WorldWideScience

Sample records for aging brain relevance

  1. The relevance of aging-related changes in brain function to rehabilitation in aging-related disease

    Directory of Open Access Journals (Sweden)

    Bruce Crosson

    2015-05-01

    Full Text Available The effects of aging on rehabilitation of aging-related diseases are rarely a design consideration in rehabilitation research. In this brief review we present strong coincidental evidence from these two fields suggesting that deficits in aging-related disease or injury are compounded by the interaction between aging-related brain changes and disease-related brain changes. Specifically, we hypothesize that some aphasia, motor, and neglect treatments using repetitive transcranial magnetic stimulation (rTMS or transcranial direct current stimulation (tDCS in stroke patients may address the aging side of this interaction. The importance of testing this hypothesis and addressing the larger aging by aging-related disease interaction is discussed. Underlying mechanisms in aging that most likely are relevant to rehabilitation of aging-related diseases also are covered.

  2. 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...

  3. Brain atrophy during aging

    International Nuclear Information System (INIS)

    Age-related brain atrophy was investigated in thousands of persons with no neurologic disturbances using X-CT and NMR-CT. Brain atrophy was minimal in 34-35 years old in both sexes, increased exponentially to the increasing age after 34-35 years, and probably resulted in dementia, such as vascular or multi-infarct dementia. Brain atrophy was significantly greater in men than in women at all ages. Brain volumes were maximal in 34-35 years old in both sexes with minimal individual differences which increased proportionally to the increasing age. Remarkable individual differences in the extent of brain atrophy (20 - 30 %) existed among aged subjects. Progression of brain atrophy was closely related to loss of mental activities independently of their ages. Our longitudinal study has revealed that the most important factors promoting brain atrophy during aging was the decrease in the cerebral blood flow. We have classified brain atrophy into sulcal and cisternal enlargement type (type I), ventricular enlargement type (type II) and mixed type (type III) according to the clinical study using NMR-CT. Brain atrophy of type I progresses significantly in almost all of the geriatric disorders. This type of brain atrophy progresses significantly in heavy smokers and drinkers. Therefore this type of brain atrophy might be caused by the decline in the blood flow in anterior and middle cerebral arteries. Brain atrophy of type II was caused by the disturbance of cerebrospinal fluid circulation after cerebral bleeding and subarachnoid bleeding. Brain atrophy of type III was seen in vascular dementia or multi-infarct dementia which was caused by loss of brain matter after multiple infarction, and was seen also in dementia of Alzheimer type in which degeneration of nerve cells results in brain atrophy. NMR-CT can easily detect small infarction (lacunae) and edematous lesions resulting from ischemia and hypertensive encephalopathy. (J.P.N.)

  4. 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

  5. Relevance to Aging and Dementia

    Directory of Open Access Journals (Sweden)

    Pinar E. Coskun

    2012-01-01

    Full Text Available Genome-wide gene deregulation and oxidative stress appear to be critical factors determining the high variability of phenotypes in Down’s syndrome (DS. Even though individuals with trisomy 21 exhibit a higher survival rate compared to other aneuploidies, most of them die in utero or early during postnatal life. While the survivors are currently predicted to live past 60 years, they suffer higher incidence of age-related conditions including Alzheimer’s disease (AD. This paper is centered on the mechanisms by which mitochondrial factors and oxidative stress may orchestrate an adaptive response directed to maintain basic cellular functions and survival in DS. In this context, the timing of therapeutic interventions should be carefully considered for the successful treatment of chronic disorders in the DS population.

  6. 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...

  7. Aging and Functional Brain Networks

    OpenAIRE

    Tomasi, Dardo; Volkow, Nora D.

    2011-01-01

    Aging is associated with changes in human brain anatomy and function and cognitive decline. Recent studies suggest the aging decline of major functional connectivity hubs in the “default-mode” network (DMN). Aging effects on other networks, however, are largely unknown. We hypothesized that aging would be associated with a decline of short- and long-range functional connectivity density (FCD) hubs in the DMN. To test this hypothesis we evaluated resting-state datasets corresponding to 913 hea...

  8. 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

  9. Neurogenesis in the aging brain

    OpenAIRE

    Veronica Galvan; Kunlin Jin

    2007-01-01

    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 cent...

  10. 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 ...

  11. Brain trace elements and aging

    International Nuclear Information System (INIS)

    Degenerative mechanisms involved in the aging process of the brain are to a certain extent counteracted by repair mechanisms. In both degenerative and recovery processes, trace elements are involved. The present study focused on the role of two minor (i.e., K and Ca) and six trace elements (i.e., Mn, Fe, Cu, Zn, Se and Rb) in the aging process. The elements were determined by PIXE in cerebral cortex and white matter, basal ganglia, brainstem and cerebellar cortex of 18 postmortem human brains, from persons without a history of neurologic or psychiatric disease who deceased between the age of 7 and 79. This age range allowed us to study the relationship between elemental concentrations and age. The most prominent findings were a concentration decrease for K and Rb and a concentration increase for the elements Ca, Fe, Zn and Se. The study supports recent findings that Ca and Fe are involved in brain degenerative processes initiated by oxygen free radicals, whereas Zn and Se are involved in immunological reactions counteracting the aging process

  12. Aging and functional brain networks

    Energy Technology Data Exchange (ETDEWEB)

    Tomasi D.; Tomasi, D.; Volkow, N.D.

    2011-07-11

    Aging is associated with changes in human brain anatomy and function and cognitive decline. Recent studies suggest the aging decline of major functional connectivity hubs in the 'default-mode' network (DMN). Aging effects on other networks, however, are largely unknown. We hypothesized that aging would be associated with a decline of short- and long-range functional connectivity density (FCD) hubs in the DMN. To test this hypothesis, we evaluated resting-state data sets corresponding to 913 healthy subjects from a public magnetic resonance imaging database using functional connectivity density mapping (FCDM), a voxelwise and data-driven approach, together with parallel computing. Aging was associated with pronounced long-range FCD decreases in DMN and dorsal attention network (DAN) and with increases in somatosensory and subcortical networks. Aging effects in these networks were stronger for long-range than for short-range FCD and were also detected at the level of the main functional hubs. Females had higher short- and long-range FCD in DMN and lower FCD in the somatosensory network than males, but the gender by age interaction effects were not significant for any of the networks or hubs. These findings suggest that long-range connections may be more vulnerable to aging effects than short-range connections and that, in addition to the DMN, the DAN is also sensitive to aging effects, which could underlie the deterioration of attention processes that occurs with aging.

  13. Natural brain-information interfaces: Recommending information by relevance inferred from human brain signals

    OpenAIRE

    Eugster, Manuel J. A.; Ruotsalo, Tuukka; Spapé, Michiel M.; Barral, Oswald; Ravaja, Niklas; Jacucci, Giulio; Kaski, Samuel

    2016-01-01

    Finding relevant information from large document collections such as the World Wide Web is a common task in our daily lives. Estimation of a user's interest or search intention is necessary to recommend and retrieve relevant information from these collections. We introduce a brain-information interface used for recommending information by relevance inferred directly from brain signals. In experiments, participants were asked to read Wikipedia documents about a selection of topics while their ...

  14. Are invertebrates relevant models in ageing research?

    DEFF Research Database (Denmark)

    Hansen, Benni Winding; Vang, Ole; Erdogan, Cihan Suleyman

    2016-01-01

    evolutionary conserved key protein kinase in the TOR pathway that regulates growth, proliferation and cell metabolism in response to nutrients, growth factors and stress. Comparing the ageing process in invertebrate model organisms with relatively short lifespan with mammals provides valuable information about...... the molecular mechanisms underlying the ageing process faster than mammal systems. Inhibition of the TOR pathway activity via either genetic manipulation or rapamycin increases lifespan profoundly in most invertebrate model organisms. This contribution will review the recent findings in invertebrates...... concerning the TOR pathway and effects of TOR inhibition by rapamycin on lifespan. Besides some contradictory results, the majority points out that rapamycin induces longevity. This suggests that administration of rapamycin in invertebrates is a promising tool for pursuing the scientific puzzle of lifespan...

  15. 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

  16. Aging in the canine and feline brain.

    Science.gov (United States)

    Vite, Charles H; Head, Elizabeth

    2014-11-01

    Aging dogs and cats show neurodegenerative features that are similar to human aging and Alzheimer disease. Neuropathologic changes with age may be linked to signs of cognitive dysfunction both in the laboratory and in a clinic setting. Less is known about cat brain aging and cognition and this represents an area for further study. Neurodegenerative diseases such as lysosomal storage diseases in dogs and cats also show similar features of human aging, suggesting some common underlying pathogenic mechanisms and also suggesting pathways that can be modified to promote healthy brain aging. PMID:25441628

  17. The brain's default network: anatomy, function, and relevance to disease.

    Science.gov (United States)

    Buckner, Randy L; Andrews-Hanna, Jessica R; Schacter, Daniel L

    2008-03-01

    Thirty years of brain imaging research has converged to define the brain's default network-a novel and only recently appreciated brain system that participates in internal modes of cognition. Here we synthesize past observations to provide strong evidence that the default network is a specific, anatomically defined brain system preferentially active when individuals are not focused on the external environment. Analysis of connectional anatomy in the monkey supports the presence of an interconnected brain system. Providing insight into function, the default network is active when individuals are engaged in internally focused tasks including autobiographical memory retrieval, envisioning the future, and conceiving the perspectives of others. Probing the functional anatomy of the network in detail reveals that it is best understood as multiple interacting subsystems. The medial temporal lobe subsystem provides information from prior experiences in the form of memories and associations that are the building blocks of mental simulation. The medial prefrontal subsystem facilitates the flexible use of this information during the construction of self-relevant mental simulations. These two subsystems converge on important nodes of integration including the posterior cingulate cortex. The implications of these functional and anatomical observations are discussed in relation to possible adaptive roles of the default network for using past experiences to plan for the future, navigate social interactions, and maximize the utility of moments when we are not otherwise engaged by the external world. We conclude by discussing the relevance of the default network for understanding mental disorders including autism, schizophrenia, and Alzheimer's disease. PMID:18400922

  18. Blood-borne revitalization of the aged brain

    Science.gov (United States)

    Castellano, Joseph M.; Kirby, Elizabeth D.; Wyss-Coray, Tony

    2016-01-01

    In the modern medical era, more diverse and effective treatment options have translated into increased life expectancy. With this increased lifespan comes increased age-associated disease and the dire need to understand the underlying causes so that therapies can be designed to mitigate the burden to health and the economy. Aging exacts a seemingly inevitable, multi-system deterioration of function that acts as a risk factor for a variety of age-related disorders, including those that devastate organs of limited regenerative potential such as the brain. Rather than studying the brain and mechanisms that govern its aging in isolation from other organ systems, an emerging approach is to understand the relatively unappreciated communication existing between the brain and the systemic environment. Revisiting classical methods of experimental physiology in animal models has uncovered surprising regenerative activity within young blood with translational implications for aging liver, muscle, brain and other organs. Surprisingly, soluble factors present in young or aged blood are sufficient to improve or impair cognitive function, respectively, suggesting an aging continuum of brain-relevant systemic factors. The age-associated plasma chemokine CCL11 has been shown to impair young brain function while GDF11 has been reported to increase the generation of neurons in aged mice. However, the identities of specific factors mediating memory-enhancing effects of young blood and their mechanisms of action remain enigmatic. Here we review recent brain rejuvenation studies in the broader context of systemic rejuvenation research. We discuss putative mechanisms for blood-borne brain rejuvenation while suggesting promising avenues for future research and development of therapies. PMID:26237737

  19. Blood-Borne Revitalization of the Aged Brain.

    Science.gov (United States)

    Castellano, Joseph M; Kirby, Elizabeth D; Wyss-Coray, Tony

    2015-10-01

    In the modern medical era, more diverse and effective treatment options have translated to increased life expectancy. With this increased life span comes increased age-associated disease and the dire need to understand underlying causes so that therapies can be designed to mitigate the burden to health and the economy. Aging exacts a seemingly inevitable multisystem deterioration of function that acts as a risk factor for a variety of age-related disorders, including those that devastate organs of limited regenerative potential, such as the brain. Rather than studying the brain and mechanisms that govern its aging in isolation from other organ systems, an emerging approach is to understand the relatively unappreciated communication that exists between the brain and systemic environment. Revisiting classical methods of experimental physiology in animal models has uncovered surprising regenerative activity in young blood with translational implications for the aging liver, muscle, brain, and other organs. Soluble factors present in young or aged blood are sufficient to improve or impair cognitive function, respectively, suggesting an aging continuum of brain-relevant systemic factors. The age-associated plasma chemokine CCL11 has been shown to impair young brain function while GDF11 has been reported to increase the generation of neurons in aged mice. However, the identities of specific factors mediating memory-enhancing effects of young blood and their mechanisms of action are enigmatic. Here we review brain rejuvenation studies in the broader context of systemic rejuvenation research. We discuss putative mechanisms for blood-borne brain rejuvenation and suggest promising avenues for future research and development of therapies. PMID:26237737

  20. 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...

  1. 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...

  2. 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

  3. Nutrition, brain aging, and neurodegeneration

    Science.gov (United States)

    The onset of age-related neurodegenerative diseases superimposed on a declining nervous system could enhance the motor and cognitive behavioral deficits that normally occur in senescence. It is likely that, in cases of severe deficits in memory or motor function, hospitalization and/or custodial car...

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

    Science.gov (United States)

    Kovacs, G G; Adle-Biassette, H; Milenkovic, I; Cipriani, S; van Scheppingen, J; Aronica, E

    2014-06-01

    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 induced by genetic or environmental factors leading to the formation of aberrant networks associated with learning disabilities. Moreover, evidence is accumulating that suggests that also late-onset neurological disorders, even Alzheimer's disease, might be considered disorders of aberrant neural development with pathological changes that are set up at early stages of development before the appearance of the symptoms. Thus, evaluating proteins and pathways that are important in age-related neurodegeneration in the developing brain together with the characterization of mechanisms important during brain development with relevance to brain aging are of crucial importance. In the present review we focus on (1) aspects of neurogenesis with relevance to aging; (2) neurodegenerative disease (NDD)-associated proteins/pathways in the developing brain; and (3) further pathways of the developing or neurodegenerating brains that show commonalities. Elucidation of complex pathogenetic routes characterizing the earliest stage of the detrimental processes that result in pathological aging represents an essential first step toward a therapeutic intervention which is able to reverse these pathological processes and prevent the onset of the disease. Based on the shared features between pathways, we conclude that prevention of NDDs of the elderly might begin during the fetal and childhood life by providing the mothers and their children a healthy environment for the fetal and childhood development. PMID:24699227

  5. Brain computed tomography findings of aged schizophrenics

    International Nuclear Information System (INIS)

    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.)

  6. 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.

  7. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  9. 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.

  10. 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.

  11. Brain-Computer Interface Based on Motor Imagery: the Most Relevant Sources of Electrical Brain Activity

    Czech Academy of Sciences Publication Activity Database

    Frolov, A. A.; Húsek, Dušan; Snášel, V.; Bobrov, P.; Mokienko, O.; Tintěra, J.; Rydlo, J.

    Cham: Springer, 2014 - (Snášel, V.; Krömer, P.; Köppen, M.; Schaefer, G.), s. 153-163. (Advances in Intelligent Systems and Computing. 223). ISBN 978-3-319-00929-2. ISSN 2194-5357. [Online World Conference on Soft Computing in Industrial Applications /17./. Anywhere on Earth, 10.12.2012-21.12.2012)] Grant ostatní: GA MŠk(CZ) ED1.1.00/02.0070; GA MŠk(CZ) EE.2.3.20.0073 Institutional support: RVO:67985807 Keywords : Image and Signal Processing * Brain-Computer Interface * Independent Component Analysis * EEG Pattern Classification * fMRI * Motor Image ry * Pattern Recognition Subject RIV: IN - Informatics, Computer Science http://dap.vsb.cz/wsc17conf/brain-computer-interface-based-on-motor- image ry---the-most-relevant-sources-of-electrical-brain-activity

  12. The relevance of brain evolution for the biomedical sciences

    OpenAIRE

    Smulders, Tom V.

    2008-01-01

    Most biomedical neuroscientists realize the importance of the study of brain evolution to help them understand the differences and similarities between their animal model of choice and the human brains in which they are ultimately interested. Many think of evolution as a linear process, going from simpler brains, as those of rats, to more complex ones, as those of humans. However, in reality, every extant species' brain has undergone as long a period of evolution as has the human brain, and e...

  13. Structural brain MRI studies in eye diseases: are they clinically relevant? A review of current findings.

    Science.gov (United States)

    Prins, Doety; Hanekamp, Sandra; Cornelissen, Frans W

    2016-03-01

    Many eye diseases reduce visual acuity or are associated with visual field defects. Because of the well-defined retinotopic organization of the connections of the visual pathways, this may affect specific parts of the visual pathways and cortex, as a result of either deprivation or transsynaptic degeneration. For this reason, over the past several years, numerous structural magnetic resonance imaging (MRI) studies have examined the association of eye diseases with pathway and brain changes. Here, we review structural MRI studies performed in human patients with the eye diseases albinism, amblyopia, hereditary retinal dystrophies, age-related macular degeneration (AMD) and glaucoma. We focus on two main questions. First, what have these studies revealed? Second, what is the potential clinical relevance of their findings? We find that all the aforementioned eye diseases are indeed associated with structural changes in the visual pathways and brain. As such changes have been described in very different eye diseases, in our view the most parsimonious explanation is that these are caused by the loss of visual input and the subsequent deprivation of the visual pathways and brain regions, rather than by transsynaptic degeneration. Moreover, and of clinical relevance, for some of the diseases - in particular glaucoma and AMD - present results are compatible with the view that the eye disease is part of a more general neurological or neurodegenerative disorder that also affects the brain. Finally, establishing structural changes of the visual pathways has been relevant in the context of new therapeutic strategies to restore retinal function: it implies that restoring retinal function may not suffice to also effectively restore vision. Future structural MRI studies can contribute to (i) further establish relationships between ocular and neurological neurodegenerative disorders, (ii) investigate whether brain degeneration in eye diseases is reversible, (iii) evaluate the use

  14. Intranasal Insulin Improves Age-Related Cognitive Deficits and Reverses Electrophysiological Correlates of Brain Aging.

    Science.gov (United States)

    Maimaiti, Shaniya; Anderson, Katie L; DeMoll, Chris; Brewer, Lawrence D; Rauh, Benjamin A; Gant, John C; Blalock, Eric M; Porter, Nada M; Thibault, Olivier

    2016-01-01

    Peripheral insulin resistance is a key component of metabolic syndrome associated with obesity, dyslipidemia, hypertension, and type 2 diabetes. While the impact of insulin resistance is well recognized in the periphery, it is also becoming apparent in the brain. Recent studies suggest that insulin resistance may be a factor in brain aging and Alzheimer's disease (AD) whereby intranasal insulin therapy, which delivers insulin to the brain, improves cognition and memory in AD patients. Here, we tested a clinically relevant delivery method to determine the impact of two forms of insulin, short-acting insulin lispro (Humalog) or long-acting insulin detemir (Levemir), on cognitive functions in aged F344 rats. We also explored insulin effects on the Ca(2+)-dependent hippocampal afterhyperpolarization (AHP), a well-characterized neurophysiological marker of aging which is increased in the aged, memory impaired animal. Low-dose intranasal insulin improved memory recall in aged animals such that their performance was similar to that seen in younger animals. Further, because ex vivo insulin also reduced the AHP, our results suggest that the AHP may be a novel cellular target of insulin in the brain, and improved cognitive performance following intranasal insulin therapy may be the result of insulin actions on the AHP. PMID:25659889

  15. Brain-Based Education: Its Pedagogical Implications and Research Relevance

    Science.gov (United States)

    Laxman, Kumar; Chin, Yap Kueh

    2010-01-01

    The brain, being the organ of learning, must be understood if classrooms are to be places of meaningful learning. Understanding the brain has the potential to alter the foundation of education, transform traditional classrooms to interactive learning environments and promote better instructional approaches amongst teachers. Brain-based education…

  16. 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.

  17. Want to Keep an Aging Brain Sharp? Try the Stairs

    Science.gov (United States)

    ... to Keep an Aging Brain Sharp? Try the Stairs Fitness is key, researchers say, and education can ... brain may want to switch from elevators to stairs, new research suggests. Fitness seemed key to sharper ...

  18. 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)

  19. 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

  20. 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)

  1. Clinical Relevance of Brain Volume Measures in Multiple Sclerosis

    DEFF Research Database (Denmark)

    De Stefano, Nicola; Airas, Laura; Grigoriadis, Nikolaos;

    2014-01-01

    Multiple sclerosis (MS) is a chronic disease with an inflammatory and neurodegenerative pathology. Axonal loss and neurodegeneration occurs early in the disease course and may lead to irreversible neurological impairment. Changes in brain volume, observed from the earliest stage of MS and...

  2. Relevance Of Human Brain Banking In Neuroscience - A National Facility

    Directory of Open Access Journals (Sweden)

    Shankar S K

    1999-01-01

    Full Text Available The lack of animal models for many of the neurodegenerative and psychiatric disorders and the fact that animal models cannot substitute for human tissue led to the establishment of Brain Banks that collect, preserve and provide fresh human tissue for researchers. One such Bank has been set up at the National Institute of Mental Health and Neurosciences funded by Dept. of Biotechnology, Dept. of Science and Technology and ICMR. Brains and tissue fluids (serum and CSF are collected at autopsy following informed consent from close relatives. One half of the fresh brain from neurodegenerative and psychiatric disorders are frozen at -70′ C while the other half and brains from infective conditions are formalin fixed which can be used for pathomorphological studies. Only fresh frozen tissues that are tested and found negative for HIV and HbsAg are provided for research. The neural tissues as well as tissue fluids that are being supplied by the Brain Bank have supported a number of research projects in diverse fields of neurosciences. Many significant discoveries that have contributed towards understanding pathogenesis of disease, their genetic basis, and evolving prognostic and diagnostic markers for neurologic disease in the CSF have been made possible by the existence of such a facility. The continued functioning of such a facility requires the close co-operation of the clinical neuroscientists, pathologists and the other neuroscientists. Increased awareness and commitment amongst the scientific fraternity is necessary to keep alive the demand and ensure uninterrupted supply of fresh tissue for research. This will help usher in the era of molecular neurobiology with the fond hope that many more of the relentlessly progressive neurodegenerative disorders will eventually find a cause and cure.

  3. Expression and relevant research of MGMT and XRCC1 gene in differentgrades of brain glioma and normal brain tissues

    Institute of Scientific and Technical Information of China (English)

    Ya-Fei Zhang

    2015-01-01

    Objective: To explore and analyze expression and relevant research of MGMT and XRCC1 gene in different grades of brain glioma and normal brain tissues. Methods: 52 cases of patients with brain glioma treated in our hospital from December 2013 to December 2014, and 50 cases of normal brain-tissue patients with intracranial hypertension were selected, and proceeding test to the surgical resection of brain tissue of the above patients to determine its MGMT and XRCC1 protein content, sequentially to record the expression of MGMT and XRCC1 of both groups. Grading of tumors to brain glioma after operation was carried out, and the expression of MGMT and XRCC1 gene in brain tissues of different patients was analyzed and compared;finally the contingency tables of X2 test was used to analyze the correlation of XRCC1and MGMT. Results:Positive rate of MGMT expression in normal brain tissue was 2%,while positive rate of MGMT expression in brain glioma was 46.2%,which was obviously higher than that in normal brain tissues (χ2=26.85, P0.05), which had no statistical significance. There were 12 cases of patients whose MGMT protein expression was positive and XRCC1 protein expression was positive; there were 18 cases of patients whose MGMT protein expression was negative and XRCC1 protein expression was negative. Contingency tables of X2 test was used to analyze the correlation of XRCC1 and MGMT, which indicated that the expression of XRCCI and MGMT in brain glioma had no correlation (r=0.9%, P=0.353), relevancy of both was r=0.9%. Conclusions: Positive rate of the expression of MGMT and XRCC1 in brain glioma was obviously higher than that in normal brain tissues, but the distribution of different grades of brain glioma had no obvious difference, and MGMT and XRCC1 expression had no obvious correlation, which needed further research.

  4. New Perspectives on Rodent Models of Advanced Paternal Age: Relevance to Autism

    Directory of Open Access Journals (Sweden)

    Claire J Foldi

    2011-06-01

    Full Text Available Offspring of older fathers have an increased risk of various adverse health outcomes, including autism and schizophrenia. With respect to biological mechanisms for this association, there are many more germline cell divisions in the life history of a sperm relative to that of an oocyte. This leads to more opportunities for copy error mutations in germ cells from older fathers. Evidence also suggests that epigenetic patterning in the sperm from older men is altered. Rodent models provide an experimental platform to examine the association between paternal age and brain development. Several rodent models of advanced paternal age (APA have been published with relevance to intermediate phenotypes related to autism. All four published APA models vary in key features creating a lack of consistency with respect to behavioural phenotypes. A consideration of common phenotypes that emerge from these APA-related mouse models may be informative in the exploration of the molecular and neurobiological correlates of APA.

  5. 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...

  6. 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...

  7. In-vivo longitudinal MRI study: an assessment of melanoma brain metastases in a clinically relevant mouse model.

    Science.gov (United States)

    Henry, Mariama N; Chen, Yuhua; McFadden, Catherine D; Simedrea, Felicia C; Foster, Paula J

    2015-04-01

    Brain metastases are an important clinical problem. Few animal models exist for melanoma brain metastases; many of which are not clinically relevant. Longitudinal MRI was implemented to examine the development of tumors in a clinically relevant mouse model of melanoma brain metastases. Fifty thousand human metastatic melanoma (A2058) cells were injected intracardially into nude mice. Three Tesla MRI was performed using a custom-built gradient insert coil and a mouse solenoid head coil. Imaging was performed on consecutive days at four time points. Tumor burden and volumes of metastases were measured from balanced steady-state free precession image data. Metastases with a disrupted blood-tumor barrier were identified from T1-weighted spin echo images acquired after administration of gadopentetic acid (Gd-DTPA). Metastases permeable to Gd-DTPA showed signal enhancement. The number of enhancing metastases was determined by comparing balanced steady-state free precession images with T1-weighted spin echo images. After the final imaging session, ex-vivo permeability and histological analyses were carried out. Imaging showed that both enhancing and nonenhancing brain metastases coexist in the brain, and that most metastases switched from the nonenhancing to the enhancing phenotype. Small numbers of brain metastases were enhancing when first detected by MRI and remained enhancing, whereas other metastases remained nonenhancing to Gd-DTPA throughout the experiment. No clear relationship existed between the permeability of brain metastases and size, brain location and age. Longitudinal in-vivo MRI is key to studying the complex and dynamic processes of metastasis and changes in the blood-tumor barrier permeability, which may lead to a better understanding of the variable responses of brain metastases to treatments. PMID:25513779

  8. The analysis of several factors relevant to brain 18F-FDG metabolism by using the statistical parameter mapping

    International Nuclear Information System (INIS)

    Objective: To study the relationship of the regional brain 18F-fluorodeoxyglucose (FDG) metabolism and aging process, the dosage of the imaging agent, the level of blood sugar to cerebral PET (cPET) image data by using statistical parameter mapping (SPM) software. Methods: 18F-FDG cPET imaging data acquired from 30 healthy volunteers were collected and analyzed with SPM by the multiple linear regression model designed with dosage of tracer, and blood sugar level as explaining variables and the 18F-FDG accumulation as responding variables. Results: It's showed that the age, dosage and sugar level were all related with the 18F-FDG accumulation in the brain. The accumulation of the radiotracer in the brain areas like cingulate gyri, inferior temporal gyri of both sides and the cerebellum increased with the tracer dosage, and the blood sugar escalating and the 18F-FDG uptake in the brain areas like frontal lobes, parietal lobes, precentral gyri of both sides and cerebellum decreased at the same time, and the aging process led to a pancephalic 18F-FDG decrease. Conclusions: The injection dosage, sugar level and the age are all related with accumulation of the 18F-FDG, and the SPM software can be used to analyze the multiple factors relevant to cPET imaging data based on voxel level and so can explain the experimental results more correctly

  9. On the relevance of glycolysis process on brain gliomas.

    Science.gov (United States)

    Kounelakis, M G; Zervakis, M E; Giakos, G C; Postma, G J; Buydens, L M C; Kotsiakis, X

    2013-01-01

    The proposed analysis considers aspects of both statistical and biological validation of the glycolysis effect on brain gliomas, at both genomic and metabolic level. In particular, two independent datasets are analyzed in parallel, one engaging genomic (Microarray Expression) data and the other metabolomic (Magnetic Resonance Spectroscopy Imaging) data. The aim of this study is twofold. First to show that, apart from the already studied genes (markers), other genes such as those involved in the human cell glycolysis significantly contribute in gliomas discrimination. Second, to demonstrate how the glycolysis process can open new ways towards the design of patient-specific therapeutic protocols. The results of our analysis demonstrate that the combination of genes participating in the glycolytic process (ALDOA, ALDOC, ENO2, GAPDH, HK2, LDHA, LDHB, MDH1, PDHB, PFKM, PGI, PGK1, PGM1 and PKLR) with the already known tumor suppressors (PTEN, Rb, TP53), oncogenes (CDK4, EGFR, PDGF) and HIF-1, enhance the discrimination of low versus high-grade gliomas providing high prediction ability in a cross-validated framework. Following these results and supported by the biological effect of glycolytic genes on cancer cells, we address the study of glycolysis for the development of new treatment protocols. PMID:22614725

  10. Reconsolidation of human memory: brain mechanisms and clinical relevance.

    Science.gov (United States)

    Schwabe, Lars; Nader, Karim; Pruessner, Jens C

    2014-08-15

    The processes of memory formation and storage are complex and highly dynamic. Once memories are consolidated, they are not necessarily fixed but can be changed long after storage. In particular, seemingly stable memories may re-enter an unstable state when they are retrieved, from which they must be re-stabilized during a process known as reconsolidation. During reconsolidation, memories are susceptible to modifications again, thus providing an opportunity to update seemingly stable memories. While initial demonstrations of memory reconsolidation came mainly from animal studies, evidence for reconsolidation in humans is now accumulating as well. Here, we review recent advances in our understanding of human memory reconsolidation. After a summary of findings on the reconsolidation of human fear and episodic memory, we focus particularly on recent neuroimaging data that provide first insights into how reconsolidation processes are implemented in the human brain. Finally, we discuss the implications of memory modifications during reconsolidation for the treatment of mental disorders such as posttraumatic stress disorder and drug addiction. PMID:24755493

  11. 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

  12. Aging. Aging-induced type I interferon signaling at the choroid plexus negatively affects brain function

    Science.gov (United States)

    Baruch, Kuti; Deczkowska, Aleksandra; David, Eyal; Castellano, Joseph M.; Miller, Omer; Kertser, Alexander; Berkutzki, Tamara; Barnett-Itzhaki, Zohar; Bezalel, Dana; Wyss-Coray, Tony; Amit, Ido; Schwartz, Michal

    2016-01-01

    Age-associated cognitive decline is affected by factors produced inside and outside the brain. We found in aged mice and humans, that the choroid plexus (CP), an epithelial interface between the brain and the circulation, shows a type I interferon (IFN-I)-dependent expression profile, often associated with anti-viral responses. This signature was induced by brain-derived signals present in the cerebrospinal fluid of aged mice. Blocking IFN-I signaling within the brain of cognitively-impaired aged mice, using IFN-I receptor neutralizing antibody, led to partial restoration of cognitive function and hippocampal neurogenesis, and reestablished IFN-II-dependent CP activity, lost in aging. Our data identify an aging-induced IFN-I signature at the CP, and demonstrate its negative influence on brain function, thereby suggesting a potential target for therapeutic intervention for age-related cognitive decline. PMID:25147279

  13. 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,...

