Nakai, Chiemi; Herranz-Pérez, Vicente; Cebrián-Silla, Arantxa; Kaneko, Naoko; García-Verdugo, José Manuel; Sawamoto, Kazunobu

    2016-10-15

    In mammals, ventricular walls of the developing brain maintain a neurogenic niche, in which radial glial cells act as neural stem cells (NSCs) and generate new neurons in the embryo. In the adult brain, the neurogenic niche is maintained in the ventricular-subventricular zone (V-SVZ) of the lateral wall of lateral ventricles and the hippocampal dentate gyrus. In the neonatal V-SVZ, radial glial cells transform into astrocytic postnatal NSCs and multiciliated ependymal cells. On the other hand, in zebrafish, radial glial cells continue to cover the surface of the adult telencephalic ventricle and maintain a higher neurogenic potential in the adult brain. However, the cell composition of the neurogenic niche of the aged zebrafish brain has not been investigated. Here we show that multiciliated ependymal cells emerge in the neurogenic niche of the aged zebrafish telencephalon. These multiciliated cells appear predominantly in the dorsal part of the ventral telencephalic ventricular zone, which also contains clusters of migrating new neurons. Scanning electron microscopy and live imaging analyses indicated that these multiple cilia beat coordinately and generate constant fluid flow within the ventral telencephalic ventricle. Analysis of the cell composition by transmission electron microscopy revealed that the neurogenic niche in the aged zebrafish contains different types of cells, with ultrastructures similar to those of ependymal cells, transit-amplifying cells, and migrating new neurons in postnatal mice. These data suggest that the transformation capacity of radial glial cells is conserved but that its timing is different between fish and mice. J. Comp. Neurol. 524:2982-2992, 2016. © 2016 Wiley Periodicals, Inc. PMID:26991819

  19. Brain Food for Alzheimer-Free Ageing: Focus on Herbal Medicines.

    Science.gov (United States)

    Hügel, Helmut M

    2015-01-01

    Healthy brain aging and the problems of dementia and Alzheimer's disease (AD) are a global concern. Beyond 60 years of age, most, if not everyone, will experience a decline in cognitive skills, memory capacity and changes in brain structure. Longevity eventually leads to an accumulation of amyloid plaques and/or tau tangles, including some vascular dementia damage. Therefore, lifestyle choices are paramount to leading either a brain-derived or a brain-deprived life. The focus of this review is to critically examine the evidence, impact, influence and mechanisms of natural products as chemopreventive agents which induce therapeutic outcomes that modulate the aggregation process of beta-amyloid (Aβ), providing measureable cognitive benefits in the aging process. Plants can be considered as chemical factories that manufacture huge numbers of diverse bioactive substances, many of which have the potential to provide substantial neuroprotective benefits. Medicinal herbs and health food supplements have been widely used in Asia since over 2,000 years. The phytochemicals utilized in traditional Chinese medicine have demonstrated safety profiles for human consumption. Many herbs with anti-amyloidogenic activity, including those containing polyphenolic constituents such as green tea, turmeric, Salvia miltiorrhiza, and Panax ginseng, are presented. Also covered in this review are extracts from kitchen spices including cinnamon, ginger, rosemary, sage, salvia herbs, Chinese celery and many others some of which are commonly used in herbal combinations and represent highly promising therapeutic natural compounds against AD. A number of clinical trials conducted on herbs to counter dementia and AD are discussed. PMID:26092628

  20. The effects of aging on dopaminergic neurotransmission: a microPET study of [11C]-raclopride binding in the aged rodent brain.

    Science.gov (United States)

    Hoekzema, E; Herance, R; Rojas, S; Pareto, D; Abad, S; Jiménez, X; Figueiras, F P; Popota, F; Ruiz, A; Torrent, È; Fernández-Soriano, F J; Rocha, M; Rovira, M; Víctor, V M; Gispert, J D

    2010-12-29

    Rodent models are frequently used in aging research to investigate biochemical age effects and aid in the development of therapies for pathological and non-pathological age-related degenerative processes. In order to validate the use of animal models in aging research and pave the way for longitudinal intervention-based animal studies, the consistency of cerebral aging processes across species needs to be evaluated. The dopaminergic system seems particularly susceptible to the aging process, and one of the most consistent findings in human brain aging research is a decline in striatal D2-like receptor (D2R) availability, quantifiable by positron emission tomography (PET) imaging. In this study, we aimed to assess whether similar age effects can be discerned in rat brains, using in vivo molecular imaging with the radioactive compound [(11)C]-raclopride. We observed a robust decline in striatal [(11)C]-raclopride uptake in the aged rats in comparison to the young control group, comprising a 41% decrement in striatal binding potential. In accordance with human studies, these results indicate that substantial reductions in D2R availability can be measured in the aged striatal complex. Our findings suggest that rat and human brains exhibit similar biochemical alterations with age in the striatal dopaminergic system, providing support for the pertinence of rodent models in aging research.

  1. Accelerated epigenetic aging in brain is associated with pre-mortem HIV-associated neurocognitive disorders.

    Science.gov (United States)

    Levine, Andrew J; Quach, Austin; Moore, David J; Achim, Cristian L; Soontornniyomkij, Virawudh; Masliah, Eliezer; Singer, Elyse J; Gelman, Benjamin; Nemanim, Natasha; Horvath, Steve

    2016-06-01

    HIV infection leads to age-related conditions in relatively young persons. HIV-associated neurocognitive disorders (HAND) are considered among the most prevalent of these conditions. To study the mechanisms underlying this disorder, researchers need an accurate method for measuring biological aging. Here, we apply a recently developed measure of biological aging, based on DNA methylation, to the study of biological aging in HIV+ brains. Retrospective analysis of tissue bank specimens and pre-mortem data was carried out. Fifty-eight HIV+ adults underwent a medical and neurocognitive evaluation within 1 year of death. DNA was obtained from occipital cortex and analyzed with the Illumina Infinium Human Methylation 450K platform. Biological age determined via the epigenetic clock was contrasted with chronological age to obtain a measure of age acceleration, which was then compared between those with HAND and neurocognitively normal individuals. The HAND and neurocognitively normal groups did not differ with regard to demographic, histologic, neuropathologic, or virologic variables. HAND was associated with accelerated aging relative to neurocognitively normal individuals, with average relative acceleration of 3.5 years. Age acceleration did not correlate with pre-mortem neurocognitive functioning or HAND severity. This is the first study to demonstrate that the epigenetic age of occipital cortex samples is associated with HAND status in HIV+ individuals pre-mortem. While these results suggest that the increased risk of a neurocognitive disorder due to HIV might be mediated by an epigenetic aging mechanism, future studies will be needed to validate the findings and dissect causal relationships and downstream effects. PMID:26689571

  2. Lack of DREAM protein enhances learning and memory and slows brain aging.

    Science.gov (United States)

    Fontán-Lozano, Angela; Romero-Granados, Rocío; del-Pozo-Martín, Yaiza; Suárez-Pereira, Irene; Delgado-García, José María; Penninger, Josef M; Carrión, Angel Manuel

    2009-01-13

    Memory deficits in aging affect millions of people and are often disturbing to those concerned. Dissection of the molecular control of learning and memory is paramount to understand and possibly enhance cognitive functions. Old-age memory loss also has been recently linked to altered Ca(2+) homeostasis. We have previously identified DREAM (downstream regulatory element antagonistic modulator), a member of the neuronal Ca(2+) sensor superfamily of EF-hand proteins, with specific roles in different cell compartments. In the nucleus, DREAM is a Ca(2+)-dependent transcriptional repressor, binding to specific DNA signatures, or interacting with nucleoproteins regulating their transcriptional properties. Also, we and others have shown that dream mutant (dream(-/-)) mice exhibit marked analgesia. Here we report that dream(-/-) mice exhibit markedly enhanced learning and synaptic plasticity related to improved cognition. Mechanistically, DREAM functions as a negative regulator of the key memory factor CREB in a Ca(2+)-dependent manner, and loss of DREAM facilitates CREB-dependent transcription during learning. Intriguingly, 18-month-old dream(-/-) mice display learning and memory capacities similar to young mice. Moreover, loss of DREAM protects from brain degeneration in aging. These data identify the Ca(2+)-regulated "pain gene" DREAM as a novel key regulator of memory and brain aging. PMID:19110430

  3. Changes in brain network efficiency and working memory performance in aging.

    Directory of Open Access Journals (Sweden)

    Matthew L Stanley

    Full Text Available Working memory is a complex psychological construct referring to the temporary storage and active processing of information. We used functional connectivity brain network metrics quantifying local and global efficiency of information transfer for predicting individual variability in working memory performance on an n-back task in both young (n = 14 and older (n = 15 adults. Individual differences in both local and global efficiency during the working memory task were significant predictors of working memory performance in addition to age (and an interaction between age and global efficiency. Decreases in local efficiency during the working memory task were associated with better working memory performance in both age cohorts. In contrast, increases in global efficiency were associated with much better working performance for young participants; however, increases in global efficiency were associated with a slight decrease in working memory performance for older participants. Individual differences in local and global efficiency during resting-state sessions were not significant predictors of working memory performance. Significant group whole-brain functional network decreases in local efficiency also were observed during the working memory task compared to rest, whereas no significant differences were observed in network global efficiency. These results are discussed in relation to recently developed models of age-related differences in working memory.

  4. Longitudinal Volumetric Brain Changes in Autism Spectrum Disorder Ages 6–35 Years

    Science.gov (United States)

    Lange, Nicholas; Travers, Brittany G.; Bigler, Erin D.; Prigge, Molly B.D.; Froehlich, Alyson L.; Nielsen, Jared A.; Cariello, Annahir N.; Zielinski, Brandon A.; Anderson, Jeffrey S.; Fletcher, P. Thomas; Alexander, Andrew A.; Lainhart, Janet E.

    2014-01-01

    LAY ABSTRACT Since the impairments associated with autism spectrum disorder (ASD) tend to persist or worsen from childhood into adulthood, it is of critical importance to examine how the brain develops over this growth epoch. We report initial findings on whole and regional longitudinal brain development in 100 male participants with ASD (226 high-quality MRI scans) compared to 56 typically developing male controls (TDCs) (117 high-quality scans) from childhood into adulthood, for a total of 156 participants scanned over an eight-year period. We provide volumetric growth curves for the entire brain, total gray matter (GM), frontal GM, temporal GM, parietal GM, occipital GM, total cortical white matter (WM), corpus callosum, caudate, thalamus, total cerebellum, and total ventricles. Mean volume of cortical WM was reduced significantly. Decreases in regional mean volumes in the ASD sample were most often due to decreases during late adolescence and adulthood. The growth curve of whole-brain volume showed increased volumes in young children with autism and subsequently decreased during adolescence to meet the TDC curve between 10 and 15 years of age. The volume of many structures continued to decline atypically into adulthood in the ASD sample. The data suggest that ASD is a dynamic disorder with complex changes in whole and regional brain volumes that change over time from childhood into adulthood. SCIENTIFIC ABSTRACT Since the impairments associated with autism spectrum disorder (ASD) tend to persist or worsen from childhood into adulthood, it is of critical importance to examine how the brain develops over this growth epoch. We report initial findings on whole and regional longitudinal brain development in 100 male participants with ASD (226 high-quality MRI scans; mean inter-scan interval 2.7 years) compared to 56 typically developing male controls (TDCs) (117 high-quality scans; mean inter-scan interval 2.6 years) from childhood into adulthood, for a total of 156

  5. Structural brain plasticity induced by physical training in adults affected by aging or disease related impairments: a systematic review

    OpenAIRE

    Van Oosterwijck, Jessica; Dhondt, Evy; Caeyenberghs, Karen; Burggraeve, Lieselot; Danneels, Lieven

    2015-01-01

    Background: Structural brain plasticity is observed as a consequence of alterations in input/behavior or of disease. For instance aging is associated with structural decline of the brain, and structural brain alterations have been identified in certain medical pathologies. While physical exercise has a positive impact on function, health status and quality of life in those affected by disease or neurodegenerative related deteriorations, the question remains if structural plasticity of the bra...

  6. Cognitive activity, cognitive function, and brain diffusion characteristics in old age.

    Science.gov (United States)

    Arfanakis, Konstantinos; Wilson, Robert S; Barth, Christopher M; Capuano, Ana W; Vasireddi, Anil; Zhang, Shengwei; Fleischman, Debra A; Bennett, David A

    2016-06-01

    The objective of this work was to test the hypotheses that a) more frequent cognitive activity in late life is associated with higher brain diffusion anisotropy and lower trace of the diffusion tensor, and b) brain diffusion characteristics partially mediate the association of late life cognitive activity with cognition. As part of a longitudinal cohort study, 379 older people without dementia rated their frequency of participation in cognitive activities, completed a battery of cognitive function tests, and underwent diffusion tensor imaging. We used tract-based spatial statistics to test the association between late life cognitive activity and brain diffusion characteristics. Clusters with statistically significant findings defined regions of interest in which we tested the hypothesis that diffusion characteristics partially mediate the association of late life cognitive activity with cognition. More frequent cognitive activity in late life was associated with higher level of global cognition after adjustment for age, sex, education, and indicators of early life cognitive enrichment (p = 0.001). More frequent cognitive activity was also related to higher fractional anisotropy in the left superior and inferior longitudinal fasciculi, left fornix, and corpus callosum, and lower trace in the thalamus (p cognitive activity with cognition was reduced by as much as 26 %. These findings suggest that the association of late life cognitive activity with cognition may be partially mediated by brain diffusion characteristics.

  7. Age dependent accumulation of N-acyl-ethanolamine phospholipids in ischemic rat brain

    DEFF Research Database (Denmark)

    Moesgaard, B.; Petersen, G.; Hansen, Harald S.;

    2000-01-01

    N-acyl-ethanolamine phospholipids (NAPE) can be formed as a stress response during neuronal injury, and they are precursors for N-acyl- ethanolamines (NAE), some of which are endocannabinoids. The levels of NAPE accumulated during post-decapitative ischemia (6 h at 37°C) were studied in rat brains...... of various age (1, 6, 12, 19, 30, and ~70 days) by the use of P NMR spectroscopy of lipid extracts. This ability to accumulate NAPE was compared with the activity of N-acyltransferase and of NAPE-hydrolyzing phospholipase D (NAPE-PLD) in brain microsomes. These two enzymes are involved in the formation...... and degradation of NAPE, respectively. The results showed that 1) the ability to accumulate NAPE during post-decapitative ischemia is especially high in the youngest rats and is markedly reduced in older brains [in 1-day-old rat brains NAPE accumulated to 1.5% of total phospholipids, while in 30-day-old rat...

  8. Age-related similarities and differences in brain activity underlying reversal learning

    Directory of Open Access Journals (Sweden)

    Kaoru eNashiro

    2013-05-01

    Full Text Available The ability to update associative memory is an important aspect of episodic memory and a critical skill for social adaptation. Previous research with younger adults suggests that emotional arousal alters brain mechanisms underlying memory updating; however, it is unclear whether this applies to older adults. Given that the ability to update associative information declines with age, it is important to understand how emotion modulates the brain processes underlying memory updating in older adults. The current study investigated this question using reversal learning tasks, where younger and older participants (age ranges 19-35 and 61-78 respectively learn a stimulus–outcome association and then update their response when contingencies change. We found that younger and older adults showed similar patterns of activation in the frontopolar OFC and the amygdala during emotional reversal learning. In contrast, when reversal learning did not involve emotion, older adults showed greater parietal cortex activity than did younger adults. Thus, younger and older adults show more similarities in brain activity during memory updating involving emotional stimuli than during memory updating not involving emotional stimuli.

  9. Cerebral hemodynamics of the aging brain: risk of Alzheimer disease and benefit of aerobic exercise

    Directory of Open Access Journals (Sweden)

    Takashi eTarumi

    2014-01-01

    Full Text Available Alzheimer disease (AD and cerebrovascular disease often coexist with advanced age. Mounting evidence indicates that the presence of vascular disease and its risk factors increase the risk of AD, suggesting a potential overlap of the underlying pathophysiological mechanisms. In particular, atherosclerosis, endothelial dysfunction, and stiffening of central elastic arteries have been shown to associate with AD. Currently, there are no effective treatments for the cure and prevention of AD. Vascular risk factors are modifiable via either pharmacological or lifestyle intervention. In this regard, habitual aerobic exercise is increasingly recognized for its benefits on brain structure and cognitive function. Considering the well-established benefits of regular aerobic exercise on vascular health, exercise-related improvements in brain structure and cognitive function may be mediated by vascular adaptations. In this review, we will present the current evidence for the physiological mechanisms by which vascular health alters the structural and functional integrity of the aging brain and how improvements in vascular health, via regular aerobic exercise, potentially benefits cognitive function.

  10. Reconfiguration of brain network architecture to support executive control in aging.

    Science.gov (United States)

    Gallen, Courtney L; Turner, Gary R; Adnan, Areeba; D'Esposito, Mark

    2016-08-01

    Aging is accompanied by declines in executive control abilities and changes in underlying brain network architecture. Here, we examined brain networks in young and older adults during a task-free resting state and an N-back task and investigated age-related changes in the modular network organization of the brain. Compared with young adults, older adults showed larger changes in network organization between resting state and task. Although young adults exhibited increased connectivity between lateral frontal regions and other network modules during the most difficult task condition, older adults also exhibited this pattern of increased connectivity during less-demanding task conditions. Moreover, the increase in between-module connectivity in older adults was related to faster task performance and greater fractional anisotropy of the superior longitudinal fasciculus. These results demonstrate that older adults who exhibit more pronounced network changes between a resting state and task have better executive control performance and greater structural connectivity of a core frontal-posterior white matter pathway.

  11. Alzheimer's disease and amyloid beta-peptide deposition in the brain: a matter of 'aging'?

    DEFF Research Database (Denmark)

    Moro, Maria Luisa; Collins, Matthew J; Cappellini, Enrico

    2010-01-01

    event in AD (Alzheimer's disease) synaptic dysfunctions. Structural alterations introduced by site-specific modifications linked to protein aging may affect Abeta production, polymerization and clearance, and therefore play a pivotal role in the pathogenesis of sporadic and genetic forms of AD. Early......Biomolecules can experience aging processes that limit their long-term functionality in organisms. Typical markers of protein aging are spontaneous chemical modifications, such as AAR (amino acid racemization) and AAI (amino acid isomerization), mainly involving aspartate and asparagine residues....... Since these modifications may affect folding and turnover, they reduce protein functionality over time and may be linked to pathological conditions. The present mini-review describes evidence of AAR and AAI involvement in the misfolding and brain accumulation of Abeta (amyloid beta-peptide), a central...

  12. Brain lesions and IQ: recovery versus decline depends on age of onset.

    Science.gov (United States)

    Duval, Julie; Braun, Claude M J; Montour-Proulx, Isabelle; Daigneault, Sylvie; Rouleau, Isabelle; Bégin, Jean

    2008-06-01

    A growing literature suggests that early lesions are associated with poorer IQ outcome. Those studies covered a restricted age range in pediatric populations only and did not control for important moderator variables. The present investigation studied IQ change in brain-lesioned children and adults (age 0 to 84 years). Altogether, 725 cases with a documented unilateral focal lesion were gathered from hospital charts and from published cases in the literature, including 240 with repeated IQ testing. Multiple regression analyses isolated the contribution of age at lesion onset to IQ change. Important mediator variables included were lesion side, site, volume, etiology, and so on. An early lesion was significantly associated with poorer postlesion IQ in time and with decline of IQ in time. Later onset lesions were associated with better postlesion IQ and recovery in time. The so-called Kennard principle is refuted, with regard to IQ.

  13. Social Determinants, Race, and Brain Health Outcomes: Findings from the Chicago Health and Aging Project.

    Science.gov (United States)

    Aggarwal, Neelum T; Everson-Rose, Susan A; Evans, Denis A

    2015-01-01

    The broad spectrum of economic and cultural diversity in the U.S. population correlates with and affects the study of behavioral aspects of health. The purpose of this article is to provide a selective overview of research findings from the Chicago Health and Aging Project (CHAP), which covers a socio-demographically diverse population in Chicago, with a focus on role-related psychosocial factors and observed racial/ethnic differences in aging outcomes. CHAP is a longitudinal, epidemiological study of common chronic conditions of aging with an emphasis on medical, psychosocial, and environmental risk factors for the decline in cognitive function across the older adult lifespan. We briefly summarize the study design and methods used in the CHAP study and characterize the study population and describe the psychosocial data, noting black-white associations as they relate to three common brain health outcomes: cognitive function and Alzheimer's Disease, stroke, and subclinical vascular disease as noted on neuroimaging. PMID:26239039

  14. Age-Related Differences in the Brain Areas outside the Classical Language Areas among Adults Using Category Decision Task

    Science.gov (United States)

    Cho, Yong Won; Song, Hui-Jin; Lee, Jae Jun; Lee, Joo Hwa; Lee, Hui Joong; Yi, Sang Doe; Chang, Hyuk Won; Berl, Madison M.; Gaillard, William D.; Chang, Yongmin

    2012-01-01

    Older adults perform much like younger adults on language. This similar level of performance, however, may come about through different underlying brain processes. In the present study, we evaluated age-related differences in the brain areas outside the typical language areas among adults using a category decision task. Our results showed that…

  15. Parameters of glucose metabolism and the aging brain: a magnetization transfer imaging study of brain macro- and micro-structure in older adults without diabetes

    OpenAIRE

    Akintola, Abimbola A.; VAN DEN BERG, Annette; Altmann-Schneider, Irmhild; Jansen, Steffy W.; van Buchem, Mark A.; Slagboom, P. Eline; Westendorp, Rudi G.; van Heemst, Diana; van der Grond, Jeroen

    2015-01-01

    Given the concurrent, escalating epidemic of diabetes mellitus and neurodegenerative diseases, two age-related disorders, we aimed to understand the relation between parameters of glucose metabolism and indices of pathology in the aging brain. From the Leiden Longevity Study, 132 participants (mean age 66 years) underwent a 2-h oral glucose tolerance test to assess glucose tolerance (fasted and area under the curve (AUC) glucose), insulin sensitivity (fasted and AUC insulin and homeostatic mo...

  16. Identification of chemicals that mimic transcriptional changes associated with autism, brain aging and neurodegeneration.

    Science.gov (United States)

    Pearson, Brandon L; Simon, Jeremy M; McCoy, Eric S; Salazar, Gabriela; Fragola, Giulia; Zylka, Mark J

    2016-03-31

    Environmental factors, including pesticides, have been linked to autism and neurodegeneration risk using retrospective epidemiological studies. Here we sought to prospectively identify chemicals that share transcriptomic signatures with neurological disorders, by exposing mouse cortical neuron-enriched cultures to hundreds of chemicals commonly found in the environment and on food. We find that rotenone, a pesticide associated with Parkinson's disease risk, and certain fungicides, including pyraclostrobin, trifloxystrobin, famoxadone and fenamidone, produce transcriptional changes in vitro that are similar to those seen in brain samples from humans with autism, advanced age and neurodegeneration (Alzheimer's disease and Huntington's disease). These chemicals stimulate free radical production and disrupt microtubules in neurons, effects that can be reduced by pretreating with a microtubule stabilizer, an antioxidant, or with sulforaphane. Our study provides an approach to prospectively identify environmental chemicals that transcriptionally mimic autism and other brain disorders.

  17. Cortical complexity as a measure of age-related brain atrophy.

    Science.gov (United States)

    Madan, Christopher R; Kensinger, Elizabeth A

    2016-07-01

    The structure of the human brain changes in a variety of ways as we age. While a sizeable literature has examined age-related differences in cortical thickness, and to a lesser degree, gyrification, here we examined differences in cortical complexity, as indexed by fractal dimensionality in a sample of over 400 individuals across the adult lifespan. While prior studies have shown differences in fractal dimensionality between patient populations and age-matched, healthy controls, it is unclear how well this measure would relate to age-related cortical atrophy. Initially computing a single measure for the entire cortical ribbon, i.e., unparcellated gray matter, we found fractal dimensionality to be more sensitive to age-related differences than either cortical thickness or gyrification index. We additionally observed regional differences in age-related atrophy between the three measures, suggesting that they may index distinct differences in cortical structure. We also provide a freely available MATLAB toolbox for calculating fractal dimensionality. PMID:27103141

  18. Brain morphometry shows effects of long-term musical practice in middle-aged keyboard players

    Directory of Open Access Journals (Sweden)

    Hanna eGärtner

    2013-09-01

    Full Text Available To what extent does musical practice change the structure of the brain? In order to understand how long-lasting musical training changes brain structure, 20 male right-handed, middle-aged professional musicians and 19 matched controls were investigated. Among the musicians, 13 were pianists or organists with intensive practice regimes. The others were either music teachers at schools or string instrumentalists, who had studied the piano at least as a subsidiary subject, and practiced less intensively. The study was based on T1-weighted MR images, which were analyzed using Deformation Field Morphometry. Cytoarchitectonic probabilistic maps of cortical areas and subcortical nuclei as well as myeloarchitectonic maps of fiber tracts were used as regions of interest to compare volume differences in the brains of musicians and controls. In addition, maps of voxel-wise volume differences were computed and analyzed.Musicians showed a significantly better symmetric motor performance as well as a greater capability of controlling hand independence than controls. Structural MRI-data revealed significant volumetric differences between the brains of keyboard players, who practiced intensively and controls in right sensorimotor areas and the corticospinal tract as well as in the entorhinal cortex and the left superior parietal lobule. Moreover, they showed also larger volumes in a comparable set of regions than the less intensively practicing musicians. The structural changes in the sensory and motor systems correspond well to the behavioral results, and can be interpreted in terms of plasticity as a result of intensive motor training. Areas of the superior parietal lobule and the entorhinal cortex might be enlarged in musicians due to their special skills in sight-playing and memorizing of scores. In conclusion, intensive and specific musical training seems to have an impact on brain structure, not only during the sensitive period of childhood but throughout

  19. Selective vulnerabilities of N-methyl-D-aspartate (NMDA receptors during brain aging

    Directory of Open Access Journals (Sweden)

    Brenna L Brim

    2010-03-01

    Full Text Available N-methyl-D-aspartate (NMDA receptors are present in high density within the cerebral cortex and hippocampus and play an important role in learning and memory. NMDA receptors are negatively affected by aging, but these effects are not uniform in many different ways. This review discusses the selective age-related vulnerabilities of different binding sites of the NMDA receptor complex, different subunits that comprise the complex, and the expression and functions of the receptor within different brain regions. Spatial reference, passive avoidance, and working memory, as well as place field stability and expansion all involve NMDA receptors. Aged animals show deficiencies in these functions, as compared to young, and some studies have identified an association between age-associated changes in the expression of NMDA receptors and poor memory performance. A number of diet and drug interventions have shown potential for reversing or slowing the effects of aging on the NMDA receptor. On the other hand, there is mounting evidence that the NMDA receptors that remain within aged individuals are not always associated with good cognitive functioning. This may be due to a compensatory response of neurons to the decline in NMDA receptor expression or a change in the subunit composition of the remaining receptors. These studies suggest that developing treatments that are aimed at preventing or reversing the effects of aging on the NMDA receptor may aid in ameliorating the memory declines that are associated with aging. However, we need to be mindful of the possibility that there may also be negative consequences in aged individuals.

  20. Cognitive reserve is associated with the functional organization of brain in healthy aging: A MEG Study

    Directory of Open Access Journals (Sweden)

    Maria Eugenia eLopez

    2014-06-01

    Full Text Available The proportion of elderly people in the population has increased rapidly in the last century and consequently healthy aging is expected to become a critical area of research in neuroscience. Evidence reveals how healthy aging depends on three main behavioral factors: social lifestyle, cognitive activity and physical activity. In this study, we focused on the role of cognitive activity, concentrating specifically on educational and occupational attainment factors, which were considered two of the main pillars of cognitive reserve.21 subjects with similar rates of social lifestyle, physical and cognitive activity were selected from a sample of 55 healthy adults. These subjects were divided into two groups according to their level of cognitive reserve; one group comprised subjects with high cognitive reserve (9 members and the other contained those with low cognitive reserve (12 members. To evaluate the cortical brain connectivity network, all participants were recorded by Magnetoencephalography (MEG while they performed a memory task (modified version of the Sternberg´s Task. We then applied two algorithms (Phase Locking Value & Phase-Lag Index to study the dynamics of functional connectivity. In response to the same task, the subjects with lower cognitive reserve presented higher functional connectivity than those with higher cognitive reserve.These results may indicate that participants with low cognitive reserve needed a greater 'effort' than those with high cognitive reserve to achieve the same level of cognitive performance. Therefore, we conclude that cognitive reserve contributes to the modulation of the functional connectivity patterns of the aging brain.

  1. Effects of long-term mindfulness meditation on brain's white matter microstructure and its aging.

    Directory of Open Access Journals (Sweden)

    Davide eLaneri

    2016-01-01

    Full Text Available Although research on the effects of mindfulness meditation (MM is increasing, still very little has been done to address its influence on the white matter (WM of the brain. We hypothesized that the practice of MM might affect the WM microstructure adjacent to five brain regions of interest associated with mindfulness. Diffusion tensor imaging was employed on samples of meditators and non-meditators (n=64 in order to investigate the effects of MM on group difference and aging. Tract-Based Spatial Statistics was used to estimate the fractional anisotrophy of the WM connected to the thalamus, insula, amygdala, hippocampus and anterior cingulate cortex. The subsequent generalized linear model analysis revealed group differences and a group-by-age interaction in all five selected regions. These data provide preliminary indications that the practice of MM might result in WM matter connectivity change and might provide evidence on its ability to help diminish age-related WM degeneration in key regions which participate in processes of mindfulness.

  2. Functional brain connectivity and cognition: effects of adult age and task demands.

    Science.gov (United States)

    Chou, Ying-Hui; Chen, Nan-Kuei; Madden, David J

    2013-08-01

    Previous neuroimaging research has documented that patterns of intrinsic (resting state) functional connectivity (FC) among brain regions covary with individual measures of cognitive performance. Here, we examined the relation between intrinsic FC and a reaction time (RT) measure of performance, as a function of age group and task demands. We obtained filtered, event-related functional magnetic resonance imaging data, and RT measures of visual search performance, from 21 younger adults (19-29 years old) and 21 healthy, older adults (60-87 years old). Age-related decline occurred in the connectivity strength in multiple brain regions, consistent with previous findings. Among 8 pairs of regions, across somatomotor, orbitofrontal, and subcortical networks, increasing FC was associated with faster responding (lower RT). Relative to younger adults, older adults exhibited a lower strength of this RT-connectivity relation and greater disruption of this relation by a salient but irrelevant display item (color singleton distractor). Age-related differences in the covariation of intrinsic FC and cognitive performance vary as a function of task demands.

  3. Brain aging and Parkinson's disease: New therapeutic approaches using drug delivery systems.

    Science.gov (United States)

    Rodríguez-Nogales, C; Garbayo, E; Carmona-Abellán, M M; Luquin, M R; Blanco-Prieto, M J

    2016-02-01

    The etiology and pathogenesis of Parkinson's disease (PD) is unknown, aging being the strongest risk factor for brain degeneration. Understanding PD pathogenesis and how aging increases the risk of disease would aid the development of therapies able to slow or prevent the progression of this neurodegenerative disorder. In this review we provide an overview of the most promising therapeutic targets and strategies to delay the loss of dopaminergic neurons observed both in PD and aging. Among them, handling alpha-synuclein toxicity, enhancing proteasome and lysosome clearance, ameliorating mitochondrial disruptions and modifying the glial environment are so far the most promising candidates. These new and conventional drugs may present problems related to their labile nature and to the difficulties in reaching the brain. Thus, we highlight the latest types of drug delivery system (DDS)-based strategies for PD treatment, including DDS for local and systemic drug delivery. Finally, the ongoing challenges for the discovery of new targets and the opportunities for DDS-based therapies to improve and efficacious PD therapy will be discussed.

  4. Characterization of monoaminergic systems in brain regions of prematurely ageing mice.

    Science.gov (United States)

    De la Fuente, Monica; Hernanz, Angel; Medina, Sonia; Guayerbas, Noelia; Fernández, Beatriz; Viveros, Maria Paz

    2003-07-01

    We have previously shown that differences in life span among members of Swiss mouse populations appear to be related to their exploration of a T-maze, with a slow exploration ("slow mice") being linked to increased levels of emotionality/anxiety, an impaired immune function and a shorter life span. Thus, we proposed the slow mice as prematurely ageing mice (PAM). We have now compared the monoaminergic systems of the PAM and of the non-prematurely ageing mice (NPAM), in discrete brain regions. PAM had decreased noradrenaline (NA) levels in all the brain regions analysed, whereas the 3-methoxy-4-hydroxyphenyl glycol (MHPG)/NA ratios were not significantly modified. PAM also showed decreased serotonine (5-HT) levels in hypothalamus, striatum and midbrain, as well as increased 5-hydroxyindol-3-acetic acid (5-HIAA)/5-HT ratios in hypothalamus and hippocampus. The dopamine (DA) content was lower in PAM in most regions, whereas the 3,4-dihydroxyphenylacetic acid (DOPAC)/DA and homovanillic acid (HVA)/DA ratios were either increased or unchanged depending on the region analysed. In most cases, the differences between PAM and NPAM involved both sexes. One exception was the hypothalamus where the differences only affected the male mice. The neurochemical alterations found in PAM resemble some changes reported for aged animals and are related with their behavioural features.

  5. The effect of ZMS on brain M receptor in aged rats

    International Nuclear Information System (INIS)

    Objective: The purpose of this work was to study the effect of ZMS, an active component of Yin tonic, Zhimu, on brain M2 receptor density of aged animals and its correlation with the effect on learning/memory ability. Methods: A dual-site competitive binding assay using 3H-quinuclidinyl benzilate (QNB) as non selective radioligand and unlabelled Methoctramine as selective competitive agent was established for measuring M2 receptor density in aged rats. Results: In addition to the change of total density of M receptors, the density of a subtype of M receptors, M2 receptor in brain was significantly decreased in aged rats [(231.8 +- 115.9) fmol·mg-1 (x-bar +- s) in young rats and (97.9 +- 46.3) fmol·mg-1 in aged rats]. When the aged rats were treated with ZMS for two months, in addition to the up-regulation of total M receptors, the M2 receptor was up-regulated significantly [being (213 +- 77) mg at a ZMS dose of 3.6 mg·kg-1·d-'1, and (212 +- 72) mg at a ZMS dose of 18 mg·kg-1·d-1]. When the correlation between M2 or total M receptor densities and the learning/memory ability measured by Y-maze performance was examined with linear regression, the correlation coefficient was remarkable (0.721 and 0.505, respectively). Conclusions: ZMS has the ability of up-regulating M2 receptor and this may be an important factor for the improvement of learning and memory by ZMS

  6. Cognitive dysfunction syndrome: a disease of canine and feline brain aging.

    Science.gov (United States)

    Landsberg, Gary M; Nichol, Jeff; Araujo, Joseph A

    2012-07-01

    Brain aging is a degenerative process manifest by impairment of cognitive function; although not all pets are affected at the same level, once cognitive decline begins it is generally a progressive disorder. Diagnosis of cognitive dysfunction syndrome (CDS) is based on recognition of behavioral signs and exclusion of other medical causes that might mimic CDS or complicate its diagnosis. Drugs, diets, and supplements are now available that might slow CDS progression by various mechanisms including reducing oxidative stress and inflammation or improving mitochondrial and neuronal function. Moreover, available therapeutics may provide some level of improvement in cognitive and clinical signs of CDS. PMID:22720812

  7. Neuroinflammation in the Aging Down Syndrome Brain; Lessons from Alzheimer's Disease

    OpenAIRE

    Wilcock, Donna M

    2012-01-01

    Down syndrome (DS) is the most genetic cause of mental retardation and is caused by the triplication of chromosome 21. In addition to the disabilities caused early in life, DS is also noted as causing Alzheimer's-disease-like pathological changes in the brain, leading to 50–70% of DS patients showing dementia by 60–70 years of age. Inflammation is a complex process that has a key role to play in the pathogenesis of Alzheimer's disease. There is relatively little understood about inflammation ...

  8. No late effect of ionizing radiation on the aging-related oxidative changes in the mouse brain

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Beom Su; Kim, Seol Wha; Jung, U Hee; Jo, Sung Kee [Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of)

    2010-09-15

    Radiation-induced late injury to normal tissue is a primary area of radiation biology research. The present study was undertaken to investigate whether the late effect of the ionizing radiation appears as an age-related oxidative status in the brain. Three groups of 4-month old C57BL/6 mice that were exposed to {sup 137}Cs {gamma}-rays at a single dose (5 Gy) or fractionated doses (1 Gy x 5 times, or 0,2 Gy x 25 times) at 2 months old were investigated for the oxidative status of their brains with both young (2-month) and old (24-month) mice. A significant (pbrains compared with that of the young mice. Malondialdehyde (MDA) content was significantly (p<0.05) increased in the old mice brain. However, any significant difference in SOD activity and MDA contents of the irradiated brain was not observed compared to age-matched control group mice. SOD activity and MDA content were observed within good parameters of brain aging and there no late effects on the age-related oxidative level in the {gamma}-ray irradiated mice brains.

  9. Aggravation of brain infarction through an increase in acrolein production and a decrease in glutathione with aging.

    Science.gov (United States)

    Uemura, Takeshi; Watanabe, Kenta; Ishibashi, Misaki; Saiki, Ryotaro; Kuni, Kyoshiro; Nishimura, Kazuhiro; Toida, Toshihiko; Kashiwagi, Keiko; Igarashi, Kazuei

    2016-04-29

    We previously reported that tissue damage during brain infarction was mainly caused by inactivation of proteins by acrolein. This time, it was tested why brain infarction increases in parallel with aging. A mouse model of photochemically induced thrombosis (PIT) was studied using 2, 6, and 12 month-old female C57BL/6 mice. The size of brain infarction in the mouse PIT model increased with aging. The volume of brain infarction in 12 month-old mice was approximately 2-fold larger than that in 2 month-old mice. The larger brain infarction in 12 month-old mice was due to an increase in acrolein based on an increase in the activity of spermine oxidase, together with a decrease in glutathione (GSH), a major acrolein-detoxifying compound in cells, based on the decrease in one of the subunits of glutathione biosynthesizing enzymes, γ-glutamylcysteine ligase modifier subunit, with aging. The results indicate that aggravation of brain infarction with aging was mainly due to the increase in acrolein production and the decrease in GSH in brain.