  14. Aging and Economic Growth: Issues Relevant to Singapore

    OpenAIRE

    Shandre M. Thangavelu; Yong Yik Wei

    2006-01-01

    The paper studies the effects of the changing age and education composition of the labour force on productivity growth in Singapore. The quality change of workers from aging and education is measured through a quality index. Quality change through education is the key driving force for the productive performance of the labour force. On the other hand, the growth in the labour quality of workers by age, and hence, its contribution to labour productivity growth is falling. To moderate the impac...

  15. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Takao, Hidemasa, E-mail: takaoh-tky@umin.ac.jp [Department of Radiology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan); Hayashi, Naoto [Department of Computational Diagnostic Radiology and Preventive Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan); Ohtomo, Kuni [Department of Radiology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan)

    2012-10-15

    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.

  17. Brain cholesterol in normal and pathological aging

    Directory of Open Access Journals (Sweden)

    Vanmierlo Tim

    2011-07-01

    Full Text Available Aberrations in cerebral cholesterol homeostasis can lead to severe neurological diseases. Recent findings strengthen the link between brain cholesterol metabolism and factors involved in synaptic plasticity, a process essential for learning and memory functions, as well as regeneration, which are affected in Alzheimer’s Disease (AD. Cholesterol homeostasis within the brain is independent of that in the rest of the body and needs to be strictly regulated for optimal brain functioning. In contrast with what was initially assumed brain cholesterol homeostasis can be modulated by extra-cerebral factors. We have found that enhancement of the cholesterol-turnover in the brain by administration of the synthetic activator of liver x receptos (LXRs, T0901317, leads to restoration of memory functions in an AD mouse-model.Memory in C57Bl6NCrl mice was not further improved by the same treatment. Moreover, it was found that in contrast with cholesterol, the structurally very similar dietary derived plant sterols can enter the brain. Plant sterols may be natural activators of LXRs. Evidence is provided suggesting that brassicasterol may be a novel additional biomarker in cerebrospinal fluid of AD patients. Insight into the regulation of cerebral cholesterol homeostasis will provide possibilities to modulate the key steps involved and may lead to the development of therapies for the prevention as well as treatment of neurodegenerative diseases such as AD.

  18. 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

  19. A Healthy Heart May Protect an Aging Brain

    Science.gov (United States)

    ... news/fullstory_157798.html A Healthy Heart May Protect an Aging Brain Study found seniors who met ... of nutritious foods from all the food groups. Limit salt, sugar, saturated fat and trans fat. Lose ...

  20. Relation of Age at Insult to Outcome of Brain Injury

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2009-05-01

    Full Text Available Cognitive and behavioral outcomes for children who sustain early brain insult (EBI were evaluated in relation to age at insult in a study at Royal Children’s Hospital, Victoria, Australia.

  1. Intrinsic Brain Connectivity Related to Age in Young and Middle Aged Adults

    OpenAIRE

    Hampson, Michelle; Tokoglu, Fuyuze; Shen, Xilin; Scheinost, Dustin; Papademetris, Xenophon; Constable, R. Todd

    2012-01-01

    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 re...

  2. 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

  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. 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

  5. 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…

  6. The role of the brain in female reproductive aging

    OpenAIRE

    Downs, Jodi L.; Wise, Phyllis M.

    2008-01-01

    In middle-aged women, follicular depletion is a critical factor mediating the menopausal transition; however, all levels of the hypothalamic-pituitary-gonadal (HPG) axis contribute to the age-related decline in reproductive function. To help elucidate the complex interactions between the ovary and brain during middle-age that lead to the onset of the menopause, we utilize animal models which share striking similarities in reproductive physiology. Our results show that during middle-age, prior...

  7. 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.

  8. 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.

  9. Nutritional Cognitive Neuroscience: Innovations for Healthy Brain Aging

    Science.gov (United States)

    Zamroziewicz, Marta K.; Barbey, Aron K.

    2016-01-01

    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 (NBPs), along with (ii) modern indices of brain health derived from high-resolution magnetic resonance imaging (MRI). 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.

  10. 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.)

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

    International Nuclear Information System (INIS)

    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.)

  12. Influence of Age on Brain Edema Formation, Secondary Brain Damage and Inflammatory Response after Brain Trauma in Mice

    Science.gov (United States)

    Timaru-Kast, Ralph; Luh, Clara; Gotthardt, Philipp; Huang, Changsheng; Schäfer, Michael K.; Engelhard, Kristin; Thal, Serge C.

    2012-01-01

    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 inflammation

  13. 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

  14. Problems in CT diagnosis of the aging brain

    International Nuclear Information System (INIS)

    The different methods of measuring the intracranial CSF spaces on CT images are described. The values obtained are demonstrated to separate the normal aging brain from the brain in senile dementia of Alzheimer's type. The CT criteria for the diagnosis of multiinfarctdementia are shown. The significance of CT studies in senile depression is discussed. The problem of vascular encephalopathy (leukoaraiosis) in normal aging of the brain and in dementia is considered in particular, and even the occurrence of intracranial space-occupying lesions and normal pressure hydrocephalus, as treatable causes of dementia and depression, are mentioned. The data and results of my own CT research on normal brain aging, dementia and depression are presented with reference to the literature. (orig.)

  15. Making sense of literary aging: Relevance of recent gerontological theory.

    Science.gov (United States)

    Hendricks, J; Leedham, C A

    1987-01-01

    Literature provides rich resources for interpretations of the meaning of aging in cross-cultural and historical circumstances. A theoretically informed understanding of such literature should be rooted in contextual understanding of literature as an art form, including considerations of style, genre, intentions of authors, and of audiences; an awareness of perspectives of analysts; and explanatory frameworks drawn from gerontology. Early theories in gerontology focus on the individual level, taking structure as a given. Second generation models-modernization and age stratification-focus on structure excluding the individual. Recent frameworks, namely political economic approaches cognizant of intentionality, and structurally informed social psychological perspectives, address the confluence of individual and structural factors. A hermenutic-dialectical framework incorporates the dynamic interplay between structural factors, individual meaning-giving and action. To illustrate, five brief vignettes from cross-cultural literature are analyzed, drawing on recent gerontological theory. A hermeneutic-dialectical approach to literature provides a forum for debate, research, and theory-building, rather than an overarching model of aging in cross-cultural context. PMID:25195534

  16. Determinants of iron accumulation in the normal aging brain.

    Science.gov (United States)

    Pirpamer, Lukas; Hofer, Edith; Gesierich, Benno; De Guio, François; Freudenberger, Paul; Seiler, Stephan; Duering, Marco; Jouvent, Eric; Duchesnay, Edouard; Dichgans, Martin; Ropele, Stefan; Schmidt, Reinhold

    2016-07-01

    In a recent postmortem study, R2* relaxometry in gray matter (GM) of the brain has been validated as a noninvasive measure for iron content in brain tissue. Iron accumulation in the normal aging brain is a common finding and relates to brain maturation and degeneration. The goal of this study was to assess the determinants of iron accumulation during brain aging. The study cohort consisted of 314 healthy community-dwelling participants of the Austrian Stroke Prevention Study. Their age ranged from 38-82 years. Quantitative magnetic resonance imaging was performed on 3T and included R2* mapping, based on a 3D multi-echo gradient echo sequence. The median of R2* values was measured in all GM regions, which were segmented automatically using FreeSurfer. We investigated 25 possible determinants for cerebral iron deposition. These included demographics, brain volume, lifestyle factors, cerebrovascular risk factors, serum levels of iron, and single nucleotide polymorphisms related to iron regulating genes (rs1800562, rs3811647, rs1799945, and rs1049296). The body mass index (BMI) was significantly related to R2* in 15/32 analyzed brain regions with the strongest correlations found in the amygdala (p = 0.0091), medial temporal lobe (p = 0.0002), and hippocampus (p ≤ 0.0001). Further associations to R2* values were found in deep GM for age and smoking. No significant associations were found for gender, GM volume, serum levels of iron, or iron-associated genetic polymorphisms. In conclusion, besides age, the BMI and smoking are the only significant determinants of brain iron accumulation in normally aging subjects. Smoking relates to iron deposition in the basal ganglia, whereas higher BMI is associated with iron content in the neocortex following an Alzheimer-like distribution. PMID:27255824

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

    DEFF Research Database (Denmark)

    Aanerud, Joel; Borghammer, Per; Chakravarty, M Mallar; Vang, Kim; Rodell, Anders B; Jónsdottir, Kristjana Y; Møller, Arne; Ashkanian, Mahmoud; Vafaee, Manouchehr S; Iversen, Peter; Johannsen, Peter; Gjedde, Albert

    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...

  18. Alzheimer's disease is not "brain aging": neuropathological, genetic, and epidemiological human studies.

    Science.gov (United States)

    Nelson, Peter T; Head, Elizabeth; Schmitt, Frederick A; Davis, Paulina R; Neltner, Janna H; Jicha, Gregory A; Abner, Erin L; Smith, Charles D; Van Eldik, Linda J; Kryscio, Richard J; Scheff, Stephen W

    2011-05-01

    Human studies are reviewed concerning whether "aging"-related mechanisms contribute to Alzheimer's disease (AD) pathogenesis. AD is defined by specific neuropathology: neuritic amyloid plaques and neocortical neurofibrillary tangles. AD pathology is driven by genetic factors related not to aging per se, but instead to the amyloid precursor protein (APP). In contrast to genes involved in APP-related mechanisms, there is no firm connection between genes implicated in human "accelerated aging" diseases (progerias) and AD. The epidemiology of AD in advanced age is highly relevant but deceptively challenging to address given the low autopsy rates in most countries. In extreme old age, brain diseases other than AD approximate AD prevalence while the impact of AD pathology appears to peak by age 95 and decline thereafter. Many distinct brain diseases other than AD afflict older human brains and contribute to cognitive impairment. Additional prevalent pathologies include cerebrovascular disease and hippocampal sclerosis, both high-morbidity brain diseases that appear to peak in incidence later than AD chronologically. Because of these common brain diseases of extreme old age, the epidemiology differs between clinical "dementia" and the subset of dementia cases with AD pathology. Additional aging-associated mechanisms for cognitive decline such as diabetes and synapse loss have been linked to AD and these hypotheses are discussed. Criteria are proposed to define an "aging-linked" disease, and AD fails all of these criteria. In conclusion, it may be most fruitful to focus attention on specific pathways involved in AD rather than attributing it to an inevitable consequence of aging. PMID:21516511

  19. 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...

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

    International Nuclear Information System (INIS)

    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.)

  1. 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.)

  2. 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

  3. 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

  4. Brain dynamics in spider-phobic individuals exposed to phobia-relevant and other emotional stimuli

    OpenAIRE

    Michalowski, Jaroslaw; Melzig, Christiane; Weike, Almut I.; Stockburger, Jessica; Schupp, Harald Thomas; Hamm, Alfons

    2009-01-01

    Dense sensor event-related brain potentials were measured in participants with spider phobia and nonfearful controls during viewing of phobia-relevant spider and standard emotional (pleasant, unpleasant, neutral) pictures. Irrespective of the picture content, spider phobia participants responded with larger P1 amplitudes than controls, suggesting increased vigilance in this group. Furthermore, spider phobia participants showed a significantly enlarged early posterior negativity (EPN) and late...

  5. Reconceptualizing Successful Aging Among Black Women and the Relevance of the Strong Black Woman Archetype

    OpenAIRE

    Baker, Tamara A.; Buchanan, NiCole T.; Mingo, Chivon A.; Roker, Rosalyn; Brown, Candace S

    2014-01-01

    Although there are multiple pathways to successful aging, little is known of what it means to age successfully among black women. There is a growing body of literature suggesting that black women experience a number of social challenges (sexism and racism) that may present as barriers to aging successfully. Applying aspects of the Strong Black Women ideal, into theoretical concepts of successful aging, may be particularly relevant in understanding which factors impair or promote the ability o...

  6. 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.

  7. 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.

  8. Glia and extracellular space in the aging brain

    Czech Academy of Sciences Publication Activity Database

    Syková, Eva

    London : The Parthenon Publishing Group, 2003 - (Genazzani, A.), s. 3-11 ISBN 1-84214-168-6 R&D Projects: GA MŠk LN00A065 Institutional research plan: CEZ:AV0Z5039906; CEZ:MSM 111300004 Keywords : Glia * extracellular space * aging brain Subject RIV: FH - Neurology

  9. 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.

  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. 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.

  12. 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.

  13. 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)

  14. Ketones and brain development: Implications for correcting deteriorating brain glucose metabolism during aging

    Directory of Open Access Journals (Sweden)

    Nugent Scott

    2016-01-01

    Full Text Available Brain energy metabolism in Alzheimer’s disease (AD is characterized mainly by temporo-parietal glucose hypometabolism. This pattern has been widely viewed as a consequence of the disease, i.e. deteriorating neuronal function leading to lower demand for glucose. This review will address deteriorating glucose metabolism as a problem specific to glucose and one that precedes AD. Hence, ketones and medium chain fatty acids (MCFA could be an alternative source of energy for the aging brain that could compensate for low brain glucose uptake. MCFA in the form of dietary medium chain triglycerides (MCT have a long history in clinical nutrition and are widely regarded as safe by government regulatory agencies. The importance of ketones in meeting the high energy and anabolic requirements of the infant brain suggest they may be able to contribute in the same way in the aging brain. Clinical studies suggest that ketogenesis from MCT may be able to bypass the increasing risk of insufficient glucose uptake or metabolism in the aging brain sufficiently to have positive effects on cognition.

  15. 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

    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......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...

  16. The Mechanosensory Lateral Line System Mediates Activation of Socially-Relevant Brain Regions during Territorial Interactions

    Science.gov (United States)

    Butler, Julie M.; Maruska, Karen P.

    2016-01-01

    Animals use multiple senses during social interactions and must integrate this information in the brain to make context-dependent behavioral decisions. For fishes, the largest group of vertebrates, the mechanosensory lateral line system provides crucial hydrodynamic information for survival behaviors, but little is known about its function in social communication. Our previous work using the African cichlid fish, Astatotilapia burtoni, provided the first empirical evidence that fish use their lateral line system to detect water movements from conspecifics for mutual assessment and behavioral choices. It is unknown, however, where this socially-relevant mechanosensory information is processed in the brain to elicit adaptive behavioral responses. To examine for the first time in any fish species which brain regions receive contextual mechanosensory information, we quantified expression of the immediate early gene cfos as a proxy for neural activation in sensory and socially-relevant brain nuclei from lateral line-intact and -ablated fish following territorial interactions. Our in situ hybridization results indicate that in addition to known lateral line processing regions, socially-relevant mechanosensory information is processed in the ATn (ventromedial hypothalamus homolog), Dl (putative hippocampus homolog), and Vs (putative medial extended amygdala homolog). In addition, we identified a functional network within the conserved social decision-making network (SDMN) whose co-activity corresponds with mutual assessment and behavioral choice. Lateral line-intact and –ablated fight winners had different patterns of co-activity of these function networks and group identity could be determined solely by activation patterns, indicating the importance of mechanoreception to co-activity of the SDMN. These data show for the first time that the mechanosensory lateral line system provides relevant information to conserved decision-making centers of the brain during

  17. The Mechanosensory Lateral Line System Mediates Activation of Socially-Relevant Brain Regions during Territorial Interactions.

    Science.gov (United States)

    Butler, Julie M; Maruska, Karen P

    2016-01-01

    Animals use multiple senses during social interactions and must integrate this information in the brain to make context-dependent behavioral decisions. For fishes, the largest group of vertebrates, the mechanosensory lateral line system provides crucial hydrodynamic information for survival behaviors, but little is known about its function in social communication. Our previous work using the African cichlid fish, Astatotilapia burtoni, provided the first empirical evidence that fish use their lateral line system to detect water movements from conspecifics for mutual assessment and behavioral choices. It is unknown, however, where this socially-relevant mechanosensory information is processed in the brain to elicit adaptive behavioral responses. To examine for the first time in any fish species which brain regions receive contextual mechanosensory information, we quantified expression of the immediate early gene cfos as a proxy for neural activation in sensory and socially-relevant brain nuclei from lateral line-intact and -ablated fish following territorial interactions. Our in situ hybridization results indicate that in addition to known lateral line processing regions, socially-relevant mechanosensory information is processed in the ATn (ventromedial hypothalamus homolog), Dl (putative hippocampus homolog), and Vs (putative medial extended amygdala homolog). In addition, we identified a functional network within the conserved social decision-making network (SDMN) whose co-activity corresponds with mutual assessment and behavioral choice. Lateral line-intact and -ablated fight winners had different patterns of co-activity of these function networks and group identity could be determined solely by activation patterns, indicating the importance of mechanoreception to co-activity of the SDMN. These data show for the first time that the mechanosensory lateral line system provides relevant information to conserved decision-making centers of the brain during territorial

  18. 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

  19. Age-related changes in neural functional connectivity and its behavioral relevance

    Directory of Open Access Journals (Sweden)

    Schlee Winfried

    2012-02-01

    Full Text Available Abstract Background Resting-state recordings are characterized by widely distributed networks of coherent brain activations. Disturbances of the default network - a set of regions that are deactivated by cognitive tasks and activated during passive states - have been detected in age-related disorders such as Alzheimer's or Parkinson's disease but alterations in the course of healthy aging still need to be explored. Results Using magnetoencephalography (MEG, the present study investigated how age-related functional resting-state brain connectivity links to cognitive performance in healthy aging in fifty-three participants ranging in age from 18 to 89 years. A beamforming technique was used to reconstruct the brain activity in source space and the interregional coupling was investigated using partial directed coherence (PDC. We found significant age-related alterations of functional resting-state connectivity. These are mainly characterized by reduced information input into the posterior cingulum/precuneus region together with an enhanced information flow to the medial temporal lobe. Furthermore, higher inflow in the medial temporal lobe subsystem was associated with weaker cognitive performance whereas stronger inflow in the posterior cluster was related to better cognitive performance. Conclusion This is the first study to show age-related alterations in subsystems of the resting state network that are furthermore associated with cognitive performance.

  20. 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.

  1. 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

  2. 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

  3. The Effects of Physical Activity, Education, and Body Mass Index on the Aging Brain

    OpenAIRE

    Ho, April J.; Raji, Cyrus A.; Becker, James T.; Lopez, Oscar L.; Kuller, Lewis H.; Hua, Xue; Dinov, Ivo D.; Stein, Jason L; Rosano, Caterina; Toga, Arthur W.; Thompson, Paul M.

    2010-01-01

    Normal human aging is accompanied by progressive brain tissue loss and cognitive decline; however, several factors are thought to influence brain aging. We applied tensor-based morphometry to high-resolution brain MRI scans to determine whether educational level or physical activity was associated with brain tissue volumes in the elderly, particularly in regions susceptible to age-related atrophy. We mapped the 3D profile of brain volume differences in 226 healthy elderly subjects (130F/96M; ...

  4. 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...

  5. 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...

  6. 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

  7. 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...... 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...

  8. 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.

  9. 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

  10. The gender difference in the brain FDG distribution with aging

    International Nuclear Information System (INIS)

    The purpose of this study is to examine the change in brain fluorodeoxyglucose (FDG) distribution with aging. Subjects were 85 men and 116 women who had no mental abnormality and no evidence of cancer in the whole body FDG-positron emission tomography (PET) study for cancer checkup. The brain data were extracted from whole body data, and stratified according to the age: 30-39 (M: 10, F: 18), 40-49 (M: 11, F: 14), 50-59 (M: 10, F: 27), 60-64 (M: 11, F: 13), 65-69 (M: 11, F: 11), 70-74 (M: 11, F: 10), 75-79 (M: 13, F: 11), over 80 (M: 8, F: 12) years. Forties or more male and female stratified age groups were compared with each gender 30's age data using Statistical Parametric Mapping (SPM)2. In the man, the FDG activity of the bilateral temporal and frontal lobes decreased and the decreased domains were expanded with aging. But in the females, the decreased domains were complicated in 40-69 years old. Dynamic changes of sex hormones in the individual female menopause may affect the complicated results in the females. Further studies are needed to confirm it. (author)

  11. 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.

  12. 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

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. NREM sleep oscillations and brain plasticity in aging

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  17. Using autopsy brain tissue to study alcohol-related brain damage in the genomic age.

    Science.gov (United States)

    Sutherland, Greg T; Sheedy, Donna; Kril, Jillian J

    2014-01-01

    The New South Wales Tissue Resource Centre at the University of Sydney, Australia, is one of the few human brain banks dedicated to the study of the effects of chronic alcoholism. The bank was affiliated in 1994 as a member of the National Network of Brain Banks and also focuses on schizophrenia and healthy control tissue. Alcohol abuse is a major problem worldwide, manifesting in such conditions as fetal alcohol syndrome, adolescent binge drinking, alcohol dependency, and alcoholic neurodegeneration. The latter is also referred to as alcohol-related brain damage (ARBD). The study of postmortem brain tissue is ideally suited to determining the effects of long-term alcohol abuse, but it also makes an important contribution to understanding pathogenesis across the spectrum of alcohol misuse disorders and potentially other neurodegenerative diseases. Tissue from the bank has contributed to 330 peer-reviewed journal articles including 120 related to alcohol research. Using the results of these articles, this review chronicles advances in alcohol-related brain research since 2003, the so-called genomic age. In particular, it concentrates on transcriptomic approaches to the pathogenesis of ARBD and builds on earlier reviews of structural changes (Harper et al. Prog Neuropsychopharmacol Biol Psychiatry 2003;27:951) and proteomics (Matsumoto et al. Expert Rev Proteomics 2007;4:539). PMID:24033426

  18. 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.

  19. Reconceptualizing successful aging among black women and the relevance of the strong black woman archetype.

    Science.gov (United States)

    Baker, Tamara A; Buchanan, NiCole T; Mingo, Chivon A; Roker, Rosalyn; Brown, Candace S

    2015-02-01

    Although there are multiple pathways to successful aging, little is known of what it means to age successfully among black women. There is a growing body of literature suggesting that black women experience a number of social challenges (sexism and racism) that may present as barriers to aging successfully. Applying aspects of the Strong Black Women ideal, into theoretical concepts of successful aging, may be particularly relevant in understanding which factors impair or promote the ability of black women to age successfully. The Strong Black Women archetype is a culturally salient ideal prescribing that black women render a guise of self-reliance, selflessness, and psychological, emotional, and physical strength. Although this ideal has received considerable attention in the behavioral sciences, it has been largely absent within the gerontology field. Nevertheless, understanding the dynamics of this cultural ideal may enhance our knowledge while developing an appreciation of the black woman's ability to age successfully. Rather than summarize the social, physical, and mental health literature focusing on health outcomes of black women, this conceptual review examines the Strong Black Women archetype and its application to the lived experiences of black women and contributions to current theories of successful aging. Focusing on successful aging exclusively among black women enhances our understanding of this group by considering their identity as women of color while recognizing factors that dictate their ability to age successfully. PMID:25416685

  20. 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.

  1. Neuroimaging Studies of Normal Brain Development and Their Relevance for Understanding Childhood Neuropsychiatric Disorders

    Science.gov (United States)

    Marsh, Rachel; Gerber, Andrew J.; Peterson, Bradley S.

    2008-01-01

    Neuroimaging findings which identify normal brain development trajectories are presented. Results show that early brain development begins with the neural tube formation and ends with myelintation. How disturbances in brain development patterns are related to childhood psychiatric disorders is examined.

  2. 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.

  3. Forecast of the Chemical Aging and Relevant Color Changes in Painting

    CERN Document Server

    Zilbergleyt, B

    2005-01-01

    The article describes the potential application of thermodynamic simulation to forecast chemical aging and relevant color changes in painting. Qualitative and numerical results were obtained by applying the method to various mixtures of pigments without and with atmospheric components. The results were compared to the legendary recommendations on incompatible pigment mixtures with about an 80 percent match regarding potential color changes in the aged mixtures. Results for the cadmium yellow-lead white and cadmium lemon-emerald green mixtures are illustrated by pictures, gradually showing color changes caused by the aging. The method of thermodynamic simulation can be a powerful tool to investigate old masterpieces, in developing new materials, and to forecast some aspects of the aging of real masterpieces.

  4. White matter lesions of the aging brain visualized on MRI

    International Nuclear Information System (INIS)

    The purpose of this report is to study the relationship between the severity of the white matter lesions (WMLs) and aging. We reviewed 215 subjects (11-88 years of age) referred for MR imaging performed between June 1988 and August 1989 on a 0.5T superconducting MR imager. The spin echo technique of image acquisition was used, with TR 1800 ms and TE 120 ms. All subjects were free from neurological abnormalities. The patterns of MR imaging of the incidental WMLs were divided into four grades; grades 0-3 (grade 0, no lesions; grade 1, lesions confined to one lobe; grade 2, lesions beyond one lobe; grade 3, confluent periventricular lesions). We investigated the relationships among the prevalence of WMLs, the grading of WMLs, age, and hypertension. Furthermore, we analyzed the grading of WMLs in relation to the degree of brain atrophy (bicaudate index) and the prevalence of basal ganglionic lesions. The mean age of grade 0 (n=90), grade 1 (n=36), grade 2 (n=58) and grade 3 (n=31) was 43.4±13.2, 57.3±7.3, 63.5±10.8 and 71.6±8.5. The statistical difference of age between grade 0 and 1 (p160 mmHg) showed higher grading of WMLs than other subjects. There was a statistical difference in the bicaudate index between grade 0 and 2 (p<0.001), and grade 0 and 3 (p<0.001). Of the 89 subjects of grade 2 or 3, 47 (53%) had basal ganglionic and/or thalamic lesions. It was confirmed that WMLs of neurologically healthy subjects significantly correlated with aging. In addition, hypertension accelerated WMLs. (author)

  5. 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

  6. Ego and Spiritual Transcendence: Relevance to Psychological Resilience and the Role of Age

    Directory of Open Access Journals (Sweden)

    Barbara Hanfstingl

    2013-01-01

    Full Text Available The paper investigates different approaches of transcendence in the sense of spiritual experience as predictors for general psychological resilience. This issue is based on the theoretical assumption that resilience does play a role for physical health. Furthermore, there is a lack of empirical evidence about the extent to which spirituality does play a role for resilience. As potential predictors for resilience, ego transcendence, spiritual transcendence, and meaning in life were measured in a sample of 265 people. The main result of a multiple regression analysis is that, in the subsample with people below 29 years, only one rather secular scale that is associated with ego transcendence predicts resilience, whereas for the older subsample of 29 years and above, spiritual transcendence gains both a positive (oneness and timelessness and a negative (spiritual insight relevance to psychological resilience. On the one hand, these results concur with previous studies that also found age-related differences. On the other hand, it is surprising that the MOS spiritual insight predicts psychological resilience negatively, the effect is increasing with age. One possible explanation concerns wisdom research. Here, an adaptive way of dealing with the age-related loss of control is assumed to be relevant to successful aging.

  7. 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.

  8. Predicting healthy older adult's brain age based on structural connectivity networks using artificial neural networks.

    Science.gov (United States)

    Lin, Lan; Jin, Cong; Fu, Zhenrong; Zhang, Baiwen; Bin, Guangyu; Wu, Shuicai

    2016-03-01

    Brain ageing is followed by changes of the connectivity of white matter (WM) and changes of the grey matter (GM) concentration. Neurodegenerative disease is more vulnerable to an accelerated brain ageing, which is associated with prospective cognitive decline and disease severity. Accurate detection of accelerated ageing based on brain network analysis has a great potential for early interventions designed to hinder atypical brain changes. To capture the brain ageing, we proposed a novel computational approach for modeling the 112 normal older subjects (aged 50-79 years) brain age by connectivity analyses of networks of the brain. Our proposed method applied principal component analysis (PCA) to reduce the redundancy in network topological parameters. Back propagation artificial neural network (BPANN) improved by hybrid genetic algorithm (GA) and Levenberg-Marquardt (LM) algorithm is established to model the relation among principal components (PCs) and brain age. The predicted brain age is strongly correlated with chronological age (r=0.8). The model has mean absolute error (MAE) of 4.29 years. Therefore, we believe the method can provide a possible way to quantitatively describe the typical and atypical network organization of human brain and serve as a biomarker for presymptomatic detection of neurodegenerative diseases in the future. PMID:26718834

  9. 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

  10. 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

      Increased oxidative stress in the brain has consistently been implied in ageing and in several degenerative brain disorders. Acting as a pivotal antioxidant in the brain, vitamin C is preferentially retained during deficiency and may play an essential role in neuroprotection during ageing. Thus......, 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...

  11. A clinically relevant model of perinatal global ischemic brain damage in rats.

    Science.gov (United States)

    Yang, Ting; Zhuang, Lei; Terrando, Niccolò; Wu, Xinmin; Jonhson, Mark R; Maze, Mervyn; Ma, Daqing

    2011-04-01

    We have designed a clinically relevant model of perinatal asphyxia providing intrapartum hypoxia in rats. On gestation day 22 SD rats were anesthetized and the uterine horns were exteriorized and placed in a water bath at 37°C for up to 20min. After this, pups were delivered from the uterus and manually stimulated to initiate breathing in an incubator at 37°C for 1 h in air. Brains were harvested and stained with cresyl violet, caspase-3, and TUNEL to detect morphological and apoptotic changes on postnatal days (PND) 1, 3, and 7. Separate cohorts were maintained until PND 50 and tested for learning and memory using Morris water maze (WM). Survival rate was decreased with longer hypoxic time, and 100% mortality was noted when hypoxia time was beyond 18min. Apoptosis was increased with the duration of hypoxia with neuronal loss and cell shrinkage in the CA1 of hippocampus. The time taken for the juveniles to locate the hidden platform during WM was increased in animals subjected to hypoxia. These data demonstrate that perinatal ischemic injury leads to neuronal death in the hippocampus and long-lasting cognitive dysfunction. This model mimics hypoxic ischemic encephalopathy in humans and may be appropriate for investigating therapeutic interventions. PMID:21281606

  12. Identification of Mood-Relevant Brain Connections Using a Continuous, Subject-Driven Rumination Paradigm.

    Science.gov (United States)

    Milazzo, Anna-Clare; Ng, Bernard; Jiang, Heidi; Shirer, William; Varoquaux, Gael; Poline, Jean Baptiste; Thirion, Bertrand; Greicius, Michael D

    2016-03-01

    Rumination, an internal cognitive state characterized by recursive thinking of current self-distress and past negative events, has been found to correlate with the development of depressive disorders. Here, we investigated the feasibility of using connectivity for distinguishing different emotional states induced by a novel free-streaming, subject-driven experimental paradigm. Connectivity between 78 functional regions of interest (ROIs) within 14 large-scale networks and 6 structural ROIs particularly relevant to emotional processing were used for classifying 4 mental states in 19 healthy controls. The 4 mental states comprised: An unconstrained period of mind wandering; a ruminative mental state self-induced by recalling a time of personal disappointment; a euphoric mental state self-induced by recalling what brings the subject joy; and a sequential episodic recollection of the events of the day. A support vector machine achieved accuracies ranging from 89% to 94% in classifying pairs of different mental states. We reported the most significant brain connections that best discriminated these mental states. In particular, connectivity changes involving the amygdala were found to be important for distinguishing the rumination condition from the other mental states. Our results demonstrated that connectivity-based classification of subject-driven emotional states constitutes a novel and effective approach for studying ruminative behavior. PMID:25331601

  13. Gene expression changes in aging Zebrafish (Danio rerio) brains are sexually dimorphic

    OpenAIRE

    Arslan-Ergul, Ayca; Adams, Michelle M

    2014-01-01

    Background Brain aging is a multi-factorial process due to both genetic and environmental factors. The zebrafish has recently become a popular model organism for examining aging and age-related diseases because as in humans they age gradually and exhibit cognitive decline. Few studies have examined the biological changes in the aging brain that may contribute to these declines and none have examined them within individuals with respect to gender. Our aim was to identify the main genetic pathw...

  14. 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...

  15. The brain as a system of nested but partially overlapping networks. Heuristic relevance of the model for brain physiology and pathology.

    Science.gov (United States)

    Agnati, L F; Guidolin, D; Fuxe, K

    2007-01-01

    A new model of the brain organization is proposed. The model is based on the assumption that a global molecular network enmeshes the entire central nervous system. Thus, brain extra-cellular and intra-cellular molecular networks are proposed to communicate at the level of special plasma membrane regions (e.g., the lipid rafts) where horizontal molecular networks can represent input/output regions allowing the cell to have informational exchanges with the extracellular environment. Furthermore, some "pervasive signals" such as field potentials, pressure waves and thermal gradients that affect large parts of the brain cellular and molecular networks are discussed. Finally, at least two learning paradigms are analyzed taking into account the possible role of Volume Transmission: the so-called model of "temporal difference learning" and the "Turing B-unorganised machine". The relevance of this new view of brain organization for a deeper understanding of some neurophysiological and neuropathological aspects of its function is briefly discussed. PMID:16906353

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

    Directory of Open Access Journals (Sweden)

    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.

  17. A scoping review of anorexia of aging correlates and their relevance to population health interventions.

    Science.gov (United States)

    Roy, Mathieu; Gaudreau, Pierrette; Payette, Hélène

    2016-10-01

    Anorexia of aging (AA, i.e., loss of appetite and/or reduction of food intake with aging) is an important public health issue. It leads to unintentional weight loss, which is an independent risk factor for morbidity and mortality among seniors. AA has mainly been studied from a biological perspective and regarded as a normal physiological consequence of aging, rather than a negative health outcome with underlying determinants. Some potentially modifiable correlates have however been found to be associated with this geriatric condition. Here, we conducted a scoping review of the literature to: 1) identify AA correlates, and 2) discuss their relevance to population health interventions. Our results indicate two main categories of AA correlates, namely, physiopathological and non-physiopathological. The first category relates to physiological dysfunctions, pathologies involving (or culminating in) biomarker dysregulation, and polypharmacy. These correlates are difficult to modify, especially through population health interventions. The second category, which contains fewer correlates, includes potentially modifiable public health targets, such as food-related properties, psychological, sociocultural, and environmental issues. We conclude that there are several AA correlates. Some of them are modifiable and could be targeted for development and implementation as appropriate population health interventions to prevent appetite loss and promote maintenance of adequate food intake in aging. PMID:27374898

  18. Gene Risk Factors for Age-Related Brain Disorders May Affect Immune System Function

    Science.gov (United States)

    ... factors for age-related brain disorders may affect immune system function June 17, 2014 Scientists have discovered gene ... risk factors for age-related neurological disorders to immune system functions, such as inflammation, offers new insights into ...

  19. Multiple Brain Markers are Linked to Age-Related Variation in Cognition.

    Science.gov (United States)

    Hedden, Trey; Schultz, Aaron P; Rieckmann, Anna; Mormino, Elizabeth C; Johnson, Keith A; Sperling, Reisa A; Buckner, Randy L

    2016-04-01

    Age-related alterations in brain structure and function have been challenging to link to cognition due to potential overlapping influences of multiple neurobiological cascades. We examined multiple brain markers associated with age-related variation in cognition. Clinically normal older humans aged 65-90 from the Harvard Aging Brain Study (N = 186) were characterized on a priori magnetic resonance imaging markers of gray matter thickness and volume, white matter hyperintensities, fractional anisotropy (FA), resting-state functional connectivity, positron emission tomography markers of glucose metabolism and amyloid burden, and cognitive factors of processing speed, executive function, and episodic memory. Partial correlation and mediation analyses estimated age-related variance in cognition shared with individual brain markers and unique to each marker. The largest relationships linked FA and striatum volume to processing speed and executive function, and hippocampal volume to episodic memory. Of the age-related variance in cognition, 70-80% was accounted for by combining all brain markers (but only ∼20% of total variance). Age had significant indirect effects on cognition via brain markers, with significant markers varying across cognitive domains. These results suggest that most age-related variation in cognition is shared among multiple brain markers, but potential specificity between some brain markers and cognitive domains motivates additional study of age-related markers of neural health. PMID:25316342

  20. 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.)

  1. 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.)

  2. Relevance of PTEN loss in brain metastasis formation in breast cancer patients.

    OpenAIRE

    Wikman, Harriet; Lamszus, Katrin; Detels, Niclas; Uslar, Liubov; Wrage, Michaela; Benner, Christian; Hohensee, Ina; Ylstra, Bauke; Eylmann, Kathrin; Zapatka, Marc; Sauter, Guido; Kemming, Dirk; Glatzel, Markus; Müller, Volkmar; Westphal, Manfred

    2012-01-01

    Introduction With the improvement of therapeutic options for the treatment of breast cancer, the development of brain metastases has become a major limitation to life expectancy in many patients. Therefore, our aim was to identify molecular markers associated with the development of brain metastases in breast cancer. Methods Patterns of chromosomal aberrations in primary breast tumors and brain metastases were compared with array-comparative genetic hybridization (CGH). The most significant r...

  3. 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

  4. The Process of Human Aging and Involution Changes in the Brain

    OpenAIRE

    Łęt, Paweł; Szabela, Anna Polak; Porzych, Katarzyna

    2013-01-01

    The aging process and systemic changes occurring in it have an impact on the brain. Commonly observed symptoms of an old age such as cognitive impairment and slowness of movement are the illustration of the changes in the brain. These changes are for brain structure, quantities of neurotransmitters and hormonal activity. We can partially modify the time and the dynamics of the development of evolutional changes through an appropriate preventive action.

  5. 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.

  6. Brain Na+, K+-ATPase Activity In Aging and Disease

    Science.gov (United States)

    de Lores Arnaiz, Georgina Rodríguez; Ordieres, María Graciela López

    2014-01-01

    , enzyme changes in diverse neurological diseases as well as during aging, have been summarized. Issues refer mainly to Na+, K+-ATPase studies in ischemia, brain injury, depression and mood disorders, mania, stress, Alzheimer´s disease, learning and memory, and neuronal hyperexcitability and epilepsy. PMID:25018677

  7. 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...

  8. Perspectives on Creating Clinically Relevant Blast Models for Mild Traumatic Brain Injury and Post Traumatic Stress Disorder Symptoms

    OpenAIRE

    Lisa eBrenner; Nazanin eBahraini; Hernández, Theresa D.

    2012-01-01

    Military personnel are returning from Iraq and Afghanistan and reporting non-specific physical (somatic), behavioral, psychological, and cognitive symptoms. Many of these symptoms are frequently associated with mild traumatic brain injury (mTBI) and/or post traumatic stress disorder (PTSD). Despite significant attention and advances in assessment and intervention for these two conditions, challenges persist. To address this, clinically relevant blast models are essential in the full character...

  9. 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

  10. Age-dependent expression of VEGFR2 in deep brain arteries in small vessel disease, CADASIL, and healthy brains.

    Science.gov (United States)

    Ahmed-Jushuf, Fiyyaz; Jiwa, Nadim S; Arwani, Anum S; Foot, Peter; Bridges, Leslie R; Kalaria, Raj N; Esiri, Margaret M; Hainsworth, Atticus H

    2016-06-01

    Vascular myocytes are central to brain aging. Small vessel disease (SVD; arteriolosclerosis) is a widespread cause of lacunar stroke and vascular dementia and is characterized by fibrosis and depletion of vascular myocytes in small penetrating arteries. Vascular endothelial growth factor (VEGF) is associated with brain aging, and Immunolabeling for vascular endothelial growth factor receptor 2 (VEGFR2) is a potent determinant of cell fate. Here, we tested whether VEGFR2 in vascular myocytes is associated with older age and SVD in human brain. Immunolabeling for VEGFR2 in deep gray matter was assessed in older people with or without moderate-severe SVD or in younger people without brain pathology or with a monogenic form of SVD (Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy). All cases were without Alzheimer's disease pathology. Myocyte VEGFR2 was associated with increasing age (p = 0.0026) but not with SVD pathology or with sclerotic index or blood vessel density. We conclude that VEGFR2 is consistently expressed in small artery myocytes of older people and may mediate effects of VEGF on brain vascular aging. PMID:27143427

  11. 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) ...

  12. 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

  13. Sources of Electrical Brain Activity Most Relevant to Performance of Brain-Computer Interface Based on Motor Imagery

    Czech Academy of Sciences Publication Activity Database

    Frolov, A.; Húsek, Dušan; Bobrov, P.; Mokienko, O.; Tintěra, J.

    Rijeka: InTech, 2013 - (Fazel-Rezai, R.), s. 175-193 ISBN 978-953-51-1134-4 R&D Projects: GA ČR GAP202/10/0262 Grant ostatní: GA MŠk(CZ) ED1.1.00/02.0070 Institutional support: RVO:67985807 Keywords : brain computer interface * BCI * EEG * fMRI * signal separation * inverse EEG task Subject RIV: IN - Informatics, Computer Science

  14. 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

    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......-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....

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

    OpenAIRE

    Katja Franke; Michael Ristow

    2014-01-01

    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 estim...

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

    OpenAIRE

    Franke, Katja; Ristow, Michael; Gaser, Christian

    2014-01-01

    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 used 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 estim...

  17. Allele-Skewed DNA Modification in the Brain: Relevance to a Schizophrenia GWAS.

    Science.gov (United States)

    Gagliano, Sarah A; Ptak, Carolyn; Mak, Denise Y F; Shamsi, Mehrdad; Oh, Gabriel; Knight, Joanne; Boutros, Paul C; Petronis, Arturas

    2016-05-01

    Numerous recent studies have suggested that phenotypic effects of DNA sequence variants can be mediated or modulated by their epigenetic marks, such as allele-skewed DNA modification (ASM). Using Affymetrix SNP microarrays, we performed a comprehensive search of ASM effects in human post-mortem brain and sperm samples (total n = 256) from individuals with major psychosis and control individuals. Depending on the phenotypic category of the brain samples, 1.4%-7.5% of interrogated SNPs exhibited ASM effects. Next, we investigated ASM in the context of genetic studies of schizophrenia and detected that brain ASM SNPs were significantly overrepresented among sub-threshold SNPs from a schizophrenia genome-wide association study (GWAS). Brain ASM SNPs showed a much stronger enrichment in a schizophrenia GWAS than in 17 large GWASs of non-psychiatric diseases and traits, arguing that ASM effects are at least partially tissue specific. Studies of germline and control brain ASM SNPs supported a causal association between ASM and schizophrenia. Finally, significantly higher proportions of ASM SNPs than of non-ASM SNPs were detected at loci exhibiting epigenetic signatures of enhancers and promoters, and they were overrepresented within transcription factor binding regions and DNase I hypersensitive sites. All of these findings collectively indicate that ASM SNPs should be prioritized in follow-up GWASs. PMID:27087318

  18. 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

  19. 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. ...

  20. 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.

  1. PROFOUND AND SEXUALLY DIMORPHIC EFFECTS OF CLINICALLY-RELEVANT LOW DOSE SCATTER IRRADIATION ON THE BRAIN AND BEHAVIOR

    Directory of Open Access Journals (Sweden)

    Anna eKovalchuk

    2016-06-01

    Full Text Available Irradiated cells can signal damage and distress to both close and distant neighbors that have not been directly exposed to the radiation (naïve bystanders. While studies have shown that such bystander effects occur in the shielded brain of animals upon body irradiation, their mechanism remains unexplored. Observed effects may be caused by some blood-borne factors; however they may also be explained, at least in part, by very small direct doses received by the brain that result from scatter or leakage. In order to establish the roles of low doses of scatter irradiation in the brain response, we developed a new model for scatter irradiation analysis whereby one rat was irradiated directly at the liver and the second rat was placed adjacent to the first and received a scatter dose to its body and brain. This work focuses specifically on the response of the latter rat brain to the low scatter irradiation dose. Here, we provide the first experimental evidence that very low, clinically relevant doses of scatter irradiation alter gene expression, induce changes in dendritic morphology, and lead to behavioral deficits in exposed animals. The results showed that exposure to radiation doses as low as 0.115 cGy caused changes in gene expression and reduced spine density, dendritic complexity, and dendritic length in the prefrontal cortex tissues of females, but not males. In the hippocampus, radiation altered neuroanatomical organization in males, but not in females. Moreover, low dose radiation caused behavioral deficits in the exposed animals. This is the first study to show that low dose scatter irradiation influences the brain and behavior in a sex-specific way.

  2. 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.

  3. Clinically Relevant Pharmacological Strategies That Reverse MDMA-Induced Brain Hyperthermia Potentiated by Social Interaction.

    Science.gov (United States)

    Kiyatkin, Eugene A; Ren, Suelynn; Wakabayashi, Ken T; Baumann, Michael H; Shaham, Yavin

    2016-01-01

    MDMA-induced hyperthermia is highly variable, unpredictable, and greatly potentiated by the social and environmental conditions of recreational drug use. Current strategies to treat pathological MDMA-induced hyperthermia in humans are palliative and marginally effective, and there are no specific pharmacological treatments to counteract this potentially life-threatening condition. Here, we tested the efficacy of mixed adrenoceptor blockers carvedilol and labetalol, and the atypical antipsychotic clozapine, in reversing MDMA-induced brain and body hyperthermia. We injected rats with a moderate non-toxic dose of MDMA (9 mg/kg) during social interaction, and we administered potential treatment drugs after the development of robust hyperthermia (>2.5 °C), thus mimicking the clinical situation of acute MDMA intoxication. Brain temperature was our primary focus, but we also simultaneously recorded temperatures from the deep temporal muscle and skin, allowing us to determine the basic physiological mechanisms of the treatment drug action. Carvedilol was modestly effective in attenuating MDMA-induced hyperthermia by moderately inhibiting skin vasoconstriction, and labetalol was ineffective. In contrast, clozapine induced a marked and immediate reversal of MDMA-induced hyperthermia via inhibition of brain metabolic activation and blockade of skin vasoconstriction. Our findings suggest that clozapine, and related centrally acting drugs, might be highly effective for reversing MDMA-induced brain and body hyperthermia in emergency clinical situations, with possible life-saving results. PMID:26105141

  4. Sexual differentiation of the human brain: relevance for gender identity, transsexualism and sexual orientation.

    NARCIS (Netherlands)

    Swaab, D.F.

    2004-01-01

    Male sexual differentiation of the brain and behavior are thought, on the basis of experiments in rodents, to be caused by androgens, following conversion to estrogens. However, observations in human subjects with genetic and other disorders show that direct effects of testosterone on the developing

  5. 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.

  6. 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...

  7. 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.

  8. 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 ...

  9. 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 ...

  10. 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 ...

  11. 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.

  12. 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

  13. Age-related changes in regional cerebral blood flow and brain volume in healthy subjects

    International Nuclear Information System (INIS)

    Using the xenon-133 inhalation method, we studied the age-related decline in regional cerebral blood flow, calculated as the initial slope index (ISI), in neurologically normal subjects without any risk factors for cerebral arteriosclerosis (154 men and 123 women), ranging in age from 19 to 88 years. The decline in the ISI was rapid in younger age groups and gradual in older age groups. The ISI was higher in women than in men older than 40 years. Using computed tomography, we studied the age-related decline in brain volume index (BVI; 100% X brain volume/cranial cavity volume) in neurologically normal subjects without any risk factors for cerebral arteriosclerosis (92 men and 49 women), ranging in age from 37 to 86 years. The decline in the BVI was gradual in younger age groups and rapid in older age groups. The BVI was higher in women than in men older than 60 years

  14. Perspectives on creating clinically relevant blast models for mild traumatic brain injury and post traumatic stress disorder symptoms

    Directory of Open Access Journals (Sweden)

    Lisa eBrenner

    2012-03-01

    Full Text Available Military personnel are returning from Iraq and Afghanistan and reporting non-specific physical (somatic, behavioral, psychological, and cognitive symptoms. Many of these symptoms are frequently associated with mild traumatic brain injury (mTBI and/or post traumatic stress disorder (PTSD. Despite significant attention and advances in assessment and intervention for these two conditions, challenges persist. To address this, clinically relevant blast models are essential in the full characterization of this type of injury, as well as in the testing and identification of potential treatment strategies. In this publication, existing diagnostic challenges and current treatment practices for mTBI and/or PTSD will be summarized, along with suggestions regarding how what has been learned from existing models of PTSD and traditional mechanism (e.g., non-blast TBI can be used to facilitate the development of clinically relevant blast models.

  15. Brain structure and joint hypermobility: relevance to the expression of psychiatric symptoms

    OpenAIRE

    Jessica A Eccles; Beacher, Felix D. C.; Gray, Marcus A.; Jones, Catherine L.; Minati, Ludovico; Harrison, Neil A.; Hugo D. Critchley

    2012-01-01

    Joint hypermobility is overrepresented among people with anxiety and can be associated with abnormal autonomic reactivity. We tested for associations between regional cerebral grey matter and hypermobility in 72 healthy volunteers using voxel-based morphometry of structural brain scans. Strikingly, bilateral amygdala volume distinguished those with from those without hypermobility. The hypermobility group scored higher for interoceptive sensitivity yet were not significantly more anxious. Our...

  16. Transport and metabolism at blood-brain interfaces and in neural cells: relevance to bilirubin-induced encephalopathy

    Directory of Open Access Journals (Sweden)

    Silvia eGazzin

    2012-05-01

    Full Text Available Bilirubin, the end-product of heme catabolism, circulates in non pathological plasma mostly as a protein-bound species. When bilirubin concentration builds up, the free fraction of the molecule increases. Unbound bilirubin then diffuses across blood-brain interfaces into the brain, where it accumulates and exerts neurotoxic effects. In this classical view of bilirubin neurotoxicity, blood-brain interfaces act merely as structural barriers impeding the penetration of the pigment-bound carrier protein, and neural cells are considered as passive targets of its toxicity. Yet, the role of blood-brain interfaces in the occurrence of bilirubin encephalopathy appears more complex than being simple barriers to the diffusion of bilirubin, and neural cells such as astrocytes and neurons can play an active role in controlling the balance between the neuroprotective and neurotoxic effects of bilirubin. This article reviews the emerging in vivo and in vitro data showing that transport and metabolic detoxification mechanisms at the blood-brain and blood-CSF barriers may modulate bilirubin flux across both cellular interfaces, and that these protective functions can be affected in chronic hyperbilirubinemia. Then the in vivo and in vitro arguments in favor of the physiological antioxidant function of intracerebral bilirubin are presented, as well as with the potential role of transporters such as ABCC-1 and metabolizing enzymes such as cytochromes P-450 in setting the cerebral cell- and structure-specific toxicity of bilirubin following hyperbilirubinemia. The relevance of these data to the pathophysiology of bilirubin-induced neurological diseases is discussed.

  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. 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.

  19. 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)

  20. Brain-Skin Connection: Stress, Inflammation and Skin Aging

    OpenAIRE

    Chen, Ying; Lyga, John

    2014-01-01

    The intricate relationship between stress and skin conditions has been documented since ancient times. Recent clinical observations also link psychological stress to the onset or aggravation of multiple skin diseases. However, the exact underlying mechanisms have only been studied and partially revealed in the past 20 years or so. In this review, the authors will discuss the recent discoveries in the field of “Brain-Skin Connection”, summarizing findings from the overlapping fields of psychol...

  1. Role of Microfluidics in Blood-Brain Barrier Permeability Cell Culture Modeling: Relevance to CNS Disorders.

    Science.gov (United States)

    Rusanov, Alexander L; Luzgina, Natalia G; Barreto, George E; Aliev, Gjumrakch

    2016-01-01

    In vitro modeling of the human blood-brain barrier (BBB) is critical for pre-clinical evaluation and predicting the permeability of newly developed potentially neurotoxic and neurotrophic drugs. Here we summarize the specific structural and functional features of endothelial cells as a key component of the BBB and compare analysis of different cell culture models in reflecting these features. Particular attention is paid to cellular models of the BBB in microfluidic devices capable of circulating nutrient media to simulate the blood flow of the brain. In these conditions, it is possible to reproduce a number of factors affecting endothelial cells under physiological conditions, including shear stress. In comparison with static cell models, concentration gradients, which determine the velocity of transport of substances, reproduce more accurately conditions of nutrient medium flow, since they eliminate the accumulation of substances near the basal membrane of cells, not typical for the situation in vivo. Co-cultivation of different types of cells forming the BBB, in separate cell chambers connected by microchannels, allows to evaluate the mutual influences of cells under normal conditions and when exposed to the test substance. New experimental possibilities that can be achieved through modeling of BBB in microfluidic devices determine the feasibility of their use in the practice for pre-clinical studies of novel drugs against neurodegenerative diseases. PMID:26831260

  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. Using autopsy brain tissue to study alcohol-related brain damage in the genomic age

    OpenAIRE

    Sutherland, Greg T.; Sheedy, Donna; Kril, Jillian J.

    2013-01-01

    The New South Wales Tissue Resource Centre (NSW TRC) at the University of Sydney, Australia is one of the few human brain banks dedicated to the study of the effects of chronic alcoholism. The bank was affiliated in 1994 as a member of the National Network of Brain Banks and also focuses on schizophrenia and healthy control tissue. Alcohol abuse is a major problem worldwide, manifesting in such conditions as fetal alcohol syndrome, adolescent binge drinking, alcohol dependency and alcoholic n...

  4. CONCENTRATION OF GLIAL FIBRILLARY ACIDIC PROTEIN INCREASES WITH AGE IN THE MOUSE AND RAT BRAIN

    Science.gov (United States)

    The role of aging in the expression of the astrocyte protein, glial fibrillary acidic protein (GFAP), was examined. n both mice and rats the concentration of GFAP increased throughout the brain as a function of aging. he largest increase (2-fold) was observed in striatum for both...

  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. 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...

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

    Directory of Open Access Journals (Sweden)

    Lars Bäckman

    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.

  8. Lifetime stress accelerates epigenetic aging in an urban, African American cohort: relevance of glucocorticoid signaling

    OpenAIRE

    Zannas, A.; Arloth, J.; Carrillo Roa, T.; Iurato, S.; Roeh, S.; Ressler, K; Nemeroff, C.; Smith, A.; Bradley, B; Heim, C; Menke, A.; Lange, J; Brueckl, T.; Ising, M; Wray, N.

    2015-01-01

    Background Chronic psychological stress is associated with accelerated aging and increased risk for aging-related diseases, but the underlying molecular mechanisms are unclear. Results We examined the effect of lifetime stressors on a DNA methylation-based age predictor, epigenetic clock. After controlling for blood cell-type composition and lifestyle parameters, cumulative lifetime stress, but not childhood maltreatment or current stress alone, predicted accelerated epigenetic aging in an ur...

  9. Dopamine D1-D2 receptor heteromer signaling pathway in the brain: emerging physiological relevance

    Directory of Open Access Journals (Sweden)

    Hasbi Ahmed

    2011-06-01

    Full Text Available Abstract Dopamine is an important catecholamine neurotransmitter modulating many physiological functions, and is linked to psychopathology of many diseases such as schizophrenia and drug addiction. Dopamine D1 and D2 receptors are the most abundant dopaminergic receptors in the striatum, and although a clear segregation between the pathways expressing these two receptors has been reported in certain subregions, the presence of D1-D2 receptor heteromers within a unique subset of neurons, forming a novel signaling transducing functional entity has been shown. Recently, significant progress has been made in elucidating the signaling pathways activated by the D1-D2 receptor heteromer and their potential physiological relevance.