  10. Effects of Long-Term Rice Bran Extract Supplementation on Survival, Cognition and Brain Mitochondrial Function in Aged NMRI Mice.

    Science.gov (United States)

    Hagl, Stephanie; Asseburg, Heike; Heinrich, Martina; Sus, Nadine; Blumrich, Eva-Maria; Dringen, Ralf; Frank, Jan; Eckert, Gunter P

    2016-09-01

    Aging represents a major risk factor for the development of neurodegenerative diseases like Alzheimer's disease (AD). As mitochondrial dysfunction plays an important role in brain aging and occurs early in the development of AD, the prevention of mitochondrial dysfunction might help to slow brain aging and the development of neurodegenerative diseases. Rice bran extract (RBE) contains high concentrations of vitamin E congeners and γ-oryzanol. We have previously shown that RBE increased mitochondrial function and protected from mitochondrial dysfunction in vitro and in short-term in vivo feeding studies. To mimic the use of RBE as food additive, we have now investigated the effects of a long-term (6 months) feeding of RBE on survival, behavior and brain mitochondrial function in aged NMRI mice. RBE administration significantly increased survival and performance of aged NMRI mice in the passive avoidance and Y-maze test. Brain mitochondrial dysfunction found in aged mice was ameliorated after RBE administration. Furthermore, data from mRNA and protein expression studies revealed an up-regulation of mitochondrial proteins in RBE-fed mice, suggesting an increase in mitochondrial content which is mediated by a peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α)-dependent mechanism. Our findings suggest that a long-term treatment with a nutraceutical containing RBE could be useful for slowing down brain aging and thereby delaying or even preventing AD. PMID:27350374

  11. Traumatic Brain Injury in Qatar: Age Matters—Insights from a 4-Year Observational Study

    Directory of Open Access Journals (Sweden)

    Moamena El-Matbouly

    2013-01-01

    Full Text Available Background. Overall traumatic brain injury (TBI incidence and related death rates vary across different age groups. Objectives. To evaluate the incidence, causes, and outcome of TBI in adolescents and young adult population in Qatar. Method. This was a retrospective review of all TBIs admitted to the trauma center between January 2008 and December 2011. Demographics, mechanism of injury, morbidity, and mortality were analyzed in different age groups. Results. A total of 1665 patients with TBI were admitted; the majority were males (92% with a mean age of 28 ± 16 years. The common mechanism of injury was motor vehicle crashes and falls from height (51% and 35%, resp.. TBI was incidentally higher in young adults (34% and middle age group (21%. The most frequent injuries were contusion (40%, subarachnoid (25%, subdural (24%, and epidural hemorrhage (18%. The mortality rate was 11% among TBI patients. Mortality rates were 8% and 12% among adolescents and young adults, respectively. The highest mortality rate was observed in elderly patients (35%. Head AIS, ISS, and age were independent predictors for mortality. Conclusion. Adolescents and adults sustain significant portions of TBI, whereas mortality is much higher in the older group. Public awareness and injury prevention campaigns should target young population.

  12. Brain nitric oxides synthase in major pelvic ganglia of aged (LETO) and diabetic (OLETF) rats.

    Science.gov (United States)

    Salama, N; Tamura, M; Tsuruo, Y; Ishimura, K; Kagawa, S

    2002-01-01

    This study was conducted to evaluate the effects of aging and diabetes mellitus (DM) on brain nitric oxide synthase (bNOS) expression in major pelvic ganglia (MPG) of rats. Otsuka Long Evans Tokushima Fatty rats (12, 30, and 70 weeks old), which are genetic models with non-insulin-dependent DM (NIDDM), and age-matched nondiabetic Long Evans Tokushima Otsuka controls were used. The MPG of all rats in this study were subjected to cryo-sectioning and staining with bNOS polyclonal AB and rhodamine-conjugated rabbit IgG. Fluorescence intensities of the stained neurons were assessed in randomly selected fields per each specimen. Animals of both groups revealed significant decline in the staining intensity of their neurons with aging and the progress of DM, but diabetic rats showed more decline than controls. In conclusion, both aging and NIDDM could decrease bNOS expression in rat MPG. However, NIDDM has a more evident effect than aging on that expression. The decrease in bNOS may cause a disturbance in functions of the target pelvic structures of these ganglia under both conditions. PMID:12230824

  13. Cyclin A2 promotes DNA repair in the brain during both development and aging.

    Science.gov (United States)

    Gygli, Patrick E; Chang, Joshua C; Gokozan, Hamza N; Catacutan, Fay P; Schmidt, Theresa A; Kaya, Behiye; Goksel, Mustafa; Baig, Faisal S; Chen, Shannon; Griveau, Amelie; Michowski, Wojciech; Wong, Michael; Palanichamy, Kamalakannan; Sicinski, Piotr; Nelson, Randy J; Czeisler, Catherine; Otero, José J

    2016-07-01

    Various stem cell niches of the brain have differential requirements for Cyclin A2. Cyclin A2 loss results in marked cerebellar dysmorphia, whereas forebrain growth is retarded during early embryonic development yet achieves normal size at birth. To understand the differential requirements of distinct brain regions for Cyclin A2, we utilized neuroanatomical, transgenic mouse, and mathematical modeling techniques to generate testable hypotheses that provide insight into how Cyclin A2 loss results in compensatory forebrain growth during late embryonic development. Using unbiased measurements of the forebrain stem cell niche, we parameterized a mathematical model whereby logistic growth instructs progenitor cells as to the cell-types of their progeny. Our data was consistent with prior findings that progenitors proliferate along an auto-inhibitory growth curve. The growth retardation inCCNA2-null brains corresponded to cell cycle lengthening, imposing a developmental delay. We hypothesized that Cyclin A2 regulates DNA repair and that CCNA2-null progenitors thus experienced lengthened cell cycle. We demonstrate that CCNA2-null progenitors suffer abnormal DNA repair, and implicate Cyclin A2 in double-strand break repair. Cyclin A2's DNA repair functions are conserved among cell lines, neural progenitors, and hippocampal neurons. We further demonstrate that neuronal CCNA2 ablation results in learning and memory deficits in aged mice. PMID:27425845

  14. Histologic assessment of the age of recent brain infarcts in man.

    Science.gov (United States)

    Chuaqui, R; Tapia, J

    1993-09-01

    In order to design a dating system based on the microscopic picture of brain infarcts of recent onset, we performed the histological examination of 31 infarcts covering the first 4 weeks of evolution in 30 autopsy cases. The date of the cerebral vascular accident was clinically established in every case. There were 13 men and 17 women with a mean age of 65 years. Hemorrhagic infarcts were found in 15 cases and anemic infarcts in 16 cases. Based on the histological features four periods were identified: the first period, from day 1 through day 4, was characterized by the predominance of eosinophilic neurons and necrotic oligodendrocytes; the second period, from day 5 through day 7, differed from the first by the appearance of macrophages and of newly formed blood vessels; the third period, from day 8 through day 14, showed neuronal ghosts, macrophages, astrocytic proliferation, gemistocytes, and absence of neutrophils; and in the fourth period, from day 15 through day 27, there were no eosinophilic neurons, and neither necrotic oligodendrocytes nor myelin in the central portion of the infarct were identified. By assessing the histological features and accurately correlating the findings with the corresponding clinical data, we have been able to describe four distinct microscopic patterns of the first month of evolution of brain infarcts. The present findings may be considered useful morphological clues to better characterize the early evolutional phase of brain infarcts in humans. PMID:8360701

  15. The effect of aging on synaptosomal Ca2+ transport in the brain.

    Science.gov (United States)

    Sun, A Y; Seaman, R N

    1977-03-01

    The effect of aging on Ca2+ -transport in synaptosomal preparations from rat brains was assessed by measuring the accumulation of radioactive 45Ca within these particles. Four groups of rats at 6, 12 24 and 30 months of age were used for this study. Synaptosomal particles were isolated from the cerebral cortex of each animal and the radioactive 45Ca inside the particles were measured after incubating the particles with media containing an energy source and 45Ca Cl2. Results indicated that the transport of 45Ca was lower in the younger rats than the older groups. A 20% increase was consistent with the old rats (30 mo) as compared with the young ones (6 mo). The increase in Ca2+ -transport across synaptic plasma membranes may be related to the transmitter release and behavioral activity after senescence. PMID:885150

  16. Age-related decreased inhibitory versus excitatory gene expression in the adult autistic brain

    Directory of Open Access Journals (Sweden)

    Louie Nathan van de Lagemaat

    2014-12-01

    Full Text Available Autism spectrum disorders (ASDs are neurodevelopmental disorders characterised by impaired social interaction and communication, and restricted behaviour and interests. A disruption in the balance of excitatory and inhibitory neurotransmission has been hypothesised to underlie these disorders. Here we demonstrate that genes of both pathways are affected by ASD, and that gene expression of inhibitory and excitatory genes is altered in the cerebral cortex of adult but not younger autistic individuals. We have developed a measure for the difference in the level of excitation and inhibition based on gene expression and observe that in this measure inhibition is decreased relative to excitation in adult ASD compared to control. This difference was undetectable in young autistic brains. Given that many psychiatric features of autism are already present at an early age, this suggests that the observed imbalance in gene expression is an ageing phenomenon in ASD rather than its underlying cause.

  17. Age-related changes in brain hemodynamics; A calibrated MRI study

    DEFF Research Database (Denmark)

    De Vis, J B; Hendrikse, J; Bhogal, A;

    2015-01-01

    INTRODUCTION: Blood oxygenation-level dependent (BOLD) magnetic resonance imaging signal changes in response to stimuli have been used to evaluate age-related changes in neuronal activity. Contradictory results from these types of experiments have been attributed to differences in cerebral blood....... A dual-echo pseudocontinuous arterial spin labeling (ASL) sequence was performed during normocapnic, hypercapnic, and hyperoxic breathing challenges. Whole brain and regional gray matter values of CBF, ASL cerebrovascular reactivity (CVR), BOLD CVR, oxygen extraction fraction (OEF), and CMRO2 were...... could potentially be explained by differences in EtCO2 . Regional CMRO2 was lower in older subjects. BOLD studies should take this into account when investigating age-related changes in neuronal activity....

  18. Cognitive activity, cognitive function, and brain diffusion characteristics in old age.

    Science.gov (United States)

    Arfanakis, Konstantinos; Wilson, Robert S; Barth, Christopher M; Capuano, Ana W; Vasireddi, Anil; Zhang, Shengwei; Fleischman, Debra A; Bennett, David A

    2016-06-01

    The objective of this work was to test the hypotheses that a) more frequent cognitive activity in late life is associated with higher brain diffusion anisotropy and lower trace of the diffusion tensor, and b) brain diffusion characteristics partially mediate the association of late life cognitive activity with cognition. As part of a longitudinal cohort study, 379 older people without dementia rated their frequency of participation in cognitive activities, completed a battery of cognitive function tests, and underwent diffusion tensor imaging. We used tract-based spatial statistics to test the association between late life cognitive activity and brain diffusion characteristics. Clusters with statistically significant findings defined regions of interest in which we tested the hypothesis that diffusion characteristics partially mediate the association of late life cognitive activity with cognition. More frequent cognitive activity in late life was associated with higher level of global cognition after adjustment for age, sex, education, and indicators of early life cognitive enrichment (p = 0.001). More frequent cognitive activity was also related to higher fractional anisotropy in the left superior and inferior longitudinal fasciculi, left fornix, and corpus callosum, and lower trace in the thalamus (p < 0.05, FWE-corrected). After controlling for fractional anisotropy or trace from these regions, the regression coefficient for the association of late life cognitive activity with cognition was reduced by as much as 26 %. These findings suggest that the association of late life cognitive activity with cognition may be partially mediated by brain diffusion characteristics. PMID:25982658

  19. Regional differences in gene expression and promoter usage in aged human brains

    KAUST Repository

    Pardo, Luba M.

    2013-02-19

    To characterize the promoterome of caudate and putamen regions (striatum), frontal and temporal cortices, and hippocampi from aged human brains, we used high-throughput cap analysis of gene expression to profile the transcription start sites and to quantify the differences in gene expression across the 5 brain regions. We also analyzed the extent to which methylation influenced the observed expression profiles. We sequenced more than 71 million cap analysis of gene expression tags corresponding to 70,202 promoter regions and 16,888 genes. More than 7000 transcripts were differentially expressed, mainly because of differential alternative promoter usage. Unexpectedly, 7% of differentially expressed genes were neurodevelopmental transcription factors. Functional pathway analysis on the differentially expressed genes revealed an overrepresentation of several signaling pathways (e.g., fibroblast growth factor and wnt signaling) in hippocampus and striatum. We also found that although 73% of methylation signals mapped within genes, the influence of methylation on the expression profile was small. Our study underscores alternative promoter usage as an important mechanism for determining the regional differences in gene expression at old age.

  20. Age-related influences of prior sleep on brain activation during verbal encoding

    Directory of Open Access Journals (Sweden)

    Michelle B Jonelis

    2012-04-01

    Full Text Available Disrupted sleep is more common in older adults (OA than younger adults (YA, often co-morbid with other conditions. How these sleep disturbances affect cognitive performance is an area of active study. We examined whether brain activation during verbal encoding correlates with sleep quantity and quality the night before testing in a group of healthy OA and YA. Twenty-seven OA (ages 59-82 and twenty-seven YA (ages 19-36 underwent one night of standard polysomnography. Twelve hours post-awakening, subjects performed a verbal encoding task while undergoing functional MRI. Analyses examined the group (OA vs. YA by prior sleep quantity (Total Sleep Time (TST or quality (Sleep Efficiency (SE interaction on cerebral activation, controlling for performance. Longer TST promoted higher levels of activation in the bilateral anterior parahippocampi in OA and lower activation levels in the left anterior parahippocampus in YA. Greater SE promoted higher activation levels in the left posterior parahippocampus and right inferior frontal gyrus in YA, but not in OA. The roles of these brain regions in verbal encoding suggest, in OA, longer sleep duration may facilitate functional compensation during cognitive challenges. By contrast, in YA, shorter sleep duration may necessitate functional compensation to maintain cognitive performance, similar to what is seen following acute sleep deprivation. Additionally, in YA, better sleep quality may improve semantic retrieval processes, thereby aiding encoding.

  1. The lateralization of intrinsic networks in the aging brain implicates the effects of cognitive training

    Directory of Open Access Journals (Sweden)

    Cheng eLuo

    2016-03-01

    Full Text Available Lateralization of function is an important organization of human brain. The distribution of intrinsic networks in the resting brain is strongly related to the cognitive function, gender and age. In this study, the longitudinal design with one year duration was used to evaluate the cognitive training effects on the lateralization of intrinsic networks among healthy older adults. The subjects were divided into two groups randomly: one with multi-domain cognitive training in three month, the other as a wait-list control group. Resting state fMRI data were acquired before training and one year after training. We analyzed the functional lateralization in ten common resting state fMRI networks. We observed statically significant training effects on the lateralization of two important RSNs related to high-level cognition: right- and left- frontoparietal networks. Especially, the lateralization of left-frontoparietal network were retained well in training group, but decreased in control group. The increased lateralization with aging was observed on the cerebellum network, in which the lateralization was significantly increased in control group although the same change tendency was observed in training group. These findings indicate that the lateralization of the high-level cognitive intrinsic networks is sensitive to the multi-domain cognitive training. This study provides a neuroimaging evidence to support that the cognitive training should have advantages to the cognitive decline in healthy older adults.

  2. Clinical implications of brain atrophy by computed tomography in patients with age-related dementia

    International Nuclear Information System (INIS)

    The purpose of the present study is to clarify the clinical significance of brain atrophy by computed tomography in age-related dementia. Eighty elderly patients with clinical diagnosis of presenile or senile dementia whose mental states were assessed clinically and by several psychometric test were studied by computed tomography. Patients with suspected cerebrovascular disorders and normal pressure hydrocephalus were excluded. Three tomographic sections through anterior and posterior horns and cella media of lateral ventricles and cortex with intracranial space of 60 - 80 cm2 were evaluated. CSF spaces (%) were measured as an index of brain atrophy. The measurement of CSF spaces (%) was carried out by the computerized planimetric method to avoid visual definition of ventricular borders. In this study, CSF spaces comprised ventricular and subarachnoid spaces. Hasegawa's dementia scale, Bender-Gestalt test and Kohs' block design test were employed for the cognitive assessment of the subjects. In two sections through lateral ventricles, significant correlations were obtained between CSF spaces (%) and scores of Hasegawa's dementia scale and Kohs' block design test. Scores of Bender-Gestalt test did not correlate with CSF spaces (%) in these two sections. In the section through cortex, no correlation were found between CSF spaces (%) and scores of any psychometric test. Also, no positive correlations were obtained between age and CSF spaces (%) in the three sections. (author)

  3. Morphological and pathological evolution of the brain microcirculation in aging and Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Jesse M Hunter

    Full Text Available Key pathological hallmarks of Alzheimer's disease (AD, including amyloid plaques, cerebral amyloid angiopathy (CAA and neurofibrillary tangles do not completely account for cognitive impairment, therefore other factors such as cardiovascular and cerebrovascular pathologies, may contribute to AD. In order to elucidate the microvascular changes that contribute to aging and disease, direct neuropathological staining and immunohistochemistry, were used to quantify the structural integrity of the microvasculature and its innervation in three oldest-old cohorts: 1 nonagenarians with AD and a high amyloid plaque load; 2 nonagenarians with no dementia and a high amyloid plaque load; 3 nonagenarians without dementia or amyloid plaques. In addition, a non-demented (ND group (average age 71 years with no amyloid plaques was included for comparison. While gray matter thickness and overall brain mass were reduced in AD compared to ND control groups, overall capillary density was not different. However, degenerated string capillaries were elevated in AD, potentially suggesting greater microvascular "dysfunction" compared to ND groups. Intriguingly, apolipoprotein ε4 carriers had significantly higher string vessel counts relative to non-ε4 carriers. Taken together, these data suggest a concomitant loss of functional capillaries and brain volume in AD subjects. We also demonstrated a trend of decreasing vesicular acetylcholine transporter staining, a marker of cortical cholinergic afferents that contribute to arteriolar vasoregulation, in AD compared to ND control groups, suggesting impaired control of vasodilation in AD subjects. In addition, tyrosine hydroxylase, a marker of noradrenergic vascular innervation, was reduced which may also contribute to a loss of control of vasoconstriction. The data highlight the importance of the brain microcirculation in the pathogenesis and evolution of AD.

  4. Age-related changes of glutathione content, glucose transport and metabolism, and mitochondrial electron transfer function in mouse brain

    International Nuclear Information System (INIS)

    To evaluate the oxidative stress-related parameters and to determine their order of appearance in the brain aging process, radionuclide experiments were carried out on male DBF1 mice at 3, 12, 24 and 30 months of age. The content of nonprotein sulfhydryl compounds, mainly glutathione, was estimated with technetium-99m meso-hexamethyl propyleneamine oxime ([99mTc]meso-HMPAO) tissue sampling. Glucose transport and metabolism was examined with [1-14C]2-deoxy-D-glucose (2-DG) tissue sampling. Mitochondrial electron transport function was estimated with [15O]O2 gas-tissue ARG. [99mTc]Meso-HMPAO uptake in brain expressed as standardized uptake value (SUV), (radioactivity in brain tissue/tissue weight)/(total administered radioactivity/body weight), reached maximum at 12 months of age and decreased at 24 and 30 months of age in every region examined. The pattern of 2-DG, expressed as SUV, showed a tendency to increase rather than decrease with aging. [15O]O2 fixation in brain slices remained constant until 24 months, while it decreased significantly at 30 months of age. The results suggested the possibility of using imaging techniques in vivo for longitudinal evaluation of the aging process and indicated reduction of nonprotein sulfhydryl compounds including GSH at the early stages of aging may also accelerate the dysfunction of mitochondrial electron transport and neurodegeneration

  5. Coordination of gene expression of arachidonic and docosahexaenoic acid cascade enzymes during human brain development and aging.

    Directory of Open Access Journals (Sweden)

    Veronica H Ryan

    Full Text Available The polyunsaturated arachidonic and docosahexaenoic acids (AA and DHA participate in cell membrane synthesis during neurodevelopment, neuroplasticity, and neurotransmission throughout life. Each is metabolized via coupled enzymatic reactions within separate but interacting metabolic cascades.AA and DHA pathway genes are coordinately expressed and underlie cascade interactions during human brain development and aging.The BrainCloud database for human non-pathological prefrontal cortex gene expression was used to quantify postnatal age changes in mRNA expression of 34 genes involved in AA and DHA metabolism.Expression patterns were split into Development (0 to 20 years and Aging (21 to 78 years intervals. Expression of genes for cytosolic phospholipases A2 (cPLA2, cyclooxygenases (COX-1 and -2, and other AA cascade enzymes, correlated closely with age during Development, less so during Aging. Expression of DHA cascade enzymes was less inter-correlated in each period, but often changed in the opposite direction to expression of AA cascade genes. Except for the PLA2G4A (cPLA2 IVA and PTGS2 (COX-2 genes at 1q25, highly inter-correlated genes were at distant chromosomal loci.Coordinated age-related gene expression during the brain Development and Aging intervals likely underlies coupled changes in enzymes of the AA and DHA cascades and largely occur through distant transcriptional regulation. Healthy brain aging does not show upregulation of PLA2G4 or PTGS2 expression, which was found in Alzheimer's disease.

  6. Long-term cognitive correlates of traumatic brain injury across adulthood and interactions with APOE genotype, sex, and age cohorts.

    OpenAIRE

    Eramudugolla, R.; Bielak, AA; Bunce, D; Easteal, S; Cherbuin, N; Anstey, KJ

    2014-01-01

    There is continuing debate about long-term effects of brain injury. We examined a range of traumatic brain injury (TBI) variables (TBI history, severity, frequency, and age of injury) as predictors of cognitive outcome over 8 years in an adult population, and interactions with apolipoprotein E (APOE) genotype, sex, and age cohorts. Three randomly sampled age cohorts (20-24, 40-44, 60-64 years at baseline; N = 6333) were each evaluated three times over 8 years. TBI variables, based on self-rep...

  7. Effect of age on neocortical brain cells in 90+ year old human females--a cell counting study

    DEFF Research Database (Denmark)

    Fabricius, Katrine; Jacobsen, Jette Stub; Pakkenberg, Bente

    2013-01-01

    An increasing number of people are living past the age of 100 years, but little is known about what differentiates centenarians from the rest of the population. In this study, brains from female subjects in 3 different age groups, 65-75 years (n = 8), 76-85 years (n = 8), and 94-105 years (n = 7...... by a significant difference in the total number of neocortical oligodendrocytes that differed significantly between the youngest (27.5 × 10(9)) and oldest (18.1. × 10(9), p = 0.006) age groups. In conclusion, very old individuals have brain neuron numbers comparable with younger individuals, which may...

  8. In vivo molecular imaging of the GABA/benzodiazepine receptor complex in the aged rat brain.

    Science.gov (United States)

    Hoekzema, Elseline; Rojas, Santiago; Herance, Raúl; Pareto, Deborah; Abad, Sergio; Jiménez, Xavier; Figueiras, Francisca P; Popota, Foteini; Ruiz, Alba; Flotats, Núria; Fernández, Francisco J; Rocha, Milagros; Rovira, Mariana; Víctor, Víctor M; Gispert, Juan D

    2012-07-01

    The GABA-ergic system, known to regulate neural tissue genesis during cortical development, has been postulated to play a role in cerebral aging processes. Using in vivo molecular imaging and voxel-wise quantification, we aimed to assess the effects of aging on the benzodiazepine (BDZ) recognition site of the GABA(A) receptor. To visualize BDZ site availability, [(11)C]-flumazenil microPET acquisitions were conducted in young and old rats. The data were analyzed and region of interest analyses were applied to validate the voxel-wise approach. We observed decreased [(11)C]-flumazenil binding in the aged rat brains in comparison with the young control group. More specifically, clusters of reduced radioligand uptake were detected in the bilateral hippocampus, cerebellum, midbrain, and bilateral frontal and parieto-occipital cortex. Our results support the pertinence of voxel-wise quantification in the analysis of microPET data. Moreover, these findings indicate that the aging process involves declines in neural BDZ recognition site availability, proposed to reflect alterations in GABA(A) receptor subunit polypeptide expression.

  9. Hippocampal neurogenesis levels predict WATERMAZE search strategies in the aging brain.

    Directory of Open Access Journals (Sweden)

    Joana Gil-Mohapel

    Full Text Available The hippocampus plays a crucial role in the formation of spatial memories, and it is thought that adult hippocampal neurogenesis may participate in this form of learning. To better elucidate the relationship between neurogenesis and spatial learning, we examined both across the entire life span of mice. We found that cell proliferation, neuronal differentiation, and neurogenesis significantly decrease with age, and that there is an abrupt reduction in these processes early on, between 1.5-3 months of age. After this, the neurogenic capacity continues to decline steadily. The initial abrupt decline in adult neurogenesis was paralleled by a significant reduction in Morris Water Maze performance, however overall learning and memory remained constant thereafter. Further analysis of the search strategies employed revealed that reductions in neurogenesis in the aging brain were strongly correlated with the adoption of spatially imprecise search strategies. Overall, performance measures of learning and memory in the Morris Water Maze were maintained at relatively constant levels in aging animals due to an increase in the use of spatially imprecise search strategies.

  10. Brain SPECT of chronic fatigue syndrome (CFS): SPM analysis of two age groups

    International Nuclear Information System (INIS)

    Full text: Chronic fatigue syndrome (CFS) is a complex disorder characterised by profound fatigue and neuropsychiatric dysfunction. Previous studies with cerebral perfusion SPECT (rCBF) scans were performed with inhomogeneous patient populations and were not analysed with Statistical Parametric Mapping (SPM). We have used SPM to study subjects with moderate CFS based on the Fukuda criteria, who were not on medication and not depressed, compared to age matched control subjects. An apparent bimodal age distribution has been observed in CFS. Subjects were therefore divided into two age groups: 16-35 or under 35 (17 CFS, 11 control) and 36-61 or over 35 (15 CFS, 15 control). HMPAO brain SPECT was acquired on a 3-head camera. After lower window scatter subtraction, reconstruction with attenuation correction (mu=0.15/cm) and editing of facial activity, scans were spatially normalised (affine + 2x3x2 nonlinear) to SPM's anatomical space. SPM statistical analysis yielded the location, amplitude and corrected p-value of significant focal rCBF deficits. They were: for under 35, left lateral temporal lobe (13%, 0.004), the left insular region (15%, 0.006) and the right lentiform nucleus (15%, 0.01); and for over 35 the left lentiform nucleus (18%, 0.01). Counts at the most significant voxel in the under 35 age group permitted separation of the CFS and control groups with sensitivity 94% and specificity 100%. We are acquiring more controls to better define the age and sex dependence of rCBF in CFS. Analysis of associated clinical variables will be used to investigate the observed differences between the two age groups. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

  11. Parameters of glucose metabolism and the aging brain: a magnetization transfer imaging study of brain macro- and micro-structure in older adults without diabetes.

    Science.gov (United States)

    Akintola, Abimbola A; van den Berg, Annette; Altmann-Schneider, Irmhild; Jansen, Steffy W; van Buchem, Mark A; Slagboom, P Eline; Westendorp, Rudi G; van Heemst, Diana; van der Grond, Jeroen

    2015-08-01

    Given the concurrent, escalating epidemic of diabetes mellitus and neurodegenerative diseases, two age-related disorders, we aimed to understand the relation between parameters of glucose metabolism and indices of pathology in the aging brain. From the Leiden Longevity Study, 132 participants (mean age 66 years) underwent a 2-h oral glucose tolerance test to assess glucose tolerance (fasted and area under the curve (AUC) glucose), insulin sensitivity (fasted and AUC insulin and homeostatic model assessment of insulin sensitivity (HOMA-IS)) and insulin secretion (insulinogenic index). 3-T brain MRI was used to detect macro-structural damage (atrophy, white matter hyper-intensities, infarcts and/or micro-bleeds) and magnetization transfer imaging (MTI) to detect loss of micro-structural homogeneity that remains otherwise invisible on conventional MRI. Macro-structurally, higher fasted glucose was significantly associated with white matter atrophy (P = 0.028). Micro-structurally, decreased magnetization transfer ratio (MTR) peak height in gray matter was associated with higher fasted insulin (P = 0.010), AUCinsulin (P = 0.001), insulinogenic index (P = 0.008) and lower HOMA-IS index (P macro-structural damage, impaired insulin action was associated more strongly with reduced micro-structural brain parenchymal homogeneity. These findings offer some insight into the association between different parameters of glucose metabolism (impairment of which is characteristic of diabetes mellitus) and brain aging.

  12. Real-Time fMRI in Neuroscience Research and Its Use in Studying the Aging Brain

    Science.gov (United States)

    Rana, Mohit; Varan, Andrew Q.; Davoudi, Anis; Cohen, Ronald A.; Sitaram, Ranganatha; Ebner, Natalie C.

    2016-01-01

    Cognitive decline is a major concern in the aging population. It is normative to experience some deterioration in cognitive abilities with advanced age such as related to memory performance, attention distraction to interference, task switching, and processing speed. However, intact cognitive functioning in old age is important for leading an independent day-to-day life. Thus, studying ways to counteract or delay the onset of cognitive decline in aging is crucial. The literature offers various explanations for the decline in cognitive performance in aging; among those are age-related gray and white matter atrophy, synaptic degeneration, blood flow reduction, neurochemical alterations, and change in connectivity patterns with advanced age. An emerging literature on neurofeedback and Brain Computer Interface (BCI) reports exciting results supporting the benefits of volitional modulation of brain activity on cognition and behavior. Neurofeedback studies based on real-time functional magnetic resonance imaging (rtfMRI) have shown behavioral changes in schizophrenia and behavioral benefits in nicotine addiction. This article integrates research on cognitive and brain aging with evidence of brain and behavioral modification due to rtfMRI neurofeedback. We offer a state-of-the-art description of the rtfMRI technique with an eye towards its application in aging. We present preliminary results of a feasibility study exploring the possibility of using rtfMRI to train older adults to volitionally control brain activity. Based on these first findings, we discuss possible implementations of rtfMRI neurofeedback as a novel technique to study and alleviate cognitive decline in healthy and pathological aging. PMID:27803662

  13. The Relevance of Short-Range Fibers to Cognitive Efficiency and Brain Activation in Aging and Dementia

    OpenAIRE

    Junling Gao; Raymond T F Cheung; Ying-Shing Chan; Leung-Wing Chu; Mak, Henry K. F.; Lee, Tatia M. C.

    2014-01-01

    The integrity of structural connectivity in a functional brain network supports the efficiency of neural processing within relevant brain regions. This study aimed to quantitatively investigate the short- and long-range fibers, and their differential roles in the lower cognitive efficiency in aging and dementia. Three groups of healthy young, healthy older adults and patients with Alzheimer's disease (AD) participated in this combined functional magnetic resonance imaging (fMRI) and diffusion...

  14. SIRT1 in the Brain – Connections with Aging-associated Disorders and Lifespan

    Directory of Open Access Journals (Sweden)

    Fanny eNg

    2015-03-01

    Full Text Available The silent mating type information regulation 2 proteins (sirtuins 1 of class III histone deacetylases have been associated with health span and longevity. SIRT1, the best studied member of the mammalian sirtuins, has a myriad of roles in multiple tissues and organs. However, a significant part of SIRT1’s role that impinges on aging and lifespan may lie in its activities in the central nervous system (CNS neurons. Systemically, SIRT1 influences energy metabolism and circadian rhythm through its activity in the hypothalamic nuclei. From a cell biological perspective, SIRT1 is a crucial component of multiple interconnected regulatory networks that modulate dendritic and axonal growth, as well as survival against stress. This neuronal cell autonomous activity of SIRT1 is also important for neuronal plasticity, cognitive functions, as well as protection against aging-associated neuronal degeneration and cognitive decline. We discuss recent findings that have shed light on the various activities of SIRT1 in the brain, which collectively impinge on aging-associated disorders and lifespan.

  15. Path Complexity in Virtual Water Maze Navigation: Differential Associations with Age, Sex, and Regional Brain Volume.

    Science.gov (United States)

    Daugherty, Ana M; Yuan, Peng; Dahle, Cheryl L; Bender, Andrew R; Yang, Yiqin; Raz, Naftali

    2015-09-01

    Studies of human navigation in virtual maze environments have consistently linked advanced age with greater distance traveled between the start and the goal and longer duration of the search. Observations of search path geometry suggest that routes taken by older adults may be unnecessarily complex and that excessive path complexity may be an indicator of cognitive difficulties experienced by older navigators. In a sample of healthy adults, we quantify search path complexity in a virtual Morris water maze with a novel method based on fractal dimensionality. In a two-level hierarchical linear model, we estimated improvement in navigation performance across trials by a decline in route length, shortening of search time, and reduction in fractal dimensionality of the path. While replicating commonly reported age and sex differences in time and distance indices, a reduction in fractal dimension of the path accounted for improvement across trials, independent of age or sex. The volumes of brain regions associated with the establishment of cognitive maps (parahippocampal gyrus and hippocampus) were related to path dimensionality, but not to the total distance and time. Thus, fractal dimensionality of a navigational path may present a useful complementary method of quantifying performance in navigation.

  16. Maternal separation produces alterations of forebrain brain-derived neurotrophic factor expression in differently aged rats

    Directory of Open Access Journals (Sweden)

    Qiong eWang

    2015-09-01

    Full Text Available Early postnatal maternal separation (MS can play an important role in the development of psychopathologies during ontogeny. In the present study, we investigated the effects of repeated MS (4 h per day from postnatal day [PND] 1–21 on the brain-derived neurotrophic factor (BDNF expression in the medial prefrontal cortex (mPFC, the nucleus accumbens (NAc and the hippocampus of male and female juvenile (PND 21, adolescent (PND 35 and young adult (PND 56 Wistar rats. The results indicated that MS increased BDNF in the CA1 and the dentate gyrus (DG of adolescent rats as well as in the DG of young adult rats. However, the expression of BDNF in the mPFC in the young adult rats was decreased by MS. Additionally, in the hippocampus, there was decreased BDNF expression with age in both the MS and socially reared rats. However, in the mPFC, the BDNF expression was increased with age in the socially reared rats; nevertheless, the BDNF expression was significantly decreased in the MS young adult rats. In the NAc, the BDNF expression was increased with age in the male NMS rats, and the young adult female MS rats had less BDNF expression than the adolescent female MS rats. The

  17. Brain Activation and Psychomotor Speed in Middle-Aged Patients with Type 1 Diabetes: Relationships with Hyperglycemia and Brain Small Vessel Disease

    Directory of Open Access Journals (Sweden)

    Misun Hwang

    2016-01-01

    Full Text Available Slower psychomotor speed is very common in patients with type 1 diabetes mellitus (T1D, but the underlying mechanisms are not clear. We propose that hyperglycemia is associated with slower psychomotor speed via disruption of brain activation. Eighty-five adults (48% women, mean age: 49.0 years, mean duration: 40.8 with childhood onset T1D were recruited for this cross-sectional study. Median response time in seconds (longer = worse performance and brain activation were measured while performing a psychomotor speed task. Exposure to hyperglycemia, measured as glycosylated hemoglobin A1c, was associated with longer response time and with higher activation in the inferior frontal gyrus and primary sensorimotor and dorsal cingulate cortex. Higher activation in inferior frontal gyrus, primary sensorimotor cortex, thalamus, and cuneus was related to longer response times; in contrast, higher activation in the superior parietal lobe was associated with shorter response times. Associations were independent of small vessel disease in the brain or other organs. In this group of middle-aged adults with T1D, the pathway linking chronic hyperglycemia with slower processing speed appears to include increased brain activation, but not small vessel disease. Activation in the superior parietal lobe may compensate for dysregulation in brain activation in the presence of hyperglycemia.

  18. Cigarette smoking accelerated brain aging and induced pre-Alzheimer-like neuropathology in rats.

    Directory of Open Access Journals (Sweden)

    Yuen-Shan Ho

    Full Text Available Cigarette smoking has been proposed as a major risk factor for aging-related pathological changes and Alzheimer's disease (AD. To date, little is known for how smoking can predispose our brains to dementia or cognitive impairment. This study aimed to investigate the cigarette smoke-induced pathological changes in brains. Male Sprague-Dawley (SD rats were exposed to either sham air or 4% cigarette smoke 1 hour per day for 8 weeks in a ventilated smoking chamber to mimic the situation of chronic passive smoking. We found that the levels of oxidative stress were significantly increased in the hippocampus of the smoking group. Smoking also affected the synapse through reducing the expression of pre-synaptic proteins including synaptophysin and synapsin-1, while there were no changes in the expression of postsynaptic protein PSD95. Decreased levels of acetylated-tubulin and increased levels of phosphorylated-tau at 231, 205 and 404 epitopes were also observed in the hippocampus of the smoking rats. These results suggested that axonal transport machinery might be impaired, and the stability of cytoskeleton might be affected by smoking. Moreover, smoking affected amyloid precursor protein (APP processing by increasing the production of sAPPβ and accumulation of β-amyloid peptide in the CA3 and dentate gyrus region. In summary, our data suggested that chronic cigarette smoking could induce synaptic changes and other neuropathological alterations. These changes might serve as evidence of early phases of neurodegeneration and may explain why smoking can predispose brains to AD and dementia.

  19. Prevalence, and Intellectual Outcome of Unilateral Focal Cortical Brain Damage as a Function of Age, Sex and Aetiology

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    C. M. J. Braun

    2002-01-01

    Full Text Available Neurologists and neuropsychologists are aware that aging men are more at risk than women for brain damage, principally because of the well known male-predominant risk for cardiovascular disease and related cerebrovascular accidents. However, a disproportion in prevalence of brain damage between the sexes in childhood may be less suspected. Furthermore, sex-specific risk for other aetiologies of brain damage may be little known, whether in the pediatric or adult populations. Proposals of a sex difference in cognitive recovery from brain damage have also been controversial. Six hundred and thirty five “consecutive” cases with cortical focal lesions including cases of all ages and both sexes were reviewed. Aetiology of the lesion was determined for each case as was postlesion IQ. Risk was highly male prevalent in all age groups, with a predominance of cardiovascular aetiology explaining much of the adult male prevalence. However, several other aetiological categories were significantly male prevalent in juveniles (mitotic, traumatic, dysplasic and adults (mitotic, traumatic. There was no sex difference in outcome (i.e., postlesion IQ of these cortical brain lesions for the cohort as a whole, after statistical removal of the influence of lesion extent, aetiology and presence of epilepsy. Mechanisms potentially responsible for sex differences in prevalence, aetiology of brain damage, and recovery, are reviewed and discussed.

  20. Bacopa monnieri as an Antioxidant Therapy to Reduce Oxidative Stress in the Aging Brain

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    Tamara Simpson

    2015-01-01

    Full Text Available The detrimental effect of neuronal cell death due to oxidative stress and mitochondrial dysfunction has been implicated in age-related cognitive decline and neurodegenerative disorders such as Alzheimer’s disease. The Indian herb Bacopa monnieri is a dietary antioxidant, with animal and in vitro studies indicating several modes of action that may protect the brain against oxidative damage. In parallel, several studies using the CDRI08 extract have shown that extracts of Bacopa monnieri improve cognitive function in humans. The biological mechanisms of this cognitive enhancement are unknown. In this review we discuss the animal studies and in vivo evidence for Bacopa monnieri as a potential therapeutic antioxidant to reduce oxidative stress and improve cognitive function. We suggest that future studies incorporate neuroimaging particularly magnetic resonance spectroscopy into their randomized controlled trials to better understand whether changes in antioxidant status in vivo cause improvements in cognitive function.

  1. The Effects of Aging, Malingering, and Traumatic Brain Injury on Computerized Trail-Making Test Performance.

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    David L Woods

    Full Text Available The trail making test (TMT is widely used to assess speed of processing and executive function. However, normative data sets gathered at different sites show significant inconsistencies. Here, we describe a computerized version of the TMT (C-TMT that increases the precision and replicability of the TMT by permitting a segment-by-segment analysis of performance and separate analyses of dwell-time, move-time, and error time. Experiment 1 examined 165 subjects of various ages and found that completion times on both the C-TMT-A (where subjects connect successively numbered circles and the C-TMT-B (where subjects connect circles containing alternating letters and numbers were strongly influenced by age. Experiment 2 examined 50 subjects who underwent three test sessions. The results of the first test session were well fit by the normative data gathered in Experiment 1. Sessions 2 and 3 demonstrated significant learning effects, particularly on the C-TMT-B, and showed good test-retest reliability. Experiment 3 examined performance in subjects instructed to feign symptoms of traumatic brain injury: 44% of subjects produced abnormal completion times on the C-TMT-A, and 18% on the C-TMT-B. Malingering subjects could be distinguished from abnormally slow controls based on (1 disproportionate increases in dwell-time on the C-TMT-A, and (2 greater deficits on the C-TMT-A than on the C-TMT-B. Experiment 4 examined the performance of 28 patients with traumatic brain injury: C-TMT-B completion times were slowed, and TBI patients showed reduced movement velocities on both tests. The C-TMT improves the reliability and sensitivity of the trail making test of processing speed and executive function.

  2. Age differences in brain systems supporting transient and sustained processes involved in prospective memory and working memory.

    Science.gov (United States)

    Peira, Nathalie; Ziaei, Maryam; Persson, Jonas

    2016-01-15

    In prospective memory (PM), an intention to act in response to an external event is formed, retained, and at a later stage, when the event occurs, the relevant action is performed. PM typically shows a decline in late adulthood, which might affect functions of daily living. The neural correlates of this decline are not well understood. Here, 15 young (6 female; age range=23-30years) and 16 older adults (5 female; age range=64-74years) were scanned with fMRI to examine age-related differences in brain activation associated with event-based PM using a task that facilitated the separation of transient and sustained components of PM. We show that older adults had reduced performance in conditions with high demands on prospective and working memory, while no age-difference was observed in low-demanding tasks. Across age groups, PM task performance activated separate sets of brain regions for transient and sustained responses. Age-differences in transient activation were found in fronto-striatal and MTL regions, with young adults showing more activation than older adults. Increased activation in young, compared to older adults, was also found for sustained PM activation in the IFG. These results provide new evidence that PM relies on dissociable transient and sustained cognitive processes, and that age-related deficits in PM can be explained by an inability to recruit PM-related brain networks in old age.

  3. The bilingual brain. Proficiency and age of acquisition of the second language.

    Science.gov (United States)

    Perani, D; Paulesu, E; Galles, N S; Dupoux, E; Dehaene, S; Bettinardi, V; Cappa, S F; Fazio, F; Mehler, J

    1998-10-01

    Functional imaging methods show differences in the pattern of cerebral activation associated with the subject's native language (L1) compared with a second language (L2). In a recent PET investigation on bilingualism we showed that auditory processing of stories in L1 (Italian) engages the temporal lobes and temporoparietal cortex more extensively than L2 (English). However, in that study the Italian subjects learned L2 late and attained a fair, but not an excellent command of this language (low proficiency, late acquisition bilinguals). Thus, the different patterns of activation could be ascribed either to age of acquisition or to proficiency level. In the current study we use a similar paradigm to evaluate the effect of early and late acquisition of L2 in highly proficient bilinguals. We studied a group of Italian-English bilinguals who acquired L2 after the age of 10 years (high proficiency, late acquisition bilinguals) and a group of Spanish-Catalan bilinguals who acquired L2 before the age of 4 years (high proficiency, early acquisition bilinguals). The differing cortical responses we had observed when low proficiency volunteers listened to stories in L1 and L2 were not found in either of the high proficiency groups in this study. Several brain areas, similar to those observed for L1 in low proficiency bilinguals, were activated by L2. These findings suggest that, at least for pairs of L1 and L2 languages that are fairly close, attained proficiency is more important than age of acquisition as a determinant of the cortical representation of L2.

  4. Plasma membrane Ca2+-ATPases:Targets of oxidative stress in brain aging and neurodegeneration

    Institute of Scientific and Technical Information of China (English)

    Asma; Zaidi

    2010-01-01

    The plasma membrane Ca2+-ATPase(PMCA)pumps play an important role in the maintenance of precise levels of intracellular Ca2+[Ca2+]i,essential to the functioning of neurons.In this article,we review evidence showing age-related changes of the PMCAs in synaptic plasma membranes(SPMs).PMCA activity and protein levels in SPMs diminish progressively with increasing age. The PMCAs are very sensitive to oxidative stress and undergo functional and structural changes when exposed to oxidants of physiological relevance.The major signatures of oxidative modification in the PMCAs are rapid inactivation,conformational changes,aggregation, internalization from the plasma membrane and proteolytic degradation.PMCA proteolysis appears to be mediated by both calpains and caspases.The predominance of one proteolytic pathway vs the other,the ensuing pattern of PMCA degradation and its consequence on pump activity depends largely on the type of insult,its intensity and duration.Experimental reduction of PMCA expression not only alters the dynamics of cellular Ca2+ handling but also has a myriad of downstream conse-quences on various aspects of cell function,indicating a broad role of these pumps.Age-and oxidation-related down-regulation of the PMCAs may play an important role in compromised neuronal function in the aging brain and its several-fold increased susceptibility to neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease,and stroke.Therapeutic approaches that protect the PMCAs and stabilize[Ca2+]i homeostasis may be capable of slowing and/or preventing neuronal degeneration.The PMCAs are therefore emerging as a new class of drug targets for therapeutic interventions in various chronic degenerative disorders.

  5. Biochemical assessment of precuneus and posterior cingulate gyrus in the context of brain aging and Alzheimer's disease.

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    Chera L Maarouf

    Full Text Available Defining the biochemical alterations that occur in the brain during "normal" aging is an important part of understanding the pathophysiology of neurodegenerative diseases and of distinguishing pathological conditions from aging-associated changes. Three groups were selected based on age and on having no evidence of neurological or significant neurodegenerative disease: 1 young adult individuals, average age 26 years (n = 9; 2 middle-aged subjects, average age 59 years (n = 5; 3 oldest-old individuals, average age 93 years (n = 6. Using ELISA and Western blotting methods, we quantified and compared the levels of several key molecules associated with neurodegenerative disease in the precuneus and posterior cingulate gyrus, two brain regions known to exhibit early imaging alterations during the course of Alzheimer's disease. Our experiments revealed that the bioindicators of emerging brain pathology remained steady or decreased with advancing age. One exception was S100B, which significantly increased with age. Along the process of aging, neurofibrillary tangle deposition increased, even in the absence of amyloid deposition, suggesting the presence of amyloid plaques is not obligatory for their development and that limited tangle density is a part of normal aging. Our study complements a previous assessment of neuropathology in oldest-old subjects, and within the limitations of the small number of individuals involved in the present investigation, it adds valuable information to the molecular and structural heterogeneity observed along the course of aging and dementia. This work underscores the need to examine through direct observation how the processes of amyloid deposition unfold or change prior to the earliest phases of dementia emergence.

  6. Regionally distinct responses of microglia and glial progenitor cells to whole brain irradiation in adult and aging rats.

    Science.gov (United States)

    Hua, Kun; Schindler, Matthew K; McQuail, Joseph A; Forbes, M Elizabeth; Riddle, David R

    2012-01-01

    Radiation therapy has proven efficacy for treating brain tumors and metastases. Higher doses and larger treatment fields increase the probability of eliminating neoplasms and preventing reoccurrence, but dose and field are limited by damage to normal tissues. Normal tissue injury is greatest during development and in populations of proliferating cells but also occurs in adults and older individuals and in non-proliferative cell populations. To better understand radiation-induced normal tissue injury and how it may be affected by aging, we exposed young adult, middle-aged, and old rats to 10 Gy of whole brain irradiation and assessed in gray- and white matter the responses of microglia, the primary cellular mediators of radiation-induced neuroinflammation, and oligodendrocyte precursor cells, the largest population of proliferating cells in the adult brain. We found that aging and/or irradiation caused only a few microglia to transition to the classically "activated" phenotype, e.g., enlarged cell body, few processes, and markers of phagocytosis, that is seen following more damaging neural insults. Microglial changes in response to aging and irradiation were relatively modest and three markers of reactivity - morphology, proliferation, and expression of the lysosomal marker CD68- were regulated largely independently within individual cells. Proliferation of oligodendrocyte precursors did not appear to be altered during normal aging but increased following irradiation. The impacts of irradiation and aging on both microglia and oligodendrocyte precursors were heterogeneous between white- and gray matter and among regions of gray matter, indicating that there are regional regulators of the neural response to brain irradiation. By several measures, the CA3 region of the hippocampus appeared to be differentially sensitive to effects of aging and irradiation. The changes assessed here likely contribute to injury following inflammatory challenges like brain irradiation and

  7. Regionally distinct responses of microglia and glial progenitor cells to whole brain irradiation in adult and aging rats.

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    Kun Hua

    Full Text Available Radiation therapy has proven efficacy for treating brain tumors and metastases. Higher doses and larger treatment fields increase the probability of eliminating neoplasms and preventing reoccurrence, but dose and field are limited by damage to normal tissues. Normal tissue injury is greatest during development and in populations of proliferating cells but also occurs in adults and older individuals and in non-proliferative cell populations. To better understand radiation-induced normal tissue injury and how it may be affected by aging, we exposed young adult, middle-aged, and old rats to 10 Gy of whole brain irradiation and assessed in gray- and white matter the responses of microglia, the primary cellular mediators of radiation-induced neuroinflammation, and oligodendrocyte precursor cells, the largest population of proliferating cells in the adult brain. We found that aging and/or irradiation caused only a few microglia to transition to the classically "activated" phenotype, e.g., enlarged cell body, few processes, and markers of phagocytosis, that is seen following more damaging neural insults. Microglial changes in response to aging and irradiation were relatively modest and three markers of reactivity - morphology, proliferation, and expression of the lysosomal marker CD68- were regulated largely independently within individual cells. Proliferation of oligodendrocyte precursors did not appear to be altered during normal aging but increased following irradiation. The impacts of irradiation and aging on both microglia and oligodendrocyte precursors were heterogeneous between white- and gray matter and among regions of gray matter, indicating that there are regional regulators of the neural response to brain irradiation. By several measures, the CA3 region of the hippocampus appeared to be differentially sensitive to effects of aging and irradiation. The changes assessed here likely contribute to injury following inflammatory challenges like

  8. Early-Onset Convulsive Seizures Induced by Brain Hypoxia-Ischemia in Aging Mice: Effects of Anticonvulsive Treatments.

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    Justin Wang

    Full Text Available Aging is associated with an increased risk of seizures/epilepsy. Stroke (ischemic or hemorrhagic and cardiac arrest related brain injury are two major causative factors for seizure development in this patient population. With either etiology, seizures are a poor prognostic factor. In spite of this, the underlying pathophysiology of seizure development is not well understood. In addition, a standardized treatment regimen with anticonvulsants and outcome assessments following treatment has yet to be established for these post-ischemic seizures. Previous studies have modeled post-ischemic seizures in adult rodents, but similar studies in aging/aged animals, a group that mirrors a higher risk elderly population, remain sparse. Our study therefore aimed to investigate early-onset seizures in aging animals using a hypoxia-ischemia (HI model. Male C57 black mice 18-20-month-old underwent a unilateral occlusion of the common carotid artery followed by a systemic hypoxic episode (8% O2 for 30 min. Early-onset seizures were detected using combined behavioral and electroencephalographic (EEG monitoring. Brain injury was assessed histologically at different times post HI. Convulsive seizures were observed in 65% of aging mice post-HI but not in control aging mice following either sham surgery or hypoxia alone. These seizures typically occurred within hours of HI and behaviorally consisted of jumping, fast running, barrel-rolling, and/or falling (loss of the righting reflex with limb spasms. No evident discharges during any convulsive seizures were seen on cortical-hippocampal EEG recordings. Seizure development was closely associated with acute mortality and severe brain injury on brain histological analysis. Intra-peritoneal injections of lorazepam and fosphenytoin suppressed seizures and improved survival but only when applied prior to seizure onset and not after. These findings together suggest that seizures are a major contributing factor to acute

  9. Effects of non-pharmacological or pharmacological interventions to promote cognition and brain plasticity in aging individuals

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    Valentina ePieramico

    2014-09-01

    Full Text Available Brain aging and aging-related neurodegenerative disorders are major health challenges faced by modern societies. Brain aging is associated with cognitive and functional decline and represents the favourable background for the onset and development of dementia. Brain aging is associated with early and subtle anatomo-functional physiological changes that often precede the appearance of clinical signs of cognitive decline. Neuroimaging approaches unveiled the functional correlates of these alterations and helped in the identification of therapeutic targets that can be potentially useful in counteracting age-dependent cognitive decline.A growing body of evidence supports the notion that cognitive stimulation and aerobic training can preserve and enhance operational skills in elderly individuals as well as reduce the incidence of dementia. This review aims at providing an extensive and critical overview of the most recent data that support the efficacy of non-pharmacological and pharmacological interventions aimed at enhancing cognition and brain plasticity in healthy elderly individuals as well as delaying the cognitive decline associated with dementia.

  10. Bmi1 is down-regulated in the aging brain and displays antioxidant and protective activities in neurons.

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    Mohamed Abdouh

    Full Text Available Aging increases the risk to develop several neurodegenerative diseases, although the underlying mechanisms are poorly understood. Inactivation of the Polycomb group gene Bmi1 in mice results in growth retardation, cerebellar degeneration, and development of a premature aging-like phenotype. This progeroid phenotype is characterized by formation of lens cataracts, apoptosis of cortical neurons, and increase of reactive oxygen species (ROS concentrations, owing to p53-mediated repression of antioxidant response (AOR genes. Herein we report that Bmi1 expression progressively declines in the neurons of aging mouse and human brains. In old brains, p53 accumulates at the promoter of AOR genes, correlating with a repressed chromatin state, down-regulation of AOR genes, and increased oxidative damages to lipids and DNA. Comparative gene expression analysis further revealed that aging brains display an up-regulation of the senescence-associated genes IL-6, p19(Arf and p16(Ink4a, along with the pro-apoptotic gene Noxa, as seen in Bmi1-null mice. Increasing Bmi1 expression in cortical neurons conferred robust protection against DNA damage-induced cell death or mitochondrial poisoning, and resulted in suppression of ROS through activation of AOR genes. These observations unveil that Bmi1 genetic deficiency recapitulates aspects of physiological brain aging and that Bmi1 over-expression is a potential therapeutic modality against neurodegeneration.

  11. Insensitivity of astrocytes to interleukin 10 signaling following peripheral immune challenge results in prolonged microglial activation in the aged brain.

    Science.gov (United States)

    Norden, Diana M; Trojanowski, Paige J; Walker, Frederick R; Godbout, Jonathan P

    2016-08-01

    Immune-activated microglia from aged mice produce exaggerated levels of cytokines. Despite high levels of microglial interleukin (IL)-10 in the aged brain, neuroinflammation was prolonged and associated with depressive-like deficits. Because astrocytes respond to IL-10 and, in turn, attenuate microglial activation, we investigated if astrocyte-mediated resolution of microglial activation was impaired with age. Here, aged astrocytes had a dysfunctional profile with higher glial fibrillary acidic protein, lower glutamate transporter expression, and significant cytoskeletal re-arrangement. Moreover, aged astrocytes had reduced expression of growth factors and IL-10 receptor-1 (IL-10R1). After in vivo lipopolysaccharide immune challenge, aged astrocytes had a molecular signature associated with reduced responsiveness to IL-10. This IL-10 insensitivity of aged astrocytes resulted in a failure to induce IL-10R1 and transforming growth factor β and resolve microglial activation. In addition, adult astrocytes reduced microglial activation when co-cultured ex vivo, whereas aged astrocytes did not. Consistent with the aging studies, IL-10R(KO) astrocytes did not augment transforming growth factor β after immune challenge and failed to resolve microglial activation. Collectively, a major cytokine-regulatory loop between activated microglia and astrocytes is impaired in the aged brain. PMID:27318131

  12. Creatine supplementation in the aging population: effects on skeletal muscle, bone and brain.

    Science.gov (United States)

    Gualano, Bruno; Rawson, Eric S; Candow, Darren G; Chilibeck, Philip D

    2016-08-01

    This narrative review aims to summarize the recent findings on the adjuvant application of creatine supplementation in the management of age-related deficits in skeletal muscle, bone and brain metabolism in older individuals. Most studies suggest that creatine supplementation can improve lean mass and muscle function in older populations. Importantly, creatine in conjunction with resistance training can result in greater adaptations in skeletal muscle than training alone. The beneficial effect of creatine upon lean mass and muscle function appears to be applicable to older individuals regardless of sex, fitness or health status, although studies with very old (>90 years old) and severely frail individuals remain scarce. Furthermore, there is evidence that creatine may affect the bone remodeling process; however, the effects of creatine on bone accretion are inconsistent. Additional human clinical trials are needed using larger sample sizes, longer durations of resistance training (>52 weeks), and further evaluation of bone mineral, bone geometry and microarchitecture properties. Finally, a number of studies suggest that creatine supplementation improves cognitive processing under resting and various stressed conditions. However, few data are available on older adults, and the findings are discordant. Future studies should focus on older adults and possibly frail elders or those who have already experienced an age-associated cognitive decline. PMID:27108136

  13. Effect of monoamine nervous transmitter and neuropeptide Y in the aged rats with myocardial injury after brain ischemia-reperfusion

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    AIM: To study the mechanism of myocardial injury after brain ischemia-reperfusion in aged rats from the changes in Dopamine (DA), Noradrenalin (NE), Epinephrine(E) and Neuropeptide Y(NPY).METHODS: Young (5 months) and aged (20 months or more) rats were divided into model groups and normal control groups, respectively. We observed the following items in rats with 60 minute reperfusion after 30 minute brain ischemia: the pathological changed of myocardium, the activities of lactic dehydrrogenase(LDH), creatine phosphokinase(CPK), the contents of NE, DA, E, NPY. RESULTS:The CPK and LDH activities in the young model rats were higher than those in the young control rats was higher than that in the young control rats (P<0.05). The serum CPK activity in the aged control rats was higher than that in the young control rats (P<0.05). The myocardial CPK activity was higher in the aged model rats compared with the young molel rats (P<0.05) and was higher in aged control rats compared with the young control rats (P<0.01). The myocardial LDH activity was lower in the aged control rats than that in the young control rats (P<0.05) and aged model rats (P<0.01). The serum NE level, the level of NE and DA in the hypothalamus were higher obviously than those in the young control rats. The serum NE contents in the two model groups (young and aged) were higher respectively than the two control rats (young and aged). The following items’ contents were higher in the aged model rats than in the young model rats: serum NE, serum E, hypothalamus NE. The hypothalamus NE and E content was lower in the aged model rats than in te aged control rats. NPY level in the brain tissue was lower in the aged control rats than that in the young control rats and aged model rats (P<0.05).CONCLUSION: The myocardial injury after brain ischemia-reperfusion was concerned with the enhanced excitability of sympathetic-adrenal system, espectially in the aged rats. However, the change in myocardial

  14. Diagnosing dementia and normal aging: clinical relevance of brain ratios and cognitive performance in a Brazilian sample

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    M.L.F. Chaves

    1999-09-01

    Full Text Available The main objective of the present study was to evaluate the diagnostic value (clinical application of brain measures and cognitive function. Alzheimer and multiinfarct patients (N = 30 and normal subjects over the age of 50 (N = 40 were submitted to a medical, neurological and cognitive investigation. The cognitive tests applied were Mini-Mental, word span, digit span, logical memory, spatial recognition span, Boston naming test, praxis, and calculation tests. The brain ratios calculated were the ventricle-brain, bifrontal, bicaudate, third ventricle, and suprasellar cistern measures. These data were obtained from a brain computer tomography scan, and the cutoff values from receiver operating characteristic curves. We analyzed the diagnostic parameters provided by these ratios and compared them to those obtained by cognitive evaluation. The sensitivity and specificity of cognitive tests were higher than brain measures, although dementia patients presented higher ratios, showing poorer cognitive performances than normal individuals. Normal controls over the age of 70 presented higher measures than younger groups, but similar cognitive performance. We found diffuse losses of tissue from the central nervous system related to distribution of cerebrospinal fluid in dementia patients. The likelihood of case identification by functional impairment was higher than when changes of the structure of the central nervous system were used. Cognitive evaluation still seems to be the best method to screen individuals from the community, especially for developing countries, where the cost of brain imaging precludes its use for screening and initial assessment of dementia.

  15. Alterations in brain neurotrophic and glial factors following early age chronic methylphenidate and cocaine administration.

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    Simchon-Tenenbaum, Yaarit; Weizman, Abraham; Rehavi, Moshe

    2015-04-01

    Attention deficit hyperactivity disorder (ADHD) overdiagnosis and a pharmacological attempt to increase cognitive performance, are the major causes for the frequent (ab)use of psychostimulants in non-ADHD individuals. Methylphenidate is a non-addictive psychostimulant, although its mode of action resembles that of cocaine, a well-known addictive and abused drug. Neuronal- and glial-derived growth factors play a major role in the development, maintenance and survival of neurons in the central nervous system. We hypothesized that methylphenidate and cocaine treatment affect the expression of such growth factors. Beginning on postnatal day (PND) 14, male Sprague Dawley rats were treated chronically with either cocaine or methylphenidate. The rats were examined behaviorally and biochemically at several time points (PND 35, 56, 70 and 90). On PND 56, rats treated with cocaine or methylphenidate from PND 14 through PND 35 exhibited increased hippocampal glial-cell derived neurotrophic factor (GDNF) mRNA levels, after 21 withdrawal days, compared to the saline-treated rats. We found a significant association between cocaine and methylphenidate treatments and age progression in the prefrontal protein expression of brain derived neurotrophic factor (BDNF). Neither treatments affected the behavioral parameters, although acute cocaine administration was associated with increased locomotor activity. It is possible that the increased hippocampal GDNF mRNA levels, may be relevant to the reduced rate of drug seeking behavior in ADHD adolescence that were maintained from childhood on methylphenidate. BDNF protein level increase with age, as well as following stimulant treatments at early age may be relevant to the neurobiology and pharmacotherapy of ADHD. PMID:25576963

  16. The age-related deficit in LTP is associated with changes in perfusion and blood-brain barrier permeability.

    Science.gov (United States)

    Blau, Christoph W; Cowley, Thelma R; O'Sullivan, Joan; Grehan, Belinda; Browne, Tara C; Kelly, Laura; Birch, Amy; Murphy, Niamh; Kelly, Aine M; Kerskens, Christian M; Lynch, Marina A

    2012-05-01

    In view of the increase in the aging population and the unavoidable parallel increase in the incidence of age-related neurodegenerative diseases, a key challenge in neuroscience is the identification of clinical signatures which change with age and impact on neuronal and cognitive function. Early diagnosis offers the possibility of early therapeutic intervention, thus magnetic resonance imaging (MRI) is potentially a powerful diagnostic tool. We evaluated age-related changes in relaxometry, blood flow, and blood-brain barrier (BBB) permeability in the rat by magnetic resonance imaging and assessed these changes in the context of the age-related decrease in synaptic plasticity. We report that T2 relaxation time was decreased with age; this was coupled with a decrease in gray matter perfusion, suggesting that the observed microglial activation, as identified by increased expression of CD11b, MHCII, and CD68 by immunohistochemistry, flow cytometry, or polymerase chain reaction (PCR), might be a downstream consequence of these changes. Increased permeability of the blood-brain barrier was observed in the perivascular area and the hippocampus of aged, compared with young, rats. Similarly there was an age-related increase in CD45-positive cells by flow cytometry, which are most likely infiltrating macrophages, with a parallel increase in the messenger mRNA expression of chemokines IP-10 and MCP-1. These combined changes may contribute to the deficit in long-term potentiation (LTP) in perforant path-granule cell synapses of aged animals.

  17. Can ketones compensate for deteriorating brain glucose uptake during aging? Implications for the risk and treatment of Alzheimer's disease.

    Science.gov (United States)

    Cunnane, Stephen C; Courchesne-Loyer, Alexandre; St-Pierre, Valérie; Vandenberghe, Camille; Pierotti, Tyler; Fortier, Mélanie; Croteau, Etienne; Castellano, Christian-Alexandre

    2016-03-01

    Brain glucose uptake is impaired in Alzheimer's disease (AD). A key question is whether cognitive decline can be delayed if this brain energy defect is at least partly corrected or bypassed early in the disease. The principal ketones (also called ketone bodies), β-hydroxybutyrate and acetoacetate, are the brain's main physiological alternative fuel to glucose. Three studies in mild-to-moderate AD have shown that, unlike with glucose, brain ketone uptake is not different from that in healthy age-matched controls. Published clinical trials demonstrate that increasing ketone availability to the brain via moderate nutritional ketosis has a modest beneficial effect on cognitive outcomes in mild-to-moderate AD and in mild cognitive impairment. Nutritional ketosis can be safely achieved by a high-fat ketogenic diet, by supplements providing 20-70 g/day of medium-chain triglycerides containing the eight- and ten-carbon fatty acids octanoate and decanoate, or by ketone esters. Given the acute dependence of the brain on its energy supply, it seems reasonable that the development of therapeutic strategies aimed at AD mandates consideration of how the underlying problem of deteriorating brain fuel supply can be corrected or delayed. PMID:26766547

  18. Biondi ring tangles in the choroid plexus of Alzheimer's disease and normal aging brains: a quantitative study.

    Science.gov (United States)

    Wen, G Y; Wisniewski, H M; Kascsak, R J

    1999-06-19

    The choroid plexus (CP) performs the vital function of producing up to 90% (450-1000 ml/day) of cerebrospinal fluid (CSF) to nourish and to protect the brain in the CSF suspension. The CP also acts as a selective barrier between blood and CSF to regulate ions and other essential molecules. However, the accumulation of intracellular inclusions called Biondi ring tangles (BRTs) in CP cells of Alzheimer's disease (AD)/aging brains may affect these vital functions of the CP. Statistical analysis of quantitative data on the numbers of CP cells containing BRTs from 54 brains (29 AD and 25 normal control), age range 1-100 years, indicated a significant difference (pbiomarker for AD in addition to NPs and NFTs.

  19. MRI of the normal brain from early childhood to middle age. Pt. 2. Age dependence of signal intensity changes on T2-weighted images

    International Nuclear Information System (INIS)

    We examined 66 healthy volunteers aged 4 to 50 years by magnetic resonance imaging (MRI) and the signal intensity was measured on T2-weighted images in numerous sites and correlated with age and sex. Using distilled water and cerebrospinal fluid (CSF) as references on each slice, we calculated the signal intensities of the brain structures. Calculated ratios between structures did not change with age, except for those of the globus pallidus and thalamus, in which the signal intensities decreased more rapidly. The signal intensities of other brain structures changed equally but this could not be discerned visually and quantitative measurements were required. The signal intensities in the white and deep grey matter decreased rapidly in the first decade and then gradually to reach a plateau after the age of 18 years. Maturation of the brain thus seems to continue until near the end of the second decade of life. No sex differences were found. Quantitative analysis requires intensity references. The CSF in the tips of the frontal horns seems to be as reliable as an external fluid reference for intensity, and can be used in routine examinations provided the frontal horns are large enough to avoid partial volume effect. (orig.)

  20. Estimating the brain pathological age of Alzheimer’s disease patients from MR image data based on the separability distance criterion

    Science.gov (United States)

    Li, Yongming; Li, Fan; Wang, Pin; Zhu, Xueru; Liu, Shujun; Qiu, Mingguo; Zhang, Jingna; Zeng, Xiaoping

    2016-10-01

    Traditional age estimation methods are based on the same idea that uses the real age as the training label. However, these methods ignore that there is a deviation between the real age and the brain age due to accelerated brain aging. This paper considers this deviation and searches for it by maximizing the separability distance value rather than by minimizing the difference between the estimated brain age and the real age. Firstly, set the search range of the deviation as the deviation candidates according to prior knowledge. Secondly, use the support vector regression (SVR) as the age estimation model to minimize the difference between the estimated age and the real age plus deviation rather than the real age itself. Thirdly, design the fitness function based on the separability distance criterion. Fourthly, conduct age estimation on the validation dataset using the trained age estimation model, put the estimated age into the fitness function, and obtain the fitness value of the deviation candidate. Fifthly, repeat the iteration until all the deviation candidates are involved and get the optimal deviation with maximum fitness values. The real age plus the optimal deviation is taken as the brain pathological age. The experimental results showed that the separability was apparently improved. For normal control-Alzheimer’s disease (NC-AD), normal control-mild cognition impairment (NC-MCI), and MCI-AD, the average improvements were 0.178 (35.11%), 0.033 (14.47%), and 0.017 (39.53%), respectively. For NC-MCI-AD, the average improvement was 0.2287 (64.22%). The estimated brain pathological age could be not only more helpful to the classification of AD but also more precisely reflect accelerated brain aging. In conclusion, this paper offers a new method for brain age estimation that can distinguish different states of AD and can better reflect the extent of accelerated aging.

  1. Inadequate supply of vitamins and DHA in the elderly: implications for brain aging and Alzheimer-type dementia.

    Science.gov (United States)

    Mohajeri, M Hasan; Troesch, Barbara; Weber, Peter

    2015-02-01

    Alzheimer's disease (AD) is the most prevalent, severe, and disabling cause of dementia worldwide. To date, AD therapy is primarily targeted toward palliative treatment of symptoms rather than prevention of disease progression. So far, no pharmacologic interventions have changed the onset or progression of AD and their use is accompanied by side effects. The major obstacle in managing AD and designing therapeutic strategies is the difficulty in retarding neuronal loss in the diseased brain once the pathologic events leading to neuronal death have started. Therefore, a promising alternative strategy is to maintain a healthy neuronal population in the aging brain for as long as possible. One factor evidently important for neuronal health and function is the optimal supply of nutrients necessary for maintaining normal functioning of the brain. Mechanistic studies, epidemiologic analyses, and randomized controlled intervention trials provide insight to the positive effects of docosahexaenoic acid (DHA) and micronutrients such as the vitamin B family, and vitamins E, C, and D, in helping neurons to cope with aging. These nutrients are inexpensive in use, have virtually no side effects when used at recommended doses, are essential for life, have established modes of action, and are broadly accepted by the general public. This review provides some evidence that the use of vitamins and DHA for the aging population in general, and for individuals at risk in particular, is a viable alternative approach to delaying brain aging and for protecting against the onset of AD pathology. PMID:25592004

  2. Sources of Variability in Working Memory in Early Childhood: A Consideration of Age, Temperament, Language, and Brain Electrical Activity

    Science.gov (United States)

    Wolfe, Christy D.; Bell, Martha Ann

    2007-01-01

    This study investigated age-related differences in working memory and inhibitory control (WMIC) in 3 1/2-, 4-, and 4 1/2-year-olds and how these differences were associated with differences in regulatory aspects of temperament, language comprehension, and brain electrical activity. A series of cognitive control tasks was administered to measure…

  3. The effect of caffeine on working memory load-­related brain activation in middle-­aged males

    NARCIS (Netherlands)

    Klaassen, Elissa; De Groot, Renate; Evers, Lisbeth; Snel, Jan; Veerman, Enno; Ligtenberg, Antoon; Jolles, Jelle; Veltman, Dick

    2012-01-01

    Klaassen, E. B., De Groot, R. H. M., Evers, E. A. T., Snel, J., Veerman, E. C. I., Ligtenberg, A. J. M., Jolles, J., & Veltman, D. J. (2013). The effect of caffeine on working memory load-related brain activation in middle-aged male. Neuropharmacology, 64, 160-167. doi:10.1016/j.neuropharm.2012.06.0

  4. Chinese Returnees from Overseas Study: An Understanding of Brain Gain and Brain Circulation in the Age of Globalization

    Science.gov (United States)

    Ma, Yuping; Pan, Suyan

    2015-01-01

    Among discussions on international academic mobility, a persistent challenge is to understand whether education abroad can become a source of brain gain, and whether globalization can offer source countries the hope that they might enjoy the benefits of freer crossborder flows in information and personnel. With reference to China, this article…

  5. Effect of a water-maze procedure on the redox mechanisms in brain parts of aged rats

    Directory of Open Access Journals (Sweden)

    Natalia Andreevna Krivova

    2015-03-01

    Full Text Available The Morris water maze (MWM is a tool for assessment of age-related cognitive deficits. In our work, MWM was used for appraisal of cognitive deficits in 11-month-old rats and investigation of the effect exerted by training in the Morris water maze on the redox mechanisms in rat brain parts. Young adult (3-month-old and aged (11-month-old male rats were trained in the water maze. Intact animals of the corresponding age were used as the reference groups. The level of pro- and antioxidant capacity in brain tissue homogenates was assessed using the chemiluminescence method.Cognitive deficits were found in 11-month-old rats: at the first day of training they showed only 30% of successful MWM trials. However, at the last training day the percentage of successful trials was equal for young adult and aged animals. This indicates that cognitive deficits in aged rats can be reversed by MWM training. Therewith, the MWM spatial learning procedure itself produces changes in different processes of redox homeostasis in 11-month-old and 3-month-old rats as compared to intact animals. Young adult rats showed a decrease in prooxidant capacity in all brain parts, while 11-month-old rats demonstrated an increase in antioxidant capacity in the olfactory bulb, pons + medulla oblongata and frontal lobe cortex. Hence, the MWM procedure activates the mechanisms that restrict the oxidative stress in brain parts. The obtained results may be an argument for further development of the animal training procedures aimed to activate the mechanisms responsible for age-related cognitive deficits. This may be useful not only for the development of training procedures applicable to human patients with age-related cognitive impairments, but also for their rehabilitation.