  10. HZE particle effects in the mammalian brain: relevance to manned space flight

    International Nuclear Information System (INIS)

    The brain of rodents has been studied following high LET neon particle irradiation with doses ranging from 10 to 1000 rad. The changes observed by light microscopy after 1000 rad irradiation, for example, include acute necrosis of interstitial cells within 36 h of exposure, necrotic neurons, hyperchromatic neuroglia, and axonal degeneration beginning at 3 months postexposure. These changes are compared with those reported following exposure to other radiation modalities. Neuronal necrosis following high LET argon particle irradiation was comparable to that with neon. Low doses (25 rad and below) of iron nuclei resulted in no visible necrotic nerve cells. Acute neuroglial cell loss or damage is discussed as to its possible role in chronic neuronal necrosis and in loss of axonal integrity

  11. Differences between chronological and brain age are related to education and self-reported physical activity.

    Science.gov (United States)

    Steffener, Jason; Habeck, Christian; O'Shea, Deirdre; Razlighi, Qolamreza; Bherer, Louis; Stern, Yaakov

    2016-04-01

    This study investigated the relationship between education and physical activity and the difference between a physiological prediction of age and chronological age (CA). Cortical and subcortical gray matter regional volumes were calculated from 331 healthy adults (range: 19-79 years). Multivariate analyses identified a covariance pattern of brain volumes best predicting CA (R(2) = 47%). Individual expression of this brain pattern served as a physiologic measure of brain age (BA). The difference between CA and BA was predicted by education and self-report measures of physical activity. Education and the daily number of flights of stairs climbed (FOSC) were the only 2 significant predictors of decreased BA. Effect sizes demonstrated that BA decreased by 0.95 years for each year of education and by 0.58 years for 1 additional FOSC daily. Effects of education and FOSC on regional brain volume were largely driven by temporal and subcortical volumes. These results demonstrate that higher levels of education and daily FOSC are related to larger brain volume than predicted by CA which supports the utility of regional gray matter volume as a biomarker of healthy brain aging. PMID:26973113

  12. Reward expectation regulates brain responses to task-relevant and task-irrelevant emotional words: ERP evidence.

    Science.gov (United States)

    Wei, Ping; Wang, Di; Ji, Liyan

    2016-02-01

    We investigated the effect of reward expectation on the processing of emotional words in two experiments using event-related potentials (ERPs). A cue indicating the reward condition of each trial (incentive vs non-incentive) was followed by the presentation of a negative or neutral word, the target. Participants were asked to discriminate the emotional content of the target word in Experiment 1 and to discriminate the color of the target word in Experiment 2, rendering the emotionality of the target word task-relevant in Experiment 1, but task-irrelevant in Experiment 2. The negative bias effect, in terms of the amplitude difference between ERPs for negative and neutral targets, was modulated by the task-set. In Experiment 1, P31 and early posterior negativity revealed a larger negative bias effect in the incentive condition than that in the non-incentive condition. However, in Experiment 2, P31 revealed a diminished negative bias effect in the incentive condition compared with that in the non-incentive condition. These results indicate that reward expectation improves top-down attentional concentration to task-relevant information, with enhanced sensitivity to the emotional content of target words when emotionality is task-relevant, but with reduced differential brain responses to emotional words when their content is task-irrelevant. PMID:26245838

  13. 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

  14. 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.

  15. A New Glucocorticoid Hypothesis of Brain Aging: Implications for Alzheimer’s Disease

    OpenAIRE

    Landfield, Philip W; Blalock, Eric M.; Chen, Kuey-Chu; Porter, Nada M.

    2007-01-01

    The original glucocorticoid (GC) hypothesis of brain aging and Alzheimer’s disease proposed that chronic exposure to GCs promotes hippocampal aging and AD. This proposition arose from a study correlating increasing plasma corticosterone with hippocampal astrocyte reactivity in aging rats. Numerous subsequent studies have found evidence consistent with this hypothesis, in animal models and in humans. However, several results emerged that were inconsistent with the hypothesis, highlighting the ...

  16. 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 ...

  17. Forecasting Age-Specific Brain Cancer Mortality Rates Using Functional Data Analysis Models

    OpenAIRE

    Pokhrel, Keshav P.; Tsokos, Chris P.

    2015-01-01

    Incidence and mortality rates are considered as a guideline for planning public health strategies and allocating resources. We apply functional data analysis techniques to model age-specific brain cancer mortality trend and forecast entire age-specific functions using exponential smoothing state-space models. The age-specific mortality curves are decomposed using principal component analysis and fit functional time series model with basis functions. Nonparametric smoothing methods are used to...

  18. 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.

  19. Early Brain Response to Low-Dose Radiation Exposure Involves Molecular Networks and Pathways Associated with Cognitive Functions, Advanced Aging and Alzheimer's Disease

    International Nuclear Information System (INIS)

    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 -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

  20. 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...

  1. Brain response during the M170 time interval is sensitive to socially relevant information.

    Science.gov (United States)

    Arviv, Oshrit; Goldstein, Abraham; Weeting, Janine C; Becker, Eni S; Lange, Wolf-Gero; Gilboa-Schechtman, Eva

    2015-11-01

    Deciphering the social meaning of facial displays is a highly complex neurological process. The M170, an event related field component of MEG recording, like its EEG counterpart N170, was repeatedly shown to be associated with structural encoding of faces. However, the scope of information encoded during the M170 time window is still being debated. We investigated the neuronal origin of facial processing of integrated social rank cues (SRCs) and emotional facial expressions (EFEs) during the M170 time interval. Participants viewed integrated facial displays of emotion (happy, angry, neutral) and SRCs (indicated by upward, downward, or straight head tilts). We found that the activity during the M170 time window is sensitive to both EFEs and SRCs. Specifically, highly prominent activation was observed in response to SRC connoting dominance as compared to submissive or egalitarian head cues. Interestingly, the processing of EFEs and SRCs appeared to rely on different circuitry. Our findings suggest that vertical head tilts are processed not only for their sheer structural variance, but as social information. Exploring the temporal unfolding and brain localization of non-verbal cues processing may assist in understanding the functioning of the social rank biobehavioral system. PMID:26423664

  2. Neuroendocrine modulation of the "menopause": insights into the aging brain.

    Science.gov (United States)

    Wise, P M

    1999-12-01

    The menopause marks the permanent end of fertility in women. It was once thought that this dramatic physiological change could be explained simply by the exhaustion of the reservoir of ovarian follicles. New data from studies performed in women and animal models make us reassess this assumption. An increasing body of evidence suggests that there are multiple pacemakers that contribute to the transition to irregular cycles, decreasing fertility, and the timing of the menopause. We will present evidence that lends credence to the possibility that a dampening and desynchronization of the precisely orchestrated neural signals lead to miscommunication between the brain and the pituitary-ovarian axis, and that this constellation of hypothalamic-pituitary-ovarian events leads to the deterioration of regular cyclicity and heralds menopausal transition. PMID:10600782

  3. 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

  4. 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

  5. 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...

  6. 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...

  7. Metabolism of choline in brain of the aged CBF-1 mouse

    International Nuclear Information System (INIS)

    In order to quantify the changes that occur in the cholinergic central nervous system with aging, we have compared acetylcholine (Ach) formation in brain cortex slice preparations from 2-year-old aged CBF-1 mouse brains and compared the findings with those in 2-4-month-old young adult mouse brain slices. Incorporation of exogenous radioactively labelled choline (31 nM [3H] choline) into acetyl choline in incubated brain slices was linear with time for 90 min. Percentage of total choline label distributed into Ach remained constant from 5 min after starting the incubation to 90 min. In contrast, distribution of label into intracellular free choline (Ch) and phosphorylcholine (Pch) changed continuously over this period suggesting that the Ch pool for Ach synthesis in brain cortex is different from that for Pch synthesis. Incorporation of radioactivity into Ach was not influenced by administration of 10 microM eserine, showing that the increment of radioactivity in Ach reflects rate of Ach formation, independently from degradation by acetylcholine esterases. Under our experimental conditions, slices from cortices of aged 24-month-old mouse brain showed a significantly greater (27%) incorporation of radioactivity into intracellular Ach than those from young, 2-4-month-old, brain cortices. Inhibitors of Ach release, 1 mM ATP or GABA, had no effect. Since concentration of radioactive precursor in the incubation medium was very low (31 nM), the Ch pool for Ach synthesis in slices was labelled without measurably changing the size of the endogenous pool. These data suggest a compensatory acceleration of Ach synthesis or else a smaller precursor pool specific for Ach synthesis into which labelled Ch migrated in aged brain

  8. 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,...

  9. 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...

  10. 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 ...

  11. 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

  12. 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)

  13. 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.

  14. 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

  15. Designing psychological co-research of emancipatory-technical relevance across age thresholds

    DEFF Research Database (Denmark)

    Chimirri, Niklas Alexander

    2015-01-01

    difficult to tackle in research projects that engage in co-research with young children: How can a researcher ensure that the young children s-he works together with benefit from the research project? Based on the critical analysis of an earlier research project implemented by the author, the contribution...... at hand suggests that PSS’ foundational notion of emancipatory relevance needs to be revisited. It argues that if a research project is to sustainably benefit young co-researchers, the technical relevance of the expected mutual emancipation should as well be explicitly considered in the project...

  16. Sustained spatial attention to vibrotactile stimulation in the flutter range: relevant brain regions and their interaction.

    Directory of Open Access Journals (Sweden)

    Dominique Goltz

    Full Text Available The present functional magnetic resonance imaging (fMRI study was designed to get a better understanding of the brain regions involved in sustained spatial attention to tactile events and to ascertain to what extent their activation was correlated. We presented continuous 20 Hz vibrotactile stimuli (range of flutter concurrently to the left and right index fingers of healthy human volunteers. An arrow cue instructed subjects in a trial-by-trial fashion to attend to the left or right index finger and to detect rare target events that were embedded in the vibrotactile stimulation streams. We found blood oxygen level-dependent (BOLD attentional modulation in primary somatosensory cortex (SI, mainly covering Brodmann area 1, 2, and 3b, as well as in secondary somatosensory cortex (SII, contralateral to the to-be-attended hand. Furthermore, attention to the right (dominant hand resulted in additional BOLD modulation in left posterior insula. All of the effects were caused by an increased activation when attention was paid to the contralateral hand, except for the effects in left SI and insula. In left SI, the effect was related to a mixture of both a slight increase in activation when attention was paid to the contralateral hand as well as a slight decrease in activation when attention was paid to the ipsilateral hand (i.e., the tactile distraction condition. In contrast, the effect in left posterior insula was exclusively driven by a relative decrease in activation in the tactile distraction condition, which points to an active inhibition when tactile information is irrelevant. Finally, correlation analyses indicate a linear relationship between attention effects in intrahemispheric somatosensory cortices, since attentional modulation in SI and SII were interrelated within one hemisphere but not across hemispheres. All in all, our results provide a basis for future research on sustained attention to continuous vibrotactile stimulation in the range

  17. Brain white matter structure and information processing speed in healthy older age.

    Science.gov (United States)

    Kuznetsova, Ksenia A; Maniega, Susana Muñoz; Ritchie, Stuart J; Cox, Simon R; Storkey, Amos J; Starr, John M; Wardlaw, Joanna M; Deary, Ian J; Bastin, Mark E

    2016-07-01

    Cognitive decline, especially the slowing of information processing speed, is associated with normal ageing. This decline may be due to brain cortico-cortical disconnection caused by age-related white matter deterioration. We present results from a large, narrow age range cohort of generally healthy, community-dwelling subjects in their seventies who also had their cognitive ability tested in youth (age 11 years). We investigate associations between older age brain white matter structure, several measures of information processing speed and childhood cognitive ability in 581 subjects. Analysis of diffusion tensor MRI data using Tract-based Spatial Statistics (TBSS) showed that all measures of information processing speed, as well as a general speed factor composed from these tests (g speed), were significantly associated with fractional anisotropy (FA) across the white matter skeleton rather than in specific tracts. Cognitive ability measured at age 11 years was not associated with older age white matter FA, except for the g speed-independent components of several individual processing speed tests. These results indicate that quicker and more efficient information processing requires global connectivity in older age, and that associations between white matter FA and information processing speed (both individual test scores and g speed), unlike some other aspects of later life brain structure, are generally not accounted for by cognitive ability measured in youth. PMID:26254904

  18. 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...

  19. Selective Attention to Emotion in the Aging Brain

    OpenAIRE

    Samanez-Larkin, Gregory R.; Robertson, Elaine R.; Mikels, Joseph A.; Carstensen, Laura L.; Gotlib, Ian H.

    2009-01-01

    A growing body of research suggests that the ability to regulate emotion remains stable or improves across the adult life span. Socioemotional selectivity theory maintains that this pattern of findings reflects the prioritization of emotional goals. Given that goal-directed behavior requires attentional control, the present study was designed to investigate age differences in selective attention to emotional lexical stimuli under conditions of emotional interference. Both neural and behaviora...

  20. 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...

  1. Mild fluid percussion injury in mice produces evolving selective axonal pathology and cognitive deficits relevant to human brain injury.

    Science.gov (United States)

    Spain, Aisling; Daumas, Stephanie; Lifshitz, Jonathan; Rhodes, Jonathan; Andrews, Peter J D; Horsburgh, Karen; Fowler, Jill H

    2010-08-01

    Mild traumatic brain injury (TBI) accounts for up to 80% of clinical TBI and can result in cognitive impairment and white matter damage that may develop and persist over several years. Clinically relevant models of mild TBI for investigation of neurobiological changes and the development of therapeutic strategies are poorly developed. In this study we investigated the temporal profile of axonal and somal injury that may contribute to cognitive impairments in a mouse model of mild TBI. Neuronal perikaryal damage (hematoxylin and eosin and Fluoro-Jade C), myelin integrity (myelin basic protein and myelin-associated glycoprotein), and axonal damage (amyloid precursor protein), were evaluated by immunohistochemistry at 4 h, 24 h, 72 h, 4 weeks, and 6 weeks after mild lateral fluid percussion brain injury (0.9 atm; righting time 167 +/- 15 sec). At 3 weeks post-injury spatial reference learning and memory were tested in the Morris water maze (MWM). Levels of damage to neuronal cell bodies were comparable in the brain-injured and sham groups. Myelin integrity was minimally altered following injury. Clear alterations in axonal damage were observed at various time points after injury. Axonal damage was localized to the cingulum at 4 h post-injury. At 4 and 6 weeks post-injury, axonal damage was evident in the external capsule, and was seen at 6 weeks in the dorsal thalamic nuclei. At 3 weeks post-injury, injured mice showed an impaired ability to learn the water maze task, suggesting injury-induced alterations in search strategy learning. The evolving localization of axonal damage points to ongoing degeneration after injury that is concomitant with a deficit in learning. PMID:20528171

  2. Relevant Repositories of Public Knowledge? Libraries, Museums and Archives in "The Information Age"

    Science.gov (United States)

    Usherwood, Bob; Wilson, Kerry; Bryson, Jared

    2005-01-01

    In a project funded by the AHRB, researchers at the University of Sheffield used a combination of quantitative and qualitative research methods to examine the perceived contemporary relevance of archives, libraries and museums. The research sought to discern how far the British people value access to these established repositories of public…

  3. Transformational Teaching in the Information Age: Making Why and How We Teach Relevant to Students

    Science.gov (United States)

    Rosebrough, Thomas R.; Leverett, Ralph G.

    2011-01-01

    Yes, it's true that today's students have tons of distractions that take their attention away from the hard work of learning. That's why it's more important than ever to establish a teaching relationship with students that makes academic learning relevant to their lives. Here's a book that explains how to do that by changing teaching practices…

  4. Taming Disruptive Technologies, or How To Remain Relevant in the Digital Age.

    Science.gov (United States)

    Blackwell, Philip

    2001-01-01

    Discusses electronic books as a disruptive technology, that is, a technology that has appeal to its users but upsets the traditional models. Highlights include a history of print technology; types of electronic books; reader devices; stakeholders, including users, librarians, and publishers; and how vendors can remain relevant. (LRW)

  5. Age Differences in Attention toward Decision-Relevant Information: Education Matters

    Science.gov (United States)

    Xing, Cai; Isaacowitz, Derek

    2011-01-01

    Previous studies suggested that older adults are more likely to engage in heuristic decision-making than young adults. This study used eye tracking technique to examine young adults' and highly educated older adults' attention toward two types of decision-relevant information: heuristic cue vs. factual cues. Surprisingly, highly educated older…

  6. 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

  7. 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

  8. 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

  9. Age-dependent differences in brain tissue microstructure assessed with neurite orientation dispersion and density imaging.

    Science.gov (United States)

    Merluzzi, Andrew P; Dean, Douglas C; Adluru, Nagesh; Suryawanshi, Gaurav S; Okonkwo, Ozioma C; Oh, Jennifer M; Hermann, Bruce P; Sager, Mark A; Asthana, Sanjay; Zhang, Hui; Johnson, Sterling C; Alexander, Andrew L; Bendlin, Barbara B

    2016-07-01

    Human aging is accompanied by progressive changes in executive function and memory, but the biological mechanisms underlying these phenomena are not fully understood. Using neurite orientation dispersion and density imaging, we sought to examine the relationship between age, cellular microstructure, and neuropsychological scores in 116 late middle-aged, cognitively asymptomatic participants. Results revealed widespread increases in the volume fraction of isotropic diffusion and localized decreases in neurite density in frontal white matter regions with increasing age. In addition, several of these microstructural alterations were associated with poorer performance on tests of memory and executive function. These results suggest that neurite orientation dispersion and density imaging is capable of measuring age-related brain changes and the neural correlates of poorer performance on tests of cognitive functioning, largely in accordance with published histological findings and brain-imaging studies of people of this age range. Ultimately, this study sheds light on the processes underlying normal brain development in adulthood, knowledge that is critical for differentiating healthy aging from changes associated with dementia. PMID:27255817

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

    Science.gov (United States)

    Petti, Manuela; Toppi, Jlenia; Mattia, Donatella; Astolfi, Laura

    2016-01-01

    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%. PMID:27006652

  11. 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.

  12. 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

  13. 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

  14. 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...

  15. 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 ...

  16. Plasticity and the Ageing Mind : An Exemplar of the Biocultural Orchestration of Brain and Behavior

    OpenAIRE

    Baltes, P.; Singer, T.

    2001-01-01

    Using research on the aging mind, support is offered for the concept of biocultural sciences. The biocultural sciences highlight the notion that human behavior is the joint and co-constructive expression of biological-genetic and cultural-societal processes and conditions. The genome determines the ontogeny of the brain, so does, however, the cultural-social environment and individual behavior. The study of the aging mind illustrates this principle of biocultural co-construction and the histo...

  17. 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...

  18. 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.

  19. ADNP: A major autism mutated gene is differentially distributed (age and gender) in the songbird brain.

    Science.gov (United States)

    Kleiman, Gal Hacohen; Barnea, Anat; Gozes, Illana

    2015-10-01

    ADNP is a protein necessary for brain development, important for brain plasticity, cognitive and social functioning, characteristics that are all impaired in autism and in the Adnp(+/-) mouse model, in a sex-dependent manner. ADNP was originally discovered as a protein that is secreted from glial cells in response to vasoactive intestinal peptide (VIP). VIP is a major neuroprotective peptide in the CNS and PNS and was also associated with social recognition in rodents and aggression, pair-bonding and parental behaviors in birds. Comparative sequence alignment revealed high evolutionary conservation of ADNP in Chordata. Despite its importance in brain function, ADNP has never been studied in birds. Zebra finches (Taeniopygia guttata) are highly social songbirds that have a sexually dichotomous anatomical brain structure, with males demonstrating a developed song system, presenting a model to study behavior and potential sexually dependent fundamental differences. Here, using quantitative real time polymerase chain reaction (qRT-PCR), we discovered sexually dichotomous and age related differences in ADNP mRNA expression in three different regions of the song bird brain-cerebellum, cerebrum, and brain stem. Higher levels of ADNP mRNA were specifically found in young male compared to the female cerebrum, while aging caused a significant 2 and 3-fold decrease in the female and male cerebrum, respectively. Furthermore, a comparison between the three tested brain regions revealed unique sex-dependent ADNP mRNA distribution patterns, affected by aging. Future studies are aimed at deciphering the function of ADNP in birds, toward a better molecular understanding of sexual dichotomy in singing behavior in birds. PMID:25895853

  20. Resolving Issues Relevant to the Education of Secondary School Aged Youth with Behavior Disorders.

    Science.gov (United States)

    Simpson, Robert G.

    The article provides a format for a workshop in which three issues which must be resolved by educators of secondary aged students with behavior disorders are discussed. The three issues to be addressed are: (1) determination of appropriate curriculum emphasis, (2) parent training/involvement in intervention strategies, and (3) criteria for…

  1. 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...

  2. 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)

  3. 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.

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

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    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.

  5. Roles of unsaturated fatty acids (especially omega-3 fatty acids) in the brain at various ages and during ageing.

    Science.gov (United States)

    Bourre, J M

    2004-01-01

    results have shown that dietary alpha-linolenic acid deficiency induces more marked abnormalities in certain cerebral structures than in others, as the frontal cortex and pituitary gland are more severely affected. These selective lesions are accompanied by behavioural disorders more particularly affecting certain tests (habituation, adaptation to new situations). Biochemical and behavioural abnormalities are partially reversed by a dietary phospholipid supplement, especially omega-3-rich egg yolk extracts or pig brain. A dose-effect study showed that animal phospholipids are more effective than plant phospholipids to reverse the consequences of alpha-linolenic acid deficiency, partly because they provide very long preformed chains. Alpha-linolenic acid deficiency decreases the perception of pleasure, by slightly altering the efficacy of sensory organs and by affecting certain cerebral structures. Age-related impairment of hearing, vision and smell is due to both decreased efficacy of the parts of the brain concerned and disorders of sensory receptors, particularly of the inner ear or retina. For example, a given level of perception of a sweet taste requires a larger quantity of sugar in subjects with alpha-linolenic acid deficiency. In view of occidental eating habits, as omega-6 fatty acid deficiency has never been observed, its impact on the brain has not been studied. In contrast, omega-9 fatty acid deficiency, specifically oleic acid deficiency, induces a reduction of this fatty acid in many tissues, except the brain (but the sciatic nerve is affected). This fatty acid is therefore not synthesized in sufficient quantities, at least during pregnancy-lactation, implying a need for dietary intake. It must be remembered that organization of the neurons is almost complete several weeks before birth, and that these neurons remain for the subject's life time. Consequently, any disturbance of these neurons, an alteration of their connections, and impaired turnover of their

  6. A preliminary empirical test of a culturally-relevant theoretical framework for the study of successful aging.

    Science.gov (United States)

    Torres, Sandra

    2003-03-01

    This article aims to shed preliminary empirical light on the assumptions underpinning a culturally relevant theoretical framework for the study of successful aging. On the basis of the Kluckhohnian theory of cultural variation, this framework suggests that congruence exists between value orientations concerned with man-nature, time, activity, and relationships, and the manner in which the construct of successful aging is understood. Methodologically speaking, the research project upon which this article is based started out by adapting and further developing the vignette-based instrument that Kluckhohn and Strodtbeck designed to test the theory of cultural variation. Vignette-based interviews were then conducted with 30 Iranian immigrants to Sweden as a preliminary test of the hypothesis of congruence. The results presented in this article suggest that, as posed in the framework in question, there is a relationship between the value orientations that people prefer and the various understandings of successful aging that they uphold. The results suggest also that there is a variety of ways in which the construct of successful aging can be understood, and that variety encompasses other ways of thinking about successful aging besides the master nature, future, productivity, and individuality-oriented views that characterize the gerontological debate. Although further research is necessary, these preliminary results do infer that this framework might offer a theoretically interesting approach to the study of individual, generational, and cross-cultural understandings of successful aging. PMID:14617959

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

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    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.

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

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    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

  9. Economic activity of middle-aged women in Serbia as relevant gender equality issue

    OpenAIRE

    Šobot Ankica

    2014-01-01

    Economic characteristics of the female population are important dimensions of contemporary gender regime. Thus, this paper focuses on disadvantageous characteristics of economic activity pointing to the range and the intensity of economic dependence of women as one of the obstacles to the improvement of their social position and reducing of gender gap. Statistical data show economic inactivity and unemployment of middle-aged women in Serbia. Also, regarding...

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

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    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.

  11. The relevance of parametric U-uptake models in ESR age calculations

    International Nuclear Information System (INIS)

    In the ESR dating three basic parametric U-uptake models have been applied for dating teeth: early U-uptake (EU: closed system), linear U-uptake (LU) and recent U-uptake (RU, it is assumed that the dose rate contribution of U in the dental tissues is zero). In many ESR dating publications it is still assumed that samples comply with one or the other parametric U-uptake model calculation or that their correct age lies somewhere between EU and LU. Observations of the spatial distribution of uranium in dental tissues show that it is difficult to predict any relationships between the relative uptake in the dental tissues. Combined U-series/ESR age estimates can give insights into the actual U-uptake. An evaluation of published data shows that for cave sites, a significant number of results fall outside the EU and LU bracket, while for open air sites, the majority of data are outside this bracket, particularly showing greatly delayed U-uptake. This may be due to changes in the hydrological system, leading to erosion which exposes the open air site. U-leaching has also been observed on samples from open air sites, in which case any reasonable age calculation is impossible.

  12. Detergent resistant membrane-associated IDE in brain tissue and cultured cells: Relevance to Aβ and insulin degradation

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    Castaño Eduardo M

    2008-12-01

    Full Text Available Abstract Background Insulin degrading enzyme (IDE is implicated in the regulation of amyloid β (Aβ steady-state levels in the brain, and its deficient expression and/or activity may be a risk factor in sporadic Alzheimer's disease (AD. Although IDE sub-cellular localization has been well studied, the compartments relevant to Aβ degradation remain to be determined. Results Our results of live immunofluorescence, immuno gold electron-microscopy and gradient fractionation concurred to the demonstration that endogenous IDE from brain tissues and cell cultures is, in addition to its other localizations, a detergent-resistant membrane (DRM-associated metallopeptidase. Our pulse chase experiments were in accordance with the existence of two pools of IDE: the cytosolic one with a longer half-life and the membrane-IDE with a faster turn-over. DRMs-associated IDE co-localized with Aβ and its distribution (DRMs vs. non-DRMs and activity was sensitive to manipulation of lipid composition in vitro and in vivo. When IDE was mis-located from DRMs by treating cells with methyl-β-cyclodextrin (MβCD, endogenous Aβ accumulated in the extracellular space and exogenous Aβ proteolysis was impaired. We detected a reduced amount of IDE in DRMs of membranes isolated from mice brain with endogenous reduced levels of cholesterol (Chol due to targeted deletion of one seladin-1 allele. We confirmed that a moderate shift of IDE from DRMs induced a substantial decrement on IDE-mediated insulin and Aβ degradation in vitro. Conclusion Our results support the notion that optimal substrate degradation by IDE may require its association with organized-DRMs. Alternatively, DRMs but not other plasma membrane regions, may act as platforms where Aβ accumulates, due to its hydrophobic properties, reaching local concentration close to its Km for IDE facilitating its clearance. Structural integrity of DRMs may also be required to tightly retain insulin receptor and IDE for

  13. Designing psychological co-research of emancipatory-technical relevance across age thresholds

    DEFF Research Database (Denmark)

    Chimirri, Niklas Alexander

    2015-01-01

    The requirement that theoretical and empirical research is to sustainably benefit not only the nominal researcher, but also the other research participants, is deeply embedded in the conceptual-analytical framework of Psychology from the Standpoint of the Subject (PSS) and its co-researcher princ......The requirement that theoretical and empirical research is to sustainably benefit not only the nominal researcher, but also the other research participants, is deeply embedded in the conceptual-analytical framework of Psychology from the Standpoint of the Subject (PSS) and its co...... design. A discussion of recent methodological developments in child-targeted Participatory Design (PD) and Human-Computer Interaction (HCI) serve as inspiration for this conceptual specification. The contribution thereby invites co-research to further investigate how emancipatory relevance cannot only to...

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

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    Jonathan List

    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.

  15. Clinically relevant depression in old age: An international study with populations from Canada, Latin America and Eastern Europe.

    Science.gov (United States)

    Ylli, Alban; Miszkurka, Malgorzata; Phillips, Susan P; Guralnik, Jack; Deshpande, Nandini; Zunzunegui, Maria Victoria

    2016-07-30

    Our aim is to assess cross-national variations in prevalence of clinically relevant depression and to examine the relationships of social and health factors with depression in five diverse populations of older adults, from Canada, Brazil, Colombia and Albania. We used the data from the International Mobility in Aging Study. Clinically relevant depression was defined as a score of ≥16 on the Center for Epidemiologic Study Depression Scale (CES-D). Poisson regressions with robust covariance correction were used to estimate prevalence ratios associated with potential risk factors. Prevalence of clinically relevant depression across research sites varied widely, being consistently higher in women than in men. It was lowest in men from Brazil (6.3%) and highest in women from Albania (46.6%). Low education and insufficient income, living alone, multiple chronic conditions, and poor physical performance were all significantly associated with depression prevalence. Poor physical performance was more strongly associated with depression in men than in women. Similar factors are associated with clinically relevant depression among men and women and across research sites. The large variation in depression prevalence population rates is unexplained by the classical individual factors considered in the study suggesting the impact of country characteristics on depression among older populations. PMID:27183110

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

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    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.

  17. 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

  18. Brain CT studies in 26 cases of aged patients with Down syndrome

    International Nuclear Information System (INIS)

    Computed tomographic images of brains from 26 individuals (10 males and 16 females) with Down syndrome were analysed for roentgenographic measurement. Their ages ranged from 14 to 47 years, the average being 28 years. The results showed that their Sylvian fissure ratio was larger in the aged group. A high incidence of calcification in basal ganglia, choroid plexus and pineal body was noted (85%). An increased Sylvian fissure ratio and a high incidence of intracranial calcification may be practically used as representatives of premature aging. Furthermore, a high incidence of mega cisterna magna implicates that it is worthy of study whether individuals with Down syndrome have a predisposition to underdevelopment of cerebellum. (author)

  19. Brain regions essential for improved lexical access in an aged aphasic patient: a case report

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    Djundja Daniela

    2006-08-01

    Full Text Available Abstract Background The relationship between functional recovery after brain injury and concomitant neuroplastic changes is emphasized in recent research. In the present study we aimed to delineate brain regions essential for language performance in aphasia using functional magnetic resonance imaging and acquisition in a temporal sparse sampling procedure, which allows monitoring of overt verbal responses during scanning. Case presentation An 80-year old patient with chronic aphasia (2 years post-onset was investigated before and after intensive language training using an overt picture naming task. Differential brain activation in the right inferior frontal gyrus for correct word retrieval and errors was found. Improved language performance following therapy was mirrored by increased fronto-thalamic activation while stability in more general measures of attention/concentration and working memory was assured. Three healthy age-matched control subjects did not show behavioral changes or increased activation when tested repeatedly within the same 2-week time interval. Conclusion The results bear significance in that the changes in brain activation reported can unequivocally be attributed to the short-term training program and a language domain-specific plasticity process. Moreover, it further challenges the claim of a limited recovery potential in chronic aphasia, even at very old age. Delineation of brain regions essential for performance on a single case basis might have major implications for treatment using transcranial magnetic stimulation.