  6. Impact of Long-Term Endurance Training vs. Guideline-Based Physical Activity on Brain Structure in Healthy Aging.

    Science.gov (United States)

    Wood, Katelyn N; Nikolov, Robert; Shoemaker, J Kevin

    2016-01-01

    Brain structure is a fundamental determinant of brain function, both of which decline with age in the adult. Whereas short-term exercise improves brain size in older adults, the impact of endurance training on brain structure when initiated early and sustained throughout life, remains unknown. We tested the hypothesis that long-term competitive aerobic training enhances cortical and subcortical mass compared to middle to older-aged healthy adults who adhere to the minimum physical activity guidelines. Observations were made in 16 masters athletes (MA; 53 ± 6 years, VO2max = 55 ± 10 ml/kg/min, training > 15 years), and 16 active, healthy, and cognitively intact subjects (HA; 58 ± 9 years, VO2max = 38 ± 7 ml/kg/min). T1-weighted structural acquisition at 3T enabled quantification of cortical thickness and subcortical gray and white matter volumes. Cardiorespiratory fitness correlated strongly with whole-brain cortical thickness. Subcortical volumetric mass at the lateral ventricles, R hippocampus, R amygdala, and anterior cingulate cortex, correlated with age but not fitness. In a region-of-interest (ROI) group-based analysis, MA expressed greater cortical thickness in the medial prefrontal cortex, pre and postcentral gyri, and insula. There was no effect of group on the rate of age-related cortical or subcortical decline. The current data suggest that lifelong endurance training that produces high levels of cardiorespiratory fitness, builds cortical reserve early in life, and sustains this benefit over the 40-70 year age span. This reserve likely has important implications for neurological health later in life. PMID:27445798

  7. Nutrition and brain aging: role of fatty acids with an epidemiological perspective

    Directory of Open Access Journals (Sweden)

    Samieri Cécilia

    2011-07-01

    Full Text Available In the absence of identified etiologic treatment for dementia, the potential preventive role of nutrition may offer an interesting perspective. The objective of the thesis of C. Samieri was to study the association between nutrition and brain aging in 1,796 subjects, aged 65 y or older, from the Bordeaux sample of the Three-City study, with a particular emphasis on fatty acids. Considering the multidimensional nature of nutritional data, several complementary strategies were used. At the global diet level, dietary patterns actually observed in the population were identified by exploratory methods. Older subjects with a ‘‘healthy’’ pattern, who consumed more than 3.5 weekly servings of fish in men and more than 6 daily servings of fruits and vegetables in women, showed a better cognitive and psychological health. Adherence to the Mediterranean diet, measured according to a score-based confirmatory method, was associated with slower global cognitive decline after 5 y of follow-up. At the nutrient biomarker level, higher plasma eicosapentaenoic acid (EPA, a long-chain omega-3 fatty acid, was associated with a decreased dementia risk, and the omega-6-to-omega-3 fatty acids ratio to an increased risk, particularly in depressed subjects. EPA was also related to slower working memory decline in depressed subjects or in carriers of the e4 allele of the ApoE gene. Docosahexaenoic acid was related to slower working memory decline only in ApoE4 carriers. Overall, this work suggests a positive impact of a healthy diet rich in fruits and vegetables and fish, and notably the Mediterranean diet, on cognition in older subjects. Long-chain n-3 PUFA, in particular EPA, may be key protective nutrients against risk of dementia and cognitive decline.

  8. Brain MRI findings in patients with initial cerebral thrombosis and the relationship between incidental findings, aging and dementia

    International Nuclear Information System (INIS)

    To estimate the relationship between aging, dementia and changes observed on magnetic resonance imaging (MRI) seen in elderly patients with cerebral thrombosis, MRI findings in 103 patients with an initial stroke event (thrombosis group) were compared with those of 37 patients with hypertension/diabetes (high risk group) and 78 patients without those disorders (low risk group). In addition to the causative lesions in the thrombosis group, periventricular hyperintensities (PVH), spotty lesions (SL), silent infarctions (SI), ventricular dilatation (VD), and cortical atrophy (CA) were analyzed in these groups. Infarctions located in the internal capsule/corona radiata were the most frequent causative lesion. Compared to the low risk group, a high incidence of patchy/diffuse PVH, SI, and severe CA was seen in both the thrombosis group and the high risk group. Widespread PVH and multiple SL increased with age in the thrombosis group, while severe CA was seen in each group. SI and VD tended to increase after age 60, though they were not significant. Dementia, diagnosed in 40 out of 78 patients, increased with age. Multivariate analysis revealed the degree of the effects of MRI findings on dementia to be marked in PVH, brain atrophy, causative lesions, and SL, in that order. These results indicated that diffuse PVH and brain atrophy, developing with age, promoted dementia in the elderly with vascular lesions. Moreover, they suggested that a variety of silent brain lesions recognized on MRI other than infarction can affect symptoms in the elderly. (author)

  9. Relationships between choline acetyl-transferase and muscarinic binding in aging rodent brain and in Alzheimers disease

    International Nuclear Information System (INIS)

    This paper examines how the relation between ChAT and muscarinic binding might be affected by aging in mouse and rat brains. Preliminary data are presented regarding this relation in postmortem cerebral cortex samples from human subjects who died with Alzheimer's disease (AD) and from age-matched controls. The effect of acetyl coenzme A (1- C 14-acetyl coenzyme A concentration on enzyme activity was determined by varying the concentration of the coenzyme in the assay medium. Assays of muscarinic binding were performed on tissue sonicates diluted with Tris-HC1 buffer using tritium-quinuclidinyl benzilate tritium-QNB as the ligand. For brain regions obtained from rats, significance of age differences were assessed by one-way analysis of variance and Bonferroni t statistics. Differences in ChAT activity and binding site density from human postmortem samples between diagnostic groups were assessed separately by region using an analysis of covariance

  10. Improved mitochondrial function in brain aging and Alzheimer disease - the new mechanism of action of the old metabolic enhancer piracetam

    Directory of Open Access Journals (Sweden)

    Kristina Leuner

    2010-09-01

    Full Text Available Piracetam, the prototype of the so-called nootropic drugs’ is used since many years in different countries to treat cognitive impairment in aging and dementia. Findings that piracetam enhances fluidity of brain mitochondrial membranes led to the hypothesis that piracetam might improve mitochondrial function, e.g. might enhance ATP synthesis. This assumption has recently been supported by a number of observations showing enhanced mitochondrial membrane potential (MMP, enhanced ATP production, and reduced sensitivity for apoptosis in a variety of cell and animal models for aging and Alzheimer disease (AD. As a specific consequence, substantial evidence for elevated neuronal plasticity as a specific effect of piracetam has emerged. Taken together, these new findings can explain many of the therapeutic effects of piracetam on cognition in aging and dementia as well as different situations of brain dysfunctions.

  11. Integrated Analysis and Visualization of Group Differences in Structural and Functional Brain Connectivity: Applications in Typical Ageing and Schizophrenia.

    Directory of Open Access Journals (Sweden)

    Carolyn D Langen

    Full Text Available Structural and functional brain connectivity are increasingly used to identify and analyze group differences in studies of brain disease. This study presents methods to analyze uni- and bi-modal brain connectivity and evaluate their ability to identify differences. Novel visualizations of significantly different connections comparing multiple metrics are presented. On the global level, "bi-modal comparison plots" show the distribution of uni- and bi-modal group differences and the relationship between structure and function. Differences between brain lobes are visualized using "worm plots". Group differences in connections are examined with an existing visualization, the "connectogram". These visualizations were evaluated in two proof-of-concept studies: (1 middle-aged versus elderly subjects; and (2 patients with schizophrenia versus controls. Each included two measures derived from diffusion weighted images and two from functional magnetic resonance images. The structural measures were minimum cost path between two anatomical regions according to the "Statistical Analysis of Minimum cost path based Structural Connectivity" method and the average fractional anisotropy along the fiber. The functional measures were Pearson's correlation and partial correlation of mean regional time series. The relationship between structure and function was similar in both studies. Uni-modal group differences varied greatly between connectivity types. Group differences were identified in both studies globally, within brain lobes and between regions. In the aging study, minimum cost path was highly effective in identifying group differences on all levels; fractional anisotropy and mean correlation showed smaller differences on the brain lobe and regional levels. In the schizophrenia study, minimum cost path and fractional anisotropy showed differences on the global level and within brain lobes; mean correlation showed small differences on the lobe level. Only

  12. Therapeutics with SPION-labeled stem cells for the main diseases related to brain aging: a systematic review

    Directory of Open Access Journals (Sweden)

    Alvarim LT

    2014-08-01

    Full Text Available Larissa T Alvarim,1,3,* Leopoldo P Nucci,2,* Javier B Mamani,1 Luciana C Marti,1 Marina F Aguiar,1,2 Helio R Silva,1,3 Gisele S Silva,1 Mariana P Nucci-da-Silva,4 Elaine A DelBel,5,6 Lionel F Gamarra1–31Hospital Israelita Albert Einstein, São Paulo, Brazil; 2Universidade Federal de São Paulo, UNIFESP, São Paulo, Brazil; 3Faculdade de Ciências Médicas da Santa Casa de São Paulo, São Paulo, Brazil; 4Departamento de Radiologia, Hospital das Clínicas, Universidade de São Paulo, Brazil; 5Universidade de São Paulo-Faculdade de Odontologia de Ribeirão Preto, São Paulo, Brazil; 6NAPNA- Núcleo de Apoio a Pesquisa em Neurociências Aplicadas, São Paulo, Brazil*These authors contributed equally to this workAbstract: The increase in clinical trials assessing the efficacy of cell therapy for structural and functional regeneration of the nervous system in diseases related to the aging brain is well known. However, the results are inconclusive as to the best cell type to be used or the best methodology for the homing of these stem cells. This systematic review analyzed published data on SPION (superparamagnetic iron oxide nanoparticle-labeled stem cells as a therapy for brain diseases, such as ischemic stroke, Parkinson’s disease, amyotrophic lateral sclerosis, and dementia. This review highlights the therapeutic role of stem cells in reversing the aging process and the pathophysiology of brain aging, as well as emphasizing nanotechnology as an important tool to monitor stem cell migration in affected regions of the brain.Keywords: iron oxide, dementia, stem cell, stroke, Parkinson’s disease, sclerosis disease, brain aging

  13. Extensive innate immune gene activation accompanies brain aging, increasing vulnerability to cognitive decline and neurodegeneration: a microarray study

    Directory of Open Access Journals (Sweden)

    Cribbs David H

    2012-07-01

    Full Text Available Abstract Background This study undertakes a systematic and comprehensive analysis of brain gene expression profiles of immune/inflammation-related genes in aging and Alzheimer’s disease (AD. Methods In a well-powered microarray study of young (20 to 59 years, aged (60 to 99 years, and AD (74 to 95 years cases, gene responses were assessed in the hippocampus, entorhinal cortex, superior frontal gyrus, and post-central gyrus. Results Several novel concepts emerge. First, immune/inflammation-related genes showed major changes in gene expression over the course of cognitively normal aging, with the extent of gene response far greater in aging than in AD. Of the 759 immune-related probesets interrogated on the microarray, approximately 40% were significantly altered in the SFG, PCG and HC with increasing age, with the majority upregulated (64 to 86%. In contrast, far fewer immune/inflammation genes were significantly changed in the transition to AD (approximately 6% of immune-related probesets, with gene responses primarily restricted to the SFG and HC. Second, relatively few significant changes in immune/inflammation genes were detected in the EC either in aging or AD, although many genes in the EC showed similar trends in responses as in the other brain regions. Third, immune/inflammation genes undergo gender-specific patterns of response in aging and AD, with the most pronounced differences emerging in aging. Finally, there was widespread upregulation of genes reflecting activation of microglia and perivascular macrophages in the aging brain, coupled with a downregulation of select factors (TOLLIP, fractalkine that when present curtail microglial/macrophage activation. Notably, essentially all pathways of the innate immune system were upregulated in aging, including numerous complement components, genes involved in toll-like receptor signaling and inflammasome signaling, as well as genes coding for immunoglobulin (Fc receptors and human

  14. [Can age-dependent cognitive functions be measured? P300 potentials--concept of brain aging--early diagnosis of dementia processes].

    Science.gov (United States)

    Kügler, C

    1996-10-10

    Event related P300 potentials as the electrophysiological substrate of cognitive functions, such as the stimulus processing time (P300 latencies) and visual attention capacity (P300 amplitudes) are suitable for the analysis of age-related changes in cognitive human brain functions. P300 investigations carried out in a total of 330 test subjects aged between 18 and 98 years, showed an overall slight prolongation of the P300 latencies by 10 ms for each decade, as well as a discrete reduction in the P300 amplitudes of 1 microV. To describe the relationship between the P300 parameters and chronological age, polynomial regression models are more suitable than linear functions. This means that in middle-age, P300 potentials change only slightly while, from about the age of 60 upwards, a noticeable acceleration in the P300 changes takes place. An interesting observation was the fact that the acceleration in the P300 latency increase occurred some 10 years earlier in women than in men, beginning in the early postmenopausal period. The polynomial course of the regression function for the age-dependence of P300 potentials might reflect the positive influence of socio-cultural factors on the aging of cognitive functions. The true extent of the age-related changes in cognitive functions, however, can be determined only with the aid of intra-individual longitudinal studies. This is of considerable importance for the early diagnosis of both metabolic and primarily degenerative encephalopathies.

  15. Imaging Vascular Disease and Amyloid in the Aging Brain: Implications for Treatment

    OpenAIRE

    Villeneuve, Sylvia; Jagust, William J.

    2015-01-01

    Vascular risk factors (e.g. hypertension, dyslipidemia and diabetes) are well known risk factors for Alzheimer’ disease. These vascular risk factors lead to vascular brain injuries, which also increase the likelihood of dementia. The advent of amyloid PET imaging has helped establish that vascular risk factors also lead to Alzheimer’s disease via pathways that are independent from vascular brain injuries, at least, when vascular brain injuries are measured as white matter lesions and infarcts...

  16. Age-dependent brain gene expression and copy number anomalies in autism suggest distinct pathological processes at young versus mature ages.

    Directory of Open Access Journals (Sweden)

    Maggie L Chow

    Full Text Available Autism is a highly heritable neurodevelopmental disorder, yet the genetic underpinnings of the disorder are largely unknown. Aberrant brain overgrowth is a well-replicated observation in the autism literature; but association, linkage, and expression studies have not identified genetic factors that explain this trajectory. Few studies have had sufficient statistical power to investigate whole-genome gene expression and genotypic variation in the autistic brain, especially in regions that display the greatest growth abnormality. Previous functional genomic studies have identified possible alterations in transcript levels of genes related to neurodevelopment and immune function. Thus, there is a need for genetic studies involving key brain regions to replicate these findings and solidify the role of particular functional pathways in autism pathogenesis. We therefore sought to identify abnormal brain gene expression patterns via whole-genome analysis of mRNA levels and copy number variations (CNVs in autistic and control postmortem brain samples. We focused on prefrontal cortex tissue where excess neuron numbers and cortical overgrowth are pronounced in the majority of autism cases. We found evidence for dysregulation in pathways governing cell number, cortical patterning, and differentiation in young autistic prefrontal cortex. In contrast, adult autistic prefrontal cortex showed dysregulation of signaling and repair pathways. Genes regulating cell cycle also exhibited autism-specific CNVs in DNA derived from prefrontal cortex, and these genes were significantly associated with autism in genome-wide association study datasets. Our results suggest that CNVs and age-dependent gene expression changes in autism may reflect distinct pathological processes in the developing versus the mature autistic prefrontal cortex. Our results raise the hypothesis that genetic dysregulation in the developing brain leads to abnormal regional patterning, excess

  17. Age-related changes in the brain antioxidant status: modulation by dietary supplementation of Decalepis hamiltonii and physical exercise.

    Science.gov (United States)

    Ravikiran, Tekupalli; Sowbhagya, Ramachandregowda; Anupama, Sindhghatta Kariyappa; Anand, Santosh; Bhagyalakshmi, Dundaiah

    2016-08-01

    The synergistic effects of physical exercise and diet have profound benefits on brain function. The present study was aimed to determine the effects of exercise and Decalepis hamiltonii (Dh) on age-related responses on the antioxidant status in discrete regions of rat brain. Male Wistar albino rats of 4 and 18 months old were orally supplemented with Dh extract and swim trained at 3 % intensity for 30 min/day, 5 days/week, for a period of 30 days. Supplementation of 100 mg Dh aqueous extract/kg body weight and its combination with exercise significantly elevated the antioxidant enzyme activities irrespective of age. Age-related and region-specific changes were observed in superoxide levels, and protein carbonyl and malondialdehyde contents, and were found to be decreased in both trained and supplemented groups. Levels of total thiols, protein, and nonprotein thiols decreased with age and significantly increased in the SW-T(+100 mg) groups. Our results demonstrated that the interactive effects of two treatments enhanced the antioxidant status and decreased the risk of protein and lipid oxidation in the rat brain. PMID:27379504

  18. Middle age onset short-term intermittent fasting dietary restriction prevents brain function impairments in male Wistar rats.

    Science.gov (United States)

    Singh, Rumani; Manchanda, Shaffi; Kaur, Taranjeet; Kumar, Sushil; Lakhanpal, Dinesh; Lakhman, Sukhwinder S; Kaur, Gurcharan

    2015-12-01

    Intermittent fasting dietary restriction (IF-DR) is recently reported to be an effective intervention to retard age associated disease load and to promote healthy aging. Since sustaining long term caloric restriction regimen is not practically feasible in humans, so use of alternate approach such as late onset short term IF-DR regimen which is reported to trigger similar biological pathways is gaining scientific interest. The current study was designed to investigate the effect of IF-DR regimen implemented for 12 weeks in middle age rats on their motor coordination skills and protein and DNA damage in different brain regions. Further, the effect of IF-DR regimen was also studied on expression of energy regulators, cell survival pathways and synaptic plasticity marker proteins. Our data demonstrate that there was an improvement in motor coordination and learning response with decline in protein oxidative damage and recovery in expression of energy regulating neuropeptides. We further observed significant downregulation in nuclear factor kappa B (NF-κB) and cytochrome c (Cyt c) levels and moderate upregulation of mortalin and synaptophysin expression. The present data may provide an insight on how a modest level of short term IF-DR, imposed in middle age, can slow down or prevent the age-associated impairment of brain functions and promote healthy aging by involving multiple regulatory pathways aimed at maintaining energy homeostasis. PMID:26318578

  19. Potentiality of foraminifera in deciphering paleo-sea levels

    Digital Repository Service at National Institute of Oceanography (India)

    Nigam, R.

    the application of the foraminiferal distributional pattern in marine sediments (with special reference to the Arabian Sea), to decipher information about the paleo-sea level. Different strategies are being followed for different conditions. For example, (1) when...

  20. Toluene effects on oxidative stress in brain regions of young-adult, middle-age, and senescent Brown Norway rats

    Energy Technology Data Exchange (ETDEWEB)

    Kodavanti, Prasada Rao S., E-mail: kodavanti.prasada@epa.gov [Neurotoxicology Branch, Toxicity Assessment Division, NHEERL, ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Royland, Joyce E. [Genetic and Cellular Toxicology Branch, Integrated Systems Toxicology Division, NHEERL, ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Richards, Judy E. [Research Core Unit, NHEERL, ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Besas, Jonathan; MacPhail, Robert C. [Neurotoxicology Branch, Toxicity Assessment Division, NHEERL, ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States)

    2011-11-15

    The influence of aging on susceptibility to environmental contaminants is not well understood. To extend knowledge in this area, we examined effects in rat brain of the volatile organic compound, toluene. The objective was to test whether oxidative stress (OS) plays a role in the adverse effects caused by toluene exposure, and if so, if effects are age-dependent. OS parameters were selected to measure the production of reactive oxygen species (NADPH Quinone oxidoreductase 1 (NQO1), NADH Ubiquinone reductase (UBIQ-RD)), antioxidant homeostasis (total antioxidant substances (TAS), superoxide dismutase (SOD), {gamma}-glutamylcysteine synthetase ({gamma}-GCS), glutathione transferase (GST), glutathione peroxidase (GPX), glutathione reductase (GRD)), and oxidative damage (total aconitase and protein carbonyls). In this study, Brown Norway rats (4, 12, and 24 months) were dosed orally with toluene (0, 0.65 or 1 g/kg) in corn oil. Four hours later, frontal cortex, cerebellum, striatum, and hippocampus were dissected, quick frozen on dry ice, and stored at - 80 Degree-Sign C until analysis. Some parameters of OS were found to increase with age in select brain regions. Toluene exposure also resulted in increased OS in select brain regions. For example, an increase in NQO1 activity was seen in frontal cortex and cerebellum of 4 and 12 month old rats following toluene exposure, but only in the hippocampus of 24 month old rats. Similarly, age and toluene effects on glutathione enzymes were varied and brain-region specific. Markers of oxidative damage reflected changes in oxidative stress. Total aconitase activity was increased by toluene in frontal cortex and cerebellum at 12 and 24 months, respectively. Protein carbonyls in both brain regions and in all age groups were increased by toluene, but step-down analyses indicated toluene effects were statistically significant only in 12 month old rats. These results indicate changes in OS parameters with age and toluene exposure

  1. Toluene effects on oxidative stress in brain regions of young-adult, middle-age, and senescent Brown Norway rats

    International Nuclear Information System (INIS)

    The influence of aging on susceptibility to environmental contaminants is not well understood. To extend knowledge in this area, we examined effects in rat brain of the volatile organic compound, toluene. The objective was to test whether oxidative stress (OS) plays a role in the adverse effects caused by toluene exposure, and if so, if effects are age-dependent. OS parameters were selected to measure the production of reactive oxygen species (NADPH Quinone oxidoreductase 1 (NQO1), NADH Ubiquinone reductase (UBIQ-RD)), antioxidant homeostasis (total antioxidant substances (TAS), superoxide dismutase (SOD), γ-glutamylcysteine synthetase (γ-GCS), glutathione transferase (GST), glutathione peroxidase (GPX), glutathione reductase (GRD)), and oxidative damage (total aconitase and protein carbonyls). In this study, Brown Norway rats (4, 12, and 24 months) were dosed orally with toluene (0, 0.65 or 1 g/kg) in corn oil. Four hours later, frontal cortex, cerebellum, striatum, and hippocampus were dissected, quick frozen on dry ice, and stored at − 80 °C until analysis. Some parameters of OS were found to increase with age in select brain regions. Toluene exposure also resulted in increased OS in select brain regions. For example, an increase in NQO1 activity was seen in frontal cortex and cerebellum of 4 and 12 month old rats following toluene exposure, but only in the hippocampus of 24 month old rats. Similarly, age and toluene effects on glutathione enzymes were varied and brain-region specific. Markers of oxidative damage reflected changes in oxidative stress. Total aconitase activity was increased by toluene in frontal cortex and cerebellum at 12 and 24 months, respectively. Protein carbonyls in both brain regions and in all age groups were increased by toluene, but step-down analyses indicated toluene effects were statistically significant only in 12 month old rats. These results indicate changes in OS parameters with age and toluene exposure resulted in oxidative

  2. Biliverdin Reductase-A correlates with inducible nitric oxide synthasein in atorvastatin treated aged canine brain

    Institute of Scientific and Technical Information of China (English)

    Fabio Di Domenico; Marzia Perluigi; Eugenio Barone

    2013-01-01

    Alzheimer’s disease is a neurodegenerative disorder characterized by progressive cognitive impairment and neuropathology. Recent preclinical and epidemiological studies proposed statins as a possible therapeutic drug for Alzheimer’s disease, but the exact mechanisms of action are stil unknown. Biliverdin reductase-A is a pleiotropic enzyme involved in cel ular stress responses. It not only transforms biliverdin-IX alpha into the antioxidant bilirubin-IX alpha but its serine/threonine/tyrosine kinase activity is able to modulate cel signaling networks. We previously reported the beneficial effects of atorvastatin treatment on biliverdin reductase-A and heme oxygenase-1 in the brains of a well characterized pre-clinical model of Alzheimer’s disease, aged beagles, together with observed improvement in cognition. Here we extend our knowledge of the effects of atorvastatin on inducible nitric oxide synthase in parietal cortex, cerebel um and liver of the same animals. We demonstrated that atorvastatin treatment (80 mg/day for 14.5 months) to aged beagles selectively increased inducible nitric oxide synthase in the parietal cortex but not in the cerebel um. In contrast, inducible nitric oxide synthase protein levels were significantly decreased in the liver. Significant positive correlations were found between biliverdin reductase-A and inducible nitric oxide synthase as wel as heme oxygenase-1 protein levels in the parietal cortex. The opposite was observed in the liver. Inducible nitric oxide synthase up-regulation in the parietal cortex was positively associated with improved biliverdin reductase-A functions, whereas the oxidative-induced impairment of biliverdin reductase-A in the liver negatively affected inducible nitric oxide synthase expression, thus suggesting a role for biliverdin reductase-A in atorvastatin-dependent inducible nitric oxide synthase changes. Interestingly, increased inducible nitric oxide synthase levels in the parietal cortex were not

  3. Amyloid beta1–42 and the phoshorylated tau threonine 231 in brains of aged cynomolgus monkeys (Macaca fascicularis)

    DEFF Research Database (Denmark)

    Darusman, Huda Shalahudin; Gjedde, Albert; Sajuthi, Dondin;

    2014-01-01

    Pathological hallmarks indicative of Alzheimer's disease (AD), which are the plaques of amyloid beta1-42 and neurofibrillary tangles, were found in brain of aged cynomolgus monkey. The aim of this study was to investigate if aged monkeys exhibiting spatial memory impairment and levels of biomarkers...... indicative of AD, had brain lesions similar to human patients suffering from senile dementia. Generating immunohistochemistry technique to biomarkers of amyloid beta1-42 and the phosphorylated tau 231, our study assessed the amyloidopathy, such as indicative to the senile plaques and cerebral amyloid......, the amyloids were found to deposit in the small veins and capillaries. In one of the affected individuals, phosphorylated tau was positively stained intracellularly of the neurons, indicating a possibility of an early stage of the formation of tangles. These findings add to the body of evidence of the utility...

  4. Effects of age on spatial information processing: relationship to senescent changes in brain noradrenergic and opioid systems

    Energy Technology Data Exchange (ETDEWEB)

    Rapp, P.R.

    1985-01-01

    A major focus in current research on aging is the identification of senescent changes in cognitive function in laboratory animals. This literature indicates that the processing of spatial information may be particularly impaired during senescence. The degree to which nonspecific factors (eg. sensory of motor deficits) contribute to behavioral impairments in aging, however, remains largely uninvestigated. In addition, few studies have attempted to identify senescent changes in brain structure and function which might underlie the behavioral manifestations of aging. In the behavioral experiments reported here, the authors tested young, middle-age, and senescent rates in several versions of a spatial memory task, the Morris water maze. The results of these investigations demonstrate that aged rats are significantly impaired in the Morris task compared to young or middle-age animals. In addition, these studies indicate that age-related deficits in the water maze reflect a specific dysfunction in the ability of older animals to effectively process spatial information rather than a senescent decline in sensory or motor functions. Using the subjects from the behavioral studies, additional investigations assessed whether age-dependent changes in neurochemical and neuroanatomical systems which are known to mediate spatial learning in young animals were related to the behavioral deficits exhibited by aged rats. The results of these studies demonstrate that a portion of senescent animals exhibit significant increases in lateral septal /sup 3/H-desmethylimipramine binding and decrease in /sup 3/H-naloxone binding in this same region as assessed by quantitative in vitro autoradiography.

  5. High preservation of CpG cytosine methylation patterns at imprinted gene loci in liver and brain of aged mice.

    Directory of Open Access Journals (Sweden)

    Silvia Gravina

    Full Text Available A gradual loss of the correct patterning of 5-methyl cytosine marks in gene promoter regions has been implicated in aging and age-related diseases, most notably cancer. While a number of studies have examined DNA methylation in aging, there is no consensus on the magnitude of the effects, particularly at imprinted loci. Imprinted genes are likely candidate to undergo age-related changes because of their demonstrated plasticity in utero, for example, in response to environmental cues. Here we quantitatively analyzed a total of 100 individual CpG sites in promoter regions of 11 imprinted and non-imprinted genes in liver and cerebral cortex of young and old mice using mass spectrometry. The results indicate a remarkably high preservation of methylation marks during the aging process in both organs. To test if increased genotoxic stress associated with premature aging would destabilize DNA methylation we analyzed two DNA repair defective mouse models showing a host of premature aging symptoms in liver and brain. However, also in these animals, at the end of their life span, we found a similarly high preservation of DNA methylation marks. We conclude that patterns of DNA methylation in gene promoters of imprinted genes are surprisingly stable over time in normal, postmitotic tissues and that the multiple documented changes with age are likely to involve exceptions to this pattern, possibly associated with specific cellular responses to age-related changes other than genotoxic stress.

  6. The Role of Free Radicals in the Aging Brain and Parkinson’s Disease: Convergence and Parallelism

    Directory of Open Access Journals (Sweden)

    Dong-Kug Choi

    2012-08-01

    Full Text Available Free radical production and their targeted action on biomolecules have roles in aging and age-related disorders such as Parkinson’s disease (PD. There is an age-associated increase in oxidative damage to the brain, and aging is considered a risk factor for PD. Dopaminergic neurons show linear fallout of 5–10% per decade with aging; however, the rate and intensity of neuronal loss in patients with PD is more marked than that of aging. Here, we enumerate the common link between aging and PD at the cellular level with special reference to oxidative damage caused by free radicals. Oxidative damage includes mitochondrial dysfunction, dopamine auto-oxidation, α-synuclein aggregation, glial cell activation, alterations in calcium signaling, and excess free iron. Moreover, neurons encounter more oxidative stress as a counteracting mechanism with advancing age does not function properly. Alterations in transcriptional activity of various pathways, including nuclear factor erythroid 2-related factor 2, glycogen synthase kinase 3β, mitogen activated protein kinase, nuclear factor kappa B, and reduced activity of superoxide dismutase, catalase and glutathione with aging might be correlated with the increased incidence of PD.

  7. The Role of Free Radicals in the Aging Brain and Parkinson’s Disease: Convergence and Parallelism

    Science.gov (United States)

    Kumar, Hemant; Lim, Hyung-Woo; More, Sandeep Vasant; Kim, Byung-Wook; Koppula, Sushruta; Kim, In Su; Choi, Dong-Kug

    2012-01-01

    Free radical production and their targeted action on biomolecules have roles in aging and age-related disorders such as Parkinson’s disease (PD). There is an age-associated increase in oxidative damage to the brain, and aging is considered a risk factor for PD. Dopaminergic neurons show linear fallout of 5–10% per decade with aging; however, the rate and intensity of neuronal loss in patients with PD is more marked than that of aging. Here, we enumerate the common link between aging and PD at the cellular level with special reference to oxidative damage caused by free radicals. Oxidative damage includes mitochondrial dysfunction, dopamine auto-oxidation, α-synuclein aggregation, glial cell activation, alterations in calcium signaling, and excess free iron. Moreover, neurons encounter more oxidative stress as a counteracting mechanism with advancing age does not function properly. Alterations in transcriptional activity of various pathways, including nuclear factor erythroid 2-related factor 2, glycogen synthase kinase 3β, mitogen activated protein kinase, nuclear factor kappa B, and reduced activity of superoxide dismutase, catalase and glutathione with aging might be correlated with the increased incidence of PD. PMID:22949875

  8. Deciphering interactions in moving animal groups.

    Directory of Open Access Journals (Sweden)

    Jacques Gautrais

    Full Text Available Collective motion phenomena in large groups of social organisms have long fascinated the observer, especially in cases, such as bird flocks or fish schools, where large-scale highly coordinated actions emerge in the absence of obvious leaders. However, the mechanisms involved in this self-organized behavior are still poorly understood, because the individual-level interactions underlying them remain elusive. Here, we demonstrate the power of a bottom-up methodology to build models for animal group motion from data gathered at the individual scale. Using video tracks of fish shoal in a tank, we show how a careful, incremental analysis at the local scale allows for the determination of the stimulus/response function governing an individual's moving decisions. We find in particular that both positional and orientational effects are present, act upon the fish turning speed, and depend on the swimming speed, yielding a novel schooling model whose parameters are all estimated from data. Our approach also leads to identify a density-dependent effect that results in a behavioral change for the largest groups considered. This suggests that, in confined environment, the behavioral state of fish and their reaction patterns change with group size. We debate the applicability, beyond the particular case studied here, of this novel framework for deciphering interactions in moving animal groups.

  9. Patch-based augmentation of Expectation-Maximization for brain MRI tissue segmentation at arbitrary age after premature birth.

    Science.gov (United States)

    Liu, Mengyuan; Kitsch, Averi; Miller, Steven; Chau, Vann; Poskitt, Kenneth; Rousseau, Francois; Shaw, Dennis; Studholme, Colin

    2016-02-15

    Accurate automated tissue segmentation of premature neonatal magnetic resonance images is a crucial task for quantification of brain injury and its impact on early postnatal growth and later cognitive development. In such studies it is common for scans to be acquired shortly after birth or later during the hospital stay and therefore occur at arbitrary gestational ages during a period of rapid developmental change. It is important to be able to segment any of these scans with comparable accuracy. Previous work on brain tissue segmentation in premature neonates has focused on segmentation at specific ages. Here we look at solving the more general problem using adaptations of age specific atlas based methods and evaluate this using a unique manually traced database of high resolution images spanning 20 gestational weeks of development. We examine the complimentary strengths of age specific atlas-based Expectation-Maximization approaches and patch-based methods for this problem and explore the development of two new hybrid techniques, patch-based augmentation of Expectation-Maximization with weighted fusion and a spatial variability constrained patch search. The former approach seeks to combine the advantages of both atlas- and patch-based methods by learning from the performance of the two techniques across the brain anatomy at different developmental ages, while the latter technique aims to use anatomical variability maps learnt from atlas training data to locally constrain the patch-based search range. The proposed approaches were evaluated using leave-one-out cross-validation. Compared with the conventional age specific atlas-based segmentation and direct patch based segmentation, both new approaches demonstrate improved accuracy in the automated labeling of cortical gray matter, white matter, ventricles and sulcal cortical-spinal fluid regions, while maintaining comparable results in deep gray matter. PMID:26702777

  10. The effects of omega 3 fatty acid supplementation on brain tissue oxidative status in aged wistar rats

    OpenAIRE

    Avramovic, N; Dragutinovic, V; Krstic, D; Colovic, MB; Trbovic, A; de Luka, S; Milovanovic, I; Popovic, T

    2012-01-01

    Background: The omega 3 fatty acids play an important role in many physiological processes. Their effect is well documented in neurodegenerative diseases and inflammatory diseases. Also, aging as a biophysiological process could be influenced by eicosapentanoic acid (EPA) and docosahexanoic acid (DHA) components of fish oil. However there are not many studies showing the effect of PUFA (polyunsaturated FA) suplementation in eldery brain functions and the response to oxidative strees. The aim ...

  11. Selective estrogen receptor modulators decrease reactive astrogliosis in the injured brain: Effects of aging and prolonged depletion of ovarian hormones

    OpenAIRE

    Barreto, G.; Santos-Galindo, M.; Diz-Chaves, Yolanda; Pernía, Olga; Carrero, P; Azcoitia, I.; Garcia-Segura, Luis M.

    2009-01-01

    After brain injury, astrocytes acquire a reactive phenotype characterized by a series of morphological and molecular modifications, including the expression of the cytoskeletal protein vimentin. Previous studies have shown that estradiol down-regulates reactive astrogliosis. In this study we assessed whether raloxifene and tamoxifen, two selective estrogen receptor modulators, have effects similar to estradiol in astrocytes. We also assessed whether aging and the timing of estrogenic therapy ...

  12. Long-Term Cognitive Sequelae After Pediatric Brain Tumor Related to Medical Risk Factors, Age, and Sex

    OpenAIRE

    Tonning Olsson, Ingrid; Perrin, Sean; Lundgren, Johan; Hjorth, Lars; Johanson, Aki

    2014-01-01

    BACKGROUND: Young age at diagnosis and treatment with cranial radiation therapy are well studied risk factors for cognitive impairment in pediatric brain tumor survivors. Other risk factors are hydrocephalus, surgery complications, and treatment with intrathecal chemotherapy. Female gender vulnerability to cognitive sequelae after cancer treatment has been evident in some studies, but no earlier studies have related this to tumor size. The purpose of our study was to find factors correlate...

  13. [Peloid therapy in the complex sanatorium treatment of children of early age with complications of perinatal brain damage].

    Science.gov (United States)

    Ponomareva, S O; Babina, L M

    2003-01-01

    The search for novel approaches to multimodality prophylaxis and treatment of sequelae of perinatal nervous system affection as well as introduction of the early diagnostic criteria are topical problems in present-day pediatric neurology. Peloid therapy efficacy in combined sanatorium treatment was studied (Peloterm unit) in 44 infants aged 1 to 3 years. They suffered from sequelae of perinatal affections of the central nervous system including infantile cerebral paralysis. A positive effect (improvement of motor and psychic-speech development) was achieved in 98% cases. This indicates validity of this method in the treatment of CNS affections following perinatal affection of the brain in infants over 1 year of age. PMID:14753007

  14. Functional metagenomics to decipher food-microbe-host crosstalk.

    Science.gov (United States)

    Larraufie, Pierre; de Wouters, Tomas; Potocki-Veronese, Gabrielle; Blottière, Hervé M; Doré, Joël

    2015-02-01

    The recent developments of metagenomics permit an extremely high-resolution molecular scan of the intestinal microbiota giving new insights and opening perspectives for clinical applications. Beyond the unprecedented vision of the intestinal microbiota given by large-scale quantitative metagenomics studies, such as the EU MetaHIT project, functional metagenomics tools allow the exploration of fine interactions between food constituents, microbiota and host, leading to the identification of signals and intimate mechanisms of crosstalk, especially between bacteria and human cells. Cloning of large genome fragments, either from complex intestinal communities or from selected bacteria, allows the screening of these biological resources for bioactivity towards complex plant polymers or functional food such as prebiotics. This permitted identification of novel carbohydrate-active enzyme families involved in dietary fibre and host glycan breakdown, and highlighted unsuspected bacterial players at the top of the intestinal microbial food chain. Similarly, exposure of fractions from genomic and metagenomic clones onto human cells engineered with reporter systems to track modulation of immune response, cell proliferation or cell metabolism has allowed the identification of bioactive clones modulating key cell signalling pathways or the induction of specific genes. This opens the possibility to decipher mechanisms by which commensal bacteria or candidate probiotics can modulate the activity of cells in the intestinal epithelium or even in distal organs such as the liver, adipose tissue or the brain. Hence, in spite of our inability to culture many of the dominant microbes of the human intestine, functional metagenomics open a new window for the exploration of food-microbe-host crosstalk. PMID:25417646

  15. Functional metagenomics to decipher food-microbe-host crosstalk.

    Science.gov (United States)

    Larraufie, Pierre; de Wouters, Tomas; Potocki-Veronese, Gabrielle; Blottière, Hervé M; Doré, Joël

    2015-02-01

    The recent developments of metagenomics permit an extremely high-resolution molecular scan of the intestinal microbiota giving new insights and opening perspectives for clinical applications. Beyond the unprecedented vision of the intestinal microbiota given by large-scale quantitative metagenomics studies, such as the EU MetaHIT project, functional metagenomics tools allow the exploration of fine interactions between food constituents, microbiota and host, leading to the identification of signals and intimate mechanisms of crosstalk, especially between bacteria and human cells. Cloning of large genome fragments, either from complex intestinal communities or from selected bacteria, allows the screening of these biological resources for bioactivity towards complex plant polymers or functional food such as prebiotics. This permitted identification of novel carbohydrate-active enzyme families involved in dietary fibre and host glycan breakdown, and highlighted unsuspected bacterial players at the top of the intestinal microbial food chain. Similarly, exposure of fractions from genomic and metagenomic clones onto human cells engineered with reporter systems to track modulation of immune response, cell proliferation or cell metabolism has allowed the identification of bioactive clones modulating key cell signalling pathways or the induction of specific genes. This opens the possibility to decipher mechanisms by which commensal bacteria or candidate probiotics can modulate the activity of cells in the intestinal epithelium or even in distal organs such as the liver, adipose tissue or the brain. Hence, in spite of our inability to culture many of the dominant microbes of the human intestine, functional metagenomics open a new window for the exploration of food-microbe-host crosstalk.