  20. 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

  1. 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

  2. Magnetic resonance imaging of the brain in normal aging and dementia

    International Nuclear Information System (INIS)

    The unusual sensitivity of magnetic resonance imaging in detecting white matter lesions has yielded striking results in studying the aging brain and in diagnosing a variety of central nervous system disorders. These lesions are most obvious in the periventricular white matter and appear as punctate or confluent hyperintense abnormalities on T2-weighted images. Their correlation with increasing age and the ensuing increase of cardiovascular risk factors suggests ischemic damage as their probable underlying pathologic cause. MRI thus may prove an early and very sensitive indicator of incipient cerebrovascular disease, adding information on the association of vascular damage with the development of dementing illness. This report is a preliminary communication of an ongoing study which is evaluating the importance of these findings in the 'normal' aging brain and different forms of dementia. 11 refs.; 1 table

  3. 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.

  4. 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

  5. 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...

  6. 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.

  7. 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

  8. 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.

  9. 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

  10. 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

  11. Ibuprofen inhibits rat brain deamidation of anandamide at pharmacologically relevant concentrations. Mode of inhibition and structure-activity relationship.

    Science.gov (United States)

    Fowler, C J; Tiger, G; Stenström, A

    1997-11-01

    The ability of rat brain (minus cerebellum) homogenates to deamidate arachidonyl ethanolamide (anandamide) was determined with a custom-synthesized substrate, arachidonyl ethanolamide-[1-3H] ([3H]anandamide). Conditions whereby initial velocities were measured were established. The homogenates deamidated anandamide with a Km value of 0.8 microM and a Vmax value of 1.73 nmol . (mg protein)-1 . min-1. The deamidation of 2 microM -3H-anandamide was inhibited by phenylmethylsulfonyl fluoride and arachidonyl trifluoromethyl ketone with IC50 values of 3.7 and 0.23 microM, respectively. Ibuprofen inhibited anandamide deamidation in a mixed fashion, with Ki and K'i values of 82 and 1420 microM. At an anandamide concentration of 2 microM, the IC50 values (in microM) of a series of compounds related in structure to ibuprofen were as follows: suprofen, 170; ibuprofen, 270; fenoprofen, 480; naproxen, 550; ketoprofen, 650; diclofenac, approximately 1000. Sulindac produced 27% inhibition at a concentration of 1000 microM, whereas isobutyric acid, hydrocinnamic acid, acetylsalicylic acid and acetaminophen were essentially inactive at concentrations relevant concentrations and that there is some specificity to the inhibition produced by ibuprofen and suprofen. PMID:9353392

  12. 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...

  13. Brain responses to language-relevant musical features in adolescent cochlear implant users before and after an intensive music training program

    DEFF Research Database (Denmark)

    Petersen, Bjørn; Weed, Ethan; Hansen, Mads;

    Brain responses to language-relevant musical features in adolescent cochlear implant users before and after an intensive music training program Petersen B.1,2, Weed E.1,3, Hansen M.1,4, Sørensen S.D.3 , Sandmann P.5 , Vuust P.1,2 1Center of Functionally Integrative Neuroscience, Aarhus University...... with a congenital hearing loss. However, recent studies indicate that to keep pace with their normal-hearing (NH) peers, supplementary measures of rehabilitation are important throughout adolescence. This study aimed to 1) investigate auditory brain processing of musical sounds relevant to prosody processing...... produced significantly higher average scores than the CI group at both sessions. Our results suggest that adolescent CI users, who have only experienced sound through the implant, show brain responses to musical stimuli resembling those of NH peers, and that this response can be altered by intensive...

  14. 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

  15. 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

  16. A Literature Review of Homelessness and Aging: Suggestions for a Policy and Practice-Relevant Research Agenda.

    Science.gov (United States)

    Grenier, Amanda; Barken, Rachel; Sussman, Tamara; Rothwell, David; Bourgeois-Guérin, Valérie; Lavoie, Jean-Pierre

    2016-03-01

    Homelessness among older people is a growing concern across Canada and is expected to rise with demographic change (Crane & Warnes, 2010; Culhane, Metraux, Byrne, Stino, & Bainbridge, 2013). Yet current knowledge, policies, and practices on homelessness largely focus on younger populations. Likewise, research and policies on aging typically overlook homelessness. Responses to homelessness among older people must address complex needs related to health, income security, and housing. Based on a comprehensive literature review, this article outlines the existing and needed research with regards to homelessness among older people. We clarify the intersections of aging and homelessness; review the relevant statistics, including estimated prevalence; discuss pathways and variations in experience; and identify gaps in knowledge. We conclude with a call for an inclusive research agenda that will help build policies and practices to reduce and ultimately to eliminate homelessness among older people in Canada. PMID:26782092

  17. Regional ADC values of the normal brain: differences due to age, gender, and laterality

    Energy Technology Data Exchange (ETDEWEB)

    Naganawa, Shinji; Ishigaki, Takeo [Department of Radiology, Nagoya University School of Medicine, 65 Tsurumai-cho, Shouwa-ku, Nagoya 466-8550 (Japan); Sato, Kimihide; Katagiri, Toshio; Mimura, Takeo [Department of Radiology, First Kamiida General Hospital (Japan)

    2003-01-01

    The purpose of this study was to evaluate the stability of measurement for apparent diffusion coefficient (ADC) values in normal brain, to clarify the effect of aging on ADC values, to compare ADC values between men and women, and to compare ADC values between right and left sides of the brain. To evaluate the stability of measurements, five normal volunteers (four men and one woman) were examined five times on different days. Then, 294 subjects with normal MR imaging (147 men and 147 women; age range 20-89 years) were measured. The ADC measurement in normal volunteers was stable. The ADC values stayed within the 5% deviation of average values in all volunteers (mean{+-}standard deviation 2.3{+-}1.2%). The ADC values gradually increased by aging in all regions. In thalamus, no significant difference was seen between right and left in the subjects under 60 years; however, right side showed higher values in the subjects over 60 years (p<0.01). In the subjects under 60 years, women showed higher values in right frontal, bilateral thalamus, and temporal (p<0.01); however, in the subjects over 60 years, no region showed difference between men and women. The knowledge obtained in this study may be helpful to understand the developmental and aging mechanisms of normal brain and may be useful for the future quantitative study as a reference. (orig.)

  18. Regional ADC values of the normal brain: differences due to age, gender, and laterality

    International Nuclear Information System (INIS)

    The purpose of this study was to evaluate the stability of measurement for apparent diffusion coefficient (ADC) values in normal brain, to clarify the effect of aging on ADC values, to compare ADC values between men and women, and to compare ADC values between right and left sides of the brain. To evaluate the stability of measurements, five normal volunteers (four men and one woman) were examined five times on different days. Then, 294 subjects with normal MR imaging (147 men and 147 women; age range 20-89 years) were measured. The ADC measurement in normal volunteers was stable. The ADC values stayed within the 5% deviation of average values in all volunteers (mean±standard deviation 2.3±1.2%). The ADC values gradually increased by aging in all regions. In thalamus, no significant difference was seen between right and left in the subjects under 60 years; however, right side showed higher values in the subjects over 60 years (p<0.01). In the subjects under 60 years, women showed higher values in right frontal, bilateral thalamus, and temporal (p<0.01); however, in the subjects over 60 years, no region showed difference between men and women. The knowledge obtained in this study may be helpful to understand the developmental and aging mechanisms of normal brain and may be useful for the future quantitative study as a reference. (orig.)

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

    Directory of Open Access Journals (Sweden)

    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.

  20. 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 ...

  1. 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

  2. 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

  3. microRNA-496 - A new, potentially aging-relevant regulator of mTOR.

    Science.gov (United States)

    Rubie, Claudia; Kölsch, Kathrin; Halajda, Beata; Eichler, Hermann; Wagenpfeil, Stefan; Roemer, Klaus; Glanemann, Matthias

    2016-01-01

    Recent findings strongly support a role for small regulatory RNAs in the regulation of human lifespan yet little information exists about the precise underlying mechanisms. Although extensive studies on model organisms have indicated that reduced activity of the nutrient response pathway, for example as a result of dietary restriction, can extend lifespan through the suppression of the protein kinase mechanistic target of rapamycin (mTOR), it still is subject of debate whether this mechanism is operative in humans as well. Here, we present findings indicating that human microRNA (miR)-496 targets 2 sites within the human mTOR 3'UTR. Coexpression of miR-496 with different fusion transcripts, consisting of the luciferase transcript and either wild-type mTOR 3'UTR or mTOR 3'UTR transcript with the miR-496 binding sites singly or combined mutated, confirmed this prediction and revealed cooperativity between the 2 binding sites. miR-496 reduced the mTOR protein level in HeLa-K cells, and the levels of miR-496 and mTOR protein were inversely correlated in Peripheral Blood Mononuclear Cells (PBMC), with old individuals (n = 40) harbouring high levels of miR-496 relative to young individuals (n = 40). Together, these findings point to the possibility that miR-496 is involved in the regulation of human aging through the control of mTOR. PMID:27097372

  4. Economic activity of middle-aged women in Serbia as relevant gender equality issue

    Directory of Open Access Journals (Sweden)

    Šobot Ankica

    2014-01-01

    Full Text Available Economic characteristics of the female population are important dimensions of contemporary gender regime. Thus, this paper focuses on disadvantageous characteristics of economic activity pointing to the range and the intensity of economic dependence of women as one of the obstacles to the improvement of their social position and reducing of gender gap. Statistical data show economic inactivity and unemployment of middle-aged women in Serbia. Also, regarding the employed women the economic disadvantages could be discussed. The indicator of this is a gender difference in earnings as a result of a smaller number of women having well-paying jobs. In the base of gender economic differences are characteristics of gender roles, and for this reason a specific “women’s work” is seen as an important segment in the improvement of the economic position of women and reducing of gender-based economic gap. [Projekat Ministarstva nauke Republike Srbije, br. 47006: Investigation of demographic phenomena with regard to public policies in Serbia

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

    Directory of Open Access Journals (Sweden)

    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.

  6. 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.)

  7. Aging is associated with dimerization and inactivation of the brain-enriched tyrosine phosphatase STEP.

    Science.gov (United States)

    Rajagopal, Sathyanarayanan; Deb, Ishani; Poddar, Ranjana; Paul, Surojit

    2016-05-01

    The STriatal-Enriched tyrosine Phosphatase (STEP) is involved in the etiology of several age-associated neurologic disorders linked to oxidative stress and is also known to play a role in neuroprotection by modulating glutamatergic transmission. However, the possible effect of aging on STEP level and activity in the brain is still unclear. In this study, using young (1 month), adult (4 months), and aged (18 months) rats, we show that aging is associated with increase in dimerization and loss of activity of STEP. Increased dimerization of STEP is primarily observed in the cortex and hippocampus and is associated with depletion of both reduced and total glutathione levels, suggesting an increase in oxidative stress. Consistent with this interpretation, studies in cell culture models of glutathione depletion and oxidative stress also demonstrate formation of dimers and higher order oligomers of STEP that involve intermolecular disulfide bond formation between multiple cysteine residues. Conversely, administration of N-acetyl cysteine, a major antioxidant that enhances glutathione biosynthesis, attenuates STEP dimerization both in the cortex and hippocampus. The findings indicate that loss of this intrinsic protective response pathway with age-dependent increase in oxidative stress may be a contributing factor for the susceptibility of the brain to age-associated neurologic disorders. PMID:27103516

  8. 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

  9. 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.

  10. 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...

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

    International Nuclear Information System (INIS)

    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)

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

    Directory of Open Access Journals (Sweden)

    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.

  13. 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.

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

    OpenAIRE

    Tamara Simpson; Matthew Pase; Con Stough

    2015-01-01

    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 improv...

  15. 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

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

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    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

  17. Sexually dimorphic brain volume interaction in college-aged binge drinkers

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    Timo L. Kvamme

    2016-01-01

    Conclusions: These findings dovetail with previous studies reporting that a state effect of BD in college-aged drinkers and the severity of alcohol use are associated with volumetric alterations in the cortical and subcortical areas of the brain. Our study indicates that these widespread volumetric changes vary differentially by gender, suggesting either sexual dimorphic endophenotypic risk factors, or differential neurotoxic sensitivities for males and females.

  18. 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...

  19. 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 ...

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

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    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.

  1. 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. PMID:26799654

  2. Novel MicroRNAs Differentially Expressed during Aging in the Mouse Brain

    OpenAIRE

    Inukai, Sachi; de Lencastre, Alexandre; Turner, Michael; Slack, Frank

    2012-01-01

    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...

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

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    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.

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. Modulative effects of COMT haplotype on age-related associations with brain morphology.

    Science.gov (United States)

    Lee, Annie; Qiu, Anqi

    2016-06-01

    Catechol-O-methyltransferase (COMT), located on chromosome 22q11.2, encodes an enzyme critical for dopamine flux in the prefrontal cortex. Genetic variants of COMT have been suggested to functionally manipulate prefrontal morphology and function in healthy adults. This study aims to investigate modulative roles of individuals COMT SNPs (rs737865, val158met, rs165599) and its haplotypes in age-related brain morphology using an Asian sample with 174 adults aged from 21 to 80 years. We showed an age-related decline in cortical thickness of the dorsal visual pathway, including the left dorsolateral prefrontal cortex, bilateral angular gyrus, right superior frontal cortex, and age-related shape compression in the basal ganglia as a function of the genotypes of the individual COMT SNPs, especially COMT val158met. Using haplotype trend regression analysis, COMT haplotype probabilities were estimated and further revealed an age-related decline in cortical thickness in the default mode network (DMN), including the posterior cingulate, precuneus, supramarginal and paracentral cortex, and the ventral visual system, including the occipital cortex and left inferior temporal cortex, as a function of the COMT haplotype. Our results provided new evidence on an antagonistic pleiotropic effect in COMT, suggesting that genetically programmed neural benefits in early life may have a potential bearing towards neural susceptibility in later life. Hum Brain Mapp 37:2068-2082, 2016. © 2016 Wiley Periodicals, Inc. PMID:26920810

  9. 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

  10. 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

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

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    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.

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

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    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.

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

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    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.

  14. 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

  15. 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

  16. Behavioral responses to and brain distribution of morphine in mature adult and aged mice

    International Nuclear Information System (INIS)

    Mature adult (3-6 mo old) and aged (2 yr old) male ICR mice were injected with 10 to 100 mg/kg morphine, s.c. The ED50 values for running behavior (as measured using Stoelting activity monitors and having each mouse serve as its own control) representing 5 times control activity was approximately 7.5 mg/kg for aged mice and approximately 17.5 mg/kg for the mature adults. The ED50 values for analgesia 1 hr after morphine administration using the tail-flick method (max. response time = 8 sec) were approx. 70 mg/kg for the aged mice and 15 mg/kg for the mature adults. One hour after injecting 3H-morphine at doses of 30 and 100 mg/kg, 0.13 and 0.14% of the doses appeared in brains of aged and mature adult mice, respectively. Regional distribution of the morphine was the same for both age groups. Expressed as percent of total brain morphine, it was as follows: cortex, 30%; midbrain, 18%; cerebellum, 17%; medulla, 12%; pons, 9%; striatum, 8% and periaqueductal gray, 6%. Expressed as g morphine/g tissue for the 2 doses, the distribution was; periaqueductal gray, 30 and 80; striatum, 9 and 34; medulla, 6 and 20 pons; 5 and 19; cerebellum, 4 and 13; midbrain 2.5 and 8.5 and cortex, 2 and 8. These results suggest that the differences in response to morphine by the two age groups were due to age-related differences in opioid receptor populations and/or affinities

  17. Behavioral responses to and brain distribution of morphine in mature adult and aged mice

    Energy Technology Data Exchange (ETDEWEB)

    Burton, C.K.; Ho, I.K.; Hoskins, B.

    1986-03-01

    Mature adult (3-6 mo old) and aged (2 yr old) male ICR mice were injected with 10 to 100 mg/kg morphine, s.c. The ED50 values for running behavior (as measured using Stoelting activity monitors and having each mouse serve as its own control) representing 5 times control activity was approximately 7.5 mg/kg for aged mice and approximately 17.5 mg/kg for the mature adults. The ED50 values for analgesia 1 hr after morphine administration using the tail-flick method (max. response time = 8 sec) were approx. 70 mg/kg for the aged mice and 15 mg/kg for the mature adults. One hour after injecting /sup 3/H-morphine at doses of 30 and 100 mg/kg, 0.13 and 0.14% of the doses appeared in brains of aged and mature adult mice, respectively. Regional distribution of the morphine was the same for both age groups. Expressed as percent of total brain morphine, it was as follows: cortex, 30%; midbrain, 18%; cerebellum, 17%; medulla, 12%; pons, 9%; striatum, 8% and periaqueductal gray, 6%. Expressed as g morphine/g tissue for the 2 doses, the distribution was; periaqueductal gray, 30 and 80; striatum, 9 and 34; medulla, 6 and 20 pons; 5 and 19; cerebellum, 4 and 13; midbrain 2.5 and 8.5 and cortex, 2 and 8. These results suggest that the differences in response to morphine by the two age groups were due to age-related differences in opioid receptor populations and/or affinities.

  18. 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.

  19. Oxidative Stress Is a Central Target for Physical Exercise Neuroprotection Against Pathological Brain Aging.

    Science.gov (United States)

    García-Mesa, Yoelvis; Colie, Sandra; Corpas, Rubén; Cristòfol, Rosa; Comellas, Francesc; Nebreda, Angel R; Giménez-Llort, Lydia; Sanfeliu, Coral

    2016-01-01

    Physical exercise is suggested for preventing or delaying senescence and Alzheimer's disease (AD). We have examined its therapeutic value in the advanced stage of AD-like pathology in 3xTg-AD female mice through voluntary wheel running from 12 to 15 months of age. Mice submitted to exercise showed improved body fitness, immunorejuvenation, improvement of behavior and cognition, and reduced amyloid and tau pathology. Brain tissue analysis of aged 3xTg-AD mice showed high levels of oxidative damage. However, this damage was decreased by physical exercise through regulation of redox homeostasis. Network analyses showed that oxidative stress was a central event, which correlated with AD-like pathology and the AD-related behaviors of anxiety, apathy, and cognitive loss. This study corroborates the importance of redox mechanisms in the neuroprotective effect of physical exercise, and supports the theory of the crucial role of oxidative stress in the switch from normal brain aging to pathological aging and AD. PMID:25720862

  20. 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

  1. 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...

  2. 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.

  3. 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.

  4. 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. PMID:27318132

  5. 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

  6. 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...

  7. 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

  8. 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.

  9. 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.

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

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    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.

  11. Effects of Flight on Gene Expression and Aging in the Honey Bee Brain and Flight Muscle

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    Michelle M. Elekonich

    2012-12-01

    Full Text Available Honey bees move through a series of in-hive tasks (e.g., “nursing” to outside tasks (e.g., “foraging” that are coincident with physiological changes and higher levels of metabolic activity. Social context can cause worker bees to speed up or slow down this process, and foragers may revert back to their earlier in-hive tasks accompanied by reversion to earlier physiological states. To investigate the effects of flight, behavioral state and age on gene expression, we used whole-genome microarrays and real-time PCR. Brain tissue and flight muscle exhibited different patterns of expression during behavioral transitions, with expression patterns in the brain reflecting both age and behavior, and expression patterns in flight muscle being primarily determined by age. Our data suggest that the transition from behaviors requiring little to no flight (nursing to those requiring prolonged flight bouts (foraging, rather than the amount of previous flight per se, has a major effect on gene expression. Following behavioral reversion there was a partial reversion in gene expression but some aspects of forager expression patterns, such as those for genes involved in immune function, remained. Combined with our real-time PCR data, these data suggest an epigenetic control and energy balance role in honey bee functional senescence.

  12. Clinical relevance of cortical spreading depression in neurological disorders: migraine, malignant stroke, subarachnoid and intracranial hemorrhage, and traumatic brain injury

    OpenAIRE

    Lauritzen, Martin; Dreier, Jens Peter; Fabricius, Martin; Hartings, Jed A.; Graf, Rudolf; Strong, Anthony John

    2010-01-01

    Cortical spreading depression (CSD) and depolarization waves are associated with dramatic failure of brain ion homeostasis, efflux of excitatory amino acids from nerve cells, increased energy metabolism and changes in cerebral blood flow (CBF). There is strong clinical and experimental evidence to suggest that CSD is involved in the mechanism of migraine, stroke, subarachnoid hemorrhage and traumatic brain injury. The implications of these findings are widespread and suggest that intrinsic br...

  13. Quantification of microangiopathic lesions in brain parenchyma and age-adjusted mean scores for the diagnostic separation of normal from pathological values in senile dementia

    International Nuclear Information System (INIS)

    Purpose: to quantify microangiopathic lesions in the cerebral white matter and to develop age-corrected cut-off values for separating normal from dementia-related pathological lesions. Materials and methods: in a memory clinic, 338 patients were investigated neuropsychiatrically by a psychological test battery and by MRI. Using a FLAIR sequence and a newly developed rating scale, white matter lesions (WMLs) were quantified with respect to localization, number and intensity, and these ratings were condensed into a score. The WML scores were correlated with the mini-mental state examination (MMSE) and clinical dementia rating (CDR) score in dementia patients. A non-linear smoothing procedure was used to calculate age-related mean values and confidence intervals, separate for cognitively intact subjects and dementia patients. Results: the WML scores correlated highly significantly with age in cognitively intact subjects and with psychometric scores in dementia patients. Age-adjusted WML scores of cognitively intact subjects were significantly different from those of dementia patients with respect to the whole brain as well as to the frontal lobe. Mean value and confidence intervals adjusted for age significantly separated dementia patients from cognitively intact subjects over an age range of 54 through 84 years. Conclusion: a rating scale for the quantification of WML was validated and age-adjusted mean values with their confidence intervals for a diagnostically relevant age range were developed. This allows an easy to handle, fast and reliable diagnosis of the vascular component in senile dementia. (orig.)

  14. 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

  15. 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

  16. 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. PMID:27037020

  17. 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

  18. 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.

  19. 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

  20. Contribution of brain atrophy on CT and aging to intelligence level. A clonological study through multivariate analysis

    Energy Technology Data Exchange (ETDEWEB)

    Kawai, Makoto (Showa Univ., Tokyo (Japan). School of Medicine)

    1984-09-01

    Decrased intellectual functions due to senility have been much discussed in connection with aging or brain atrophy 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 atrophy 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 chronological 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 aspects of the deteriorating phenomena of intellectual level 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 deterioration 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 deterioration and above mentioned two factors.

  1. Association of Alzheimer disease GWAS loci with MRI-markers of brain aging

    Science.gov (United States)

    Chauhan, Ganesh; Adams, Hieab H.H.; Bis, Joshua C; Weinstein, Galit; Yu, Lei; Töglhofer, Anna Maria; Smith, Albert Vernon; van der Lee, Sven; Gottesman, Rebecca F; Thomson, Russell; Wang, Jing; Yang, Qiong; Niessen, Wiro J.; Lopez, Oscar L; Becker, James T; Phan, Thanh G; Beare, Richard J; Arfanakis, Konstantinos; Fleischman, Debra; Vernooij, Meike W.; Mazoyer, Bernard; Schmidt, Helena; Srikanth, Velandai; Knopman, Dave S; Jack, Clifford R; Amouyel, Philippe; Hofman, Albert; DeCarli, Charlie; Tzourio, Christophe; van Duijn, Cornelia M; Bennett, David A; Schmidt, Reinhold; Longstreth, William T; Mosley, Thomas H; Fornage, Myriam; Launer, Lenore J; Seshadri, Sudha; Ikram, M Arfan; Debette, Stephanie

    2015-01-01

    Whether novel risk variants of Alzheimer’s disease (AD) identified through genome-wide association studies (GWAS) also influence MRI-based intermediate phenotypes of AD in the general population is unclear. We studied association of 24 AD risk loci with intracranial volume (ICV), total brain volume (TBV), hippocampal volume (HV), white matter hyperintensity (WMH) burden, and brain infarcts in a meta-analysis of genetic association studies from large population-based samples (N=8,175–11,550). In single-SNP based tests, AD risk allele of APOE (rs2075650) was associated with smaller HV (p=0.0054) and CD33 (rs3865444) with smaller ICV (p=0.0058) In gene-based tests, there was associations of HLA-DRB1 with TBV (p=0.0006) and BIN1 with HV (p=0.00089). A weighted AD genetic risk score was associated with smaller HV (beta±SE=−0.047±0.013, p=0.00041), even after excluding the APOE locus (p=0.029). However, only association of AD genetic risk score with HV, including APOE, was significant after multiple testing correction (including number of independent phenotypes tested). These results suggest that novel AD genetic risk variants may contribute to structural brain aging in non-demented older community persons. PMID:25670335

  2. 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

  3. 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

  4. 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....

  5. Neuroenhancement of the Aging Brain: Restoring Skill Acquisition in Old Subjects

    Science.gov (United States)

    Zimerman, Máximo; Nitsch, Marie; Giraux, Pascal; Gerloff, Christian; Cohen, Leonardo G.; Hummel, Friedhelm C.

    2016-01-01

    Objective Decline in cognitive functions, including impaired acquisition of novel skills, is a feature of older age that impacts activities of daily living, independence, and integration in modern societies. Methods We tested whether the acquisition of a complex motor skill can be enhanced in old subjects by the application of transcranial direct current stimulation (tDCS) to the motor cortex. Results The main finding was that old participants experienced substantial improvements when training was applied concurrent with tDCS, with effects lasting for at least 24 hours. Interpretation These results suggest noninvasive brain stimulation as a promising and safe tool to potentially assist functional independence of aged individuals in daily life. PMID:23225625

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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)

  11. Assessment of the quality of safety relevant SSC's by analysis of transients and events within the scope of aging management

    International Nuclear Information System (INIS)

    In the context of ageing management in the EnBW nuclear power stations Philippsburg and Neckarwestheim, the quality standard of the safety-relevant components must be monitored regularly. In the case of the mechanical components of Category M 1 (integrity concept with assured quality and exclusion of component failure), this means: Monitoring loads and water chemistry as potential damage mechanisms and monitoring the consequences of possible damage mechanisms (non-destructive testing etc.). In Category M 2, quality must be ensured and common mode failure must be excluded. These are mostly the external systems. Here, too, minimum quality must be ensured, e.g. by recurrent inspections, functional testing, inspection and maintenance. In both groups, also results of incidents and failure reports are considered. Quality assurance is component-specific including all measures for ensuring and maintaining quality. It is also checked whether the methods applied are sufficient and appropriate against the background of current knowledge. The summarized results of the evaluations (normally, in the form of so-called 'status sheets' with data tables) are presented and explained annually in a status report or status discussion. The contribution explains the procedure and presents concrete examples

  12. 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

  13. 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.

  14. Serum metabolites from walnut-fed aged rats attenuate stress-induced neurotoxicity in brain cells in vitro

    Science.gov (United States)

    The shift in equilibrium towards excess reactive oxygen or nitrogen species production from innate antioxidant defense in brain is a critical factor in the declining neural functions and cognitive deficits accompanying age. In aging, there are noticeable alterations in the membrane microenvironment,...

  15. 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)...

  16. Clinical relevance of cortical spreading depression in neurological disorders: migraine, malignant stroke, subarachnoid and intracranial hemorrhage, and traumatic brain injury

    DEFF Research Database (Denmark)

    Lauritzen, Martin; Dreier, Jens Peter; Fabricius, Martin;

    2011-01-01

    Cortical spreading depression (CSD) and depolarization waves are associated with dramatic failure of brain ion homeostasis, efflux of excitatory amino acids from nerve cells, increased energy metabolism and changes in cerebral blood flow (CBF). There is strong clinical and experimental evidence to...... pathophysiological mechanism for this group of acute neurological disorders. The findings have implications for monitoring and treatment of patients with acute brain disorders in the intensive care unit. Drawing on the large body of experimental findings from animal studies of CSD obtained during decades we suggest...

  17. 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.

  18. Self-esteem modulates automatic attentional responses to self-relevant stimuli: evidence from event-related brain potentials

    OpenAIRE

    Jie eChen; Qing eShui; Yiping eZhong

    2015-01-01

    Previous studies have widely shown that self-esteem modulates the attention bias towards social rejection or emotion-related information. However, little is known about the influences of self-esteem on attention bias towards self-relevant stimuli. We aimed to investigate neural correlates that underlie the modulation effect of self-esteem on self-relevant processing. Event-related potentials (ERP) were recorded for subjects’ own names and close others’ names (the names of their friends) while...

  19. 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...

  20. Diffusion tensor trace mapping in normal adult brain using single-shot EPI technique: A methodological study of the aging brain

    International Nuclear Information System (INIS)

    Purpose: To quantify age-related changes of the average diffusion coefficient value in normal adult brain using orientation-independent diffusion tensor trace mapping and to address the methodological influences on diffusion quantification. Material and Methods: Fifty-four normal subjects (aged 20-79 years) were studied on a 1.5-T whole-body MR medical unit using a diffusion-weighted single-shot echo-planar imaging technique. Orientation-independent diffusion tensor trace maps were constructed for each subject using diffusion-weighted MR measurements in four different directions using a tetrahedral gradient combination pattern. The global average (including cerebral spinal fluid) and the tissue average of diffusion coefficients in adult brains were determined by analyzing the diffusion coefficient distribution histogram for the entire brain. Methodological influences on the measured diffusion coefficient were also investigated by comparing the results obtained using different experimental settings. Results: Both global and tissue averages of the diffusion coefficient are significantly correlated with age (p<0.03). The global average of the diffusion coefficient increases 3% per decade after the age of 40, whereas the increase in the tissue average of diffusion coefficient is about 1% per decade. Experimental settings for self-diffusion measurements, such as data acquisition methods and number of b-values, can slightly influence the statistical distribution histogram of the diffusion tensor trace and its average value. Conclusion: Increased average diffusion coefficient in adult brains with aging are consistent with findings regarding structural changes in the brain that have been associated with aging. The study also demonstrates that it is desirable to use the same experimental parameters for diffusion coefficient quantification when comparing between different subjects and groups of interest

  1. 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.

  2. 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

  3. Age and gender based biomechanical shape and size analysis of the pediatric brain.

    Science.gov (United States)

    Danelson, Kerry A; Geer, Carol P; Stitzel, Joel D; Slice, Dennis E; Takhounts, Erik G

    2008-11-01

    Injuries caused by motor vehicle crashes (MVCs) are the leading cause of head injury and death for children in the United States. This study aims to describe the shape and size (morphologic) changes of the cerebrum, cerebellum, brainstem, and ventricles of the pediatric occupant to better predict injury and assess how these changes affect finite element model (FEM) response. To quantify morphologic differences in the brain, a Generalized Procrustes Analysis (GPA) with a sliding landmark method was conducted to isolate morphologic changes using magnetic resonance images of 63 normal subjects. This type of geometric morphometric analysis was selected for its ability to identify homologous landmarks on structures with few true landmarks and isolate the shape and size of the individuals studied. From the resulting landmark coordinates, the shape and size changes were regressed against age to develop a model describing morphologic changes in the pediatric brain as a function of age. The most statistically significant shape change was in the cerebrum with p-values of 0.00346 for males and 0.00829 for females. The age-based model explains over 80% of the variation in size in the cerebrum. Using size and shape models, affine transformations were applied to the SIMon FEM to determine differences in response given differences in size and size plus shape. The geometric centroid of the elements exceeding 15% strain was calculated and compared to the geometric centroid of the entire structure. Given the same Haversine pulse, the centroid location, a metric for the spatial distribution of the elements exceeding an injury threshold, varied based on which transformation was applied to the model. To assess the overall response of the model, three injury metrics were examined to determine the magnitude of the metrics each element sustained and the overall volume of elements that experienced that value. These results suggested that the overall response of the model was driven by the

  4. Mannosylated liposomal cytidine 5' diphosphocholine prevent age related global moderate cerebral ischemia reperfusion induced mitochondrial cytochrome c release in aged rat brain.

    Science.gov (United States)

    Ghosh, S; Das, N; Mandal, A K; Dungdung, S R; Sarkar, S

    2010-12-29

    Mitochondrial dysfunctions generating from cerebral ischemia-reperfusion exert a potential threat on neuronal cell survival and hence, accelerate the aging process and age dependent neuropathology. Thirty min moderate cerebral ischemia induced by bilateral common carotid artery occlusion (BCCAO) followed by 30 min reperfusion caused an increased diene production, depleted glutathione (GSH) content, reduced superoxide dismutase (SOD) and catalase activities and pyramidal neuronal loss in young (2 months old) and aged (20 months old) rat brain compared to sham operated controls. Cytidine 5' diphosphocholine (CDP-Choline) is a known neuroprotective drug. CDP-Choline after metabolism in the liver suffers hydrolysis and splits into cytidine and choline before entering systemic circulation and hardly circumvents blood brain barrier (BBB) as such. Previous reports show CDP-Choline liposomes significantly increased in vivo uptake compared to "free drug" administration in cerebral ischemia. To enhance the therapeutic concentration build up in brain we sought to formulate mannosylated liposomal CDP-Choline (MLCDP) utilizing the mannose receptors. We tested the therapeutic supremacy of MLCDP over liposomal CDP-Choline (LCDP) in global moderate cerebral ischemia reperfusion induced neuronal damage. CDP-Choline in MLCDP delivery system was found potent to exert substantial protection against global moderate cerebral ischemia reperfusion induced mitochondrial damage in aged rat brain. Membrane lipid peroxidation, GSSG/GSH ratio and reactive oxygen species (ROS) generation in cerebral tissue were found to be higher in aged, compared to young rat. Further decline of those parameters was observed in aged rat brain by the induction of global moderate cerebral ischemia and reperfusion. MLCDP treatment when compared to free or LCDP treatment prevented global moderate cerebral ischemia-reperfusion induced mitochondrial damage as evident ultra structurally and release of cytochrome c

  5. 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.

  6. 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

  7. Alzheimer’s disease: relevant molecular and physiopathological events affecting amyloid-β brain balance and the putative role of PPARs

    Science.gov (United States)

    Zolezzi, Juan M.; Bastías-Candia, Sussy; Santos, Manuel J.; Inestrosa, Nibaldo C.

    2014-01-01

    Alzheimer’s disease (AD) is the most common form of age-related dementia. With the expected aging of the human population, the estimated morbidity of AD suggests a critical upcoming health problem. Several lines of research are focused on understanding AD pathophysiology, and although the etiology of the disease remains a matter of intense debate, increased brain levels of amyloid-β (Aβ) appear to be a critical event in triggering a wide range of molecular alterations leading to AD. It has become evident in recent years that an altered balance between production and clearance is responsible for the accumulation of brain Aβ. Moreover, Aβ clearance is a complex event that involves more than neurons and microglia. The status of the blood-brain barrier (BBB) and choroid plexus, along with hepatic functionality, should be considered when Aβ balance is addressed. Furthermore, it has been proposed that exposure to sub-toxic concentrations of metals, such as copper, could both directly affect these secondary structures and act as a seeding or nucleation core that facilitates Aβ aggregation. Recently, we have addressed peroxisomal proliferator-activated receptors (PPARs)-related mechanisms, including the direct modulation of mitochondrial dynamics through the PPARγ-coactivator-1α (PGC-1α) axis and the crosstalk with critical aging- and neurodegenerative-related cellular pathways. In the present review, we revise the current knowledge regarding the molecular aspects of Aβ production and clearance and provide a physiological context that gives a more complete view of this issue. Additionally, we consider the different structures involved in AD-altered Aβ brain balance, which could be directly or indirectly affected by a nuclear receptor (NR)/PPAR-related mechanism. PMID:25120477

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Neuropsychiatric disease relevance of circulating anti-NMDA receptor autoantibodies depends on blood-brain barrier integrity.

    Science.gov (United States)

    Hammer, C; Stepniak, B; Schneider, A; Papiol, S; Tantra, M; Begemann, M; Sirén, A-L; Pardo, L A; Sperling, S; Mohd Jofrry, S; Gurvich, A; Jensen, N; Ostmeier, K; Lühder, F; Probst, C; Martens, H; Gillis, M; Saher, G; Assogna, F; Spalletta, G; Stöcker, W; Schulz, T F; Nave, K-A; Ehrenreich, H

    2014-10-01

    In 2007, a multifaceted syndrome, associated with anti-NMDA receptor autoantibodies (NMDAR-AB) of immunoglobulin-G isotype, has been described, which variably consists of psychosis, epilepsy, cognitive decline and extrapyramidal symptoms. Prevalence and significance of NMDAR-AB in complex neuropsychiatric disease versus health, however, have remained unclear. We tested sera of 2817 subjects (1325 healthy, 1081 schizophrenic, 263 Parkinson and 148 affective-disorder subjects) for presence of NMDAR-AB, conducted a genome-wide genetic association study, comparing AB carriers versus non-carriers, and assessed their influenza AB status. For mechanistic insight and documentation of AB functionality, in vivo experiments involving mice with deficient blood-brain barrier (ApoE(-/-)) and in vitro endocytosis assays in primary cortical neurons were performed. In 10.5% of subjects, NMDAR-AB (NR1 subunit) of any immunoglobulin isotype were detected, with no difference in seroprevalence, titer or in vitro functionality between patients and healthy controls. Administration of extracted human serum to mice influenced basal and MK-801-induced activity in the open field only in ApoE(-/-) mice injected with NMDAR-AB-positive serum but not in respective controls. Seropositive schizophrenic patients with a history of neurotrauma or birth complications, indicating an at least temporarily compromised blood-brain barrier, had more neurological abnormalities than seronegative patients with comparable history. A common genetic variant (rs524991, P=6.15E-08) as well as past influenza A (P=0.024) or B (P=0.006) infection were identified as predisposing factors for NMDAR-AB seropositivity. The >10% overall seroprevalence of NMDAR-AB of both healthy individuals and patients is unexpectedly high. Clinical significance, however, apparently depends on association with past or present perturbations of blood-brain barrier function. PMID:23999527

  11. MRI of the incisural plane: assessment of normal brain stem position by age and transtentorial brain stem shift in disease

    International Nuclear Information System (INIS)

    The standardization on MRI of an anatomic plane passing through the tectum of the midbrain based on fixed landmarks allows assessment of the position of the brain stem during development and in normal adulthood, and comparison with its position in disease states. The level of the tectum relative to this incisural plane changes during normal cranial growth as well as in the presence of masses, frank brain stem herniation correlating with altered consciousness. (orig.)

  12. Effects of MDMA and related analogs on plasma 5-HT: Relevance to 5-HT transporters in blood and brain

    OpenAIRE

    Yubero-Lahoz, Samanta; Ayestas, Mario A; Blough, Bruce E; Partilla, John S; Rothman, Richard B.; de la Torre, Rafael; Baumann, Michael H.

    2011-01-01

    (±)-3,4-Methylenedioxymethamphetamine (MDMA) is an illicit drug that evokes transporter-mediated release of serotonin (5-HT) in the brain. 5-HT transporter (SERT) proteins are also expressed in non-neural tissues (e.g., blood), and evidence suggests that MDMA targets platelet SERT to increase plasma 5-HT. Here we tested two hypotheses related to the effects of MDMA on circulating 5-HT. First, to determine if MDMA metabolites might contribute to actions of the drug in vivo, we used in vitro mi...

  13. Sources of EEG activity most relevant to performance of brain-computer interface based on motor imagery

    Czech Academy of Sciences Publication Activity Database

    Frolov, A.; Húsek, Dušan; Bobrov, P.; Korshakov, A.V.; Chernikova, L.; Konovalov, R.; Mokienko, O.

    2012-01-01

    Roč. 22, č. 1 (2012), s. 21-37. ISSN 1210-0552 R&D Projects: GA ČR GAP202/10/0262 Grant ostatní: GA MŠk(CZ) ED1.1.00/02.0070 Institutional research plan: CEZ:AV0Z10300504 Keywords : brain-computer interface * independent component analysis * pattern classification * motor imagery * inverse problem * fMRI * EEG Subject RIV: IN - Informatics, Computer Science Impact factor: 0.362, year: 2012

  14. Interactions of AChE with Aβ Aggregates in Alzheimer’s Brain: Therapeutic Relevance of IDN 5706

    Directory of Open Access Journals (Sweden)

    Francisco Javier Carvajal

    2011-09-01

    Full Text Available Acetylcholinesterase (AChE; EC 3.1.1.7 plays a crucial role in the rapid hydrolysis of the neurotransmitter acetylcholine, in the central and peripheral nervous system and might also participate in non-cholinergic mechanism related to neurodegenerative diseases. Alzheimer’s disease (AD is a neurodegenerative disorder characterized by a progressive deterioration of cognitive abilities, amyloid-β peptide (Aβ accumulation and synaptic alterations. We have previously shown that AChE is able to accelerate the Aβ peptide assembly into Alzheimer-type aggregates increasing its neurotoxicity. Furthermore, AChE activity is altered in brain and blood of Alzheimer’s patients. The enzyme associated to amyloid plaques changes its enzymatic and pharmacological properties, as well as, increases its resistant to low pH, inhibitors and excess of substrate. Here, we reviewed the effects of IDN 5706, a hyperforin derivative that has potential preventive effects on the development of AD. Our results show that treatment with IDN5706 for 10 weeks increases brain AChE activity in seven month-old double transgenic mice (APPswe - PS1 and decreases the content of AChE associated with different types of amyloid plaques in this Alzheimer’s model. We concluded that early treatment with IDN 5706 decreases AChE-Aβ interaction and this effect might be of therapeutic interest in the treatment of AD.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. 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

  17. 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

  18. 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

  19. Identifying diagnostically-relevant resting state brain functional connectivity in the ventral posterior complex via genetic data mining in autism spectrum disorder.

    Science.gov (United States)

    Baldwin, Philip R; Curtis, Kaylah N; Patriquin, Michelle A; Wolf, Varina; Viswanath, Humsini; Shaw, Chad; Sakai, Yasunari; Salas, Ramiro

    2016-05-01

    Exome sequencing and copy number variation analyses continue to provide novel insight to the biological bases of autism spectrum disorder (ASD). The growing speed at which massive genetic data are produced causes serious lags in analysis and interpretation of the data. Thus, there is a need to develop systematic genetic data mining processes that facilitate efficient analysis of large datasets. We report a new genetic data mining system, ProcessGeneLists and integrated a list of ASD-related genes with currently available resources in gene expression and functional connectivity of the human brain. Our data-mining program successfully identified three primary regions of interest (ROIs) in the mouse brain: inferior colliculus, ventral posterior complex of the thalamus (VPC), and parafascicular nucleus (PFn). To understand its pathogenic relevance in ASD, we examined the resting state functional connectivity (RSFC) of the homologous ROIs in human brain with other brain regions that were previously implicated in the neuro-psychiatric features of ASD. Among them, the RSFC of the VPC with the medial frontal gyrus (MFG) was significantly more anticorrelated, whereas the RSFC of the PN with the globus pallidus was significantly increased in children with ASD compared with healthy children. Moreover, greater values of RSFC between VPC and MFG were correlated with severity index and repetitive behaviors in children with ASD. No significant RSFC differences were detected in adults with ASD. Together, these data demonstrate the utility of our data-mining program through identifying the aberrant connectivity of thalamo-cortical circuits in children with ASD. Autism Res 2016, 9: 553-562. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. PMID:26451751

  20. Cardiorespiratory fitness is associated with brain structure, cognition, and mood in a middle-aged cohort at risk for Alzheimer's disease.

    Science.gov (United States)

    Boots, Elizabeth A; Schultz, Stephanie A; Oh, Jennifer M; Larson, Jordan; Edwards, Dorothy; Cook, Dane; Koscik, Rebecca L; Dowling, Maritza N; Gallagher, Catherine L; Carlsson, Cynthia M; Rowley, Howard A; Bendlin, Barbara B; LaRue, Asenath; Asthana, Sanjay; Hermann, Bruce P; Sager, Mark A; Johnson, Sterling C; Okonkwo, Ozioma C

    2015-09-01

    Cardiorespiratory fitness (CRF) is an objective measure of habitual physical activity (PA), and has been linked to increased brain structure and cognition. The gold standard method for measuring CRF is graded exercise testing (GXT), but GXT is not feasible in many settings. The objective of this study was to examine whether a non-exercise estimate of CRF is related to gray matter (GM) volumes, white matter hyperintensities (WMH), cognition, objective and subjective memory function, and mood in a middle-aged cohort at risk for Alzheimer's disease (AD). Three hundred and fifteen cognitively healthy adults (mean age =58.58 years) enrolled in the Wisconsin Registry for Alzheimer's Prevention underwent structural MRI scanning, cognitive testing, anthropometric assessment, venipuncture for laboratory tests, and completed a self-reported PA questionnaire. A subset (n = 85) underwent maximal GXT. CRF was estimated using a previously validated equation incorporating sex, age, body-mass index, resting heart rate, and self-reported PA. Results indicated that the CRF estimate was significantly associated with GXT-derived peak oxygen consumption, validating its use as a non-exercise CRF measure in our sample. Support for this finding was seen in significant associations between the CRF estimate and several cardiovascular risk factors. Higher CRF was associated with greater GM volumes in several AD-relevant brain regions including the hippocampus, amygdala, precuneus, supramarginal gyrus, and rostral middle frontal gyrus. Increased CRF was also associated with lower WMH and better cognitive performance in Verbal Learning & Memory, Speed & Flexibility, and Visuospatial Ability. Lastly, CRF was negatively correlated with self- and informant-reported memory complaints, and depressive symptoms. Together, these findings suggest that habitual participation in physical activity may provide protection for brain structure and cognitive function, thereby decreasing future risk for AD

  1. Can passive mobilization provide clinically-relevant brain stimulation? A pilot EEG and NIRS study on healthy subjects.

    Science.gov (United States)

    Pittaccio, Simone; Garavaglia, Lorenzo; Molteni, Erika; Guanziroli, Eleonora; Zappasodi, Filippo; Beretta, Elena; Strazzer, Sandra; Molteni, Franco; Villa, Elena; Passaretti, Francesca

    2013-01-01

    Lower limb rehabilitation is a fundamental part of post-acute care in neurological disease. Early commencement of active workout is often prevented by paresis, thus physical treatment may be delayed until patients regain some voluntary command of their muscles. Passive mobilization of the affected joints is mostly delivered in order to safeguard tissue properties and shun circulatory problems. The present paper investigates the potential role of early passive motion in stimulating cortical areas of the brain devoted to the control of the lower limb. An electro-mechanical mobilizer for the ankle joint (Toe-Up!) was implemented utilizing specially-designed shape-memory-alloy-based actuators. This device was constructed to be usable by bedridden subjects. Besides, the slowness and gentleness of the imparted motion, make it suitable for patients in a very early stage of their recovery. The mobilizer underwent technical checks to confirm reliability and passed the required safety tests for electric biomedical devices. Four healthy volunteers took part in the pre-clinical phase of the study. The protocol consisted in measuring of brain activity by EEG and NIRS in four different conditions: rest, active dorsiflexion of the ankle, passive mobilization of the ankle, and assisted motion of the same joint. The acquired data were processed to obtain maps of cortical activation, which were then compared. The measurements collected so far show that there is a similar pattern of activity between active and passive/assisted particularly in the contralateral premotor areas. This result, albeit based on very few observations, might suggest that passive motion provides somatosensory afferences that are processed in a similar manner as for voluntary control. Should this evidence be confirmed by further trials on healthy individuals and neurological patients, it could form a basis for a clinical use of early passive exercise in supporting central functional recovery. PMID:24110495

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

    Science.gov (United States)

    Patterson, Susan L

    2015-09-01

    Older individuals often experience declines in cognitive function after events (e.g. infection, or injury) that trigger activation of the immune system. This occurs at least in part because aging sensitizes the response of microglia (the brain's resident immune cells) to signals triggered by an immune challenge. In the aging brain, microglia respond to these signals by producing more pro-inflammatory cytokines (e.g. interleukin-1beta or IL-1β) and producing them for longer than microglia in younger brains. This exaggerated inflammatory response can compromise processes critical for optimal cognitive functioning. Interleukin-1β is central to the inflammatory response and is a key mediator and modulator of an array of associated biological functions; thus its production and release is usually very tightly regulated. This review will focus on the impact of dysregulated production of IL-1β on hippocampus dependent-memory systems and associated synaptic plasticity processes. The neurotrophin brain-derived neurotrophic factor (BNDF) helps to protect neurons from damage caused by infection or injury, and it plays a critical role in many of the same memory and hippocampal plasticity processes compromised by dysregulated production of IL-1β. This suggests that an exaggerated brain inflammatory response, arising from aging and a secondary immune challenge, may erode the capacity to provide the BDNF needed for memory-related plasticity processes at hippocampal synapses. This article is part of a Special Issue entitled 'Neuroimmunology and Synaptic Function'. PMID:25549562

  3. Differences in age-related effects on brain volume in Down syndrome as compared to Williams syndrome and typical development

    Science.gov (United States)

    2014-01-01

    Background Individuals with Down Syndrome (DS) are reported to experience early onset of brain aging. However, it is not well understood how pre-existing neurodevelopmental effects versus neurodegenerative processes might be contributing to the observed pattern of brain atrophy in younger adults with DS. The aims of the current study were to: (1) to confirm previous findings of age-related changes in DS compared to adults with typical development (TD), (2) to test for an effect of these age-related changes in a second neurodevelopmental disorder, Williams syndrome (WS), and (3) to identify a pattern of regional age-related effects that are unique to DS. Methods High-resolution T1-weighted MRI of the brains of subjects with DS, WS, and TD controls were segmented, and estimates of regional brain volume were derived using FreeSurfer. A general linear model was employed to test for age-related effects on volume between groups. Secondary analyses in the DS group explored the relationship between brain volume and neuropsychological tests and APOE. Results Consistent with previous findings, the DS group showed significantly greater age-related effects relative to TD controls in total gray matter and in regions of the orbitofrontal cortex and the parietal cortex. Individuals with DS also showed significantly greater age-related effects on volume of the left and right inferior lateral ventricles (LILV and RILV, respectively). There were no significant differences in age-related effects on volume when comparing the WS and TD groups. In the DS group, cognitive tests scores measuring signs of dementia and APOE ϵ4 carrier status were associated with LILV and RILV volume. Conclusions Individuals with DS demonstrated a unique pattern of age-related effects on gray matter and ventricular volume, the latter of which was associated with dementia rating scores in the DS group. Results may indicate that early onset of brain aging in DS is primarily due to DS

  4. 1,3-Dinitrobenzene Induces Age- and Region-Specific Oxidation to Mitochondria-Related Proteins in Brain

    OpenAIRE

    Kubik, Laura L.; Landis, Rory W.; Remmer, Henriette; Bergin, Ingrid L; Philbert, Martin A.

    2015-01-01

    Regions of the brain with high energy requirements are especially sensitive to perturbations in mitochondrial function. Hence, neurotoxicant exposures that target mitochondria in regions of high energy demand have the potential to accelerate mitochondrial damage inherently occurring during the aging process. 1,3-Dinitrobenzene (DNB) is a model neurotoxicant that selectively targets mitochondria in brainstem nuclei innervated by the eighth cranial nerve. This study investigates the role of age...

  5. Redox proteomic profiling of neuroketal-adducted proteins in human brain: Regional vulnerability at middle age increases in the elderly.

    Science.gov (United States)

    Domínguez, Mayelín; de Oliveira, Eliandre; Odena, María Antonia; Portero, Manuel; Pamplona, Reinald; Ferrer, Isidro

    2016-06-01

    Protein lipoxidation was assessed in the parietal cortex (PC), frontal cortex (FC), and cingulate gyrus (CG) in middle-aged and old-aged individuals with no clinical manifestations of cognitive impairment, in order to increase understanding of regional brain vulnerability to oxidative damage during aging. Twenty-five lipoxidized proteins were identified in all the three regions although with regional specificities, by using redox proteomics to detect target proteins of neuroketals (NKT) adduction. The number of cases with NKT-adducted proteins was higher in old-aged individuals but most oxidized proteins were already present in middle-aged individuals. Differences in vulnerability to oxidation were dependent on the sub-cellular localization, secondary structure, and external exposition of certain amino acids. Lipoxidized proteins included those involved in energy metabolism, cytoskeleton, proteostasis, neurotransmission and O2/CO2, and heme metabolism. Total NKT and soluble oligomer levels were estimated employing slot-blot, and these were compared between age groups. Oligomers increased with age in PC and FC; NKT significantly increased with age in FC, whereas total NKT and oligomer levels were not modified in CG, thus highlighting differences in brain regional vulnerability with age. Oligomers significantly correlated with NKT levels in the three cortical regions, suggesting that protein NKT adduction parallels soluble oligomer formation. PMID:26968793

  6. Age-related differences in metabolites in the posterior cingulate cortex and hippocampus of normal ageing brain: A 1H-MRS study

    International Nuclear Information System (INIS)

    Objective: To study age-related metabolic changes in N-acetylaspartate (NAA), total creatine (tCr), choline (Cho) and myo-inositol (Ins). Materials and methods: Proton magnetic resonance spectroscopy (1H-MRS) was performed in the posterior cingulate cortex (PCC) and the left hippocampus (HC) of 90 healthy subjects (42 women and 48 men aged 18–76 years, mean ± SD, 48.4 ± 16.8 years). Both metabolite ratios and absolute metabolite concentrations were evaluated. Analysis of covariance (ANCOVA) and linear regression were used for statistical analysis. Results: Metabolite ratios Ins/tCr and Ins/H2O were found significantly increased with age in the PCC (P 2O was only observed in the PCC (P 1H-MRS results in these specific brain regions can be important to differentiate normal ageing from age-related pathologies such as mild cognitive impairment (MCI) and Alzheimer's disease.

  7. 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

  8. Insights on the Functional Interactions between miRNAs and Copy Number Variations in the Aging Brain

    Directory of Open Access Journals (Sweden)

    Ronald Bontrop

    2013-10-01

    Full Text Available MicroRNAs (miRNAs are regulatory genetic elements that coordinate the expression of thousands of genes and play important roles in brain aging and neurodegeneration. DNA polymorphisms affecting miRNA biogenesis, dosage and gene targeting may represent potentially functional variants. The consequences of single nucleotide polymorphisms (SNPs affecting miRNA function were previously demonstrated by both experimental and computational methods. However, little is known about how copy number variations (CNVs influence miRNA metabolism and regulatory networks. We discuss potential mechanisms of CNVs-mediated effects on miRNA function and regulation that might have consequences for brain aging. We argue that CNVs, which potentially can alter miRNA expression, regulation or target gene recognition, are possible functional variants and should be considered high priority candidates in genotype-phenotype mapping studies of brain-related disorders.

  9. 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.)

  10. Whole-brain grey matter density predicts balance stability irrespective of age and protects older adults from falling.

    Science.gov (United States)

    Boisgontier, Matthieu P; Cheval, Boris; van Ruitenbeek, Peter; Levin, Oron; Renaud, Olivier; Chanal, Julien; Swinnen, Stephan P

    2016-03-01

    Functional and structural imaging studies have demonstrated the involvement of the brain in balance control. Nevertheless, how decisive grey matter density and white matter microstructural organisation are in predicting balance stability, and especially when linked to the effects of ageing, remains unclear. Standing balance was tested on a platform moving at different frequencies and amplitudes in 30 young and 30 older adults, with eyes open and with eyes closed. Centre of pressure variance was used as an indicator of balance instability. The mean density of grey matter and mean white matter microstructural organisation were measured using voxel-based morphometry and diffusion tensor imaging, respectively. Mixed-effects models were built to analyse the extent to which age, grey matter density, and white matter microstructural organisation predicted balance instability. Results showed that both grey matter density and age independently predicted balance instability. These predictions were reinforced when the level of difficulty of the conditions increased. Furthermore, grey matter predicted balance instability beyond age and at least as consistently as age across conditions. In other words, for balance stability, the level of whole-brain grey matter density is at least as decisive as being young or old. Finally, brain grey matter appeared to be protective against falls in older adults as age increased the probability of losing balance in older adults with low, but not moderate or high grey matter density. No such results were observed for white matter microstructural organisation, thereby reinforcing the specificity of our grey matter findings. PMID:26979897

  11. 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

  12. Cancer and aging: a multidisciplinary medicinal chemistry approach on relevant biological targets such as proteasome, sirtuins and interleukin 6

    OpenAIRE

    Parenti, Marco Daniele

    2015-01-01

    It is well known that ageing and cancer have common origins due to internal and environmental stress and share some common hallmarks such as genomic instability, epigenetic alteration, aberrant telomeres, inflammation and immune injury. Moreover, ageing is involved in a number of events responsible for carcinogenesis and cancer development at the molecular, cellular, and tissue levels. Ageing could represent a “blockbuster” market because the target patient group includes potentially every...