  16. Challenges of deciphering gastric cancer heterogeneity.

    Science.gov (United States)

    Hudler, Petra

    2015-10-01

    Gastric cancer is in decline in most developed countries; however, it still accounts for a notable fraction of global mortality and morbidity related to cancer. High-throughput methods are rapidly changing our view and understanding of the molecular basis of gastric carcinogenesis. Today, it is widely accepted that the molecular complexity and heterogeneity, both inter- and intra-tumour, of gastric adenocarcinomas present significant obstacles in elucidating specific biomarkers for early detection of the disease. Although genome-wide sequencing and gene expression studies have revealed the intricate nature of the molecular changes that occur in tumour landscapes, the collected data and results are complex and sometimes contradictory. Several aberrant molecules have already been tested in clinical trials, although their diagnostic and prognostic utilities have not been confirmed thus far. The gold standard for the detection of sporadic gastric cancer is still the gastric endoscopy, which is considered invasive. In addition, genome-wide association studies have confirmed that genetic variations are important contributors to increased cancer risk and could participate in the initiation of malignant transformation. This hypothesis could in part explain the late onset of sporadic gastric cancers. The elaborate interplay of polymorphic low penetrance genes and lifestyle and environmental risk factors requires additional research to decipher their relative impacts on tumorigenesis. The purpose of this article is to present details of the molecular heterogeneity of sporadic gastric cancers at the DNA, RNA, and proteome levels and to discuss issues relevant to the translation of basic research data to clinically valuable tools. The focus of this work is the identification of relevant molecular changes that could be detected non-invasively. PMID:26457012

  17. Chronic pyruvate supplementation increases exploratory activity and brain energy reserves in young and middle-aged mice

    Directory of Open Access Journals (Sweden)

    Hennariikka eKoivisto

    2016-03-01

    Full Text Available Numerous studies have reported neuroprotective effects of pyruvate when given in systemic injections. Impaired glucose uptake and metabolism are found in Alzheimer's disease (AD and in AD mouse models. We tested whether dietary pyruvate supplementation is able to provide added energy supply to brain and thereby attenuate aging- or AD-related cognitive impairment. Mice received ~ 800 mg/kg/day Na-pyruvate in their chow for 2- 6 months. In middle-aged wild-type mice and in 6.5-month-old APP/PS1 mice, pyruvate facilitated spatial learning and increased exploration of a novel odor. However, in passive avoidance task for fear memory, the treatment group was clearly impaired. Independent of age, long-term pyruvate increased explorative behavior, which likely explains the paradoxical impairment in passive avoidance. We also assessed pyruvate effects on body weight, muscle force and endurance, and found no effects. Metabolic post-mortem assays revealed increased energy compounds in nuclear magnetic resonance spectroscopy as well as increased brain glycogen storages in the pyruvate group. Pyruvate supplementation may counteract aging-related behavioral impairment but its beneficial effect seems related to increased explorative activity rather than direct memory enhancement.

  18. Age of second language acquisition in multilinguals has an impact on gray matter volume in language-associated brain areas.

    Science.gov (United States)

    Kaiser, Anelis; Eppenberger, Leila S; Smieskova, Renata; Borgwardt, Stefan; Kuenzli, Esther; Radue, Ernst-Wilhelm; Nitsch, Cordula; Bendfeldt, Kerstin

    2015-01-01

    Numerous structural studies have established that experience shapes and reshapes the brain throughout a lifetime. The impact of early development, however, is still a matter of debate. Further clues may come from studying multilinguals who acquired their second language at different ages. We investigated adult multilinguals who spoke three languages fluently, where the third language was learned in classroom settings, not before the age of 9 years. Multilinguals exposed to two languages simultaneously from birth (SiM) were contrasted with multinguals who acquired their first two languages successively (SuM). Whole brain voxel based morphometry revealed that, relative to SuM, SiM have significantly lower gray matter volume in several language-associated cortical areas in both hemispheres: bilaterally in medial and inferior frontal gyrus, in the right medial temporal gyrus and inferior posterior parietal gyrus, as well as in the left inferior temporal gyrus. Thus, as shown by others, successive language learning increases the volume of language-associated cortical areas. In brains exposed early on and simultaneously to more than one language, however, learning of additional languages seems to have less impact. We conclude that - at least with respect to language acquisition - early developmental influences are maintained and have an effect on experience-dependent plasticity well into adulthood.

  19. Age of second language acquisition in multilinguals has an impact on gray matter volume in language-associated brain areas.

    Science.gov (United States)

    Kaiser, Anelis; Eppenberger, Leila S; Smieskova, Renata; Borgwardt, Stefan; Kuenzli, Esther; Radue, Ernst-Wilhelm; Nitsch, Cordula; Bendfeldt, Kerstin

    2015-01-01

    Numerous structural studies have established that experience shapes and reshapes the brain throughout a lifetime. The impact of early development, however, is still a matter of debate. Further clues may come from studying multilinguals who acquired their second language at different ages. We investigated adult multilinguals who spoke three languages fluently, where the third language was learned in classroom settings, not before the age of 9 years. Multilinguals exposed to two languages simultaneously from birth (SiM) were contrasted with multinguals who acquired their first two languages successively (SuM). Whole brain voxel based morphometry revealed that, relative to SuM, SiM have significantly lower gray matter volume in several language-associated cortical areas in both hemispheres: bilaterally in medial and inferior frontal gyrus, in the right medial temporal gyrus and inferior posterior parietal gyrus, as well as in the left inferior temporal gyrus. Thus, as shown by others, successive language learning increases the volume of language-associated cortical areas. In brains exposed early on and simultaneously to more than one language, however, learning of additional languages seems to have less impact. We conclude that - at least with respect to language acquisition - early developmental influences are maintained and have an effect on experience-dependent plasticity well into adulthood. PMID:26106338

  20. Age-related white matter degradation rule of normal human brain: the evidence from diffusion tensor magnetic resonance imaging

    Institute of Scientific and Technical Information of China (English)

    Zhang Xiang; Li Baoqing; Shan Baoci

    2014-01-01

    Background Diffusion tensor imaging can evaluate white matter function in human brain.Fractional anisotropy is the most important parameter.This study aimed to find regional reduction of fractional anisotropy (FA) with aging in the whole brain and the changing rules of anisotropy with aging.Methods Fifty volunteers from 20 to 75 years old were divided into five consecutive age groups; a young group and four senior groups.FA values were calculated with diffusion tensor imaging (DTI) studio software.The difference of FA between the young group and the four senior groups were analyzed by analysis of voxel-level height threshold in Statistic Parametric Mapping (SPM),and the regions with decreased FA were obtained.The FA values of these regions were then extracted using an in-house developed program,and a multiple linear regression model was built to assess the influence of age and sex on the FA values of these regions.Results Eight regions,including frontal lobe,postcentral gyrus,optic radiation,hippocampus,cerebella hemisphere,corona radiate,corpus callosum and internal capsule,were found to have decreased FA.There was a strong negative correlation between age and the FA in the frontal lobe,postcentral gyrus,optic radiation,hippocampus,and cerebella hemisphere,while a weaker negative correlation in the corona radiate,corpus callosum,and internal capsule was found.The FA reduction in the frontal lobe,postcentral gyrus,optic radiation,hippocampus and cerebella hemisphere were found earlier than in the corona radiate,corpus callosum and internal capsule.There was no correlation between sex and FA in these regions.Conclusions The FA in the subcortical white matter area reduces earlier than that in deep white matter.The areas with decreased FA continuously enlarge with aqing.The FAs in these regions have a strong negative correlation with age.

  1. Preserving brain function in aging: The anti-glycative potential of berry fruit

    Science.gov (United States)

    Advanced glycation end-products (AGEs) are naturally occurring macromolecules that are formed in vivo by the non-enzymatic modification of proteins, lipids, or nucleic acids by sugar, even in the absence of hyperglycemia. In the diet, AGEs are found in animal products, and additional AGEs are produc...

  2. Mammalian Target of Rapamycin: Its Role in Early Neural Development and in Adult and Aged Brain Function.

    Science.gov (United States)

    Garza-Lombó, Carla; Gonsebatt, María E

    2016-01-01

    The kinase mammalian target of rapamycin (mTOR) integrates signals triggered by energy, stress, oxygen levels, and growth factors. It regulates ribosome biogenesis, mRNA translation, nutrient metabolism, and autophagy. mTOR participates in various functions of the brain, such as synaptic plasticity, adult neurogenesis, memory, and learning. mTOR is present during early neural development and participates in axon and dendrite development, neuron differentiation, and gliogenesis, among other processes. Furthermore, mTOR has been shown to modulate lifespan in multiple organisms. This protein is an important energy sensor that is present throughout our lifetime its role must be precisely described in order to develop therapeutic strategies and prevent diseases of the central nervous system. The aim of this review is to present our current understanding of the functions of mTOR in neural development, the adult brain and aging. PMID:27378854

  3. Spatiotemporal Molecular Approach of in utero Electroporation to Functionally Decipher Endophenotypes in Neurodevelopmental Disorders

    Science.gov (United States)

    Kolk, Sharon Margriet; de Mooij-Malsen, Annetrude Johanne; Martens, Gerard Julianus Maria

    2011-01-01

    We have only just begun to decipher the complexity of our brain, including its maturation. Correct brain development and communication among brain areas are crucial for proper cognitive behavior. Brain area-specific genes expressed within a particular time window direct neurodevelopmental events such as proliferation, migration, axon guidance, dendritic arborization, and synaptogenesis. These genes can pose as susceptibility factors in neurodevelopmental disorders eventually resulting in area-specific cognitive deficits. Therefore, in utero electroporation (IUE)-mediated gene transfer can aid in creating valuable animal models in which the regionality and time of expression can be restricted for the targeted gene(s). Moreover, through the use of cell-type-specific molecular constructs, expression can be altered in a particular neuronal subset within a distinct area such that we are now able to causally link the function of that gene in that brain region to the etiology of the disorder. Thus, IUE-mediated gene transfer is an attractive molecular technique to spatiotemporally address the developmental aspects of gene function in relation to neurodevelopmental disorder-associated endophenotypes. PMID:22065947

  4. Spatiotemporal molecular approach of in utero electroporation to functionally decipher endophenotypes in neurodevelopmental disorders

    Directory of Open Access Journals (Sweden)

    Sharon Margriet Kolk

    2011-11-01

    Full Text Available We have only just begun to decipher the complexity of our brain including its maturation. Correct brain development and communication among brain areas are crucial for proper cognitive behavior. Brain area-specific genes expressed within a particular time window direct neurodevelopmental events such as proliferation, migration, axon guidance, dendritic arborization and synaptogenesis. These genes can pose as susceptibility factors in neurodevelopmental disorders eventually resulting in area-specific cognitive deficits. Therefore, in utero electroporation-mediated gene transfer can aid in creating valuable animal models in which the regionality and time of expression can be restricted for the targeted gene(s. Moreover, through the use of cell-type specific molecular constructs, expression can be altered in a particular neuronal subset within a distinct area such that we are now able to causally link the function of that gene in that brain region to the etiology of the disorder. Thus, in utero electroporation-mediated gene transfer is an attractive molecular technique to spatiotemporally address the developmental aspects of gene function in relation to neurodevelopmental disorder-associated endophenotypes.

  5. Preserving Brain Function in Aging: The Anti-glycative Potential of Berry Fruit.

    Science.gov (United States)

    Thangthaeng, Nopporn; Poulose, Shibu M; Miller, Marshall G; Shukitt-Hale, Barbara

    2016-09-01

    Advanced glycation end products (AGEs) are naturally occurring macromolecules that are formed in vivo by the non-enzymatic modification of proteins, lipids, or nucleic acids by sugar, even in the absence of hyperglycemia. In the diet, AGEs are found in animal products, and additional AGEs are produced when those foods are cooked at high temperatures. Studies have linked AGEs to various age-related physiological changes, including wrinkles, diabetic complications, and neurodegenerative disease, including Alzheimer's disease. Dietary berry fruits have been shown to reduce the severity or slow the progression of many physiological changes and disease pathologies that accompany aging. Emerging evidence has shown that the phytochemicals found in berry fruits exhibit anti-glycative activity. In this review, we briefly summarize the current evidence supporting the neuroprotective anti-glycative activity of berry fruits and their potential to preserve cognitive function during aging. PMID:27166828

  6. Hormone-brain-aging relationships, broadly reactive with imidazole-containing dipeptides: targeting of telomere attrition as an aging biomarker and dynamic telomerase activity flirting.

    Science.gov (United States)

    Babizhayev, Mark A; Vishnyakova, Khava S; Yegorov, Yegor E

    2015-03-01

    It has been documented that telomere-associated cellular senescence may contribute to certain age-related disorders, and telomere length (TL) may be an informative biomarker of healthy aging. Hormone-brain-aging behavior-modulated telomere dynamics and changes in telomerase activity are consistent elements of cellular alterations associated with changes in proliferative state, and these processes are consequently considered as the new therapeutic drug targets for physiological control with advanced drug delivery and nutritional formulations. We raise and support a therapeutic concept of using nonhydrolyzed forms of naturally occurring neuron-specific imidazole dipeptide-based compounds carnosine and carcinine, making it clinically possible that slowing down the rate of telomere shortening could slow down the human aging process in specific tissues where proliferative senescence is known to occur, with the demonstrated evidence of telomere shortening that appeared to be a hallmark of oxidative stress and disease. Carnosine released from skeletal muscle during exercise may be transported into the hypothalamic tuberomammillary nucleus (TMN) histamine neurons and hydrolyzed. The resulting L-histidine may subsequently be converted into histamine, which could be responsible for the effects of carnosine on neurotransmission and hormone-like antiaging physiological function. The preliminary longitudinal studies of elderly individuals suggest that longer telomeres are associated with better survival, and an advanced oral nutritional support with nonhydrolyzed carnosine (or carcinine and patented compositions thereof) is a useful therapeutic tool for a critical TL maintenance that may fundamentally be applied in the treatment of age-related sight-threatening eye disorders, prolonged life expectancy, increased survival and chronological age of an organism in health control, smoking behavior, and disease. "Our pleasures were simple-they included survival." -Dwight D

  7. Cognitive reserve is associated with the functional organization of the brain in healthy aging: a MEG study.

    Science.gov (United States)

    López, María E; Aurtenetxe, Sara; Pereda, Ernesto; Cuesta, Pablo; Castellanos, Nazareth P; Bruña, Ricardo; Niso, Guiomar; Maestú, Fernando; Bajo, Ricardo

    2014-01-01

    The proportion of elderly people in the population has increased rapidly in the last century and consequently "healthy aging" is expected to become a critical area of research in neuroscience. Evidence reveals how healthy aging depends on three main behavioral factors: social lifestyle, cognitive activity, and physical activity. In this study, we focused on the role of cognitive activity, concentrating specifically on educational and occupational attainment factors, which were considered two of the main pillars of cognitive reserve (CR). Twenty-one subjects with similar rates of social lifestyle, physical and cognitive activity were selected from a sample of 55 healthy adults. These subjects were divided into two groups according to their level of CR; one group comprised subjects with high CR (9 members) and the other one contained those with low CR (12 members). To evaluate the cortical brain connectivity network, all participants were recorded by Magnetoencephalography (MEG) while they performed a memory task (modified version of the Sternberg's Task). We then applied two algorithms [Phase Locking Value (PLV) and Phase Lag Index (PLI)] to study the dynamics of functional connectivity. In response to the same task, the subjects with lower CR presented higher functional connectivity than those with higher CR. These results may indicate that participants with low CR needed a greater "effort" than those with high CR to achieve the same level of cognitive performance. Therefore, we conclude that CR contributes to the modulation of the functional connectivity patterns of the aging brain. PMID:24982632

  8. Age-related differences in functional nodes of the brain cortex - a high model order group ICA study

    Directory of Open Access Journals (Sweden)

    Harri Littow

    2010-08-01

    Full Text Available Functional MRI measured with blood oxygen dependent (BOLD contrast in the absence of intermittent tasks reflects spontaneous activity of so called resting state networks (RSN of the brain. Group level independent component analysis (ICA of BOLD data can separate the human brain cortex into 42 independent RSNs. In this study we evaluated age related effects from primary motor and sensory, and, higher level control RSNs. 168 healthy subjects were scanned and divided into three groups: 55 adolescents (ADO, 13.2 ± 2.4 yrs, 59 young adults (YA, 22.2 ± 0.6yrs , and 54 older adults (OA, 42.7 ± 0.5 yrs, all with normal IQ. High model order group probabilistic ICA components (70 were calculated and dual regression analysis was used to compare 21 RSN’s spatial differences between groups. The power spectra were derived from individual ICA mixing matrix time series of the group analyses for frequency domain analysis. We show that primary sensory and motor networks tend to alter more in younger age groups, whereas associative and higher level cognitive networks consolidate and re-arrange until older adulthood. The change has a common trend: both spatial extent and the low frequency power of the RSN’s reduce with increasing age. We interpret these result as a sign of normal pruning via focusing of activity to less distributed local hubs.

  9. Age-Related Changes in Transient and Oscillatory Brain Responses to Auditory Stimulation during Early Adolescence

    Science.gov (United States)

    Poulsen, Catherine; Picton, Terence W.; Paus, Tomas

    2009-01-01

    Maturational changes in the capacity to process quickly the temporal envelope of sound have been linked to language abilities in typically developing individuals. As part of a longitudinal study of brain maturation and cognitive development during adolescence, we employed dense-array EEG and spatiotemporal source analysis to characterize…

  10. Imaging of Age-related Brain Changes: A Population-based Approach

    NARCIS (Netherlands)

    M.W. Vernooij (Meike)

    2009-01-01

    textabstractThe objective of the studies described in this thesis was to investigate with magnetic resonance imaging (MRI) brain changes that may function as preclinical imaging markers for neurodegenerative and cerebrovascular disease. For this goal, advanced MRI techniques were applied in the Rott

  11. Age-and Brain Region-Specific Differences in Mitochondrial Bioenergetics in Brown Norway Rats

    Science.gov (United States)

    Mitochondria are central regulators of energy homeostasis and play a pivotal role in mechanisms of cellular senescence. The objective of the present study was to evaluate mitochondrial bio­-energetic parameters in five brain regions [brainstem (BS), frontal cortex (FC), cereb...

  12. Type 2 diabetes and cognition: Neuropsychological sequelae of vascular risk factors in the ageing brain

    NARCIS (Netherlands)

    Van den Berg, E.

    2009-01-01

    Type 2 diabetes mellitus (T2DM) is associated with slowly progressive changes in the brain, a complication referred to as diabetic encephalopathy. Previous studies have shown that patients with T2DM show mild to moderate decrements in cognitive functioning and an increased risk of dementia. The cent

  13. Magnetization transfer ratio in the brain of preterm subjects: age-related changes during the first 2 years of life

    Energy Technology Data Exchange (ETDEWEB)

    Xydis, Vassilios; Astrakas, Loukas; Zikou, Anastasia; Argyropoulou, Maria I. [University of Ioannina, Department of Radiology, Medical School, Ioannina (Greece); Pantou, Kostandina; Andronikou, Styliani [Medical School University of Ioannina, Neonatology Clinic, Child Health Department, Ioannina (Greece)

    2006-01-01

    To study the progress of myelination in preterm-born subjects by measuring the MT ratio (MTR) from birth, up to 24 months of corrected age.One hundred twenty-five preterm subjects (64 males and 61 females of gestational age 33{+-}2.4 weeks with chronologic and corrected age of 9.3{+-}5.1 and 7.7{+-}5.1 months, respectively) with normal brain MR using classic sequences were further evaluated for MTR by using a three-dimensional gradient-echo sequence (TR=32/TE=8/flip angle=6 4 mm/2 mm overlapping sections) with and without magnetization transfer prepulse. The magnetization transfer ratio was calculated as: MTR=(SIo-SIm)/SIo x 100%, where SIm refers to signal intensity from an image acquired with a MT prepulse and SIo the signal intensity from the image acquired without a MT prepulse. MTR increased asymptotically in the genu (R{sup 2}=0.85) and splenium (R{sup 2}=0.85) of the corpus callosum, the white matter of the frontal lobe (R{sup 2}=0.91) and occipital lobe (R{sup 2}=0.82), thalamus (R{sup 2}=0.86), caudate nucleus (R{sup 2}=0.67) and putamen (R{sup 2}=0.71), reaching the 95% of the final value at the corrected age 18.7, 17.7, 15.6, 12.9, 10.4, 9.2 and 6.4 months, respectively. This study shows age-related changes of the brain MTR and provides data that may be useful to assess disturbances in the progress of myelination. (orig.)

  14. Brain-derived neurotrophic factor (BDNF) gene: a gender-specific role in cognitive function during normal cognitive aging of the MEMO-Study?

    OpenAIRE

    Laing, Katharine R.; Mitchell, David; Wersching, Heike; Czira, Maria E.; Berger, Klaus; Baune, Bernhard T

    2011-01-01

    Cognitive aging processes are underpinned by multiple processes including genetic factors. The brain-derived neurotrophic factor (BDNF) has been suggested to be involved in age-related cognitive decline in otherwise healthy individuals. The gender-specific role of the BDNF gene in cognitive aging remains unclear. The identification of genetic biomarkers might be a useful approach to identify individuals at risk of cognitive decline during healthy aging processes. The aim of this study was to ...

  15. Decrease in age-related tau hyperphosphorylation and cognitive improvement following vitamin D supplementation are associated with modulation of brain energy metabolism and redox state

    OpenAIRE

    Briones, Teresita L; Darwish, Hala

    2014-01-01

    In the present study we examined whether vitamin D supplementation can reduce age-related tau hyperphosphorylation and cognitive impairment by enhancing brain energy homeostasis and protein phosphatase-2A (PP2A) activity, and modulating the redox state. Male F344 rats age 20 months (aged) and 6 months (young) were randomly assigned to either vitamin D supplementation or no supplementation (control). Rats were housed in pairs and the supplementation group (n=10 young and n=10 aged) received su...

  16. Postnatal Age Influences Hypoglycemia-induced Poly(ADP-ribose) Polymerase-1 Activation in the Brain Regions of Rats

    OpenAIRE

    Rao, Raghavendra; Sperr, Dustin; Ennis, Kathleen; Tran, Phu

    2009-01-01

    Poly(ADP-ribose) polymerase-1 (PARP-1) overactivation plays a significant role in hypoglycemia-induced brain injury in adult rats. To determine the influence of postnatal age on PARP-1 activation, developing and adult male rats were subjected to acute hypoglycemia of equivalent severity and duration. The expression of PARP-1 and its downstream effectors, apoptosis inducing factor (Aifm1), caspase 3 (Casp3), NF-κB (Nfkb1) and bcl-2 (Bcl2), and cellular poly(ADP-ribose) (PAR) polymer expression...

  17. Neuroinflammation not associated with cholinergic degeneration in aged-impaired brain

    OpenAIRE

    McQuail, Joseph A.; Riddle, David R.; Nicolle, Michelle M.

    2010-01-01

    Degeneration of the cholinergic neurons in the basal forebrain and elevation of inflammatory markers are well-established hallmarks of Alzheimer's disease; however, the interplay of these processes in normal aging is not extensively studied. Consequently, we conducted a neuroanatomical investigation to quantify cholinergic neurons and activated microglia in the medial septum/vertical diagonal band (MS/VDB) of young (6 months) and aged (28 months) Fisher 344 × Brown Norway F1 rats. Aged rats i...

  18. Neurogenetic effects on cognition in aging brains: A window of opportunity for intervention?

    OpenAIRE

    Ivar Reinvang; Deary, Ian J; Fjell, Anders M.; Vidar M Steen; Thomas Espeseth; Raja Parasuraman

    2010-01-01

    Knowledge of genetic influences on cognitive aging can constrain and guide interventions aimed at limiting age-related cognitive decline in older adults. Progress in understanding the neural basis of cognitive aging also requires a better understanding of the neurogenetics of cognition. This selective review article describes studies aimed at deriving specific neurogenetic information from three parallel and interrelated phenotype based approaches: psychometric constructs, cognitive neuroscie...

  19. Cytoskeletal Pathologies of Age-Related Diseases between Elderly Sri Lankan (Colombo) and Indian (Bangalore) Brain Samples.

    Science.gov (United States)

    Wijesinghe, Printha; Shankar, S K; Chickabasaviah, Yasha T; Gorrie, Catherine; Amaratunga, Dhammika; Hulathduwa, Sanjayah; Kumara, K Sunil; Samarasinghe, Kamani; Suh, Yoo Hun; Steinbusch, H W; De Silva, K Ranil D

    2016-01-01

    Within South Asia, Sri Lanka represents fastest aging with 13% of the population was aged over 60's in 2011, whereas in India it was 8%. Majority of the Sri Lankan population based genetic studies have confirmed their origin on Indian mainland. As there were inadequate data on aging cytoskeletal pathologies of these two nations with their close genetic affiliations, we performed a comparison on their elderly. Autopsy brain samples of 50 individuals from Colombo, Sri Lanka (mean age 72.1 yrs ± 7.8, mean ± S.D.) and 42 individuals from Bangalore, India (mean age 65.9 yrs ± 9.3) were screened for neurodegenerative pathologies using immunohistochemical techniques. A total of 79 cases with incomplete clinical history (Colombo- 47 and Bangalore- 32) were subjected to statistical analysis and 13 cases, clinically diagnosed with dementia and/or Parkinsonism disorders were excluded. As per National Institute on Aging- Alzheimer's Association guidelines, between Colombo and Bangalore samples, Alzheimer's disease neuropathologic change for intermediate/ high level was 4.25% vs. 3.12% and low level was 19.15% vs. 15.62% respectively. Pathologies associated with Parkinsonism including brainstem predominant Lewy bodies- 6.4% and probable progressive supra nuclear palsy- 2.13% were found solely in Colombo samples. Alzheimer related pathologies were not different among elders, however, in Colombo males, neurofibrillary tangle grade was significantly higher in the region of hippocampus (odds ratio = 1.46, 95% confidence interval = 0.07-0.7) and at risk in midbrain substantia nigra (p = 0.075). Other age-related pathologies including spongiform changes (p Colombo samples. Taken together, aging cytoskeletal pathologies are comparatively higher in elderly Sri Lankans and this might be due to their genetic, dietary and/ or environmental variations.

  20. The Association of Menopausal Age and NT-proBrain Natriuretic Peptide: The Multi-Ethnic Study of Atherosclerosis

    Science.gov (United States)

    Ebong, Imo A.; Watson, Karol E.; Goff, David C.; Bluemke, David A.; Srikanthan, Preethi; Horwich, Tamara; Bertoni, Alain G.

    2014-01-01

    Objective Menopausal age could affect the risk of developing cardiovascular disease (CVD). The purpose of this study was to investigate the associations of early menopause (menopause occurring before 45 years of age) and menopausal age with NT-pro brain natriuretic peptide (NT-proBNP), a potential risk marker of CVD and heart failure (HF). Methods Our cross-sectional study included 2275 postmenopausal women, aged 45–85 years, without clinical CVD (2000–2002), from the Multi-Ethnic Study of Atherosclerosis. Participants were classified as having or not having early menopause. NT-proBNP was log-transformed. Multivariable linear regression was used for analysis. Results There were 561 women with early menopause. The median NT-proBNP value was 79.0 (41.1–151.6) pg/ml for all participants with values of 83.4 (41.4–164.9) pg/ml and 78.0 (40.8–148.3) pg/ml for women with and without early menopause respectively. The mean (SD) age was 65 (10.1) and 65 (8.9) years for women with and without early menopause respectively. There were no significant interactions between menopausal age and ethnicity. In multivariable analysis, early menopause was associated with a 10.7% increase in NT-proBNP while each year increase in menopausal age was associated with a 0.7% decrease in NT-proBNP. Conclusion Early menopause is associated with greater NT-proBNP levels while each year increase in menopausal age is associated with lower NT-proBNP levels in postmenopausal women. PMID:25290536

  1. Systemic Effects of Fractionated, Whole-Brain Irradiation in Young Adult and Aging Rats

    OpenAIRE

    Forbes, M. E.; Paitsel, M.; Bourland, J. D.; Riddle, D. R.

    2013-01-01

    Cranial irradiation is a critical and effective treatment for primary brain tumors and metastases. Unfortunately, most patients who are treated and survive for more than a few months develop neural and cognitive problems as the result of radiation-induced normal tissue injury. The neurobiological mechanisms underlying these cognitive deficits remain largely unknown and there are no validated treatments to prevent or ameliorate them; thus, there is a significant and continuing need for preclin...

  2. Effects of Early Onset of Nimodipine Treatment on Microvascular Integrity in the Aging Rat Brain

    NARCIS (Netherlands)

    de Jong, Giena; Horváth, E.; Luiten, P.G.M.

    1990-01-01

    We studied the effects of long-term treatment with 1,4-dihydropyridine nimodipine on age-related changes of the cerebral microvasculature in layers I, III, and V of the frontoparietal motor cortex of aged (30 months) male Wistar rats. Ultrastructural alterations of microvessels can either be attribu

  3. EFFECTS OF TOLUENE ON BRAIN OXIDATIVE STRESS PARAMETERS IN AGING BROWN NORWAY RATS

    Science.gov (United States)

    Aging-related susceptibility to environmental chemicals is poorly understood. Oxidative stress (OS) appears to play an important role in susceptibility and disease in old age. The objectives of this study, therefore, were to test whether OS is a potential toxicity pathway for tol...

  4. Global view of transcriptome in the brains of aged NR2B transgenic mice*****

    Institute of Scientific and Technical Information of China (English)

    Chunxia Li; Men Su; Huimin Wang; Yinghe Hu

    2013-01-01

    NR2B subunits are involved in regulating aging, in particular, age-related learning and memory deficits. We examined 19-month-old NR2B transgenic mice and their littermate controls. First, we detected expression of the NR2B subunit gene, Grin2b, in the neocortex of transgenic mice using real-time PCR. Next, we used microarrays to examine differences in neocortical gene expression. Pathway and signal-net analyses identified multiple pathways altered in the transgenic mice, in-cluding the P53, Jak-STAT, Wnt, and Notch pathways, as wel as regulation of the actin cytoskeleton and neuroactive ligand-receptor interactions. Further signal-net analysis highlighted the P53 and insulin-like growth factor pathways as key regulatory pathways. Our results provide new insight into understanding the molecular mechanisms of NR2B regulated age-related memory storage, normal organismal aging and age-related disease.

  5. Obesity and age-related alterations in the gene expression of zinc-transporter proteins in the human brain

    DEFF Research Database (Denmark)

    Olesen, R H; Hyde, T M; Kleinman, J E;

    2016-01-01

    The incidence of Alzheimer's disease (AD) is increasing. Major risk factors for AD are advancing age and diabetes. Lately, obesity has been associated with an increased risk of dementia. Obese and diabetic individuals are prone to decreased circulating levels of zinc, reducing the amount of zinc...... participate in intracellular zinc homeostasis. Altered expression of zinc-regulatory proteins has been described in AD patients. Using microarray data from human frontal cortex (BrainCloud), this study investigates expression of the SCLA30A (ZNT) and SCLA39A (ZIP) families of genes in a Caucasian and African...... expression similar to what is seen in the early stages of AD. Increasing BMI also correlated with reduced expression of ZNT6. In conclusion, we found that the expression of genes that regulate intracellular zinc homeostasis in the human frontal cortex is altered with increasing age and affected by increasing...

  6. Prolonged rote learning produces delayed memory facilitation and metabolic changes in the hippocampus of the ageing human brain.

    LENUS (Irish Health Repository)

    Roche, Richard Ap

    2009-01-01

    BACKGROUND: Repeated rehearsal is one method by which verbal material may be transferred from short- to long-term memory. We hypothesised that extended engagement of memory structures through prolonged rehearsal would result in enhanced efficacy of recall and also of brain structures implicated in new learning. Twenty-four normal participants aged 55-70 (mean = 60.1) engaged in six weeks of rote learning, during which they learned 500 words per week every week (prose, poetry etc.). An extensive battery of memory tests was administered on three occasions, each six weeks apart. In addition, proton magnetic resonance spectroscopy (1H-MRS) was used to measure metabolite levels in seven voxels of interest (VOIs) (including hippocampus) before and after learning. RESULTS: Results indicate a facilitation of new learning that was evident six weeks after rote learning ceased. This facilitation occurred for verbal\\/episodic material only, and was mirrored by a metabolic change in left posterior hippocampus, specifically an increase in NAA\\/(Cr+Cho) ratio. CONCLUSION: Results suggest that repeated activation of memory structures facilitates anamnesis and may promote neuronal plasticity in the ageing brain, and that compliance is a key factor in such facilitation as the effect was confined to those who engaged fully with the training.

  7. Elevation of Brain Magnesium Potentiates Neural Stem Cell Proliferation in the Hippocampus of Young and Aged Mice.

    Science.gov (United States)

    Jia, Shanshan; Liu, Yunpeng; Shi, Yang; Ma, Yihe; Hu, Yixin; Wang, Meiyan; Li, Xue

    2016-09-01

    In the adult brain, neural stem cells (NSCs) can self-renew and generate all neural lineage types, and they persist in the sub-granular zone (SGZ) of the hippocampus and the sub-ventricular zone (SVZ) of the cortex. Here, we show that dietary-supplemented - magnesium-L-threonate (MgT), a novel magnesium compound designed to elevate brain magnesium regulates the NSC pool in the adult hippocampus. We found that administration of both short- and long-term regimens of MgT, increased the number of hippocampal NSCs. We demonstrated that in young mice, dietary supplementation with MgT significantly enhanced NSC proliferation in the SGZ. Importantly, in aged mice that underwent long-term (12-month) supplementation with MgT, MgT did not deplete the hippocampal NSC reservoir but rather curtailed the age-associated decline in NSC proliferation. We further established an association between extracellular magnesium concentrations and NSC self-renewal in vitro by demonstrating that elevated Mg(2+) concentrations can maintain or increase the number of cultured hippocampal NSCs. Our study also suggests that key signaling pathways for cell growth and proliferation may be candidate targets for Mg(2+) 's effects on NSC self-renewal. J. Cell. Physiol. 231: 1903-1912, 2016. © 2016 Wiley Periodicals, Inc. PMID:26754806

  8. Decrease in age-related tau hyperphosphorylation and cognitive improvement following vitamin D supplementation are associated with modulation of brain energy metabolism and redox state.

    Science.gov (United States)

    Briones, T L; Darwish, H

    2014-03-14

    In the present study we examined whether vitamin D supplementation can reduce age-related tau hyperphosphorylation and cognitive impairment by enhancing brain energy homeostasis and protein phosphatase 2A (PP2A) activity, and modulating the redox state. Male F344 rats aged 20 months (aged) and 6 months (young) were randomly assigned to either vitamin D supplementation or no supplementation (control). Rats were housed in pairs and the supplementation group (n=10 young and n=10 aged) received subcutaneous injections of vitamin D (1, α25-dihydroxyvitamin D3) for 21 days. Control animals (n=10 young and n=10 aged) received equal volume of normal saline and behavioral testing in the water maze started on day 14 after the initiation of vitamin D supplementation. Tau phosphorylation, markers of brain energy metabolism (ADP/ATP ratio and adenosine monophosphate-activated protein kinase) and redox state (levels of reactive oxygen species, activity of superoxide dismutase, and glutathione levels) as well as PP2A activity were measured in hippocampal tissues. Our results extended previous findings that: (1) tau phosphorylation significantly increased during aging; (2) markers of brain energy metabolism and redox state are significantly decreased in aging; and (3) aged rats demonstrated significant learning and memory impairment. More importantly, we found that age-related changes in brain energy metabolism, redox state, and cognitive function were attenuated by vitamin D supplementation. No significant differences were seen in tau hyperphosphorylation, markers of energy metabolism and redox state in the young animal groups. Our data suggest that vitamin D ameliorated the age-related tau hyperphosphorylation and cognitive decline by enhancing brain energy metabolism, redox state, and PP2A activity making it a potentially useful therapeutic option to alleviate the effects of aging.

  9. Age-related learning and memory deficits in rats: role of altered brain neurotransmitters, acetylcholinesterase activity and changes in antioxidant defense system

    OpenAIRE

    Haider, Saida; Saleem, Sadia; Perveen, Tahira; Tabassum, Saiqa; Batool, Zehra; Sadir, Sadia; Liaquat, Laraib; Madiha, Syeda

    2014-01-01

    Oxidative stress from generation of increased reactive oxygen species or free radicals of oxygen has been reported to play an important role in the aging. To investigate the relationship between the oxidative stress and memory decline during aging, we have determined the level of lipid peroxidation, activities of antioxidant enzymes, and activity of acetylcholine esterase (AChE) in brain and plasma as well as biogenic amine levels in brain from Albino–Wistar rats at age of 4 and 24 months. Th...