  13. Measuring the effects of aging and sex on regional brain stiffness with MR elastography in healthy older adults.

    Science.gov (United States)

    Arani, Arvin; Murphy, Matthew C; Glaser, Kevin J; Manduca, Armando; Lake, David S; Kruse, Scott A; Jack, Clifford R; Ehman, Richard L; Huston, John

    2015-05-01

    Changes in tissue composition and cellular architecture have been associated with neurological disease, and these in turn can affect biomechanical properties. Natural biological factors such as aging and an individual's sex also affect underlying tissue biomechanics in different brain regions. Understanding the normal changes is necessary before determining the efficacy of stiffness imaging for neurological disease diagnosis and therapy monitoring. The objective of this study was to evaluate global and regional changes in brain stiffness as a function of age and sex, using improved MRE acquisition and processing that have been shown to provide median stiffness values that are typically reproducible to within 1% in global measurements and within 2% for regional measurements. Furthermore, this is the first study to report the effects of age and sex over the entire cerebrum volume and over the full frontal, occipital, parietal, temporal, deep gray matter/white matter (insula, deep gray nuclei and white matter tracts), and cerebellum volumes. In 45 volunteers, we observed a significant linear correlation between age and brain stiffness in the cerebrum (Psensory-motor regions (P=.32) of the brain, and a weak linear trend was observed in the deep gray matter/white matter (P=.075). A multiple linear regression model predicted an annual decline of 0.011 ± 0.002 kPa in cerebrum stiffness with a theoretical median age value (76 years old) of 2.56 ± 0.08 kPa. Sexual dimorphism was observed in the temporal (P=.03) and occipital (P=.001) lobes of the brain, but no significant difference was observed in any of the other brain regions (P>.20 for all other regions). The model predicted female occipital and temporal lobes to be 0.23 kPa and 0.09 kPa stiffer than males of the same age, respectively. This study confirms that as the brain ages, there is softening; however, the changes are dependent on region. In addition, stiffness effects due to sex exist in the occipital and

  14. 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…

  15. 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.

  16. Flight restriction prevents associative learning deficits but not changes in brain protein-adduct formation during honeybee ageing.

    Science.gov (United States)

    Tolfsen, Christina C; Baker, Nicholas; Kreibich, Claus; Amdam, Gro V

    2011-04-15

    Honeybees (Apis mellifera) senesce within 2 weeks after they discontinue nest tasks in favour of foraging. Foraging involves metabolically demanding flight, which in houseflies (Musca domestica) and fruit flies (Drosophila melanogaster) is associated with markers of ageing such as increased mortality and accumulation of oxidative damage. The role of flight in honeybee ageing is incompletely understood. We assessed relationships between honeybee flight activity and ageing by simulating rain that confined foragers to their colonies most of the day. After 15 days on average, flight-restricted foragers were compared with bees with normal (free) flight: one group that foraged for ∼15 days and two additional control groups, for flight duration and chronological age, that foraged for ∼5 days. Free flight over 15 days on average resulted in impaired associative learning ability. In contrast, flight-restricted foragers did as well in learning as bees that foraged for 5 days on average. This negative effect of flight activity was not influenced by chronological age or gustatory responsiveness, a measure of the bees' motivation to learn. Contrasting their intact learning ability, flight-restricted bees accrued the most oxidative brain damage as indicated by malondialdehyde protein adduct levels in crude cytosolic fractions. Concentrations of mono- and poly-ubiquitinated brain proteins were equal between the groups, whereas differences in total protein amounts suggested changes in brain protein metabolism connected to forager age, but not flight. We propose that intense flight is causal to brain deficits in aged bees, and that oxidative protein damage is unlikely to be the underlying mechanism. PMID:21430210

  17. 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

  18. Age-related changes in brain perfusion of normal subjects detected by 99mTc-HMPAO SPECT

    International Nuclear Information System (INIS)

    Previous functional imaging data generally show impairment in global cerebral blood flow (CBF) with age. Conflicting data, however, concerning age-related changes in regional CBF (rCBF) have been reported. We examined the relative rCBF in a sample of healthy subjects of various ages, to define and localize any age-related CBF reduction. Twenty-seven healthy subjects (17 male, 10 female; mean age 49 ± 15, range 26-71, median 47 years) were studied by 99mTc-HMPAO brain SPECT. The younger age group consisted of subjects below, the older group above 47 years of age, respectively. Analysis was performed by applying three preformed templates, each containing delineated regions of interest (ROIs), to three transaxial brain slices at approximately 4, 6, and 7 cm above the orbitomeatal line (OML). The average number of counts for each ROI was normalized to mean uptake of the cerebellum and of the whole brain slice. Globally, 99mTc-HMPAO uptake ratio normalized to cerebellum was significantly decreased in older subjects, affecting both hemispheres. A slight left-to-right asymmetry was observed in HMPAO uptake of the whole study group. It did not, however, change with age. Regionally, both cortical and subcortical structures of older subjects were involved: uptake ratio to cerebellum was significantly lower (after correction for multiple testing) in the left basal ganglia and in the left superior temporal, right frontal and bilateral occipital cortices at 4 cm above the OML. At 6 cm above the OML, reduced uptake ratios were identified in the left frontal and bilateral parietal areas. At 7 cm, reduced uptake was detected in the right frontal and left occipital cortices. Most of these differences were reduced when uptake was normalized to whole slice, whereas an increase in uptake ratios was observed in the cingulate cortex of the elderly. An inverse correlation between age and HMPAO uptake ratios normalized to cerebellum was observed in a number of brain regions. These

  19. The Phosphatidylinositol 3-Kinase/mTor Pathway as a Therapeutic Target for Brain Aging and Neurodegeneration

    Directory of Open Access Journals (Sweden)

    David Heras-Sandoval

    2011-08-01

    Full Text Available Many pathological conditions are associated with phosphatidylinositol 3-kinase (PI3K dysfunction, providing an incentive for the study of the effects of PI3K modulation in different aspects of diabetes, cancer, and aging. The PI3K/AKT/mTOR pathway is a key transducer of brain metabolic and mitogenic signals involved in neuronal proliferation, differentiation, and survival. In several models of neurodegenerative diseases associated with aging, the PI3K/AKT pathway has been found to be dysregulated, suggesting that two or more initiating events may trigger disease formation in an age-related manner. The search for chemical compounds able to modulate the activity of the PI3K/AKT/mTOR pathway is emerging as a potential therapeutic strategy for the treatment and/or prevention of some metabolic defects associated with brain aging. In the current review, we summarize some of the critical actions of PI3K in brain function as well as the evidence of its involvement in aging and Alzheimer’s disease.

  20. Lipid-laden cells differentially distributed in the aging brain are functionally active and correspond to distinct phenotypes.

    Science.gov (United States)

    Shimabukuro, Marilia Kimie; Langhi, Larissa Gutman Paranhos; Cordeiro, Ingrid; Brito, José M; Batista, Claudia Maria de Castro; Mattson, Mark P; Mello Coelho, Valeria de

    2016-01-01

    We characterized cerebral Oil Red O-positive lipid-laden cells (LLC) of aging mice evaluating their distribution, morphology, density, functional activities and inflammatory phenotype. We identified LLC in meningeal, cortical and neurogenic brain regions. The density of cerebral LLC increased with age. LLC presenting small lipid droplets were visualized adjacent to blood vessels or deeper in the brain cortical and striatal parenchyma of aging mice. LLC with larger droplets were asymmetrically distributed in the cerebral ventricle walls, mainly located in the lateral wall. We also found that LLC in the subventricular region co-expressed beclin-1 or LC3, markers for autophagosome or autophagolysosome formation, and perilipin (PLIN), a lipid droplet-associated protein, suggesting lipophagic activity. Some cerebral LLC exhibited β galactosidase activity indicating a senescence phenotype. Moreover, we detected production of the pro-inflammatory cytokine TNF-α in cortical PLIN(+) LLC. Some cortical NeuN(+) neurons, GFAP(+) glia limitans astrocytes, Iba-1(+) microglia and S100β(+) ependymal cells expressed PLIN in the aging brain. Our findings suggest that cerebral LLC exhibit distinct cellular phenotypes and may participate in the age-associated neuroinflammatory processes. PMID:27029648

  1. 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)

  2. Prenatal immune challenge is an environmental risk factor for brain and behavior change relevant to schizophrenia: evidence from MRI in a mouse model.

    Directory of Open Access Journals (Sweden)

    Qi Li

    Full Text Available OBJECTIVES: Maternal infection during pregnancy increases risk of severe neuropsychiatric disorders, including schizophrenia and autism, in the offspring. The most consistent brain structural abnormality in patients with schizophrenia is enlarged lateral ventricles. However, it is unknown whether the aetiology of ventriculomegaly in schizophrenia involves prenatal infectious processes. The present experiments tested the hypothesis that there is a causal relationship between prenatal immune challenge and emergence of ventricular abnormalities relevant to schizophrenia in adulthood. METHOD: We used an established mouse model of maternal immune activation (MIA by the viral mimic PolyI:C administered in early (day 9 or late (day 17 gestation. Automated voxel-based morphometry mapped cerebrospinal fluid across the whole brain of adult offspring and the results were validated by manual region-of-interest tracing of the lateral ventricles. Parallel behavioral testing determined the existence of schizophrenia-related sensorimotor gating abnormalities. RESULTS: PolyI:C-induced immune activation, in early but not late gestation, caused marked enlargement of lateral ventricles in adulthood, without affecting total white and grey matter volumes. This early exposure disrupted sensorimotor gating, in the form of prepulse inhibition. Identical immune challenge in late gestation resulted in significant expansion of 4(th ventricle volume but did not disrupt sensorimotor gating. CONCLUSIONS: Our results provide the first experimental evidence that prenatal immune activation is an environmental risk factor for adult ventricular enlargement relevant to schizophrenia. The data indicate immune-associated environmental insults targeting early foetal development may have more extensive neurodevelopmental impact than identical insults in late prenatal life.

  3. 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

  4. 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.

  5. Influence of age on the passage of paraquat through the blood-brain barrier in rats: a distribution and pathological examination

    International Nuclear Information System (INIS)

    Experiments were performed to determine the extent of paraquat entry into the brain of neonatal and elderly rats, as compared with adult rats, which may be dependent on the efficacy of the blood-brain barrier. A single, median lethal dose (20 mg/kg s.c.) of paraquat containing [14C]paraquat was administered to neonatal (10 day old), adult (3 month old) and elderly (18 month old) rats. In contrast to the adult and elderly rats where paraquat levels fell over the 24 h post-dosing period to negligible levels, paraquat concentrations in neonatal brains did not decrease with time between 0.5 and 24 h following dosing. The distribution of [14C]paraquat was measured in selective brain regions using quantitative autoradiography in all three age groups of rats, 30 min and 24 h following dosing. Autoradiography demonstrated that brain paraquat distributions were similar in the rat age groups. Most of the paraquat was confined to regions outside the blood-brain barrier and to brain regions that lack a complete blood-brain barrier e.g. dorsal hypothalamus, area postrema and the anterior olfactory bulb. Between 0.5 h and 24 h following dosing, paraquat concentrations in deeper brain structures, some distance away from the sites of entry, began to slowly increase in all the rat age groups. By 24 h following dosing, a majority of brain regions examined using quantitative autoradiography revealed significantly higher paraquat concentrations in neonatal brains as compared to brain regions of adult and elderly rats. Despite increased paraquat entry into neonatal brain, we could find no evidence for paraquat-induced neuronal cell damage following a detailed histopathological examination of perfused-fixed brains. In conclusion, impaired blood-brain barrier integrity in neonatal brain thus permitting more paraquat to enter than in adult brain, did not result in neuronal damage

  6. Diverse antidepressants increase CDP-diacylglycerol production and phosphatidylinositide resynthesis in depression-relevant regions of the rat brain

    Directory of Open Access Journals (Sweden)

    Undieh Ashiwel S

    2008-01-01

    Full Text Available Abstract Background Major depression is a serious mood disorder affecting millions of adults and children worldwide. While the etiopathology of depression remains obscure, antidepressant medications increase synaptic levels of monoamine neurotransmitters in brain regions associated with the disease. Monoamine transmitters activate multiple signaling cascades some of which have been investigated as potential mediators of depression or antidepressant drug action. However, the diacylglycerol arm of phosphoinositide signaling cascades has not been systematically investigated, even though downstream targets of this cascade have been implicated in depression. With the ultimate goal of uncovering the primary postsynaptic actions that may initiate cellular antidepressive signaling, we have examined the antidepressant-induced production of CDP-diacylglycerol which is both a product of diacylglycerol phosphorylation and a precursor for the synthesis of physiologically critical glycerophospholipids such as the phosphatidylinositides. For this, drug effects on [3H]cytidine-labeled CDP-diacylglycerol and [3H]inositol-labeled phosphatidylinositides were measured in response to the tricyclics desipramine and imipramine, the selective serotonin reuptake inhibitors fluoxetine and paroxetine, the atypical antidepressants maprotiline and nomifensine, and several monoamine oxidase inhibitors. Results Multiple compounds from each antidepressant category significantly stimulated [3H]CDP-diacylglycerol accumulation in cerebrocortical, hippocampal, and striatal tissues, and also enhanced the resynthesis of inositol phospholipids. Conversely, various antipsychotics, anxiolytics, and non-antidepressant psychotropic agents failed to significantly induce CDP-diacylglycerol or phosphoinositide synthesis. Drug-induced CDP-diacylglycerol accumulation was independent of lithium and only partially dependent on phosphoinositide hydrolysis, thus indicating that antidepressants

  7. 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

  8. Computational morphometry for detecting changes in brain structure due to development, aging, learning, disease and evolution

    OpenAIRE

    Christian Gaser

    2009-01-01

    The brain, like any living tissue, is constantly changing in response to genetic and environmental cues and their interaction, leading to changes in brain function and structure, many of which are now in reach of neuroimaging techniques. Computational morphometry on the basis of Magnetic Resonance (MR) images has become the method of choice for studying macroscopic changes of brain structure across time scales. Thanks to computational advances and sophisticated study designs, both the minimal...

  9. 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...

  10. Aging and Loss of Circulating 17β-Estradiol Alters the Alternative Splicing of ERβ in the Female Rat Brain.

    Science.gov (United States)

    Shults, Cody L; Pinceti, Elena; Rao, Yathindar S; Pak, Toni R

    2015-11-01

    Loss of circulating 17β-estradiol (E2) that occurs during menopause can have detrimental effects on cognitive function. The efficacy of hormone replacement therapy declines as women become farther removed from the menopausal transition, yet the molecular mechanisms underlying this age-related switch in E2 efficacy are unknown. We hypothesized that aging and varying lengths of E2 deprivation alters the ratio of alternatively spliced estrogen receptor (ER)β isoforms in the brain of female rats. Further, we tested whether changes in global transcriptional activity and splicing kinetics regulate the alternative splicing of ERβ. Our results revealed brain region-specific changes in ERβ alternative splicing in both aging and E2-deprivation paradigms and showed that ERβ could mediate E2-induced alternative splicing. Global transcriptional activity, as measured by phosphorylated RNA polymerase II, was also regulated by age and E2 in specific brain regions. Finally, we show that inhibition of topoisomerase I resulted in increased ERβ2 splice variant expression. PMID:26295370

  11. 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

  12. 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

  13. 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

  14. Major Histocompatibility Complex class I proteins are critical for maintaining neuronal structural complexity in the aging brain.

    Science.gov (United States)

    Lazarczyk, Maciej J; Kemmler, Julia E; Eyford, Brett A; Short, Jennifer A; Varghese, Merina; Sowa, Allison; Dickstein, Daniel R; Yuk, Frank J; Puri, Rishi; Biron, Kaan E; Leist, Marcel; Jefferies, Wilfred A; Dickstein, Dara L

    2016-01-01

    Major histocompatibility complex class I (MHCI) proteins have been implicated in neuronal function through the modulation of neuritogenesis, synaptogenesis, synaptic plasticity, and memory consolidation during development. However, the involvement of MHCI in the aged brain is unclear. Here we demonstrate that MHCI deficiency results in significant dendritic atrophy along with an increase in thin dendritic spines and a reduction in stubby spines in the hippocampus of aged (12 month old) mice. Ultrastructural analyses revealed a decrease in spine head diameter and post synaptic density (PSD) area, as well as an increase in overall synapse density, and non-perforated, small spines. Interestingly, we found that the changes in synapse density and morphology appear relatively late (after the age of 6 months). Finally, we found a significant age dependent increase in the levels of the glutamate receptor, GluN2B in aged MHCI knockout mice, with no change in GluA2/3, VGluT1, PSD95 or synaptophysin. These results indicate that MHCI may be also be involved in maintaining brain integrity at post-developmental stages notably in the modulation of neuronal and spine morphology and synaptic function during non-pathological aging which could have significant implications for cognitive function. PMID:27229916

  15. Development of fetal brain of 20 weeks gestational age: Assessment with post-mortem Magnetic Resonance Imaging

    International Nuclear Information System (INIS)

    Background: The 20th week gestational age (GA) is at mid-gestation and corresponds to the age at which the termination of pregnancy in several countries and the first Magnetic Resonance Imaging (MRI) can be performed, and at which the premature babies may survive. However, at present, very little is known about the exact anatomical character at this GA. Objective: To delineate the developing fetal brain of 20 weeks GA and obtain the three dimensional visualization model. Materials and methods: 20 fetal specimens were scanned by 3.0 T and 7.0 T post-mortem MRI, and the three dimensional visualization model was obtained with Amira 4.1. Results: Most of the sulci or their anlage, except the postcentral sulcus and intraparietal sulcus, were present. The laminar organization, described as layers with different signal intensities, was most clearly distinguished at the parieto-occipital lobe and peripheral regions of the hippocampus. The basal nuclei could be clearly visualized, and the brain stem and cerebellum had formed their common shape. On the visualization model, the shape and relative relationship of the structures could be appropriately delineated. The ranges of normal values of the brain structures were obtained, but no sexual dimorphisms or cerebral asymmetries were found. Conclusions: The developing fetal brain of 20 weeks GA can be clearly delineated on 3.0 T and 7.0 T post-mortem MRIs, and the three dimensional visualization model supplies great help in precise cognition of the immature brain. These results may have positive influences on the evaluation of the fetal brain in the uterus.

  16. 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

  17. N-Acetylmannosamine improves sleep-wake quality in middle-aged mice: relevance to autonomic nervous function.

    Science.gov (United States)

    Kuwahara, Masayoshi; Ito, Koichi; Hayakawa, Koji; Yagi, Shintaro; Shiota, Kunio

    2015-01-01

    Aging is associated with a variety of physiological changes originating peripherally and centrally, including within the autonomic nervous system. Sleep-wake disturbances constitute reliable hallmarks of aging in several animal species and humans. Recent studies have been interested in N-acetylmannosamine (ManNAc) a potential therapeutic agent for improving quality of life, as well as preventing age-related cognitive decline. In this study, ManNAc (5.0 mg/ml) was administered in the drinking water of middle-aged male C57BL/6J mice (55 weeks old) for 7 days. Mice were housed under a 12:12 h light:dark cycle at 23-24 °C. We evaluated bio-behavioral activity using electrocardiogram, body temperature and locomotor activity recorded by an implanted telemetry transmitter. To estimate sleep-wake profile, surface electroencephalogram and electromyogram leads connected to a telemetry transmitter were also implanted in mice. Autonomic nervous activity was evaluated using power spectral analysis of heart rate variability. ManNAc-treated mice spent more time in a wakeful state and less time in slow wave sleep during the dark phase. Parasympathetic nervous activity was increased following ManNAc treatment, then the sympatho-vagal balance was shifted predominance of parasympathetic nervous system. Furthermore, improvement in sleep-wake pattern was associated with increased parasympathetic nervous activity. These results suggest that ManNAc treatment can improve bio-behavioral activity and sleep-wake quality in middle-aged mice. This may have implications for improving sleep patterns in elderly humans. PMID:25443216

  18. 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

  19. 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.

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

    International Nuclear Information System (INIS)

    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 3H-desmethylimipramine binding and decrease in 3H-naloxone binding in this same region as assessed by quantitative in vitro autoradiography

  1. 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.

  2. Application of Fuzzy Cluster Analysis Method in Evaluating Relevant Index and Recognizing Risks of Coronary Heart Disease in the Aged

    Institute of Scientific and Technical Information of China (English)

    耿辉; 杨玉坤

    2003-01-01

    The risk recognition model for preventing and monitoring the Coronary Heart Diseases (CHD) in the aged is proposed, which is based on the testing results of four indexes and includes Low Density Lipoprotein (LDL), Total Cholesterol (TC), Triglyceridemia (TG)and age. Some people who took the health checkup in Shanghai Xinhua Hospital are classified into 3 groups,and each group is associated with prevalence risk of contracting CHD. Then the fuzzy recognition method is applied to evaluate the risk of CHD. The accuracy rate is up to 85%. The model is applicable to not only analysis of risk in medical but also analysis of risk in finance, insurance and some other fields.

  3. 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

  4. 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 ...

  5. 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 ...

  6. Radiotherapy of brain metastases and glioblastomas in elderly patients; Radiotherapie des metastases cerebrales et des glioblastomes chez le sujet age

    Energy Technology Data Exchange (ETDEWEB)

    Lauche, O.; Kerr, C.; Riou, O.; Dhermain, F. [Institut Gustave-Roussy, Villejuif (France)

    2011-10-15

    As the occurrence of malignant gliomas and brain metastases is increasing in elderly people, the authors report the definition of an optimal therapeutic strategy for these patients. For patients in good health condition, a prospective randomized showed a modest benefit of radiotherapy alone with respect to support cares in terms of survival. The radiotherapy scheme is discussed in terms of dose and number of fractions. It seems that the physiological age is a strong prognosis factor. Short communication

  7. 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...

  8. Forgetting no-longer-relevant prospective memory intentions is (sometimes) harder with age but easier with forgetting practice.

    Science.gov (United States)

    Bugg, Julie M; Scullin, Michael K; Rauvola, Rachel S

    2016-06-01

    In young adults, it has been shown that prospective memory (PM) commission errors, the erroneous performance of a previously relevant intention, are less likely for repeatedly performed intentions (than never performed intentions). We examined whether this pattern holds for older adults, for whom impaired response inhibition processes might heighten risk of commission errors for repeatedly performed PM intentions. Older adults encoded a PM intention to press a key when a target word appeared during an ongoing lexical decision task. Target words were presented 4 (repeatedly) or 0 times before participants were instructed the PM task was finished and should not be performed again. Target words were then (re)presented and commission errors were recorded. Experiment 1 demonstrated it was easier for older adults to forget (deactivate) a PM intention that was performed repeatedly (4-target condition) than one that was never performed (0-target condition). However, older adults were more likely to make commission errors than young adults in the 4- but not the 0-target condition. Experiments 2 and 3 examined whether distinct strategies reduce commission errors. Whereas a preparatory instructional strategy produced inconsistent effects, forgetting practice was highly effective in producing floor levels of commission errors for older and young adults in the 4-target condition. Findings are interpreted within the dual-mechanisms account of PM commission errors, which highlights the interplay of spontaneous retrieval and cognitive control in the forgetting of previously relevant intentions. Practically, the findings provide first evidence of a translational strategy that older adults may use to minimize commission errors. (PsycINFO Database Record PMID:27064599

  9. [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

  10. The antioxidant effect of astaxanthin is higher in young mice than aged: a region specific study on brain.

    Science.gov (United States)

    Al-Amin, Md Mamun; Akhter, Samiha; Hasan, Ahmed Tasdid; Alam, Tanzir; Nageeb Hasan, S M; Saifullah, A R M; Shohel, Mohammad

    2015-10-01

    Astaxanthin is a potential antioxidant which shows neuroprotective property. We aimed to investigate the age-dependent and region-specific antioxidant effects of astaxanthin in mice brain. Animals were divided into 4 groups; treatment young (3 months, n = 6) (AY), treatment old (16 months, n = 6) (AO), placebo young (3 months, n = 6) (PY) and placebo old (16 months, n = 6) (PO) groups. Treatment group was given astaxanthin (2 mg/kg/day, body weight), and placebo group was given 100 μl of 0.9% normal saline orally to the healthy Swiss albino mice for 4 weeks. The level of non-enzymatic oxidative markers namely malondialdehyde (MDA); nitric oxide (NO); advanced protein oxidation product (APOP); glutathione (GSH) and the activity of enzymatic antioxidants i.e.; catalase (CAT) and superoxide dismutase (SOD) were determined from the isolated brain regions. Treatment with astaxanthin significantly (p Astaxanthin markedly (p astaxanthin is age-dependent, higher in young in compared to the aged brain. PMID:26116165

  11. Computational morphometry for detecting changes in brain structure due to development, aging, learning, disease and evolution

    Directory of Open Access Journals (Sweden)

    Christian Gaser

    2009-08-01

    Full Text Available The brain, like any living tissue, is constantly changing in response to genetic and environmental cues and their interaction, leading to changes in brain function and structure, many of which are now in reach of neuroimaging techniques. Computational morphometry on the basis of Magnetic Resonance (MR images has become the method of choice for studying macroscopic changes of brain structure across time scales. Thanks to computational advances and sophisticated study designs, both the minimal extent of change necessary for detection and, consequently, the minimal periods over which such changes can be detected have been reduced considerably during the last few years. On the other hand, the growing availability of MR images of more and more diverse brain populations also allows more detailed inferences about brain changes that occur over larger time scales, way beyond the duration of an average research project. On this basis, a whole range of issues concerning the structures and functions of the brain are now becoming addressable, thereby providing ample challenges and opportunities for further contributions from neuroinformatics to our understanding of the brain and how it changes over a lifetime and in the course of evolution.

  12. Somatostatinergic systems: an update on brain functions in normal and pathological aging

    Directory of Open Access Journals (Sweden)

    CécileViollet

    2012-12-01

    Full Text Available Somatostatin is highly expressed in mammalian brain and is involved in many brain functions such as motor activity, sleep, sensory and cognitive processes. Five somatostatin receptors have been described: sst1, sst2 (A and B, sst3 to 5, all belonging to the G-protein-coupled receptor family. During the recent years, numerous studies contributed to clarify the role of somatostatin systems, especially long-range somatostatinergic interneurons, in several functions they have been previously involved in. New advances have also been made on the alterations of SRIF systems in several brain diseases and on the potential therapeutic target they represent in these pathologies.

  13. MRI T2 mapping of the asymptomatic supraspinatus tendon by age and imaging plane using clinically relevant subregions

    International Nuclear Information System (INIS)

    Purpose: Diagnosis of partial rotator cuff tears and tendonopathy using conventional MRI has proven variable. Quantitative T2 mapping may have application for assessing rotator cuff health. In order to evaluate the usefulness of T2 mapping for the rotator cuff, methods must be refined for mapping the supraspinatus tendon, and normative T2 values must first be acquired. Materials and methods: This study was IRB approved. Thirty asymptomatic volunteers (age: 18–62) were evaluated with sagittal and coronal T2 mapping sequences. Manual segmentation of tendon and muscle as a unit and tendon alone was performed twice by two independent raters. Segmentations were divided into medial, middle and lateral subregions and mean T2 values calculated. Results: Anatomic comparison of mean T2 values illustrated highest values in the medial region, lowest values in the lateral region, and intermediate values for the middle region upon coronal segmentation (p < 0.001). In sagittal segmentations, there were higher values in the medial region and no significant differences between the lateral and middle subregions. No significant differences were found with comparison across age groups. Inter and intra-rater segmentation repeatability was excellent, with coefficients ranging from 0.85 to 0.99. Conclusion: T2 mapping illustrated anatomic variation along the supraspinatus muscle-tendon unit with low standard deviations and excellent repeatability, suggesting that changes in structure due to degeneration or changes associated with healing after repair may be detectable

  14. MRI T2 mapping of the asymptomatic supraspinatus tendon by age and imaging plane using clinically relevant subregions

    Energy Technology Data Exchange (ETDEWEB)

    Anz, Adam W., E-mail: anz.adam.w@gmail.com [The Steadman Clinic, Vail, CO (United States); Lucas, Erin P., E-mail: erin.lucas14@gmail.com [Steadman Philippon Research Institute, Vail, CO (United States); Fitzcharles, Eric K., E-mail: ericfitzcharles@gmail.com [Steadman Philippon Research Institute, Vail, CO (United States); Surowiec, Rachel K., E-mail: Rachel.surowiec@sprivail.org [Steadman Philippon Research Institute, Vail, CO (United States); Millett, Peter J., E-mail: drmillett@thesteadmanclinic.com [The Steadman Clinic, Vail, CO (United States); Ho, Charles P., E-mail: Charles.ho@sprivail.org [Steadman Philippon Research Institute, Vail, CO (United States)

    2014-05-15

    Purpose: Diagnosis of partial rotator cuff tears and tendonopathy using conventional MRI has proven variable. Quantitative T2 mapping may have application for assessing rotator cuff health. In order to evaluate the usefulness of T2 mapping for the rotator cuff, methods must be refined for mapping the supraspinatus tendon, and normative T2 values must first be acquired. Materials and methods: This study was IRB approved. Thirty asymptomatic volunteers (age: 18–62) were evaluated with sagittal and coronal T2 mapping sequences. Manual segmentation of tendon and muscle as a unit and tendon alone was performed twice by two independent raters. Segmentations were divided into medial, middle and lateral subregions and mean T2 values calculated. Results: Anatomic comparison of mean T2 values illustrated highest values in the medial region, lowest values in the lateral region, and intermediate values for the middle region upon coronal segmentation (p < 0.001). In sagittal segmentations, there were higher values in the medial region and no significant differences between the lateral and middle subregions. No significant differences were found with comparison across age groups. Inter and intra-rater segmentation repeatability was excellent, with coefficients ranging from 0.85 to 0.99. Conclusion: T2 mapping illustrated anatomic variation along the supraspinatus muscle-tendon unit with low standard deviations and excellent repeatability, suggesting that changes in structure due to degeneration or changes associated with healing after repair may be detectable.