  10. Gender and education impact on brain aging: A general cognitive factor approach.

    OpenAIRE

    Proust-Lima, Cecile; Amieva, Hélène; Letenneur, Luc; Orgogozo, Jean-Marc; Jacqmin-Gadda, Hélène; Dartigues, Jean-François

    2008-01-01

    This article may not exactly replicate the final version published in the APA journal. It is not the copy of record. International audience In cognitive aging research, the study of a general cognitive factor has been shown to have a substantial explanatory power over the study of isolated tests. The authors aimed at differentiating the impact of gender and education on global cognitive change with age from their differential impact on 4 psychometric tests using a new latent process app...

  11. Selective Vulnerabilities of N-methyl-D-aspartate (NMDA) Receptors During Brain Aging

    OpenAIRE

    Magnusson, Kathy R.; Brenna L Brim; Das, Siba R.

    2010-01-01

    N-methyl-D-aspartate (NMDA) receptors are present in high density within the cerebral cortex and hippocampus and play an important role in learning and memory. NMDA receptors are negatively affected by aging, but these effects are not uniform in many different ways. This review discusses the selective age-related vulnerabilities of different binding sites of the NMDA receptor complex, different subunits that comprise the complex, and the expression and functions of the receptor within differe...

  12. 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.

  13. Deciphering living networks : Perturbation strategies for functional genomics

    NARCIS (Netherlands)

    Fuente van Bentem, A. de la

    2006-01-01

    Thesis: Deciphering living networks: Perturbation strategies for functional genomics Alberto de la Fuente alf@crs4.it Molecular Cell Physiology Free University Amsterdam Advisors: Prof.Dr. H.V. Westerhoff Prof.Dr. J.L. Snoep Supervisor: Dr. P.J. Mendes Using modern experimental techn

  14. Dietary Vitamin D Deficiency in Rats from Middle- to Old-age Leads to Elevated Tyrosine Nitration and Proteomics Changes in Levels of Key Proteins in Brain: Implications for Low Vitamin D-dependent Age-Related Cognitive Decline

    OpenAIRE

    Keeney, Jeriel T. R.; Förster, Sarah; Sultana, Rukhsana; Brewer, Lawrence D.; Caitlin S Latimer; Cai, Jian; Klein, Jon B.; Porter, Nada M.; Butterfield, D. Allan

    2013-01-01

    In addition to the well-known effects of vitamin D (VitD) in maintaining bone health, there is increasing appreciation that this vitamin may serve important roles in other organs and tissues, including the brain. Given that VitD deficiency is especially widespread among the elderly, it is important to understand how the range of serum VitD levels that mimic those found in humans (from low to high) affects the brain during aging from middle-age to old-age. To address this issue, twenty-seven m...

  15. Building Creativity Training: Drawing with Left Hand to Stimulate Left Brain in Children Age 5-7 Years Old

    Science.gov (United States)

    Saputra, Yanty Hardi; Sabana, Setiawan

    2016-01-01

    Researcher and professionals that started researching about brains since 1930 believe that left brain is a rational brain, which is tightly related with the IO, rational thinking, arithmetic thinking, verbal, segmental, focus, serial (linear), finding the differences, and time management, Meanwhile right brain is the part of brain that controlled…

  16. Stress-associated H3K4 methylation accumulates during postnatal development and aging of rhesus macaque brain.

    Science.gov (United States)

    Han, Yixing; Han, Dali; Yan, Zheng; Boyd-Kirkup, Jerome D; Green, Christopher D; Khaitovich, Philipp; Han, Jing-Dong J

    2012-12-01

    Epigenetic modifications are critical determinants of cellular and developmental states. Epigenetic changes, such as decreased H3K27me3 histone methylation on insulin/IGF1 genes, have been previously shown to modulate lifespan through gene expression regulation. However, global epigenetic changes during aging and their biological functions, if any, remain elusive. Here, we examined the histone modification H3K4 dimethylation (H3K4me2) in the prefrontal cortex of individual rhesus macaques at different ages by chromatin immunoprecipitation, followed by deep sequencing (ChIP-seq) at the whole genome level. Through integrative analysis of the ChIP-seq profiles with gene expression data, we found that H3K4me2 increased at promoters and enhancers globally during postnatal development and aging, and those that correspond to gene expression changes in cis are enriched for stress responses, such as the DNA damage response. This suggests that metabolic and environmental stresses experienced by an organism are associated with the progressive opening of chromatin. In support of this, we also observed increased expression of two H3K4 methyltransferases, SETD7 and DPY30, in aged macaque brain. PMID:22978322

  17. The effects of ecstasy (MDMA on brain serotonin transporters are dependent on age-of-first exposure in recreational users and animals.

    Directory of Open Access Journals (Sweden)

    Anne Klomp

    Full Text Available RATIONALE AND OBJECTIVE: Little is known on the effects of ecstasy (MDMA, a potent 5-HT-releaser and neurotoxin exposure on brain development in teenagers. The objective of this study was to investigate whether in humans, like previous observations made in animals, the effects of MDMA on the 5-HT system are dependent on age-of-first exposure. METHODS: 5-HT transporter (SERT densities in the frontal cortex and midbrain were assessed with [(123I]β-CIT single photon emission computed tomography in 33 users of ecstasy. Subjects were stratified for early-exposed users (age-at-first exposure 14-18 years; developing brain, and late-exposed users (age-at-first exposure 18-36 years; mature brain. In parallel, we investigated the effects of age experimentally with MDMA in early-exposed (adolescent rats and late-exposed (adult rats using the same radioligand. RESULTS: On average, five years after first exposure, we found a strong inverse relationship, wherein age-at-first exposure predicted 79% of the midbrain SERT variability in early (developing brain exposed ecstasy users, whereas this was only 0.3% in late (mature brain exposed users (p=0.007. No such effect was observed in the frontal cortex. In rats, a significant age-BY-treatment effect (p<0.01 was observed as well, however only in the frontal cortex. CONCLUSIONS: These age-related effects most likely reflect differences in the maturational stage of the 5-HT projection fields at age-at-first exposure and enhanced outgrowth of the 5-HT system due to 5-HT's neurotrophic effects. Ultimately, our findings stress the need for more knowledge on the effects of pharmacotherapies that alter brain 5-HT levels in the pediatric population.

  18. Age and heat exposure-dependent changes in antioxidant enzymes activities in rat's liver and brain mitochondria: role of alpha-tocopherol.

    Science.gov (United States)

    Stojkovski, V; Hadzi-Petrushev, N; Ilieski, V; Sopi, R; Gjorgoski, I; Mitrov, D; Jankulovski, N; Mladenov, M

    2013-01-01

    To investigate the role of mitochondrial antioxidant capacity during increased susceptibility to heat accompanied by the aging, young and aged Wistar rats were exposed on heat for 60 min. After heat exposure, hepatic and brain mitochondria were isolated. Our results revealed changes in antioxidant enzyme activities in liver and brain mitochondria from young and to a greater extent in aged rats. Our measurements of MnSOD, GPx and GR activity indicate greater reactive oxygen species production from the mitochondria of aged heat exposed in comparison to young heat exposed rats. Also in the aged rats, the effect of alpha-tocopherol treatment in the prevention of oxidative stress occurred as a result of heat exposure, is less pronounced. Taken together, our data suggest that mitochondria in aged rats are more vulnerable and less able to prevent oxidative changes that occur in response to acute heat exposure.

  19. Genes Related to Fatty Acid β-Oxidation Play a Role in the Functional Decline of the Drosophila Brain with Age.

    Science.gov (United States)

    Laranjeira, António; Schulz, Joachim; Dotti, Carlos G

    2016-01-01

    In living organisms, ageing is widely considered to be the result of a multifaceted process consisting of the progressive accumulation of damage over time, having implications both in terms of function and survival. The study of ageing presents several challenges, from the different mechanisms implicated to the great diversity of systems affected over time. In the current study, we set out to identify genes involved in the functional decline of the brain with age and study its relevance in a tissue dependent manner using Drosophila melanogaster as a model system. Here we report the age-dependent upregulation of genes involved in the metabolic process of fatty acid β-oxidation in the nervous tissue of female wild-type flies. Downregulation of CG10814, dHNF4 and lipid mobilizing genes bmm and dAkh rescues the functional decline of the brain with age, both at the cellular and behaviour level, while over-expression worsens performance. Our data proposes the occurrence of a metabolic alteration in the fly brain with age, whereby the process of β-oxidation of fatty acids experiences a genetic gain-of-function. This event proved to be one of the main causes contributing to the functional decline of the brain with age. PMID:27518101

  20. Obesity and the Ageing Brain: Could Leptin Play a Role in Neurodegeneration?

    Directory of Open Access Journals (Sweden)

    G. H. Doherty

    2011-01-01

    Full Text Available Obesity and ageing are both characteristics of the human population that are on the increase across the globe. It has long been established that ageing is the major risk factor for neurodegenerative conditions such as Alzheimer's disease, and it is becoming increasingly evident that obesity is another such factor. Leptin resistance or insensitivity has been uncovered as a cause of obesity, and in addition the leptin signalling system is less potent in the elderly. Taken together, these findings reveal that this molecule may be a link between neurodegeneration and obesity or ageing. It is now known that leptin has beneficial effects on both the survival and neurophysiology of the neurons that are lost in Alzheimer's disease suggesting that it may be an important research target in the quest for strategies to prevent, halt, or cure this condition.

  1. Assessment of regional glucose metabolism in aging brain and dementia with positron-emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Reivich, M.; Alavi, A.; Ferris, S.; Christman, D.; Fowler, J.; MacGregor, R.; Farkas, T.; Greenberg, J.; Dann, R.; Wolf, A.

    1981-01-01

    This paper explores the alterations in regional glucose metabolism that occur in elderly subjects and those with senile dementia compared to normal young volunteers. Results showed a tendency for the frontal regions to have a lower metabolic rate in patients with dementia although this did not reach the level of significance when compared to the elderly control subjects. The changes in glucose metabolism were symmetrical in both the left and right hemispheres. There was a lack of correlation between the mean cortical metabolic rates for glucose and the global mental function in the patients with senile dementia. This is at variance with most of the regional cerebral blood flow data that has been collected. This may be partly related to the use of substrates other than glucose by the brain in elderly and demented subjects. (PSB)

  2. Exposure to radiation accelerates normal brain aging and produces deficits in spatial learning and memory

    Science.gov (United States)

    Shukitt-Hale, B.; Casadesus, G.; Carey, A.; Rabin, B. M.; Joseph, J. A.

    Previous studies have shown that radiation exposure, particularly to particles of high energy and charge (HZE particles), produces deficits in spatial learning and memory. These adverse behavioral effects are similar to those seen in aged animals. It is possible that these shared effects may be produced by the same mechanism; oxidative stress damage to the central nervous system caused by an increased release of reactive oxygen species is likely responsible for the deficits seen in aging and following irradiation. Both aged and irradiated rats display cognitive impairment in tests of spatial learning and memory such as the Morris water maze and the radial arm maze. These rats have decrements in the ability to build spatial representations of the environment and they utilize non-spatial strategies to solve tasks. Furthermore, they show a lack of spatial preference, due to a decline in the ability to process or retain place (position of a goal with reference to a "map" provided by the configuration of numerous cues in the environment) information. These declines in spatial memory occur in measures dependent on both reference and working memory, and in the flexibility to reset mental images. These results show that irradiation with high-energy particles produces age-like decrements in cognitive behavior that may impair the ability of astronauts to perform critical tasks during long-term space travel beyond the magnetosphere. Supported by NASA Grants NAG9-1190 and NAG9-1529

  3. TOXICITY PATHWAY ANALYSIS IN AGING BROWN NORWAY RAT BRAIN FOLLOWING ACUTE TOLUENE EXPOSURE

    Science.gov (United States)

    The influence of aging on susceptibility to environmental stressors is poorly understood. To investigate the contribution of different life stages on response to toxicants, we examined the effects of acute exposure by oral gavage of the volatile organic solvent toluene (0.00, 0.3...

  4. Roles for the pro-neurotrophin receptor sortilin in neuronal development, aging and brain injury

    DEFF Research Database (Denmark)

    Jansen, Pernille; Giehl, Klaus; Nyengaard, Jens R;

    2007-01-01

    apoptosis of sympathetic neurons, it did prevent their age-dependent degeneration. Furthermore, in an injury protocol, lesioned corticospinal neurons in Sort1(-/-) mice were protected from death. Thus, the sortilin pathway has distinct roles in pro-neurotrophin-induced apoptotic signaling in pathological...

  5. Stroke: 'time is brain' after stroke, regardless of age and severity.

    Science.gov (United States)

    Audebert, Heinrich J; Sobesky, Jan

    2014-12-01

    Two recent studies highlight the importance of prompt, coordinated intervention after stroke. A meta-analysis confirms that intravenous thrombolysis is effective within 4.5 h of onset, irrespective of age (below or above 80 years) and stroke severity. Another study demonstrates successful reorganization of care through centralization of stroke services in England. PMID:25330727

  6. Late-onset intermittent fasting dietary restriction as a potential intervention to retard age-associated brain function impairments in male rats

    OpenAIRE

    Singh, Rumani; Lakhanpal, Dinesh; Kumar, Sushil; Sharma, Sandeep; Kataria, Hardeep; Kaur, Manpreet; Kaur, Gurcharan

    2011-01-01

    Lifelong dietary restriction (DR) is known to have many potential beneficial effects on brain function as well as delaying the onset of neurological diseases. In the present investigation, the effect of late-onset short-term intermittent fasting dietary restriction (IF-DR) regimen was studied on motor coordination and cognitive ability of ageing male rats. These animals were further used to estimate protein carbonyl content and mitochondrial complex I–IV activity in different regions of brain...

  7. The use of bone age for bone mineral density interpretation in a cohort of pediatric brain tumor patients

    Energy Technology Data Exchange (ETDEWEB)

    Morris, E.B. [St. Jude Children' s Research Hospital, Department of Oncology, Memphis, TN (United States); St. Jude Children' s Research Hospital, Division of Cancer Survivorship, Memphis, TN (United States); Shelso, John [St. Jude Children' s Research Hospital, Department of Endocrinology, Memphis, TN (United States); Smeltzer, Matthew P.; Li, Chin-Shang [St. Jude Children' s Research Hospital, Department of Biostatistics, Memphis, TN (United States); Thomas, Nicole A.; Karimova, E.J.; Merchant, Thomas [St. Jude Children' s Research Hospital, Department of Radiological Sciences, Memphis, TN (United States); Gajjar, Amar [St. Jude Children' s Research Hospital, Department of Oncology, Memphis, TN (United States); Kaste, Sue C. [St. Jude Children' s Research Hospital, Department of Oncology, Memphis, TN (United States); St. Jude Children' s Research Hospital, Department of Radiological Sciences, Memphis, TN (United States)

    2008-12-15

    Skeletal bone accretion occurs throughout childhood. The integrity of this process can influence future adult bone health and the risk of osteoporosis. Although surveillance of children who are at risk of poor bone accretion is important, the most appropriate method to monitor childhood bone health has not been established. Previous investigators have proposed using bone age (BA) rather than chronological age (CA) when interpreting bone mineral density (BMD) values in children. To investigate the value of BA assessment for BMD measurement in a cohort of children at risk of poor accretion. A cohort of 163 children with brain tumors who completed both a BMD assessment (quantitative computed tomography, QCT) and who had a BA within a 6-month interval were identified. The difference in BMD Z-scores determined by CA and BA was determined. The impact of salient clinical features was assessed. No significant difference between CA and BA Z-scores was detected in the overall cohort (P = 0.056). However, the scores in 18 children (all boys between the ages of 11 years and 15 years) were statistically determined to be outliers from the values in the rest of the cohort. Interpretation of BMD with BA measurement might be appropriate and affect treatment decisions in peripubertal males. (orig.)

  8. The Cognitive Aging of Episodic Memory: A View Based On The Event-Related Brain Potential (ERP

    Directory of Open Access Journals (Sweden)

    David eFriedman

    2013-08-01

    Full Text Available A cardinal feature of older-adult cognition is a decline, relative to the young, in the encoding and retrieval of personally-relevant events, i.e. episodic memory (EM. A consensus holds that familiarity, a relatively automatic feeling of knowing that can support recognition-memory judgments, is preserved with aging. By contrast, recollection, which requires the effortful, strategic recovery of contextual detail, declines as we age. Over the last decade, ERPs have become increasingly important tools in the study of the aging of EM, because a few, well-researched EM effects have been associated with the cognitive processes thought to underlie successful EM performance. EM effects are operationalized by subtracting the ERPs elicited by correctly-rejected, new items from those to correctly recognized, old items. Although highly controversial, the mid-frontal effect (a positive component between ~300 and 500 ms, maximal at fronto-central scalp sites is thought to reflect familiarity-based recognition. A positivity between ~500 and 800 ms, maximal at left-parietal scalp, has been labeled the left-parietal EM effect. A wealth of evidence suggests that this brain activity reflects recollection-based retrieval. Here, I review the ERP evidence in support of the hypothesis that familiarity is maintained while recollection is compromised in older relative to young adults. I consider the possibility that the inconsistency in findings may be due to individual differences in performance, executive function and quality of life indices, such as socio-economic status.

  9. Advanced brain aging: relationship with epidemiologic and genetic risk factors, and overlap with Alzheimer disease atrophy patterns.

    Science.gov (United States)

    Habes, M; Janowitz, D; Erus, G; Toledo, J B; Resnick, S M; Doshi, J; Van der Auwera, S; Wittfeld, K; Hegenscheid, K; Hosten, N; Biffar, R; Homuth, G; Völzke, H; Grabe, H J; Hoffmann, W; Davatzikos, C

    2016-01-01

    We systematically compared structural imaging patterns of advanced brain aging (ABA) in the general-population, herein defined as significant deviation from typical BA to those found in Alzheimer disease (AD). The hypothesis that ABA would show different patterns of structural change compared with those found in AD was tested via advanced pattern analysis methods. In particular, magnetic resonance images of 2705 participants from the Study of Health in Pomerania (aged 20-90 years) were analyzed using an index that captures aging atrophy patterns (Spatial Pattern of Atrophy for Recognition of BA (SPARE-BA)), and an index previously shown to capture atrophy patterns found in clinical AD (Spatial Patterns of Abnormality for Recognition of Early Alzheimer's Disease (SPARE-AD)). We studied the association between these indices and risk factors, including an AD polygenic risk score. Finally, we compared the ABA-associated atrophy with typical AD-like patterns. We observed that SPARE-BA had significant association with: smoking (Ppatterns of atrophy were partially overlapping with, but notably deviating from those typically found in AD. Subjects with ABA had higher SPARE-AD values; largely due to the partial spatial overlap of associated patterns in temporal regions. The AD polygenic risk score was significantly associated with SPARE-AD but not with SPARE-BA. Our findings suggest that ABA is likely characterized by pathophysiologic mechanisms that are distinct from, or only partially overlapping with those of AD. PMID:27045845

  10. A Dietary Treatment Improves Cerebral Blood Flow and Brain Connectivity in Aging apoE4 Mice

    Directory of Open Access Journals (Sweden)

    Maximilian Wiesmann

    2016-01-01

    Full Text Available APOE ε4 (apoE4 polymorphism is the main genetic determinant of sporadic Alzheimer’s disease (AD. A dietary approach (Fortasyn including docosahexaenoic acid, eicosapentaenoic acid, uridine, choline, phospholipids, folic acid, vitamins B12, B6, C, and E, and selenium has been proposed for dietary management of AD. We hypothesize that the diet could inhibit AD-like pathologies in apoE4 mice, specifically cerebrovascular and connectivity impairment. Moreover, we evaluated the diet effect on cerebral blood flow (CBF, functional connectivity (FC, gray/white matter integrity, and postsynaptic density in aging apoE4 mice. At 10–12 months, apoE4 mice did not display prominent pathological differences compared to wild-type (WT mice. However, 16–18-month-old apoE4 mice revealed reduced CBF and accelerated synaptic loss. The diet increased cortical CBF and amount of synapses and improved white matter integrity and FC in both aging apoE4 and WT mice. We demonstrated that protective mechanisms on vascular and synapse health are enhanced by Fortasyn, independent of apoE genotype. We further showed the efficacy of a multimodal translational approach, including advanced MR neuroimaging, to study dietary intervention on brain structure and function in aging.

  11. A Dietary Treatment Improves Cerebral Blood Flow and Brain Connectivity in Aging apoE4 Mice.

    Science.gov (United States)

    Wiesmann, Maximilian; Zerbi, Valerio; Jansen, Diane; Haast, Roy; Lütjohann, Dieter; Broersen, Laus M; Heerschap, Arend; Kiliaan, Amanda J

    2016-01-01

    APOE ε4 (apoE4) polymorphism is the main genetic determinant of sporadic Alzheimer's disease (AD). A dietary approach (Fortasyn) including docosahexaenoic acid, eicosapentaenoic acid, uridine, choline, phospholipids, folic acid, vitamins B12, B6, C, and E, and selenium has been proposed for dietary management of AD. We hypothesize that the diet could inhibit AD-like pathologies in apoE4 mice, specifically cerebrovascular and connectivity impairment. Moreover, we evaluated the diet effect on cerebral blood flow (CBF), functional connectivity (FC), gray/white matter integrity, and postsynaptic density in aging apoE4 mice. At 10-12 months, apoE4 mice did not display prominent pathological differences compared to wild-type (WT) mice. However, 16-18-month-old apoE4 mice revealed reduced CBF and accelerated synaptic loss. The diet increased cortical CBF and amount of synapses and improved white matter integrity and FC in both aging apoE4 and WT mice. We demonstrated that protective mechanisms on vascular and synapse health are enhanced by Fortasyn, independent of apoE genotype. We further showed the efficacy of a multimodal translational approach, including advanced MR neuroimaging, to study dietary intervention on brain structure and function in aging. PMID:27034849

  12. Multisensory causal inference in the brain

    OpenAIRE

    Christoph Kayser; Ladan Shams

    2015-01-01

    © 2015 Kayser, Shams. At any given moment, our brain processes multiple inputs from its different sensory modalities (vision, hearing, touch, etc.). In deciphering this array of sensory information, the brain has to solve two problems: (1) which of the inputs originate from the same object and should be integrated and (2) for the sensations originating from the same object, how best to integrate them. Recent behavioural studies suggest that the human brain solves these problems using optimal ...

  13. Early Brain Response to Low-Dose Radiation Exposure Involves Molecular Networks and Pathways Associated with Cognitive Functions, Advanced Aging and Alzheimer's Disease

    Energy Technology Data Exchange (ETDEWEB)

    Lowe, Xiu R; Bhattacharya, Sanchita; Marchetti, Francesco; Wyrobek, Andrew J.

    2008-06-06

    Understanding the cognitive and behavioral consequences of brain exposures to low-dose ionizing radiation has broad relevance for health risks from medical radiation diagnostic procedures, radiotherapy, environmental nuclear contamination, as well as earth orbit and space missions. Analyses of transcriptome profiles of murine brain tissue after whole-body radiation showed that low-dose exposures (10 cGy) induced genes not affected by high dose (2 Gy), and low-dose genes were associated with unique pathways and functions. The low-dose response had two major components: pathways that are consistently seen across tissues, and pathways that were brain tissue specific. Low-dose genes clustered into a saturated network (p < 10{sup -53}) containing mostly down-regulated genes involving ion channels, long-term potentiation and depression, vascular damage, etc. We identified 9 neural signaling pathways that showed a high degree of concordance in their transcriptional response in mouse brain tissue after low-dose radiation, in the aging human brain (unirradiated), and in brain tissue from patients with Alzheimer's disease. Mice exposed to high-dose radiation did not show these effects and associations. Our findings indicate that the molecular response of the mouse brain within a few hours after low-dose irradiation involves the down-regulation of neural pathways associated with cognitive dysfunctions that are also down regulated in normal human aging and Alzheimer's disease.

  14. Quantitative sodium MRI of the human brain at 9.4 T provides assessment of tissue sodium concentration and cell volume fraction during normal aging.

    Science.gov (United States)

    Thulborn, Keith; Lui, Elaine; Guntin, Jonathan; Jamil, Saad; Sun, Ziqi; Claiborne, Theodore C; Atkinson, Ian C

    2016-02-01

    Sodium ion homeostasis is a fundamental property of viable tissue, allowing the tissue sodium concentration to be modeled as the tissue cell volume fraction. The modern neuropathology literature using ex vivo tissue from selected brain regions indicates that human brain cell density remains constant during normal aging and attributes the volume loss that occurs with advancing age to changes in neuronal size and dendritic arborization. Quantitative sodium MRI performed with the enhanced sensitivity of ultrahigh-field 9.4 T has been used to investigate tissue cell volume fraction during normal aging. This cross-sectional study (n = 49; 21-80 years) finds that the in vivo tissue cell volume fraction remains constant in all regions of the brain with advancing age in individuals who remain cognitively normal, extending the ex vivo literature reporting constant neuronal cell density across the normal adult age range. Cell volume fraction, as measured by quantitative sodium MRI, is decreased in diseases of cell loss, such as stroke, on a time scale of minutes to hours, and in response to treatment of brain tumors on a time scale of days to weeks. Neurodegenerative diseases often have prodromal periods of decades in which regional neuronal cell loss occurs prior to clinical presentation. If tissue cell volume fraction can detect such early pathology, this quantitative parameter may permit the objective measurement of preclinical disease progression. This current study in cognitively normal aging individuals provides the basis for the pursuance of investigations directed towards such neurodegenerative diseases.

  15. Brain Basics

    Medline Plus

    Full Text Available ... Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah is a middle-aged woman ... new memories. hypothalmic-pituitary-adrenal (HPA) axis —A brain-body ... stress. impulse —An electrical communication signal sent between neurons ...

  16. Functional connectivity in the developing brain: A longitudinal study from 4 to 9 months of age

    OpenAIRE

    Damaraju, E; Caprihan, A.; Lowe, J R; Allen, E A; Calhoun, V D; Phillips, J.P.

    2013-01-01

    We characterize the development of intrinsic connectivity networks (ICNs) from 4 to 9 months of age with resting state magnetic resonance imaging performed on sleeping infants without sedative medication. Data is analyzed with independent component analysis (ICA). Using both low (30 components) and high (100 components) ICA model order decompositions, we find that the functional network connectivity (FNC) map is largely similar at both 4 and 9 months. However at 9 months the connectivity stre...

  17. Benefits of Physical Exercise on the Aging Brain: The Role of the Prefrontal Cortex

    OpenAIRE

    Berchicci, Marika; Lucci, Giuliana; Di Russo, Francesco

    2013-01-01

    Motor planning in older adults likely relies on the overengagement of the prefrontal cortex (PFC) and is associated with slowness of movement and responses. Does a physically active lifestyle counteract the overrecruitment of the PFC during action preparation? This study used high-resolution electroencephalography to measure the effect of physical exercise on the executive functions of the PFC preceding a visuomotor discriminative task. A total of 130 participants aged 15–86 were divided into...

  18. Age-related Differences in Brain Activity during True and False Memory Retrieval

    OpenAIRE

    Dennis, Nancy A.; Kim, Hongkeun; Cabeza, Roberto

    2008-01-01

    Compared to young adults, older adults show not only a reduction in true memories but also an increase in false memories. We investigated the neural bases of these age effects using functional magnetic resonance imaging and a false memory task that resembles the Deese–Roediger–McDermott (DRM) paradigm. Young and older participants were scanned during a word recognition task that included studied words and new words that were strongly associated with studied words (critical lures). During corr...

  19. Hippocampal Neurogenesis Levels Predict WATERMAZE Search Strategies in the Aging Brain

    OpenAIRE

    Joana Gil-Mohapel; Brocardo, Patricia S.; Will Choquette; Russ Gothard; Simpson, Jessica M.; Christie, Brian R

    2013-01-01

    The hippocampus plays a crucial role in the formation of spatial memories, and it is thought that adult hippocampal neurogenesis may participate in this form of learning. To better elucidate the relationship between neurogenesis and spatial learning, we examined both across the entire life span of mice. We found that cell proliferation, neuronal differentiation, and neurogenesis significantly decrease with age, and that there is an abrupt reduction in these processes early on, between 1.5-3 m...

  20. Kids, candy, brain and behavior: Age differences in responses to candy gains and losses

    OpenAIRE

    Luking, Katherine R.; Joan L. Luby; Barch, Deanna M

    2014-01-01

    The development of reward-related neural systems, from adolescence through adulthood, has received much recent attention in the developmental neuroimaging literature. However, few studies have investigated behavioral and neural responses to both gains and losses in pre-pubertal child populations. To address this gap in the literature, in the present study healthy children aged 7–11 years and young-adults completed an fMRI card-guessing game using candy pieces delivered post-scan as an incenti...

  1. Type 2 diabetes mellitus, cognition and brain in aging: A brief review

    OpenAIRE

    Kumar, Rajeev; Looi, Jeffrey C. L.; Raphael, Beverley

    2009-01-01

    Diabetes mellitus is a complex disease with many potential complications. Whilst there have been inconsistent results in regard to an association between cognition and type 2 diabetes, there is evidence that verbal memory and processing speed are the cognitive domains usually impaired. In elderly diabetic subjects, other cognitive domains may also be involved, due to ageing. Glycemic control is implicated in the development of cognitive dysfunction, although more research is needed in this ar...

  2. Online Games Training Aging Brains:Limited transfer to cognitive control functions

    Directory of Open Access Journals (Sweden)

    Jesse eVan Muijden

    2012-08-01

    Full Text Available The prevalence of age-related cognitive decline will increase due to graying of the global population. The goal of the present study was to test whether playing online cognitive training games can improve cognitive control (CC in healthy older adults. Fifty-four older adults (age 60-77 played five different cognitive training games online for 30 minutes a day over a period of seven weeks (game group. Another group of 20 older adults (age 61-73 instead answered quiz questions about documentaries online (documentary group. Transfer was assessed by means of a cognitive test battery administered before and after the intervention. The test battery included measures of working memory updating, set shifting, response inhibition, attention and inductive reasoning. Compared with the documentary group, the game group showed larger improvement of inhibition (Stop-Signal task and inductive reasoning (Raven-SPM, whereas the documentary group showed more improvement in selective attention (UFoV-3. These effects qualify as transfer effects, because response inhibition, inductive reasoning and selective attention were not targeted by the interventions. However, because seven other indicators of CC did not show benefits of game training and some of those that did suffered from potential baseline differences, the study as a whole provides only modest support for the potential of videogame training to improve CC in healthy older adults.

  3. Synchronizing an aging brain: can entraining circadian clocks by food slow Alzheimer's Disease?

    Directory of Open Access Journals (Sweden)

    Brianne Alyssia Kent

    2014-09-01

    Full Text Available Alzheimer’s disease (AD is a global epidemic. Unfortunately, we are still without effective treatments or a cure for this disease, which is having devastating consequences for patients, their families, and societies around the world. Until effective treatments are developed, promoting overall health may hold potential for delaying the onset or preventing neurodegenerative diseases such as AD. In particular, chronobiological concepts may provide a useful framework for identifying the earliest signs of age-related disease as well as inexpensive and noninvasive methods for promoting health. It is well reported that AD is associated with disrupted circadian functioning to a greater extent than normal aging. However, it is unclear if the central circadian clock (i.e., the suprachiasmatic nucleus is dysfunctioning, or whether the synchrony between the central and peripheral clocks that control behaviour and metabolic processes are becoming uncoupled. Desynchrony of rhythms can negatively affect health, increasing morbidity and mortality in both animal models and humans. If the uncoupling of rhythms is contributing to AD progression or exacerbating symptoms, then it may be possible to draw from the food-entrainment literature to identify mechanisms for re-synchronizing rhythms to improve overall health and reduce the severity of symptoms. The following review will briefly summarize the circadian system, its potential role in AD, and propose using a feeding-related neuropeptide, such as ghrelin, to synchronize uncoupled rhythms. Synchronizing rhythms may be an inexpensive way to promote healthy aging and delay the onset of neurodegenerative disease such as AD.

  4. Voluntary exercise promotes beneficial anti-aging mechanisms in SAMP8 female brain.

    Science.gov (United States)

    Bayod, Sergi; Guzmán-Brambila, Carolina; Sanchez-Roige, Sandra; Lalanza, Jaume F; Kaliman, Perla; Ortuño-Sahagun, Daniel; Escorihuela, Rosa M; Pallàs, Mercè

    2015-02-01

    Regular physical exercise mediates health and longevity promotion involving Sirtuin 1 (SIRT1)-regulated pathways. The anti-aging activity of SIRT1 is achieved, at least in part, by means of fine-tuning the adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway by preventing the transition of an originally pro-survival program into a pro-aging mechanism. Additionally, SIRT1 promotes mitochondrial function and reduces the production of reactive oxygen species (ROS) through regulating peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), the master controller of mitochondrial biogenesis. Here, by using senescence-accelerated mice prone 8 (SAMP8) as a model for aging, we determined the effect of wheel-running as a paradigm for long-term voluntary exercise on SIRT1-AMPK pathway and mitochondrial functionality measured by oxidative phosphorylation (OXPHOS) complex content in the hippocampus and cortex. We found differential activation of SIRT1 in both tissues and hippocampal-specific activation of AMPK. These findings correlated well with significant changes in OXPHOS in the hippocampal, but not in the cerebral cortex, area. Collectively, the results revealed greater benefits of the exercise in the wheel-running intervention in a murine model of senescence, which was directly related with mitochondrial function and which was mediated through the modulation of SIRT1 and AMPK pathways. PMID:25027560

  5. Online games training aging brains: limited transfer to cognitive control functions.

    Science.gov (United States)

    van Muijden, Jesse; Band, Guido P H; Hommel, Bernhard

    2012-01-01

    The prevalence of age-related cognitive decline will increase due to graying of the global population. The goal of the present study was to test whether playing online cognitive training games can improve cognitive control (CC) in healthy older adults. Fifty-four older adults (age 60-77) played five different cognitive training games online for 30 min a day over a period of seven weeks (game group). Another group of 20 older adults (age 61-73) instead answered quiz questions about documentaries online (documentary group). Transfer was assessed by means of a cognitive test battery administered before and after the intervention. The test battery included measures of working memory updating, set shifting, response inhibition, attention, and inductive reasoning. Compared with the documentary group, the game group showed larger improvement of inhibition (Stop-Signal task) and inductive reasoning (Raven-SPM), whereas the documentary group showed more improvement in selective attention (UFoV-3). These effects qualify as transfer effects, because response inhibition, inductive reasoning and selective attention were not targeted by the interventions. However, because seven other indicators of CC did not show benefits of game training and some of those that did suffered from potential baseline differences, the study as a whole provides only modest support for the potential of videogame training to improve CC in healthy older adults. PMID:22912609

  6. Evaluation of auditory brain-stem evoked response in middle: Aged type 2 diabetes mellitus with normal hearing subjects

    Directory of Open Access Journals (Sweden)

    Debadatta Mahallik

    2014-01-01

    Full Text Available Background: Diabetes mellitus (DM is commonly metabolic disorders of carbohydrate in which blood glucose levels are abnormally high due to relative or absolute insulin deficiency. In addition, it is characterized by abnormal metabolism of fat, protein resulting from insulin deficit or insulin action, or both. There are two broad categories of DM are designated as type 1 and type 2. Type 2 diabetes is due to predominantly insulin resistance with relative insulin deficiency noninsulin-dependent DM. Type 2 diabetes is much more common than insulin-dependent DM. Objectives: The aim of this study was to assess, if there is any abnormality in neural conduction in auditory brain-stem pathway in type 2 DM patients having normal hearing sensitivity when compared to age-matched healthy populations. Materials and Methods: This study included middle - aged 25 subjects having normal hearing with diabetes type 2 mellitus. All were submitted to the full audiological history taking, otological examination, basic audiological evaluation and auditory brain-stem response audiometry which was recorded in both ears, followed by calculation of the absolute latencies of wave I, III and V, as well as interpeak latencies I-III, III-V, I-V. Results: Type 2 DM patients showed significant prolonged absolute latencies of I, III (P = 0.001 and interpeak latencies I-III, III-V and I-V in left ear (P = 0.001 and absolute latencies of I, V (P = 0.001, interpeak latencies III-V was statistically significant in right ear. Conclusions: The prolonged absolute latencies and interpeak latencies suggests abnormal neural firing synchronization or in the transmission in the auditory pathways in normal hearing type 2 diabetes mellitus patients.

  7. Effects of Physical Exercise Combined with Nutritional Supplements on Aging Brain Related Structures and Functions: A Systematic Review.

    Science.gov (United States)

    Schättin, Alexandra; Baur, Kilian; Stutz, Jan; Wolf, Peter; de Bruin, Eling D

    2016-01-01

    Age-related decline in gray and white brain matter goes together with cognitive depletion. To influence cognitive functioning in elderly, several types of physical exercise and nutritional intervention have been performed. This paper systematically reviews the potential additive and complementary effects of nutrition/nutritional supplements and physical exercise on cognition. The search strategy was developed for EMBASE, Medline, PubMed, Cochrane, CINAHL, and PsycInfo databases and focused on the research question: "Is the combination of physical exercise with nutrition/nutritional supplementation more effective than nutrition/nutritional supplementation or physical exercise alone in effecting on brain structure, metabolism, and/or function?" Both mammalian and human studies were included. In humans, randomized controlled trials that evaluated the effects of nutrition/nutritional supplements and physical exercise on cognitive functioning and associated parameters in healthy elderly (>65 years) were included. The systematic search included English and German language literature without any limitation of publication date. The search strategy yielded a total of 3129 references of which 67 studies met the inclusion criteria; 43 human and 24 mammalian, mainly rodent, studies. Three out of 43 human studies investigated a nutrition/physical exercise combination and reported no additive effects. In rodent studies, additive effects were found for docosahexaenoic acid supplementation when combined with physical exercise. Although feasible combinations of physical exercise/nutritional supplements are available for influencing the brain, only a few studies evaluated which possible combinations of nutrition/nutritional supplementation and physical exercise might have an effect on brain structure, metabolism and/or function. The reason for no clear effects of combinatory approaches in humans might be explained by the misfit between the combinations of nutritional methods with

  8. Age-dependent neuroplasticity mechanisms in Alzheimer Tg2576 mice following modulation of brain amyloid-β levels.

    Directory of Open Access Journals (Sweden)

    Anna M Lilja

    Full Text Available The objective of this study was to investigate the effects of modulating brain amyloid-β (Aβ levels at different stages of amyloid pathology on synaptic function, inflammatory cell changes and hippocampal neurogenesis, i.e. processes perturbed in Alzheimer's disease (AD. Young (4- to 6-month-old and older (15- to 18-month-old APP(SWE transgenic (Tg2576 mice were treated with the AD candidate drug (+-phenserine for 16 consecutive days. We found significant reductions in insoluble Aβ1-42 levels in the cortices of both young and older transgenic mice, while significant reductions in soluble Aβ1-42 levels and insoluble Aβ1-40 levels were only found in animals aged 15-18 months. Autoradiography binding with the amyloid ligand Pittsburgh Compound B ((3H-PIB revealed a trend for reduced fibrillar Aβ deposition in the brains of older phenserine-treated Tg2576 mice. Phenserine treatment increased cortical synaptophysin levels in younger mice, while decreased interleukin-1β and increased monocyte chemoattractant protein-1 and tumor necrosis factor-alpha levels were detected in the cortices of older mice. The reduction in Aβ1-42 levels was associated with an increased number of bromodeoxyuridine-positive proliferating cells in the hippocampi of both young and older Tg2576 mice. To determine whether the increased cell proliferation was accompanied by increased neuronal production, the endogenous early neuronal marker doublecortin (DCX was examined in the dentate gyrus (DG using immunohistochemical detection. Although no changes in the total number of DCX(+-expressing neurons were detected in the DG in Tg2576 mice at either age following (+-phenserine treatment, dendritic arborization was increased in differentiating neurons in young Tg2576 mice. Collectively, these findings indicate that reducing Aβ1-42 levels in Tg2576 mice at an early pathological stage affects synaptic function by modulating the maturation and plasticity of newborn neurons in

  9. Age and haplotype variations within FADS1 interact and associate with alterations in fatty acid composition in human male cortical brain tissue.

    Directory of Open Access Journals (Sweden)

    Erika Freemantle

    Full Text Available UNLABELLED: Fatty acids (FA play an integral role in brain function and alterations have been implicated in a variety of complex neurological disorders. Several recent genomic studies have highlighted genetic variability in the fatty acid desaturase (FADS1/2/3 gene cluster as an important contributor to FA alterations in serum lipids as well as measures of FA desaturase index estimated by ratios of relevant FAs. The contribution to alterations of FAs within the brain by local synthesis is still a matter of debate. Thus, the impact of genetic variants in FADS genes on gene expression and brain FA levels is an important avenue to investigate. METHODS: Analyses were performed on brain tissue from prefrontal cortex Brodmann area 47 (BA47 of 61 male subjects of French Canadian ancestry ranging in age from young adulthood to middle age (18-58 years old, with the exception of one teenager (15 years old. Haplotype tagging SNPs were selected using the publicly available HapMap genotyping dataset in conjunction with Haploview. DNA sequencing was performed by the Sanger method and gene expression was measured by quantitative real-time PCR. FAs in brain tissue were analysed by gas chromatography. Variants in the FADS1 gene region were sequenced and analyzed for their influence on both FADS gene expression and FAs in brain tissue. RESULTS: Our results suggest an association of the minor haplotype with alteration in estimated fatty acid desaturase activity. Analysis of the impact of DNA variants on expression and alternative transcripts of FADS1 and FADS2, however, showed no differences. Furthermore, there was a significant interaction between haplotype and age on certain brain FA levels. DISCUSSION: This study suggests that genetic variability in the FADS genes cluster, previously shown to be implicated in alterations in peripheral FA levels, may also affect FA composition in brain tissue, but not likely by local synthesis.

  10. Preprocessing Algorithm for Deciphering Historical Inscriptions Using String Metric

    Directory of Open Access Journals (Sweden)

    Lorand Lehel Toth

    2016-07-01

    Full Text Available The article presents the improvements in the preprocessing part of the deciphering method (shortly preprocessing algorithm for historical inscriptions of unknown origin. Glyphs used in historical inscriptions changed through time; therefore, various versions of the same script may contain different glyphs for each grapheme. The purpose of the preprocessing algorithm is reducing the running time of the deciphering process by filtering out the less probable interpretations of the examined inscription. However, the first version of the preprocessing algorithm leads incorrect outcome or no result in the output in certain cases. Therefore, its improved version was developed to find the most similar words in the dictionary by relaying the search conditions more accurately, but still computationally effectively. Moreover, a sophisticated similarity metric used to determine the possible meaning of the unknown inscription is introduced. The results of the evaluations are also detailed.

  11. 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. PMID:25575679

  12. Aging, the metabolic syndrome, and ischemic stroke: redefining the approach for studying the blood-brain barrier in a complex neurological disease.

    Science.gov (United States)

    Lucke-Wold, Brandon P; Logsdon, Aric F; Turner, Ryan C; Rosen, Charles L; Huber, Jason D

    2014-01-01

    The blood-brain barrier (BBB) has many important functions in maintaining the brain's immune-privileged status. Endothelial cells, astrocytes, and pericytes have important roles in preserving vasculature integrity. As we age, cell senescence can contribute to BBB compromise. The compromised BBB allows an influx of inflammatory cytokines to enter the brain. These cytokines lead to neuronal and glial damage. Ultimately, the functional changes within the brain can cause age-related disease. One of the most prominent age-related diseases is ischemic stroke. Stroke is the largest cause of disability and is third largest cause of mortality in the United States. The biggest risk factors for stroke, besides age, are results of the metabolic syndrome. The metabolic syndrome, if unchecked, quickly advances to outcomes that include diabetes, hypertension, cardiovascular disease, and obesity. The contribution from these comorbidities to BBB compromise is great. Some of the common molecular pathways activated include: endoplasmic reticulum stress, reactive oxygen species formation, and glutamate excitotoxicity. In this chapter, we examine how age-related changes to cells within the central nervous system interact with comorbidities. We then look at how comorbidities lead to increased risk for stroke through BBB disruption. Finally, we discuss key molecular pathways of interest with a focus on therapeutic targets that warrant further investigation.

  13. Age- and Sex-Associated Changes in Cerebral Glucose Metabolism in Normal Healthy Subjects: Statistical Parametric Mapping Analysis of F-18 Fluorodeoxyglucose Brain Positron Emission Tomography

    Energy Technology Data Exchange (ETDEWEB)

    Kim, In-Ju; Kim, Seong-Jang; Kim, Yong-Ki (Dept. of Nuclear Medicine, Pusan National Univ. Hospital, Busan (Korea); Medical Research Institute, Pusan National Univ., Busan (Korea)). e-mail: growthkim@daum.net/growthkim@pusan.ac.kr)

    2009-12-15

    Background: The age- and sex-associated changes of brain development are unclear and controversial. Several previous studies showed conflicting results of a specific pattern of cerebral glucose metabolism or no differences of cerebral glucose metabolism in association with normal aging process and sex. Purpose: To investigate the effects of age and sex on changes in cerebral glucose metabolism in healthy subjects using fluorine-18 fluorodeoxyglucose (F-18 FDG) brain positron emission tomography (PET) and statistical parametric mapping (SPM) analysis. Material and Methods: Seventy-eight healthy subjects (32 males, mean age 46.6+-18.2 years; 46 females, mean age 40.6+-19.8 years) underwent F-18 FDG brain PET. Using SPM, age- and sex-associated changes in cerebral glucose metabolism were investigated. Results: In males, a negative correlation existed in several gray matter areas, including the right temporopolar (Brodmann area [BA] 38), right orbitofrontal (BA 47), left orbitofrontal gyrus (BA 10), left dorsolateral frontal gyrus (BA 8), and left insula (BA 13) areas. A positive relationship existed in the left claustrum and left thalamus. In females, negative changes existed in the left caudate body, left temporopolar area (BA 38), right orbitofrontal gyri (BA 47 and BA 10), and right dorsolateral prefrontal cortex (BA 46). A positive association was demonstrated in the left subthalamic nucleus and the left superior frontal gyrus. In white matter, an age-associated decrease in FDG uptake in males was shown in the left insula, and increased FDG uptake was found in the left corpus callosum. The female group had an age-associated negative correlation of FDG uptake only in the right corpus callosum. Conclusion: Using SPM, we found not only similar areas of brain, but also sex-specific cerebral areas of age-associated changes of FDG uptake

  14. Age- and Sex-Associated Changes in Cerebral Glucose Metabolism in Normal Healthy Subjects: Statistical Parametric Mapping Analysis of F-18 Fluorodeoxyglucose Brain Positron Emission Tomography

    International Nuclear Information System (INIS)

    Background: The age- and sex-associated changes of brain development are unclear and controversial. Several previous studies showed conflicting results of a specific pattern of cerebral glucose metabolism or no differences of cerebral glucose metabolism in association with normal aging process and sex. Purpose: To investigate the effects of age and sex on changes in cerebral glucose metabolism in healthy subjects using fluorine-18 fluorodeoxyglucose (F-18 FDG) brain positron emission tomography (PET) and statistical parametric mapping (SPM) analysis. Material and Methods: Seventy-eight healthy subjects (32 males, mean age 46.6±18.2 years; 46 females, mean age 40.6±19.8 years) underwent F-18 FDG brain PET. Using SPM, age- and sex-associated changes in cerebral glucose metabolism were investigated. Results: In males, a negative correlation existed in several gray matter areas, including the right temporopolar (Brodmann area [BA] 38), right orbitofrontal (BA 47), left orbitofrontal gyrus (BA 10), left dorsolateral frontal gyrus (BA 8), and left insula (BA 13) areas. A positive relationship existed in the left claustrum and left thalamus. In females, negative changes existed in the left caudate body, left temporopolar area (BA 38), right orbitofrontal gyri (BA 47 and BA 10), and right dorsolateral prefrontal cortex (BA 46). A positive association was demonstrated in the left subthalamic nucleus and the left superior frontal gyrus. In white matter, an age-associated decrease in FDG uptake in males was shown in the left insula, and increased FDG uptake was found in the left corpus callosum. The female group had an age-associated negative correlation of FDG uptake only in the right corpus callosum. Conclusion: Using SPM, we found not only similar areas of brain, but also sex-specific cerebral areas of age-associated changes of FDG uptake

  15. Differences between patterns of brain activity associated with semantics and those linked with phonological processing diminish with age.

    Directory of Open Access Journals (Sweden)

    Ruben Martins

    Full Text Available It is widely believed that language function tends to show little age-related performance decline. Indeed, some older individuals seem to use compensatory mechanisms to maintain a high level of performance when submitted to lexical tasks. However, how these mechanisms affect cortical and subcortical activity during semantic and phonological processing has not been extensively explored. The purpose of this study was to look at the effect of healthy aging on cortico-subcortical routes related to semantic and phonological processing using a lexical analogue of the Wisconsin Cart-Sorting Task. Our results indicate that while young adults tend to show increased activity in the ventrolateral prefrontal cortex, the dorsolateral prefrontal cortex, the fusiform gyrus, the ventral temporal lobe and the caudate nucleus during semantic decisions and in the posterior Broca's area (area 44, the temporal lobe (area 37, the temporoparietal junction (area 40 and the motor cortical regions during phonological decisions, older individuals showed increased activity in the dorsolateral prefrontal cortex and motor cortical regions during both semantic and phonological decisions. Furthermore, when semantic and phonological decisions were contrasted with each other, younger individuals showed significant brain activity differences in several regions while older individuals did not. Therefore, in older individuals, the semantic and phonological routes seem to merge into a single pathway. These findings represent most probably neural reserve/compensation mechanisms, characterized by a decrease in specificity, on which the elderly rely to maintain an adequate level of performance.

  16. Aging parents' caregiving and rehabilitating a brain-injured son: an autoethnography of a 10-year journey.

    Science.gov (United States)

    Hassan, Syed Tajuddin Syed; Jamaludin, Husna

    2014-01-01

    This autoethnography withdraws from information accumulated through a 10-year period of daily-weekly-monthly descriptive observation-recording (triangulated- parents & house-helper) of caregiving and rehabilitating of our brain injured son (survivor/care-receiver). We present it as an interactive voice of verbal conversation, thoughts, insights, and interpretations. It is delivered as a series of articulation intra-pulsated with our interrogation of societal-cultural-religious perspectives, norms and biases, and aligns with the CAP (Creative Analytical Practices) method of Ellis. This autoethnography glows from the richness of information which encapsulates the challenges confronting us the aging parent caregivers, the gradual incremental mind mending achievement of our son, and the interactive verbalizations and thoughts, of the caregivers, care-receiver, and other persons. The overwhelming mental and physical pain and struggle of the survivor and the aging caregivers and their sense of celebratory-satisfaction with rehabilitation progress are highlighted. Interpretation and valuation of positive and negative responses of other persons provide a critical matrix to this autoethnography. We intend to inform other caregivers and relevant healthcare professionals through this autoethnography. PMID:25763170

  17. Aging parents' caregiving and rehabilitating a brain-injured son: an autoethnography of a 10-year journey.

    Science.gov (United States)

    Hassan, Syed Tajuddin Syed; Jamaludin, Husna

    2014-01-01

    This autoethnography withdraws from information accumulated through a 10-year period of daily-weekly-monthly descriptive observation-recording (triangulated- parents & house-helper) of caregiving and rehabilitating of our brain injured son (survivor/care-receiver). We present it as an interactive voice of verbal conversation, thoughts, insights, and interpretations. It is delivered as a series of articulation intra-pulsated with our interrogation of societal-cultural-religious perspectives, norms and biases, and aligns with the CAP (Creative Analytical Practices) method of Ellis. This autoethnography glows from the richness of information which encapsulates the challenges confronting us the aging parent caregivers, the gradual incremental mind mending achievement of our son, and the interactive verbalizations and thoughts, of the caregivers, care-receiver, and other persons. The overwhelming mental and physical pain and struggle of the survivor and the aging caregivers and their sense of celebratory-satisfaction with rehabilitation progress are highlighted. Interpretation and valuation of positive and negative responses of other persons provide a critical matrix to this autoethnography. We intend to inform other caregivers and relevant healthcare professionals through this autoethnography.

  18. Aging parents’ caregiving and rehabilitating a brain-injured son: an autoethnography of a 10-year journey

    Science.gov (United States)

    Hassan, Syed Tajuddin Syed; Jamaludin, Husna

    2014-01-01

    This autoethnography withdraws from information accumulated through a 10-year period of daily-weekly-monthly descriptive observation-recording (triangulated- parents & house-helper) of caregiving and rehabilitating of our brain injured son (survivor/care-receiver). We present it as an interactive voice of verbal conversation, thoughts, insights, and interpretations. It is delivered as a series of articulation intra-pulsated with our interrogation of societal-cultural-religious perspectives, norms and biases, and aligns with the CAP (Creative Analytical Practices) method of Ellis. This autoethnography glows from the richness of information which encapsulates the challenges confronting us the aging parent caregivers, the gradual incremental mind mending achievement of our son, and the interactive verbalizations and thoughts, of the caregivers, care-receiver, and other persons. The overwhelming mental and physical pain and struggle of the survivor and the aging caregivers and their sense of celebratory-satisfaction with rehabilitation progress are highlighted. Interpretation and valuation of positive and negative responses of other persons provide a critical matrix to this autoethnography. We intend to inform other caregivers and relevant healthcare professionals through this autoethnography. PMID:25763170

  19. An Antioxidant Dietary Supplement Improves Brain-Derived Neurotrophic Factor Levels in Serum of Aged Dogs: Preliminary Results

    Directory of Open Access Journals (Sweden)

    Sara Sechi

    2015-01-01

    Full Text Available Biological aging is characterized by a progressive accumulation of oxidative damage and decreased endogenous antioxidant defense mechanisms. The production of oxidants by normal metabolism damages proteins, lipids, and nucleotides, which may contribute to cognitive impairment. In this study 36 dogs were randomly divided into four groups and fed croquettes of different compositions for 6 months. We monitored derivatives of reactive oxygen metabolites (dROMs and biological antioxidant potential (BAP levels in dogs’ plasma samples as well as brain-derived neurotrophic factor (BDNF serum levels at the beginning and at the end of the dietary regime. Our results showed that a dietary regime, enriched with antioxidants, induced a significant decrease of plasma levels of dROMs (p<0.005 and a significant increase in BDNF serum levels (p<0.005 after six months. Thus, we hypothesized a possible role of the diet in modulating pro- and antioxidant species as well as BDNF levels in plasma and serum, respectively. In conclusion the proposed diet enriched with antioxidants might be considered a valid alternative and a valuable strategy to counteract aging-related cognitive decline in elderly dogs.

  20. Effects of environmental contaminant exposure on visual brain development: a prospective electrophysiological study in school-aged children.

    Science.gov (United States)

    Ethier, Audrey-Anne; Muckle, Gina; Bastien, Célyne; Dewailly, Éric; Ayotte, Pierre; Arfken, Cynthia; Jacobson, Sandra W; Jacobson, Joseph L; Saint-Amour, Dave

    2012-10-01

    The Inuit from Nunavik (Northern Québec) are one of the most highly exposed populations to environmental contaminants in North America mainly due to the bioaccumulation of contaminants in fish and marine mammals that constitute an important part of their diet. This follow-up study aimed to assess the impact of exposure to contaminants on visual brain development in school-age Inuit children (mean age=10.9 years). Concentrations of polychlorinated biphenyls (PCBs), mercury (Hg), and lead (Pb) were measured in umbilical cord blood and again in blood samples at the time of testing, reflecting pre- and current exposure, respectively. Pattern-reversal visual evoked potentials (VEPs) were scalp-recorded at the occipital cortex. Visual stimulation consisted of achromatic gratings presented at four visual contrast levels: 95%, 30%, 12% and 4%. The relation between environmental contaminant body burdens and VEPs was examined by regression analysis controlling for confounding variables, including fish nutrients and other toxicants. No significant association was found for PCB exposure after statistical adjustments. Cord blood mercury level was associated with a reduction of the N75 amplitude at the highest contrast level and with a delay of the N75 latency at the 12% contrast level. Prenatal exposure to lead was associated with a delay of the N150 latency at most contrast levels. This study suggests that heavy metal exposure, in particular during the gestational period, can impair the development of visual processing.

  1. Differences between patterns of brain activity associated with semantics and those linked with phonological processing diminish with age.

    Science.gov (United States)

    Martins, Ruben; Simard, France; Monchi, Oury

    2014-01-01

    It is widely believed that language function tends to show little age-related performance decline. Indeed, some older individuals seem to use compensatory mechanisms to maintain a high level of performance when submitted to lexical tasks. However, how these mechanisms affect cortical and subcortical activity during semantic and phonological processing has not been extensively explored. The purpose of this study was to look at the effect of healthy aging on cortico-subcortical routes related to semantic and phonological processing using a lexical analogue of the Wisconsin Cart-Sorting Task. Our results indicate that while young adults tend to show increased activity in the ventrolateral prefrontal cortex, the dorsolateral prefrontal cortex, the fusiform gyrus, the ventral temporal lobe and the caudate nucleus during semantic decisions and in the posterior Broca's area (area 44), the temporal lobe (area 37), the temporoparietal junction (area 40) and the motor cortical regions during phonological decisions, older individuals showed increased activity in the dorsolateral prefrontal cortex and motor cortical regions during both semantic and phonological decisions. Furthermore, when semantic and phonological decisions were contrasted with each other, younger individuals showed significant brain activity differences in several regions while older individuals did not. Therefore, in older individuals, the semantic and phonological routes seem to merge into a single pathway. These findings represent most probably neural reserve/compensation mechanisms, characterized by a decrease in specificity, on which the elderly rely to maintain an adequate level of performance.

  2. The Locus Coeruleus: Essential for Maintaining Cognitive Function and the Aging Brain.

    Science.gov (United States)

    Mather, Mara; Harley, Carolyn W

    2016-03-01

    Research on cognitive aging has focused on how decline in various cortical and hippocampal regions influence cognition. However, brainstem regions play essential modulatory roles, and new evidence suggests that, among these, the integrity of the locus coeruleus (LC)-norepinephrine (NE) system plays a key role in determining late-life cognitive abilities. The LC is especially vulnerable to toxins and infection and is often the first place Alzheimer's-related pathology appears, with most people showing at least some tau pathology by their mid-20s. On the other hand, NE released from the LC during arousing, mentally challenging, or novel situations helps to protect neurons from damage, which may help to explain how education and engaging careers prevent cognitive decline in later years. PMID:26895736

  3. Atorvastatin prevents age-related and amyloid-β-induced microglial activation by blocking interferon-γ release from natural killer cells in the brain

    Directory of Open Access Journals (Sweden)

    Clarke Rachael

    2011-03-01

    Full Text Available Abstract Background Microglial function is modulated by several factors reflecting the numerous receptors expressed on the cell surface, however endogenous factors which contribute to the age-related increase in microglial activation remain largely unknown. One possible factor which may contribute is interferon-γ (IFNγ. IFNγ has been shown to increase in the aged brain and potently activates microglia, although its endogenous cell source in the brain remains unidentified. Methods Male Wistar rats were used to assess the effect of age and amyloid-β (Aβ on NK cell infiltration into the brain. The effect of the anti-inflammatory compound, atorvastatin was also assessed under these conditions. We measured cytokine and chemokine (IFNγ, IL-2, monocyte chemoattractant protein-1 (MCP-1 and IFNγ-induced protein 10 kDa (IP-10, expression in the brain by appropriate methods. We also looked at NK cell markers, CD161, NKp30 and NKp46 using flow cytometry and western blot. Results Natural killer (NK cells are a major source of IFNγ in the periphery and here we report the presence of CD161+ NKp30+ cells and expression of CD161 and NKp46 in the brain of aged and Aβ-treated rats. Furthermore, we demonstrate that isolated CD161+ cells respond to interleukin-2 (IL-2 by releasing IFNγ. Atorvastatin, the HMG-CoA reductase inhibitor, attenuates the increase in CD161 and NKp46 observed in hippocampus of aged and Aβ-treated rats. This was paralleled by a decrease in IFNγ, markers of microglial activation and the chemokines, MCP-1 and IP-10 which are chemotactic for NK cells. Conclusions We propose that NK cells contribute to the age-related and Aβ-induced neuroinflammatory changes and demonstrate that these changes can be modulated by atorvastatin treatment.

  4. Dopamine D1, D2, D3 receptors, vesicular monoamine transporter type-2 (VMAT2 and dopamine transporter (DAT densities in aged human brain.

    Directory of Open Access Journals (Sweden)

    Jianjun Sun

    Full Text Available The dopamine D(1, D(2, D(3 receptors, vesicular monoamine transporter type-2 (VMAT2, and dopamine transporter (DAT densities were measured in 11 aged human brains (aged 77-107.8, mean: 91 years by quantitative autoradiography. The density of D(1 receptors, VMAT2, and DAT was measured using [(3H]SCH23390, [(3H]dihydrotetrabenazine, and [(3H]WIN35428, respectively. The density of D(2 and D(3 receptors was calculated using the D(3-preferring radioligand, [(3H]WC-10 and the D(2-preferring radioligand [(3H]raclopride using a mathematical model developed previously by our group. Dopamine D(1, D(2, and D(3 receptors are extensively distributed throughout striatum; the highest density of D(3 receptors occurred in the nucleus accumbens (NAc. The density of the DAT is 10-20-fold lower than that of VMAT2 in striatal regions. Dopamine D(3 receptor density exceeded D(2 receptor densities in extrastriatal regions, and thalamus contained a high level of D(3 receptors with negligible D(2 receptors. The density of dopamine D(1 linearly correlated with D(3 receptor density in the thalamus. The density of the DAT was negligible in the extrastriatal regions whereas the VMAT2 was expressed in moderate density. D(3 receptor and VMAT2 densities were in similar level between the aged human and aged rhesus brain samples, whereas aged human brain samples had lower range of densities of D(1 and D(2 receptors and DAT compared with the aged rhesus monkey brain. The differential density of D(3 and D(2 receptors in human brain will be useful in the interpretation of PET imaging studies in human subjects with existing radiotracers, and assist in the validation of newer PET radiotracers having a higher selectivity for dopamine D(2 or D(3 receptors.

  5. Atorvastatin prevents age-related and amyloid-beta-induced microglial activation by blocking interferon-gamma release from natural killer cells in the brain

    LENUS (Irish Health Repository)

    Lyons, Anthony

    2011-03-31

    Abstract Background Microglial function is modulated by several factors reflecting the numerous receptors expressed on the cell surface, however endogenous factors which contribute to the age-related increase in microglial activation remain largely unknown. One possible factor which may contribute is interferon-γ (IFNγ). IFNγ has been shown to increase in the aged brain and potently activates microglia, although its endogenous cell source in the brain remains unidentified. Methods Male Wistar rats were used to assess the effect of age and amyloid-β (Aβ) on NK cell infiltration into the brain. The effect of the anti-inflammatory compound, atorvastatin was also assessed under these conditions. We measured cytokine and chemokine (IFNγ, IL-2, monocyte chemoattractant protein-1 (MCP-1) and IFNγ-induced protein 10 kDa (IP-10)), expression in the brain by appropriate methods. We also looked at NK cell markers, CD161, NKp30 and NKp46 using flow cytometry and western blot. Results Natural killer (NK) cells are a major source of IFNγ in the periphery and here we report the presence of CD161+ NKp30+ cells and expression of CD161 and NKp46 in the brain of aged and Aβ-treated rats. Furthermore, we demonstrate that isolated CD161+ cells respond to interleukin-2 (IL-2) by releasing IFNγ. Atorvastatin, the HMG-CoA reductase inhibitor, attenuates the increase in CD161 and NKp46 observed in hippocampus of aged and Aβ-treated rats. This was paralleled by a decrease in IFNγ, markers of microglial activation and the chemokines, MCP-1 and IP-10 which are chemotactic for NK cells. Conclusions We propose that NK cells contribute to the age-related and Aβ-induced neuroinflammatory changes and demonstrate that these changes can be modulated by atorvastatin treatment.

  6. Animating Brains

    Science.gov (United States)

    Borck, Cornelius

    2016-01-01

    A recent paper famously accused the rising field of social neuroscience of using faulty statistics under the catchy title ‘Voodoo Correlations in Social Neuroscience’. This Special Issue invites us to take this claim as the starting point for a cross-cultural analysis: in which meaningful ways can recent research in the burgeoning field of functional imaging be described as, contrasted with, or simply compared to animistic practices? And what light does such a reading shed on the dynamics and effectiveness of a century of brain research into higher mental functions? Reviewing the heated debate from 2009 around recent trends in neuroimaging as a possible candidate for current instances of ‘soul catching’, the paper will then compare these forms of primarily image-based brain research with older regimes, revolving around the deciphering of the brain’s electrical activity. How has the move from a decoding paradigm to a representational regime affected the conceptualisation of self, psyche, mind and soul (if there still is such an entity)? And in what ways does modern technoscience provide new tools for animating brains? PMID:27292322

  7. Knowledge of Mild Traumatic Brain Injury: Effects of age, locality, occupation, media and sports participation

    Directory of Open Access Journals (Sweden)

    2015-09-01

    Results: Misconceptions about TBI were reported by participants, irrespective of gender, locality, occupation, or history of sports participation. There were no significant differences in knowledge scores across these demographic groups. In particular, healthcare and education workers did not score any higher than other occupations. At least 40% of respondents answered either incorrectly or “I don’t know” on items related to gender differences, the utility of neuroimaging, and patient insight into their impairments. For those in non-medical, professional occupations, the older they were the less they knew about TBI (r = -.299, p = 0.009. In contrast, a positive correlation (r = 0.268, p = 0.018 was found between age and TBI knowledge for workers in healthcare or education. Conclusions: Misconceptions about TBI are present in Australia and are consistent across genders, localities, occupations and sport participation groups. A concern is that risk for misconceptions is not lower in healthcare or education professions. This suggests that professional development for groups most likely to be the frontline referral resources and supports for head injured children and adults may require further training.

  8. Effect of propofol on brain-derived neurotrophic factor and tyrosine kinase receptor B in the hippocampus of aged rats with chronic cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Gang Chen; Qiang Fu; Jiangbei Cao; Weidong Mi

    2012-01-01

    We intraperitoneally injected 10 and 50 mg/kg of propofol for 7 consecutive days to treat a rat model of chronic cerebral ischemia. A low-dose of propofol promoted the expression of brain-derived neurotrophic factor, tyrosine kinase receptor B, phosphorylated cAMP response element binding protein, and cAMP in the hippocampus of aged rats with chronic cerebral ischemia, but a high-dose of propofol inhibited their expression. Results indicated that the protective effect of propofol against cerebral ischemia in aged rats is related to changes in the expression of brain-derived neurotrophic factor and tyrosine kinase receptor B in the hippocampus, and that the cAMP-cAMP responsive element binding protein pathway is involved in the regulatory effect of propofol on brain-derived neurotrophic factor expression.

  9. Effects of Shenlong Decoction on Learning and Memory Abilities as well as SOD and MDA in Brain-aging Model Mice Induced by D-Galactose

    Institute of Scientific and Technical Information of China (English)

    Liu Yi; Wang Fawei; Yang Minghui; Zheng Qingping; Wang Youjing

    2006-01-01

    @@ Brain aging (dementia) model mice were made by cervical subcutaneous injection of D-galactose solution.Learning and memory abilities were detected with water maze test and superoxide dismulase(SOD)activities and malondiadehyde (MDA) contents in the liver and brain were determined after intragastrical administration of Shenlong Decoction (参龙汤) for 6 weeks. The results indicated that the swimming time was shortened and the correct swimming times increased, SOD activity raised and MDA content decreased in the three Shenlong Decoction groups with different doses as compared with the model group. It is concluded that Shenlong Decoction has the effects of anti-free radical injuries and improving the learning and memory abilities of the brain-aging mice induced by D-galactose.

  10. Voxel-based analysis of whole-brain effects of age and gender on dopamine transporter SPECT imaging in healthy subjects

    International Nuclear Information System (INIS)

    Several studies have shown age- and gender-related differences in striatal dopamine transporter (DaT) binding. These studies were based on a striatal region on interest approach that may have underestimated these effects and could not evaluate extrastriatal regions. Our aim was to determine the effects at the voxel level of age and gender on whole-brain DaT distribution using [123I]FP-CIT SPECT in healthy subjects. We performed a whole-brain [123I]FP-CIT SPECT voxel-based analysis using SPM8 and a standardized normalization template (p < 0.05, corrected using the false discovery rate method) in 51 healthy subjects aged from 21 to 79 years. We found an age-related DaT binding decrease in the striatum, anterior cingulate/medial frontal cortices and insulo-opercular cortices. Also DaT binding ratios were higher in women than men in the striatum and opercular cortices. This study showed both striatal and extrastriatal age-related and gender-related differences in DaT binding in healthy subjects using a whole-brain voxel-based non-a priori approach. These differences highlight the need for careful age and gender matching in DaT analyses of neuropsychiatric disorders. (orig.)

  11. Evidence for novel age-dependent network structures as a putative primo vascular network in the dura mater of the rat brain.

    Science.gov (United States)

    Lee, Ho-Sung; Kang, Dai-In; Yoon, Seung Zhoo; Ryu, Yeon Hee; Lee, Inhyung; Kim, Hoon-Gi; Lee, Byung-Cheon; Lee, Ki Bog

    2015-07-01

    With chromium-hematoxylin staining, we found evidence for the existence of novel age-dependent network structures in the dura mater of rat brains. Under stereomicroscopy, we noticed that chromium-hematoxylin-stained threadlike structures, which were barely observable in 1-week-old rats, were networked in specific areas of the brain, for example, the lateral lobes and the cerebella, in 4-week-old rats. In 7-week-old rats, those structures were found to have become larger and better networked. With phase contrast microscopy, we found that in 1-week-old rats, chromium-hematoxylin-stained granules were scattered in the same areas of the brain in which the network structures would later be observed in the 4- and 7-week-old rats. Such age-dependent network structures were examined by using optical and transmission electron microscopy, and the following results were obtained. The scattered granules fused into networks with increasing age. Cross-sections of the age-dependent network structures demonstrated heavily-stained basophilic substructures. Transmission electron microscopy revealed the basophilic substructures to be clusters with high electron densities consisting of nanosized particles. We report these data as evidence for the existence of age-dependent network structures in the dura mater, we discuss their putative functions of age-dependent network structures beyond the general concept of the dura mater as a supporting matrix. PMID:26330833

  12. Evidence for novel age-dependent network structures as a putative primo vascular network in the dura mater of the rat brain

    Directory of Open Access Journals (Sweden)

    Ho-Sung Lee

    2015-01-01

    Full Text Available With chromium-hematoxylin staining, we found evidence for the existence of novel age-dependent network structures in the dura mater of rat brains. Under stereomicroscopy, we noticed that chromium-hematoxylin-stained threadlike structures, which were barely observable in 1-week-old rats, were networked in specific areas of the brain, for example, the lateral lobes and the cerebella, in 4-week-old rats. In 7-week-old rats, those structures were found to have become larger and better networked. With phase contrast microscopy, we found that in 1-week-old rats, chromium-hematoxylin-stained granules were scattered in the same areas of the brain in which the network structures would later be observed in the 4- and 7-week-old rats. Such age-dependent network structures were examined by using optical and transmission electron microscopy, and the following results were obtained. The scattered granules fused into networks with increasing age. Cross-sections of the age-dependent network structures demonstrated heavily-stained basophilic substructures. Transmission electron microscopy revealed the basophilic substructures to be clusters with high electron densities consisting of nanosized particles. We report these data as evidence for the existence of age-dependent network structures in the dura mater, we discuss their putative functions of age-dependent network structures beyond the general concept of the dura mater as a supporting matrix.

  13. Evidence for novel age-dependent network structures as a putative primo vascular network in the dura mater of the rat brain

    Institute of Scientific and Technical Information of China (English)

    Ho-Sung Lee; Dai-In Kang; Seung Zhoo Yoon; Yeon Hee Ryu; Inhyung Lee; Hoon-Gi Kim; Byung-Cheon Lee; Ki Bog Lee

    2015-01-01

    With chromium-hematoxylin staining, we found evidence for the existence of novel age-depen-dent network structures in the dura mater of rat brains. Under stereomicroscopy, we noticed that chromium-hematoxylin-stained threadlike structures, which were barely observable in 1-week-old rats, were networked in specific areas of the brain, for example, the lateral lobes and the cerebella, in 4-week-old rats. In 7-week-old rats, those structures were found to have become larger and better networked. With phase contrast microscopy, we found that in 1-week-old rats, chromium-hematoxylin-stained granules were scattered in the same areas of the brain in which the network structures would later be observed in the 4- and 7-week-old rats. Such age-depen-dent network structures were examined by using optical and transmission electron microscopy, and the following results were obtained. The scattered granules fused into networks with increas-ing age. Cross-sections of the age-dependent network structures demonstrated heavily-stained basophilic substructures. Transmission electron microscopy revealed the basophilic substructures to be clusters with high electron densities consisting of nanosized particles. We report these data as evidence for the existence of age-dependent network structures in the dura mater, we discuss their putative functions of age-dependent network structures beyond the general concept of the dura mater as a supporting matrix.

  14. Age, sex and NK1 receptors in the human brain -- a positron emission tomography study with [¹¹C]GR205171.

    Science.gov (United States)

    Engman, Jonas; Åhs, Fredrik; Furmark, Tomas; Linnman, Clas; Pissiota, Anna; Appel, Lieuwe; Frans, Örjan; Långström, Bengt; Fredrikson, Mats

    2012-08-01

    The substance P/neurokinin 1 (SP/NK1) system has been implicated in the processing of negative affect. Its role seems complex and findings from animal studies have not been easily translated to humans. Brain imaging studies on NK1 receptor distribution in humans have revealed an abundance of receptors in cortical, striatal and subcortical areas, including the amygdala. A reduction in NK1 receptors with increasing age has been reported in frontal, temporal, and parietal cortices, as well as in hippocampal areas. Also, a previous study suggests sex differences in cortical and subcortical areas, with women displaying fewer NK1 receptors. The present PET study explored NK1 receptor availability in men (n=9) and women (n=9) matched for age varying between 20 and 50years using the highly specific NK1 receptor antagonist [¹¹C]GR205171 and a reference tissue model with cerebellum as the reference region. Age by sex interactions in the amygdala and the temporal cortex reflected a lower NK1 receptor availability with increasing age in men, but not in women. A general age-related decline in NK1 receptor availability was evident in the frontal, temporal, and occipital cortices, as well as in the brainstem, caudate nucleus, and thalamus. Women had lower NK1 receptor availability in the thalamus. The observed pattern of NK1 receptor distribution in the brain might have functional significance for brain-related disorders showing age- and sex-related differences in prevalence. PMID:22225860

  15. Voxel-based analysis of whole-brain effects of age and gender on dopamine transporter SPECT imaging in healthy subjects

    Energy Technology Data Exchange (ETDEWEB)

    Eusebio, Alexandre; Azulay, Jean-Philippe [APHM, Hopital de la Timone, Service de Neurologie et Pathologie du Mouvement, Marseille (France); CNRS, Aix-Marseille Univ, Institut de Neurosciences de la Timone, Marseille (France); Ceccaldi, Mathieu [APHM, Hopital de la Timone, Service de Neurologie et de Neuropsychologie, Marseille (France); Aix-Marseille Univ, UMR Inserm 1106, Institut de Neurosciences des Systemes, Marseille (France); Girard, Nadine [APHM, Hopital de la Timone, Service de Neuroradiologie diagnostique et interventionnelle, Marseille (France); Mundler, Olivier [APHM, Hopital de la Timone, Service Central de Biophysique et Medecine Nucleaire, Marseille (France); Aix-Marseille Univ, CERIMED, Marseille (France); Guedj, Eric [CNRS, Aix-Marseille Univ, Institut de Neurosciences de la Timone, Marseille (France); APHM, Hopital de la Timone, Service Central de Biophysique et Medecine Nucleaire, Marseille (France); Aix-Marseille Univ, CERIMED, Marseille (France)

    2012-11-15

    Several studies have shown age- and gender-related differences in striatal dopamine transporter (DaT) binding. These studies were based on a striatal region on interest approach that may have underestimated these effects and could not evaluate extrastriatal regions. Our aim was to determine the effects at the voxel level of age and gender on whole-brain DaT distribution using [{sup 123}I]FP-CIT SPECT in healthy subjects. We performed a whole-brain [{sup 123}I]FP-CIT SPECT voxel-based analysis using SPM8 and a standardized normalization template (p < 0.05, corrected using the false discovery rate method) in 51 healthy subjects aged from 21 to 79 years. We found an age-related DaT binding decrease in the striatum, anterior cingulate/medial frontal cortices and insulo-opercular cortices. Also DaT binding ratios were higher in women than men in the striatum and opercular cortices. This study showed both striatal and extrastriatal age-related and gender-related differences in DaT binding in healthy subjects using a whole-brain voxel-based non-a priori approach. These differences highlight the need for careful age and gender matching in DaT analyses of neuropsychiatric disorders. (orig.)

  16. The impact of glucose disorders on cognition and brain volumes in the elderly: the Sydney Memory and Ageing Study

    OpenAIRE

    Samaras, Katherine; Lutgers, Helen L.; Kochan, Nicole A.; Crawford, John D.; Campbell, Lesley V; Wen, Wei; Slavin, Melissa J.; Baune, Bernard T.; Lipnicki, Darren M; Brodaty, Henry; Julian N Trollor; Perminder S Sachdev

    2014-01-01

    Type 2 diabetes predicts accelerated cognitive decline and brain atrophy. We hypothesized that impaired fasting glucose (IFG) and incident glucose disorders have detrimental effects on global cognition and brain volume. We further hypothesized that metabolic and inflammatory derangements accompanying hyperglycaemia contribute to change in brain structure and function. This was a longitudinal study of a community-dwelling elderly cohort with neuropsychological testing (n = 880) and brain volum...

  17. Serum BDNF correlates with connectivity in the (pre)motor hub in the aging human brain--a resting-state fMRI pilot study.

    Science.gov (United States)

    Mueller, Karsten; Arelin, Katrin; Möller, Harald E; Sacher, Julia; Kratzsch, Jürgen; Luck, Tobias; Riedel-Heller, Steffi; Villringer, Arno; Schroeter, Matthias L

    2016-02-01

    Brain-derived neurotrophic factor (BDNF) has been discussed to be involved in plasticity processes in the human brain, in particular during aging. Recently, aging and its (neurodegenerative) diseases have increasingly been conceptualized as disconnection syndromes. Here, connectivity changes in neural networks (the connectome) are suggested to be the most relevant and characteristic features for such processes or diseases. To further elucidate the impact of aging on neural networks, we investigated the interaction between plasticity processes, brain connectivity, and healthy aging by measuring levels of serum BDNF and resting-state fMRI data in 25 young (mean age 24.8 ± 2.7 (SD) years) and 23 old healthy participants (mean age, 68.6 ± 4.1 years). To identify neural hubs most essentially related to serum BDNF, we applied graph theory approaches, namely the new data-driven and parameter-free approach eigenvector centrality (EC) mapping. The analysis revealed a positive correlation between serum BDNF and EC in the premotor and motor cortex in older participants in contrast to young volunteers, where we did not detect any association. This positive relationship between serum BDNF and EC appears to be specific for older adults. Our results might indicate that the amount of physical activity and learning capacities, leading to higher BDNF levels, increases brain connectivity in (pre)motor areas in healthy aging in agreement with rodent animal studies. Pilot results have to be replicated in a larger sample including behavioral data to disentangle the cause for the relationship between BDNF levels and connectivity. PMID:26827656

  18. The moderating effects of sex and age on the association between traumatic brain injury and harmful psychological correlates among adolescents.

    Directory of Open Access Journals (Sweden)

    Gabriela Ilie

    Full Text Available BACKGROUND: Although it is well established that sex is a risk factor in acquiring a traumatic brain injury (TBI among adolescents, it has not been established whether it also moderates the influence of other TBI psychological health correlates. METHODS AND FINDINGS: Data were derived from a 2011 population-based cross-sectional school survey, which included 9,288 Ontario 7th-12th graders who completed anonymous self-administered questionnaires in classrooms. Response rate was 62%. Preliminary analyses found no evidence of nonresponse bias in the reporting of TBI. TBI was defined as a hit or blow to the head that resulted in a 5 minutes loss of consciousness or at least one overnight hospitalization due to symptoms associated with it. Reports of lifetime TBI were more common among males than females (23.1%, 95% CI: 20.5, 25.8 vs. 17.1%, 95% CI: 14.7, 19.8. Thirteen correlates were examined and included cigarette smoking, elevated psychological distress, suicide ideation, bully victimization (at school, as well as cyber bullying, bullying others, cannabis use, cannabis dependence and drug use problems, physical injuries, daily smoking, drinking alcohol, binge drinking, use of cannabis, and poor academic performance. Among the outcomes examined, sex moderated the relationship between lifetime TBI and cigarette smoking. In addition, sex and age jointly moderated the relationship between lifetime TBI and daily smoking, alcohol use and physical injuries. Late adolescent males who reported lifetime TBI, relative to females, displayed elevated daily smoking and injuries, whereas their females counterparts displayed elevated past year drinking. Possible bias related to self-report procedures and the preclusion of causal inferences due to the cross-sectional nature of the data are limitations of this study. CONCLUSIONS: TBI differences in outcomes need to be assessed for potential moderating effects of sex and age. Results have important implications for

  19. Vascular-derived TGF-β increases in the stem cell niche and perturbs neuro-genesis during aging and following irradiation in the adult mouse brain

    International Nuclear Information System (INIS)

    Neuro-genesis decreases during aging and following cranial radiotherapy, causing a progressive cognitive decline that is currently untreatable. However, functional neural stem cells remained present in the sub-ventricular zone of high dose irradiated and aged mouse brains. We therefore investigated whether alterations in the neurogenic niches are perhaps responsible for the neuro-genesis decline. This hypothesis was supported by the absence of proliferation of neural stem cells that were engrafted into the vascular niches of irradiated host brains. Moreover, we observed a marked increase in TGF-β1 production by endothelial cells in the stem cell niche in both middle-aged and irradiated mice. In co-cultures, irradiated brain endothelial cells induced the apoptosis of neural stem/progenitor cells via TGF-β/Smad3 signalling. Strikingly, the blockade of TGF-β signalling in vivo using a neutralizing antibody or the selective inhibitor SB-505124 significantly improved neuro-genesis in aged and irradiated mice, prevented apoptosis and increased the proliferation of neural stem/progenitor cells. These findings suggest that anti-TGF-β-based therapy may be used for future interventions to prevent neurogenic collapse following radiotherapy or during aging. (authors)

  20. H2O2-mediated DNA damage and repair in the brain cells in the aging rats detected by comet assay

    Institute of Scientific and Technical Information of China (English)

    Suming ZhangM.D., Ph.D; Zongchao Han, M.D.; Siyu Fang, M.D.; Ruan Yang, M.D; Wei Wang, M.D., Ph. D

    2000-01-01

    Objective: To identify the relation between DNA damage susceptibility/ DNA repair capability and aging process after insults, an observation of H2O2_induced DNA damage and the kinetics of DNA repair in senescent murine brain cells with the alkaline single cell gel electrophoresis (SCGE/Comet assay) was made. Methods: The dissociated brain cells harvested in the area of the cerebral cortex, hippocampus, basal gang]ion from 3-month (n=10), 8-month (n=8) and 26-month (n=5) old rats were respectively treated with H2O2 in gradient doses for 10 min, or without H2O2 as controls. The cells embedded in agarose were lysed, helix-untied, electrophoresed, stained with a fluorescence DNA binding stain, viewed under a fluorescence microscope. Individual image was optically recorded. The frequency of the tailed cells and the grade of tails wereused to analyze single strand breaks of DNA and injury intensity. Results: By the cell and DNA image like comets, a linear increase was noticed in vulnerability of DNA both to H2O2 doses and to the age. Regarding the damaged region of the brain, the cortex cells were more vulnerable to the insult than the hippocampus/basal ganglionic cells. Whatever aging or not the cells were, the maximum of ratio of DNA repair was only within 1 hour during the incubation for 0.5-4 hours after the insults. Furthermore, the more aging, the less ratio of DNA repair of sick cells. Conclusion: The DNA damagesusceptibility and the DNA repair capability of individual cells, whatever its age is, can be detected by this brain cell injury model. Comet assay is a sensitive way to find out DNA damage and repair of the cells. It should be more difficult for the cells to cope with an acute and excessive than with a persistent, chronic and mild DNA damage which is more related to an accumulating injury, the aging.

  1. Can Ketones Help Rescue Brain Fuel Supply in Later Life? Implications for Cognitive Health during Aging and the Treatment of Alzheimer's Disease.

    Science.gov (United States)

    Cunnane, Stephen C; Courchesne-Loyer, Alexandre; Vandenberghe, Camille; St-Pierre, Valérie; Fortier, Mélanie; Hennebelle, Marie; Croteau, Etienne; Bocti, Christian; Fulop, Tamas; Castellano, Christian-Alexandre

    2016-01-01

    We propose that brain energy deficit is an important pre-symptomatic feature of Alzheimer's disease (AD) that requires closer attention in the development of AD therapeutics. Our rationale is fourfold: (i) Glucose uptake is lower in the frontal cortex of people >65 years-old despite cognitive scores that are normal for age. (ii) The regional deficit in brain glucose uptake is present in adults energy deficit needs to be overcome in order to successfully develop more effective therapeutics for AD. At present, oral ketogenic supplements are the most promising means of achieving this goal. PMID:27458340

  2. Can Ketones Help Rescue Brain Fuel Supply in Later Life? Implications for Cognitive Health during Aging and the Treatment of Alzheimer’s Disease

    Science.gov (United States)

    Cunnane, Stephen C.; Courchesne-Loyer, Alexandre; Vandenberghe, Camille; St-Pierre, Valérie; Fortier, Mélanie; Hennebelle, Marie; Croteau, Etienne; Bocti, Christian; Fulop, Tamas; Castellano, Christian-Alexandre

    2016-01-01

    We propose that brain energy deficit is an important pre-symptomatic feature of Alzheimer’s disease (AD) that requires closer attention in the development of AD therapeutics. Our rationale is fourfold: (i) Glucose uptake is lower in the frontal cortex of people >65 years-old despite cognitive scores that are normal for age. (ii) The regional deficit in brain glucose uptake is present in adults energy deficit needs to be overcome in order to successfully develop more effective therapeutics for AD. At present, oral ketogenic supplements are the most promising means of achieving this goal. PMID:27458340

  3. Deciphering Parameter Sensitivity in the BvgAS Signal Transduction.

    Directory of Open Access Journals (Sweden)

    Tarunendu Mapder

    Full Text Available To understand the switching of different phenotypic phases of Bordetella pertussis, we propose an optimized mathematical framework for signal transduction through BvgAS two-component system. The response of the network output to the sensory input has been demonstrated in steady state. An analysis in terms of local sensitivity amplification characterizes the nature of the molecular switch. The sensitivity analysis of the model parameters within the framework of various correlation coefficients helps to decipher the contribution of the modular structure in signal propagation. Once classified, the model parameters are tuned to generate the behavior of some novel strains using simulated annealing, a stochastic optimization technique.

  4. Deciphering Parameter Sensitivity in the BvgAS Signal Transduction.

    Science.gov (United States)

    Mapder, Tarunendu; Talukder, Srijeeta; Chattopadhyay, Sudip; Banik, Suman K

    2016-01-01

    To understand the switching of different phenotypic phases of Bordetella pertussis, we propose an optimized mathematical framework for signal transduction through BvgAS two-component system. The response of the network output to the sensory input has been demonstrated in steady state. An analysis in terms of local sensitivity amplification characterizes the nature of the molecular switch. The sensitivity analysis of the model parameters within the framework of various correlation coefficients helps to decipher the contribution of the modular structure in signal propagation. Once classified, the model parameters are tuned to generate the behavior of some novel strains using simulated annealing, a stochastic optimization technique.

  5. Deciphering Parameter Sensitivity in the BvgAS Signal Transduction.

    Science.gov (United States)

    Mapder, Tarunendu; Talukder, Srijeeta; Chattopadhyay, Sudip; Banik, Suman K

    2016-01-01

    To understand the switching of different phenotypic phases of Bordetella pertussis, we propose an optimized mathematical framework for signal transduction through BvgAS two-component system. The response of the network output to the sensory input has been demonstrated in steady state. An analysis in terms of local sensitivity amplification characterizes the nature of the molecular switch. The sensitivity analysis of the model parameters within the framework of various correlation coefficients helps to decipher the contribution of the modular structure in signal propagation. Once classified, the model parameters are tuned to generate the behavior of some novel strains using simulated annealing, a stochastic optimization technique. PMID:26812153

  6. Deciphering Parameter Sensitivity in the BvgAS Signal Transduction

    Science.gov (United States)

    Mapder, Tarunendu; Talukder, Srijeeta; Chattopadhyay, Sudip; Banik, Suman K.

    2016-01-01

    To understand the switching of different phenotypic phases of Bordetella pertussis, we propose an optimized mathematical framework for signal transduction through BvgAS two-component system. The response of the network output to the sensory input has been demonstrated in steady state. An analysis in terms of local sensitivity amplification characterizes the nature of the molecular switch. The sensitivity analysis of the model parameters within the framework of various correlation coefficients helps to decipher the contribution of the modular structure in signal propagation. Once classified, the model parameters are tuned to generate the behavior of some novel strains using simulated annealing, a stochastic optimization technique. PMID:26812153

  7. Reviews in modern astronomy, deciphering the universe through spectroscopy

    CERN Document Server

    von Berlepsch, Regina

    2011-01-01

    This 22nd volume in the series contains 15 invited reviews and highlight contributions from outstanding speakers presented during the 2009 annual meeting of the Astronomical Society on the subject of ""Deciphering the Universe through Spectroscopy"", held in Potsdam, Germany. Topics range from the measurements of magnetic fields on the surface of the sun via detailed measurements of abundances in stellar atmospheres to the kinematics of the universe at its largest scales. The result is a systematic overview of the latest astronomical and cosmological research.

  8. Sleep fragmentation and sepsis differentially impact blood-brain barrier integrity and transport of tumor necrosis factor-α in aging.

    Science.gov (United States)

    Opp, Mark R; George, Amrita; Ringgold, Kristyn M; Hansen, Kim M; Bullock, Kristin M; Banks, William A

    2015-11-01

    The factors by which aging predisposes to critical illness are varied, complex, and not well understood. Sepsis is considered a quintessential disease of old age because the incidence and mortality of severe sepsis increases in old and the oldest old individuals. Aging is associated with dramatic changes in sleep quality and quantity and sleep increasingly becomes fragmented with age. In healthy adults, sleep disruption induces inflammation. Multiple aspects of aging and of sleep dysregulation interact via neuroimmune mechanisms. Tumor necrosis factor-α (TNF), a cytokine involved in sleep regulation and neuroimmune processes, exerts some of its effects on the CNS by crossing the blood-brain barrier (BBB). In this study we examined the impact of sepsis, sleep fragmentation, and aging on BBB disruption and TNF transport into brain. We used the cecal ligation and puncture (CLP) model of sepsis in young and aged mice that were either undisturbed or had their sleep disrupted. There was a dichotomous effect of sepsis and sleep disruption with age: sepsis disrupted the BBB and increased TNF transport in young mice but not in aged mice, whereas sleep fragmentation disrupted the BBB and increased TNF transport in aged mice, but not in young mice. Combining sleep fragmentation and CLP did not produce a greater effect on either of these BBB parameters than did either of these manipulations alone. These results suggest that the mechanisms by which sleep fragmentation and sepsis alter BBB functions are fundamentally different from one another and that a major change in the organism's responses to those insults occurs with aging.

  9. Assessment of structural connectivity in the preterm brain at term equivalent age using diffusion MRI and T2 relaxometry: a network-based analysis.

    Science.gov (United States)

    Pannek, Kerstin; Hatzigeorgiou, Xanthy; Colditz, Paul B; Rose, Stephen

    2013-01-01

    Preterm birth is associated with a high prevalence of adverse neurodevelopmental outcome. Non-invasive techniques which can probe the neural correlates underpinning these deficits are required. This can be achieved by measuring the structural network of connections within the preterm infant's brain using diffusion MRI and tractography. We used diffusion MRI and T2 relaxometry to identify connections with altered white matter properties in preterm infants compared to term infants. Diffusion and T2 data were obtained from 9 term neonates and 18 preterm-born infants (born <32 weeks gestational age) at term equivalent age. Probabilistic tractography incorporating multiple fibre orientations was used in combination with the Johns Hopkins neonatal brain atlas to calculate the structural network of connections. Connections of altered diffusivity or T2, as well as their relationship with gestational age at birth and postmenstrual age at the time of MRI, were identified using the network based statistic framework. A total of 433 connections were assessed. FA was significantly reduced in 17, and T2 significantly increased in 18 connections in preterm infants, following correction for multiple comparisons. Cortical networks associated with affected connections mainly involved left frontal and temporal cortical areas: regions which are associated with working memory, verbal comprehension and higher cognitive function--deficits which are often observed later in children and adults born preterm. Gestational age at birth correlated with T2, but not diffusion in several connections. We found no association between diffusion or T2 and postmenstrual age at the time of MRI in preterm infants. This study demonstrates that alterations in the structural network of connections can be identified in preterm infants at term equivalent age, and that incorporation of non-diffusion measures such as T2 in the connectome framework provides complementary information for the assessment of brain

  10. Assessment of structural connectivity in the preterm brain at term equivalent age using diffusion MRI and T2 relaxometry: a network-based analysis.

    Directory of Open Access Journals (Sweden)

    Kerstin Pannek

    Full Text Available Preterm birth is associated with a high prevalence of adverse neurodevelopmental outcome. Non-invasive techniques which can probe the neural correlates underpinning these deficits are required. This can be achieved by measuring the structural network of connections within the preterm infant's brain using diffusion MRI and tractography. We used diffusion MRI and T2 relaxometry to identify connections with altered white matter properties in preterm infants compared to term infants. Diffusion and T2 data were obtained from 9 term neonates and 18 preterm-born infants (born <32 weeks gestational age at term equivalent age. Probabilistic tractography incorporating multiple fibre orientations was used in combination with the Johns Hopkins neonatal brain atlas to calculate the structural network of connections. Connections of altered diffusivity or T2, as well as their relationship with gestational age at birth and postmenstrual age at the time of MRI, were identified using the network based statistic framework. A total of 433 connections were assessed. FA was significantly reduced in 17, and T2 significantly increased in 18 connections in preterm infants, following correction for multiple comparisons. Cortical networks associated with affected connections mainly involved left frontal and temporal cortical areas: regions which are associated with working memory, verbal comprehension and higher cognitive function--deficits which are often observed later in children and adults born preterm. Gestational age at birth correlated with T2, but not diffusion in several connections. We found no association between diffusion or T2 and postmenstrual age at the time of MRI in preterm infants. This study demonstrates that alterations in the structural network of connections can be identified in preterm infants at term equivalent age, and that incorporation of non-diffusion measures such as T2 in the connectome framework provides complementary information for the

  11. Long-term Neuroglial Cocultures as a Brain Aging Model: Hallmarks of Senescence, MicroRNA Expression Profiles, and Comparison With In Vivo Models.

    Science.gov (United States)

    Bigagli, Elisabetta; Luceri, Cristina; Scartabelli, Tania; Dolara, Piero; Casamenti, Fiorella; Pellegrini-Giampietro, Domenico E; Giovannelli, Lisa

    2016-01-01

    Our purpose was to evaluate long-term neuroglial cocultures as a model for investigating senescence in the nervous system and to assess its similarities with in vivo models. To this aim, we maintained the cultures from 15 days in vitro (mature cultures) up to 27 days in vitro (senescent cultures), measuring senescence-associated, neuronal, dendritic, and astrocytic markers. Whole microRNA expression profiles were compared with those measured in the cortex of 18- and 24-month-old C57Bl/6J aged mice and of transgenic TgCRND8 mice, a model of amyloid-β deposition. Neuroglial cocultures displayed features of cellular senescence (increased senescence-associated-β-galactosidase activity, oxidative stress, γ-H2AX expression, IL-6 production, astrogliosis) that were concentration dependently counteracted by the antiaging compound resveratrol (1-5 µM). Among the 1,080 microRNAs analyzed, 335 were downregulated or absent in 27 compared with 15 days in vitro and resveratrol reversed this effect. A substantial overlapping was found between age-associated changes in microRNA expression profiles in vitro and in TgCRND8 mice but not in physiologically aged mice, indicating that this culture model displays more similarities with pathological than physiological brain aging. Our results demonstrate that neuroglial cocultures aged in vitro can be useful for investigating the cellular and molecular mechanisms of brain aging and for preliminary testing of protective compounds. PMID:25568096

  12. Long-term Neuroglial Cocultures as a Brain Aging Model: Hallmarks of Senescence, MicroRNA Expression Profiles, and Comparison With In Vivo Models.

    Science.gov (United States)

    Bigagli, Elisabetta; Luceri, Cristina; Scartabelli, Tania; Dolara, Piero; Casamenti, Fiorella; Pellegrini-Giampietro, Domenico E; Giovannelli, Lisa

    2016-01-01

    Our purpose was to evaluate long-term neuroglial cocultures as a model for investigating senescence in the nervous system and to assess its similarities with in vivo models. To this aim, we maintained the cultures from 15 days in vitro (mature cultures) up to 27 days in vitro (senescent cultures), measuring senescence-associated, neuronal, dendritic, and astrocytic markers. Whole microRNA expression profiles were compared with those measured in the cortex of 18- and 24-month-old C57Bl/6J aged mice and of transgenic TgCRND8 mice, a model of amyloid-β deposition. Neuroglial cocultures displayed features of cellular senescence (increased senescence-associated-β-galactosidase activity, oxidative stress, γ-H2AX expression, IL-6 production, astrogliosis) that were concentration dependently counteracted by the antiaging compound resveratrol (1-5 µM). Among the 1,080 microRNAs analyzed, 335 were downregulated or absent in 27 compared with 15 days in vitro and resveratrol reversed this effect. A substantial overlapping was found between age-associated changes in microRNA expression profiles in vitro and in TgCRND8 mice but not in physiologically aged mice, indicating that this culture model displays more similarities with pathological than physiological brain aging. Our results demonstrate that neuroglial cocultures aged in vitro can be useful for investigating the cellular and molecular mechanisms of brain aging and for preliminary testing of protective compounds.

  13. Deciphering the evolutionary history of open and closed mitosis.

    Science.gov (United States)

    Sazer, Shelley; Lynch, Michael; Needleman, Daniel

    2014-11-17

    The origin of the nucleus at the prokaryote-to-eukaryote transition represents one of the most important events in the evolution of cellular organization. The nuclear envelope encircles the chromosomes in interphase and is a selectively permeable barrier between the nucleoplasm and cytoplasm and an organizational scaffold for the nucleus. It remains intact in the 'closed' mitosis of some yeasts, but loses its integrity in the 'open' mitosis of mammals. Instances of both types of mitosis within two evolutionary clades indicate multiple evolutionary transitions between open and closed mitosis, although the underlying genetic changes that influenced these transitions remain unknown. A survey of the diversity of mitotic nuclei that fall between these extremes is the starting point from which to determine the physiologically relevant characteristics distinguishing open from closed mitosis and to understand how they evolved and why they are retained in present-day organisms. The field is now poised to begin addressing these issues by defining and documenting patterns of mitotic nuclear variation within and among species and mapping them onto a phylogenic tree. Deciphering the evolutionary history of open and closed mitosis will complement cell biological and genetic approaches aimed at deciphering the fundamental organizational principles of the nucleus.

  14. Deciphering an Image Cipher Based on Mixed Transformed Logistic Maps

    Science.gov (United States)

    Liu, Yuansheng; Fan, Hua; Xie, Eric Yong; Cheng, Ge; Li, Chengqing

    2015-12-01

    Since John von Neumann suggested utilizing Logistic map as a random number generator in 1947, a great number of encryption schemes based on Logistic map and/or its variants have been proposed. This paper re-evaluates the security of an image cipher based on transformed logistic maps and proves that the image cipher can be deciphered efficiently under two different conditions: (1) two pairs of known plain-images and the corresponding cipher-images with computational complexity of O(218 + L); (2) two pairs of chosen plain-images and the corresponding cipher-images with computational complexity of O(L), where L is the number of pixels in the plain-image. In contrast, the required condition in the previous deciphering method is 87 pairs of chosen plain-images and the corresponding cipher-images with computational complexity of O(27 + L). In addition, three other security flaws existing in most Logistic-map-based ciphers are also reported.

  15. Envirotyping for deciphering environmental impacts on crop plants.

    Science.gov (United States)

    Xu, Yunbi

    2016-04-01

    Global climate change imposes increasing impacts on our environments and crop production. To decipher environmental impacts on crop plants, the concept "envirotyping" is proposed, as a third "typing" technology, complementing with genotyping and phenotyping. Environmental factors can be collected through multiple environmental trials, geographic and soil information systems, measurement of soil and canopy properties, and evaluation of companion organisms. Envirotyping contributes to crop modeling and phenotype prediction through its functional components, including genotype-by-environment interaction (GEI), genes responsive to environmental signals, biotic and abiotic stresses, and integrative phenotyping. Envirotyping, driven by information and support systems, has a wide range of applications, including environmental characterization, GEI analysis, phenotype prediction, near-iso-environment construction, agronomic genomics, precision agriculture and breeding, and development of a four-dimensional profile of crop science involving genotype (G), phenotype (P), envirotype (E) and time (T) (developmental stage). In the future, envirotyping needs to zoom into specific experimental plots and individual plants, along with the development of high-throughput and precision envirotyping platforms, to integrate genotypic, phenotypic and envirotypic information for establishing a high-efficient precision breeding and sustainable crop production system based on deciphered environmental impacts. PMID:26932121

  16. Envirotyping for deciphering environmental impacts on crop plants.

    Science.gov (United States)

    Xu, Yunbi

    2016-04-01

    Global climate change imposes increasing impacts on our environments and crop production. To decipher environmental impacts on crop plants, the concept "envirotyping" is proposed, as a third "typing" technology, complementing with genotyping and phenotyping. Environmental factors can be collected through multiple environmental trials, geographic and soil information systems, measurement of soil and canopy properties, and evaluation of companion organisms. Envirotyping contributes to crop modeling and phenotype prediction through its functional components, including genotype-by-environment interaction (GEI), genes responsive to environmental signals, biotic and abiotic stresses, and integrative phenotyping. Envirotyping, driven by information and support systems, has a wide range of applications, including environmental characterization, GEI analysis, phenotype prediction, near-iso-environment construction, agronomic genomics, precision agriculture and breeding, and development of a four-dimensional profile of crop science involving genotype (G), phenotype (P), envirotype (E) and time (T) (developmental stage). In the future, envirotyping needs to zoom into specific experimental plots and individual plants, along with the development of high-throughput and precision envirotyping platforms, to integrate genotypic, phenotypic and envirotypic information for establishing a high-efficient precision breeding and sustainable crop production system based on deciphered environmental impacts.

  17. The need to unify neuropathological assessments of vascular alterations in the ageing brain Multicentre survey by the BrainNet Europe consortium

    NARCIS (Netherlands)

    Alafuzoff, Irina; Gelpi, Ellen; Al-Sarraj, Safa; Arzberger, Thomas; Attems, Johannes; Bodi, Istvan; Bogdanovic, Nenad; Budka, Herbert; Bugiani, Orso; Englund, Elisabet; Ferrer, Isidro; Gentleman, Stephen; Giaccone, Giorgio; Graeber, Manuel B.; Hortobagyi, Tibor; Hoeftberger, Romana; Ironside, James W.; Jellinger, Kurt; Kavantzas, Nikolaos; King, Andrew; Korkolopoulou, Penelope; Kovacs, Gabor G.; Meyronet, David; Monoranu, Camelia; Parchi, Piero; Patsouris, Efstratios; Roggendorf, Wolfgang; Rozemuller, Annemieke; Seilhean, Danielle; Streichenberger, Nathalie; Thal, Dietmar R.; Wharton, Stephen B.; Kretzschmar, Hans

    2012-01-01

    Here, we summarise the results after carrying out a large survey regarding the assessment of vascular alterations, both vessel changes and vascular lesions in an inter-laboratory setting. In total, 32 neuropathologists from 22 centres, most being members of BrainNet Europe (BNE), participated by fil

  18. The emergence of age-dependent social cognitive deficits after generalized insult to the developing brain: a longitudinal prospective analysis using susceptibility-weighted imaging.

    Science.gov (United States)

    Ryan, Nicholas P; Catroppa, Cathy; Cooper, Janine M; Beare, Richard; Ditchfield, Michael; Coleman, Lee; Silk, Timothy; Crossley, Louise; Beauchamp, Miriam H; Anderson, Vicki A

    2015-05-01

    Childhood and adolescence are critical periods for maturation of neurobiological processes that underlie complex social and emotional behavior including Theory of Mind (ToM). While structural correlates of ToM are well described in adults, less is known about the anatomical regions subsuming these skills in the developing brain or the impact of cerebral insult on the acquisition and establishment of high-level social cognitive skills. This study aimed to examine the differential influence of age-at-insult and brain pathology on ToM in a sample of children and adolescents with traumatic brain injury (TBI). Children and adolescents with TBI (n = 112) were categorized according to timing of brain insult: (i) middle childhood (5-9 years; n = 41); (ii) late childhood (10-11 years; n = 39); and (iii) adolescence (12-15 years; n = 32) and group-matched for age, gender, and socioeconomic status to a typically developing (TD) control group (n = 43). Participants underwent magnetic resonance imaging including a susceptibility-weighted imaging (SWI) sequence 2-8 weeks postinjury and were assessed on a battery of ToM tasks at 6- and 24-months after injury. Results showed that for adolescents with TBI, social cognitive dysfunction at 6- and 24-months postinjury was associated with diffuse neuropathology and a greater number of lesions detected using SWI. In the late childhood TBI group, we found a time-dependent emergence of social cognitive impairment, linked to diffuse neuropathology. The middle childhood TBI group demonstrated performance unrelated to SWI pathology and comparable to TD controls. Findings indicate that the full extent of social cognitive deficits may not be realized until the associated skills reach maturity. Evidence for brain structure-function relationships suggests that the integrity of an anatomically distributed network of brain regions and their connections is necessary for the acquisition and establishment of high-level social

  19. Brain Basics

    Medline Plus

    Full Text Available ... Basics in Real Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah is a middle-aged woman who seemed to have it all. She was happily married and successful in business. Then, after a serious setback at work, she lost interest ...

  20. Modulation of intestinal microbiota by the probiotic VSL#3 resets brain gene expression and ameliorates the age-related deficit in LTP.

    Directory of Open Access Journals (Sweden)

    Eleonora Distrutti

    Full Text Available The intestinal microbiota is increasingly recognized as a complex signaling network that impacts on many systems beyond the enteric system modulating, among others, cognitive functions including learning, memory and decision-making processes. This has led to the concept of a microbiota-driven gut-brain axis, reflecting a bidirectional interaction between the central nervous system and the intestine. A deficit in synaptic plasticity is one of the many changes that occurs with age. Specifically, the archetypal model of plasticity, long-term potentiation (LTP, is reduced in hippocampus of middle-aged and aged rats. Because the intestinal microbiota might change with age, we have investigated whether the age-related deficit in LTP might be attenuated by changing the composition of intestinal microbiota with VSL#3, a probiotic mixture comprising 8 Gram-positive bacterial strains. Here, we report that treatment of aged rats with VSL#3 induced a robust change in the composition of intestinal microbiota with an increase in the abundance of Actinobacteria and Bacterioidetes, which was reduced in control-treated aged rats. VSL#3 administration modulated the expression of a large group of genes in brain tissue as assessed by whole gene expression, with evidence of a change in genes that impact on inflammatory and neuronal plasticity processes. The age-related deficit in LTP was attenuated in VSL#3-treated aged rats and this was accompanied by a modest decrease in markers of microglial activation and an increase in expression of BDNF and synapsin. The data support the notion that intestinal microbiota can be manipulated to positively impact on neuronal function.

  1. Brain Basics

    Medline Plus

    Full Text Available ... sends impulses and extends from cell bodies to meet and deliver impulses to another nerve cell. Axons ... in Real Life—How Depression affects the Brain Meet Sarah Sarah is a middle-aged woman who ...

  2. Impact of preterm birth on inhibition abilities in neutral and emotional contexts in school age children: neuropsychological and brain imaging aspects

    OpenAIRE

    Reveillon, Morgane

    2014-01-01

    Being born preterm is associated with an increased risk of adverse neurodevelopmental functioning, including long-term difficulties in executive functions. Among executive functions, difficulties in major inhibition processes such as response inhibition and interference control have been reported at both brain and behavior levels in preterm samples. However, no consensus exists regarding inhibition difficulties at late school age and information is lacking regarding their underlying neural co...

  3. P15.08NEUROPSYCHOLOGICAL OUTCOMES AFTER MICROSURGICAL RESECTION OF BRAIN TUMORS: THE PREDICTIVE VALUE OF COGNITIVE BACKGROUND, AGE AND EDUCATION

    OpenAIRE

    Sindorio, C.; Abbritti, R.V.; Otera, R.; Quattropani, M.C.; Germanò, A.

    2014-01-01

    INTRODUCTION: Neuropsychological assessment of patients suffering from brain tumors provides a functional map of cognitive impairment regarding memory, attention, visuospatial and visuo-constructive abilities related to the tumor's location. Several studies reported the clinical and prognostic value of pre and post-operative cognitive and behavioral assessment in neuroncology. Some authors demonstrated that age, education and gender may influence the cognitive functions, while others argued t...

  4. Age-Dependent Increase of Brain Copper Levels and Expressions of Copper Regulatory Proteins in the Subventricular Zone and Choroid Plexus

    Directory of Open Access Journals (Sweden)

    Sherleen eFu

    2015-06-01

    Full Text Available Our recent data suggest a high accumulation of Cu in the subventricular zone (SVZ along the wall of brain ventricles. Anatomically, SVZ is in direct contact with cerebrospinal fluid (CSF, which is secreted by a neighboring tissue choroid plexus. Changes in Cu regulatory gene expressions in the SVZ and choroid plexus as the function of aging may determine Cu levels in the CSF and SVZ. This study was designed to investigate associations between age, Cu levels, and Cu regulatory genes in SVZ and plexus. The SVZ and choroid plexus were dissected from brains of 3-week, 10-week or 9-month old male rats. Analyses by atomic absorption spectroscopy revealed that the SVZ of adult and old animals contained the highest Cu level compared with other tested brain regions. Significant positive correlations between age and Cu levels in SVZ and plexus were observed; the SVZ Cu level of old animals was 7.5- and 5.8-fold higher than those of young and adult rats (p<0.01, respectively. Quantitation by qPCR of the transcriptional expressions of Cu regulatory proteins showed that the SVZ expressed the highest level of Cu storage protein MTs, while the choroid plexus expressed the high level of Cu transporter protein Ctr1. Noticeably, Cu levels in the SVZ were positively associated with type B slow proliferating cell marker Gfap (p<0.05, but inversely associated with type A proliferating neuroblast marker Dcx (p<0.05 and type C transit amplifying progenitor marker Nestin (p<0.01. Dmt1 had significant positive correlations with age and Cu levels in the plexus (p<0.01. These findings suggest that Cu levels in all tested brain regions are increased as the function of age. The SVZ shows a different expression pattern of Cu-regulatory genes from the choroid plexus. The age-related increase of MTs and decrease of Ctr1 may contribute to the high Cu level in this neurogenesis active brain region.

  5. Effects of body mass index and age on N-terminal pro brain natriuretic peptide are associated with glomerular filtration rate in chronic heart failure patients

    DEFF Research Database (Denmark)

    Schou, Morten; Gustafsson, Finn; Kistorp, Caroline N;

    2007-01-01

    BACKGROUND: Obesity is a state characterized by glomerular hyperfiltration and age-related decreases in glomerular filtration rate (GFR). Body mass index (BMI), age, and GFR are associated with plasma concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) in chronic heart failure...... (CHF) patients. We hypothesized that the effects of BMI and age on plasma concentrations of NT-proBNP are associated with GFR. METHODS: We obtained clinical data and laboratory test results from 345 CHF patients at the baseline visit in our heart failure clinic and examined the hypothesis using...... multiple linear regression models. RESULTS: Age (P = 0.0184), BMI (P = 0.0098), hemoglobin (P = 0.0043), heart rhythm (P GFR estimated by the Cockcroft and Gault equation, the parameter...

  6. Resting state brain activity and functional brain mapping

    Institute of Scientific and Technical Information of China (English)

    Zhao Xiaohu; Wang Peijun; Tang Xiaowei

    2007-01-01

    Functional brain imaging studies commonly use either resting or passive task states as their control conditions, and typically identify the activation brain region associated with a specific task by subtracting the resting from the active task conditions. Numerous studies now suggest, however, that the resting state may not reflect true mental "rest" conditions. The mental activity that occurs during"rest" might therefore greatly influence the functional neuroimaging observations that are collected through the usual subtracting analysis strategies. Exploring the ongoing mental processes that occur during resting conditions is thus of particular importance for deciphering functional brain mapping results and obtaining a more comprehensive understanding of human brai