  15. Ischemia Alters the Expression of Connexins in the Aged Human Brain

    OpenAIRE

    Taizen Nakase; Tetsuya Maeda; Yasuji Yoshida; Ken Nagata

    2009-01-01

    Although the function of astrocytic gap junctions under ischemia is still under debate, increased expression of connexin 43 (Cx43) has been observed in ischemic brain lesions, suggesting that astrocytic gap junctions could provide neuronal protection against ischemic insult. Moreover, different connexin subtypes may play different roles in pathological conditions. We used immunohistochemical analysis to investigate alterations in the expression of connexin subtypes in human stroke brains. Sev...

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

    OpenAIRE

    Zhang Y; Hodgson N.W.; Trivedi M.S.; Abdolmaleky H.M.; Fournier M.; Cuenod M.; Do K.Q.; Deth R.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...

  17. Effect of aging on alpha-1 adrenergic stimulation of phosphoinositide hydrolysis in various regions of rat brain

    International Nuclear Information System (INIS)

    The effects of aging were examined on the ability of alpha-1 adrenergic receptor agonists to stimulate phosphoinositide hydrolysis in three brain regions. Tissue minces of thalamus, cerebral cortex and hippocampus from 3-, 18- and 28-month-old male Fischer 344 rats were prelabeled with [3H]myoinositol. Exposure of these prelabeled minces to phenylephrine and (-)-norepinephrine revealed that accumulation of [3H]inositol phosphates was selectively reduced by 20 to 30% in the thalamus and cerebral cortex of the oldest age group. Analysis of concentration-response and competition binding curves indicated that this decrease was due to diminished agonist efficacy rather than diminished receptor affinity. The reduction in responsiveness to phenylephrine and (-)-norepinephrine in the cerebral cortex and the lack of any changes in the hippocampus parallel previously reported changes in the density of alpha-1 adrenergic receptors with aging. These data indicate that the ability of alpha-1 adrenergic receptor agonists to stimulate phosphoinositide hydrolysis is reduced in some, but not all, brain regions of aged Fischer 344 rats

  18. 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.

  19. Headache, migraine, and structural brain lesions and function: population based Epidemiology of Vascular Ageing-MRI study

    International Nuclear Information System (INIS)

    Objective: To evaluate the association of overall and specific headaches with volume of white matter hyper-intensities, brain infarcts, and cognition. Design: Population based, cross sectional study. Setting: Epidemiology of Vascular Ageing study, Nantes, France. Participants: 780 participants (mean age 69, 58.5% women) with detailed headache assessment. Main outcome measures: Brain scans were evaluated for volume of white matter hyper-intensities (by fully automated imaging processing) and for classification of infarcts (by visual reading with a standardised assessment grid). Cognitive function was assessed by a battery of tests including the mini-mental state examination. Results: 163 (20.9%) participants reported a history of severe headache and 116 had migraine, of whom 17 (14.7%) reported aura symptoms. An association was found between any history of severe headache and increasing volume of white matter hyper-intensities. The adjusted odds ratio of being in the highest third for total volume of white matter hyper-intensities was 2.0 (95% confidence interval 1.3 to 3.1, P for trend 0.002) for participants with any history of severe headache when compared with participants without severe headache being in the lowest third. The association pattern was similar for all headache types. Migraine with aura was the only headache type strongly associated with volume of deep white matter hyper-intensities (highest third odds ratio 12.4, 1.6 to 99.4, P for trend 0.005) and with brain infarcts (3.4, 1.2 to 9.3). The location of infarcts was predominantly outside the cerebellum and brain stem. Evidence was lacking for cognitive impairment for any headache type with or without brain lesions. Conclusions: In this population based study, any history of severe headache was associated with an increased volume of white matter hyper-intensities. Migraine with aura was the only headache type associated with brain infarcts. Evidence that headache of any type by itself or in

  20. Real-Time Mass Spectrometry Monitoring of Oak Wood Toasting: Elucidating Aroma Development Relevant to Oak-aged Wine Quality

    Science.gov (United States)

    Farrell, Ross R.; Wellinger, Marco; Gloess, Alexia N.; Nichols, David S.; Breadmore, Michael C.; Shellie, Robert A.; Yeretzian, Chahan

    2015-11-01

    We introduce a real-time method to monitor the evolution of oak aromas during the oak toasting process. French and American oak wood boards were toasted in an oven at three different temperatures, while the process-gas was continuously transferred to the inlet of a proton-transfer-reaction time-of-flight mass spectrometer for online monitoring. Oak wood aroma compounds important for their sensory contribution to oak-aged wine were tentatively identified based on soft ionization and molecular mass. The time-intensity profiles revealed toasting process dynamics illustrating in real-time how different compounds evolve from the oak wood during toasting. Sufficient sensitivity was achieved to observe spikes in volatile concentrations related to cracking phenomena on the oak wood surface. The polysaccharide-derived compounds exhibited similar profiles; whilst for lignin-derived compounds eugenol formation differed from that of vanillin and guaiacol at lower toasting temperatures. Significant generation of oak lactone from precursors was evident at 225 oC. Statistical processing of the real-time aroma data showed similarities and differences between individual oak boards and oak wood sourced from the different origins. This study enriches our understanding of the oak toasting process and demonstrates a new analytical approach for research on wood volatiles.

  1. 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

  2. EFFECTS OF AGE, DIETARY AND BEHAVIORAL ENRICHMENT ON BRAIN MITOCHONDRIA IN A CANINE MODEL OF HUMAN AGING

    OpenAIRE

    Head, E; Nukala, V. N.; Fenoglio, K.A.; Muggenburg, B. A.; Cotman, C W; Sullivan, P. G.

    2009-01-01

    Dogs develop cognitive decline and a progressive accumulation of oxidative damage. In a previous longitudinal study, we demonstrated that aged dogs treated with either an antioxidant diet or with behavioral enrichment show cognitive improvement. The antioxidant diet included cellular antioxidants (Vitamins E, C, fruits and vegetables) and mitochondrial co-factors (lipoic acid and carnitine). Behavioral enrichment consisted of physical exercise, social enrichment and cognitive training. We hyp...

  3. 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.

  4. 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

    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...... changes associated with molecular aging also have significant long-term consequences for Abeta folding and turnover. New fast, reproducible and accurate methods for the screening of protein aging markers in biological samples may contribute to improve diagnostic and therapeutic approaches in AD....

  5. Ischemia Alters the Expression of Connexins in the Aged Human Brain

    Directory of Open Access Journals (Sweden)

    Taizen Nakase

    2009-01-01

    Full Text Available Although the function of astrocytic gap junctions under ischemia is still under debate, increased expression of connexin 43 (Cx43 has been observed in ischemic brain lesions, suggesting that astrocytic gap junctions could provide neuronal protection against ischemic insult. Moreover, different connexin subtypes may play different roles in pathological conditions. We used immunohistochemical analysis to investigate alterations in the expression of connexin subtypes in human stroke brains. Seven samples, sectioned after brain embolic stroke, were used for the analysis. Data, evaluated semiquantitatively by computer-assisted densitometry, was compared between the intact hemisphere and ischemic lesions. The results showed that the coexpression of Cx32 and Cx45 with neuronal markers was significantly increased in ischemic lesions. Cx43 expression was significantly increased in the colocalization with astrocytes and relatively increased in the colocalization with neuronal marker in ischemic lesions. Therefore, Cx32, Cx43, and Cx45 may respond differently to ischemic insult in terms of neuroprotection.

  6. 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...

  7. 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

  8. 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

    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...... available for crucial intracellular processes. In the brain, zinc co-localizes with glutamate in synaptic vesicles, and modulates NMDA receptor activity. Intracellular zinc is involved in apoptosis and fluctuations in cytoplasmic Zn(2+) affect modulation of intracellular signaling. The ZNT and ZIP proteins...... 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...

  9. Brain training for silver gamers: effects of age and game form on effectiveness, efficiency, self-assessment, and gameplay experience.

    Science.gov (United States)

    Nacke, Lennart E; Nacke, Anne; Lindley, Craig A

    2009-10-01

    In recent years, an aging demographic majority in the Western world has come to the attention of the game industry. The recently released "brain-training" games target this population, and research investigating gameplay experience of the elderly using this game form is lacking. This study employs a 2 x 2 mixed factorial design (age group: young and old x game form: paper and Nintendo DS) to investigate effects of age and game form on usability, self-assessment, and gameplay experience in a supervised field study. Effectiveness was evaluated in task completion time, efficiency as error rate, together with self-assessment measures (arousal, pleasure, dominance) and game experience (challenge, flow, competence, tension, positive and negative affect). Results indicate players, regardless of age, are more effective and efficient using pen-and-paper than using a Nintendo DS console. However, the game is more arousing and induces a heightened sense of flow in digital form for gamers of all ages. Logic problem-solving challenges within digital games may be associated with positive feelings for the elderly but with negative feelings for the young. Thus, digital logic-training games may provide positive gameplay experience for an aging Western civilization. PMID:19772440

  10. 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

  11. 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.

  12. Age and Haplotype Variations within FADS1 Interact and Associate with Alterations in Fatty Acid Composition in Human Male Cortical Brain Tissue

    OpenAIRE

    Freemantle, Erika; Lalovic, Aleksandra; Mechawar, Naguib; Turecki, Gustavo

    2012-01-01

    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 matte...

  13. 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

  14. 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…

  15. 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...

  16. 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

  17. 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 ...

  18. 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...

  19. The multi-facet aspects of cell sentience and their relevance for the integrative brain actions: role of membrane protein energy landscape.

    Science.gov (United States)

    Agnati, Luigi F; Marcoli, Manuela; Maura, Guido; Fuxe, Kjell; Guidolin, Diego

    2016-06-01

    Several ion channels can be randomly and spontaneously in an open state, allowing the exchange of ion fluxes between extracellular and intracellular environments. We propose that the random changes in the state of ion channels could be also due to proteins exploring their energy landscapes. Indeed, proteins can modify their steric conformation under the effects of the physicochemical parameters of the environments with which they are in contact, namely, the extracellular, intramembrane and intracellular environments. In particular, it is proposed that the random walk of proteins in their energy landscape is towards attractors that can favor the open or close condition of the ion channels and/or intrinsic activity of G-protein-coupled receptors. The main aspect of the present proposal is that some relevant physicochemical parameters of the environments (e.g. molecular composition, temperature, electrical fields) with which some signaling-involved plasma membrane proteins are in contact alter their conformations. In turn, these changes can modify their information handling via a modulatory action on their random walk towards suitable attractors of their energy landscape. Thus, spontaneous and/or signal-triggered electrical activities of neurons occur that can have emergent properties capable of influencing the integrative actions of brain networks. Against this background, Cook's hypothesis on 'cell sentience' is developed by proposing that physicochemical parameters of the environments with which the plasma-membrane proteins of complex cellular networks are in contact fulfill a fundamental role in their spontaneous and/or signal-triggered activity. Furthermore, it is proposed that a specialized organelle, the primary cilium, which is present in most cells (also neurons and astrocytes), could be of peculiar importance to pick up chemical signals such as ions and transmitters and to detect physical signals such as pressure waves, thermal gradients, and local field

  20. 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...

  1. 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...

  2. Medial Temporal Lobe Contributions to Intra-Item Associative Recognition Memory in the Aging Brain

    OpenAIRE

    Dalton, Marshall Axel; Tu, Sicong; Hornberger, Michael; Hodges, John Russel; Piguet, Olivier

    2014-01-01

    Aging is associated with a decline in episodic memory function. This is accompanied by degradation of and functional changes in the medial temporal lobe (MTL) which subserves mnemonic processing. To date no study has investigated age-related functional change in MTL substructures during specific episodic memory processes such as intra-item associative memory. The aim of this study was to characterize age-related change in the neural correlates of intra-item associative memory processing. Sixt...

  3. 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...

  4. Training the brain to overcome the effect of aging on the human eye

    OpenAIRE

    Polat, Uri; Schor, Clifton; Tong, Jian-Liang; Zomet, Ativ; Lev, Maria; Yehezkel, Oren; Sterkin, Anna; Levi, Dennis M.

    2012-01-01

    Presbyopia, from the Greek for aging eye, is, like death and taxes, inevitable. Presbyopia causes near vision to degrade with age, affecting virtually everyone over the age of 50. Presbyopia has multiple negative effects on the quality of vision and the quality of life, due to limitations on daily activities – in particular, reading. In addition presbyopia results in reduced near visual acuity, reduced contrast sensitivity, and slower processing speed. Currently available solutions, such as o...

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

    Directory of Open Access Journals (Sweden)

    HannaGärtner

    2013-09-01

    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 life.

  6. Label-Free Quantitative LC–MS Proteomics of Alzheimer’s Disease and Normally Aged Human Brains

    Energy Technology Data Exchange (ETDEWEB)

    Andreev, Victor P.; Petyuk, Vladislav A.; Brewer, Heather M.; Karpievitch, Yuliya V.; Xie, Fang; Clarke, Jennifer; Camp, David; Smith, Richard D.; Lieberman, Andrew P.; Albin, Roger L.; Nawaz, Zafar; El Hokayem, Jimmy; Myers, Amanda J.

    2012-06-01

    Quantitative proteomics analysis of cortical samples of 10 Alzheimer’s disease (AD) brains versus 10 normally aged brains was performed by following the accurate mass and time tag (AMT) approach with the high resolution LTQ Orbitrap mass spectrometer. More than 1400 proteins were identified and quantitated. A conservative approach of selecting only the consensus results of four normalization methods was suggested and used. A total of 197 proteins were shown to be significantly differentially abundant (p-values <0.05, corrected for multiplicity of testing) in AD versus control brain samples. Thirty-seven of these proteins were reported as differentially abundant or modified in AD in previous proteomics and transcriptomics publications. The rest to the best of our knowledge are new. Mapping of the discovered proteins with bioinformatic tools revealed significant enrichment with differentially abundant proteins of pathways and processes known to be important in AD, including signal transduction, regulation of protein phosphorylation, immune response, cytoskeleton organization, lipid metabolism, energy production, and cell death.

  7. AGE-RELATED CHANGES IN RECEPTOR-MEDIATED PHOSPHOINOSITIDE HYDROLYSIS IN VARIOUS REGIONS OF RAT BRAIN

    Science.gov (United States)

    The effects of age on cholinergic markers and receptor-stimulated phosphoinositide hydrolysis was dined in the frontal cortex and striatum of male Fischer-344 rats. holine acetyltransferase activity was decreased 27% in the striatum of aged (24 month) rats cared to young (3 month...

  8. 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...

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

    OpenAIRE

    Wang, Qiong; Shao, Feng; Wang, Weiwen

    2015-01-01

    Early life adversity, such as postnatal maternal separation (MS), play a central role in the development of psychopathologies during individual ontogeny. In this 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...

  10. 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...

  11. 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.

  12. Re: Making Health and Care Systems Fit for and Ageing Population. Why We Wrote It, Who We Wrote It For, and How Relevant It Might Be to Canada

    Science.gov (United States)

    Oliver, David

    2014-01-01

    In response to the commentary(1) in this month’s Canadian Geriatrics Journal by Andrew and Rockwood on the recent paper I co-wrote with King’s Fund colleagues—“Making Health and Care Systems Fit for an Ageing Population”(2)—I wanted to pen a very personal response, not least because of my visits to health systems in Ontario and Alberta and conversations with many Canadian colleagues that are fresh in my mind. The paper was certainly the most important and influential thing I have written, and was an attempt to weave all the elements of good practice in health care for older people into one overarching narrative. Whilst its biggest target audience is UK health services, I hope it has some relevance to Canada and might stimulate some constructive conversations. PMID:25452827

  13. Age-related changes in receptor-mediated phosphoinositide hydrolysis in various regions of rat brain

    International Nuclear Information System (INIS)

    The effects of age on cholinergic markers and receptor-stimulated phosphoinositide hydrolysis was examined in the frontal cortex and striatum of male Fischer-344 rats. Choline acetyltransferase activity was decreased 27% in the striatum of aged rats compared to young controls. Muscarinic receptor density as measured by [3H]-quinuclidinyl benzilate binding showed a similar 26% decrease in the striatum of aged rats. Phosphoinositide hydrolysis was measured by the release of inositol phosphate (IP) from tissue slices prelabeled with [3H]myoinositol in response to carbachol, norepinephrine, and quisqualate. In the cortex, stimulated IP release was significantly greater in slices from aged rats compared to young rats for all three agonists. In contrast, stimulated IP release was significantly decreased in striatal slices from aged rats compared to young for all three agonists. These data indicate a differential effect of age on agonist-stimulated phosphoinositide hydrolysis in the cortex and striatum. The decreased responsiveness in the latter area may result from the age-related loss of postsynaptic receptors

  14. 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.

  15. 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

  16. Prolonged rote learning produces delayed memory facilitation and metabolic changes in the hippocampus of the ageing human brain

    Directory of Open Access Journals (Sweden)

    Prendergast Julie

    2009-11-01

    Full Text Available Abstract 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.

  17. Description and classification of normal and pathological aging processes based on brain magnetic resonance imaging morphology measures.

    Science.gov (United States)

    Perez-Gonzalez, Jorge Luis; Yanez-Suarez, Oscar; Bribiesca, Ernesto; Cosío, Fernando Arámbula; Jiménez, Juan Ramón; Medina-Bañuelos, Veronica

    2014-10-01

    We present a discrete compactness (DC) index, together with a classification scheme, based both on the size and shape features extracted from brain volumes, to determine different aging stages: healthy controls (HC), mild cognitive impairment (MCI), and Alzheimer's disease (AD). A set of 30 brain magnetic resonance imaging (MRI) volumes for each group was segmented and two indices were measured for several structures: three-dimensional DC and normalized volumes (NVs). The discrimination power of these indices was determined by means of the area under the curve (AUC) of the receiver operating characteristic, where the proposed compactness index showed an average AUC of 0.7 for HC versus MCI comparison, 0.9 for HC versus AD separation, and 0.75 for MCI versus AD groups. In all cases, this index outperformed the discrimination capability of the NV. Using selected features from the set of DC and NV measures, three support vector machines were optimized and validated for the pairwise separation of the three classes. Our analysis shows classification rates of up to 98.3% between HC and AD, 85% between HC and MCI, and 93.3% for MCI and AD separation. These results outperform those reported in the literature and demonstrate the viability of the proposed morphological indices to classify different aging stages. PMID:26158061

  18. 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...

  19. 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...

  20. 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...

  1. Mitochondrial DNA mutations. Brain developmental and ageing consequences, and possible treatments

    OpenAIRE

    Ross, Jaime M.

    2012-01-01

    Ageing is a complex process that involves cellular senescence, a gradual loss of tissue homeostasis, and decline in organ function. Abundant evidence implicates mitochondria in ageing suggesting: (i) accumulation of mitochondrial DNA (mtDNA) damage, (ii) progressive respiratory chain dysfunction, and (iii) increased reactive oxygen species production. The “Mitochondrial Theory of Aging”, first proposed by Denham Harman in 1972, suggests that damage to mtDNA slowly accumulates with time and ca...

  2. 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...

  3. Aging of the cingulum in the human brain: Preliminary study of a diffusion tensor imaging study.

    Science.gov (United States)

    Jang, Sung Ho; Kwon, Yong Hyun; Lee, Mi Young; Kim, Jae-Ryong; Seo, Jeong Pyo

    2016-01-01

    The cingulum, a major structure of the limbic system, is closely associated with memory function. In the current study, we investigated aging of the cingulum according to the location of the cingulum in each part of the cingulum after dividing the cingulum into five parts in normal subjects, using DTT parameters (fractional anisotropy (FA) and fiber number (FN)). Ninety healthy subjects (males: 44, females: 46, mean age: 49.0 years; range: 20-78 years) were enrolled in this study. Subjects were categorized according to six groups by age intervals of 10 years; each age group consisted of 15 subjects. The cingulum was divided into five parts (anterior, anterior superior, posterior superior cingulum, posterior, and inferior cingulum). The FA and FN of each part were measured. The FA value indicates the degree of directionality and integrity of white matter microstructures such as axons, myelin, and microtubules, and the FN reflects the total number of fibers in a neural tract. Age-related decline in the FA value may indicate demyelination, and a decline in the number of myelinated fibers of a neural tract can also lead to a decline of the FN. Significant differences in the FA value of the anterior cingulum and anterior superior cingulum, and the FN of the inferior cingulum were observed between age groups (AVOVA, pLSD post hoc test, p<0.05). Aging of the cingulum began at both ends of the cingulum in the 20s or 30s, and progressed steadily at a near continuous rate over the lifespan and a significant degenerative aging effect at both ends of the cingulum occurred into the 60s, compared with the 20s or 30s. PMID:26598020

  4. 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…

  5. 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.

  6. 99mTc-ECD brain perfusion SPET: variability, asymmetry and effects of age and gender in healthy adults

    International Nuclear Information System (INIS)

    Reliable and high-resolution reference data for regional cerebral blood flow measured with single-photon emission tomography (SPET) are necessary for optimal clinical and research use. Therefore, a large dataset of normal technetium-99m labelled ethylene cysteine dimer (ECD) perfusion SPET in carefully screened healthy volunteers with an age range spanning six decades was created, with correction for non-uniform attenuation and scatter and based on an anatomically standardised analysis. Eighty-nine healthy volunteers, stratified for gender (46 females, 43 males; age 20-81 years), were included. Twelve volunteers underwent repeated 99mTc-ECD SPET after 2.5±2.3 weeks. An automated whole-brain volume of interest analysis with MANOVA as well as voxelwise analysis using SPM99 was conducted. Average intersubject variability was 4.8% while intrasubject reproducibility was 3.0%. An age-related decline in tracer uptake was found in the anterior cingulate gyrus, bilateral basal ganglia, left prefrontal, left lateral frontal and left superior temporal and insular cortex (all P=0.001-0.02). There was an overall increase in right/left asymmetry with age, which was most pronounced in the frontal and temporal neocortex. The most significant correlations between AI and age decade were found in the prefrontal (R=0.35, P=0.001) and superior temporal neocortex (R=0.43, P99mTc-ECD perfusion SPET under a wide variety of clinical circumstances in relation to normal variations and highlights the importance of both age- and gender-specific normal datasets for optimal analysis sensitivity. (orig.)

  7. Brain aging in humans, chimpanzees (Pan troglodytes), and rhesus macaques (Macaca mulatta): magnetic resonance imaging studies of macro- and microstructural changes

    OpenAIRE

    Chen, Xu; Errangi, Bhargav; Li, Longchuan; Glasser, Matthew F.; Westlye, Lars T.; Fjell, Anders M.; Walhovd, Kristine B; Hu, Xiaoping; Herndon, James G; Preuss, Todd M.; Rilling, James K.

    2013-01-01

    Among primates, humans are uniquely vulnerable to many age-related neurodegenerative disorders. We used structural and diffusion magnetic resonance imaging (MRI) to examine the brains of chimpanzees and rhesus monkeys across each species' adult lifespan, and compared these results with published findings in humans. As in humans, gray matter volume decreased with age in chimpanzees and rhesus monkeys. Also like humans, chimpanzees showed a trend for decreased white matter volume with age, but ...

  8. Transport characteristics of guanidino compounds at the blood-brain barrier and blood-cerebrospinal fluid barrier: relevance to neural disorders

    Directory of Open Access Journals (Sweden)

    Tachikawa Masanori

    2011-02-01

    Full Text Available Abstract Guanidino compounds (GCs, such as creatine, phosphocreatine, guanidinoacetic acid, creatinine, methylguanidine, guanidinosuccinic acid, γ-guanidinobutyric acid, β-guanidinopropionic acid, guanidinoethane sulfonic acid and α-guanidinoglutaric acid, are present in the mammalian brain. Although creatine and phosphocreatine play important roles in energy homeostasis in the brain, accumulation of GCs may induce epileptic discharges and convulsions. This review focuses on how physiologically important and/or neurotoxic GCs are distributed in the brain under physiological and pathological conditions. Transporters for GCs at the blood-brain barrier (BBB and the blood-cerebrospinal fluid (CSF barrier (BCSFB have emerged as substantial contributors to GCs distribution in the brain. Creatine transporter (CRT/solute carrier (SLC 6A8 expressed at the BBB regulates creatine concentration in the brain, and represents a major pathway for supply of creatine from the circulating blood to the brain. CRT may be a key factor facilitating blood-to-brain guanidinoacetate transport in patients deficient in S-adenosylmethionine:guanidinoacetate N-methyltransferase, the creatine biosynthetic enzyme, resulting in cerebral accumulation of guanidinoacetate. CRT, taurine transporter (TauT/SLC6A6 and organic cation transporter (OCT3/SLC22A3 expressed at the BCSFB are involved in guanidinoacetic acid or creatinine efflux transport from CSF. Interestingly, BBB efflux transport of GCs, including guanidinoacetate and creatinine, is negligible, though the BBB has a variety of efflux transport systems for synthetic precursors of GCs, such as amino acids and neurotransmitters. Instead, the BCSFB functions as a major cerebral clearance system for GCs. In conclusion, transport of GCs at the BBB and BCSFB appears to be the key determinant of the cerebral levels of GCs, and changes in the transport characteristics may cause the abnormal distribution of GCs in the brain seen

  9. A study of histopathological spectrum and expression of Ki-67, TP53 in primary brain tumors of pediatric age group

    Directory of Open Access Journals (Sweden)

    Subhalakshmi Sengupta

    2012-01-01

    Full Text Available Objectives: The primary brain tumors are the second most common cause of death due to malignancies in children. This study was done to analyze the histological spectrum of primary brain tumors in children and also to find out the expression of p53 and Ki67 in some of the common pediatric brain tumors. Materials and Methods: This study was done over a period of 2.5 years. The patients were followed up until 6 months to determine the outcome. We examined H and E sections from 61 pediatric brain tumors and also performed immunohistochemical stains with p53 and Ki67 on 52 of these samples. Results: Of the 61 cases of pediatric brain tumors the commonest were pilocytic astrocytomas and medulloblastomas both constituting 22.9% of total cases, followed by high grade gliomas, that is, anaplastic astrocytoma and glioblastoma taken together (14.7%, diffuse astrocytomas (11.4%, ependymomas (8.1%, and oligodendrogliomas (4.9%. Other cases comprised craniopharyngiomas, astroblastomas, and gangliocytoma. The mean age of presentation was 9.3 years, male children being more commonly affected. Ki67 labeling index (LI and p53 expression in pilocytic astrocytomas and diffuse astrocytomas were significantly lower than that of high-grade astrocytomas. However, there was no significant difference of expression of these two antigens in pilocytic astrocytomas and diffuse astrocytomas. It was found that Ki67 LI was a better marker for distinguishing between grades of astrocytoma than p53 (P=0.000 and P=0.002, respectively. The survival in cases of pilocytic astrocytomas was far better than high-grade gliomas. However, there was no significant difference in survival between pilocytic astrocytoma and diffuse infiltrating astrocytoma. There was significant positive correlation between expression of p53 and Ki67 LI in cases of medulloblastomas. Both p53 (P=0.002 and Ki67 LI (P=0.000 taken individually correlated well with survival in these cases. Also, Ki67 LI is better

  10. 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)

  11. Complex and region-specific changes in astroglial markers in the aging brain

    Czech Academy of Sciences Publication Activity Database

    Rodríguez, J. J.; Yeh, C. Y.; Terzieva, S.; Olabarria, M.; Kulijewicz-Nawrot, Magdaléna; Verkhratsky, A.

    2014-01-01

    Roč. 35, č. 1 (2014), s. 15-23. ISSN 0197-4580 R&D Projects: GA ČR(CZ) GBP304/12/G069; GA ČR(CZ) GAP304/11/0184 Institutional support: RVO:68378041 Keywords : astrocytes * aging * GFAP Subject RIV: FH - Neurology Impact factor: 5.013, year: 2014

  12. Sex on the brain! Associations between sexual activity and cognitive function in older age

    Science.gov (United States)

    Wright, Hayley; Jenks, Rebecca A.

    2016-01-01

    Background: the relationship between cognition and sexual activity in healthy older adults is under-researched. A limited amount of research in this area has shown that sexual activity is associated with better cognition in older men. The current study explores the possible mediating factors in this association in men and women, and attempts to provide an explanation in terms of physiological influences on cognitive function. Methods: using newly available data from Wave 6 of the English Longitudinal Study of Ageing, the current study explored associations between sexual activity and cognition in adults aged 50–89 (n = 6,833). Two different tests of cognitive function were analysed: number sequencing, which broadly relates to executive function, and word recall, which broadly relates to memory. Results: after adjusting for age, education, wealth, physical activity, depression, cohabiting, self-rated health, loneliness and quality of life, there were significant associations between sexual activity and number sequencing and recall in men. However, in women there was a significant association between sexual activity and recall, but not number sequencing. Conclusions: possible mediators of these associations (e.g. neurotransmitters) are discussed. The cross-sectional nature of the analysis is limiting, but provides a promising avenue for future explorations and longitudinal studies. The findings have implications for the promotion of sexual counselling in healthcare settings, where maintaining a healthy sex life in older age could be instrumental in improving cognitive function and well-being. PMID:26826237

  13. 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

  14. 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...

  15. 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

  16. 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...

  17. Behavioral, neurochemical and morphological changes induced by the overexpression of munc18-1a in brain of mice: relevance to schizophrenia

    OpenAIRE

    Castro, E; Sánchez-Blázquez, Pilar; Pazos, Ángel; Garzón, Javier; Meana, J J

    2013-01-01

    Overexpression of the mammalian homolog of the unc-18 gene (munc18-1) has been described in the brain of subjects with schizophrenia. Munc18-1 protein is involved in membrane fusion processes, exocytosis and neurotransmitter release. A transgenic mouse strain that overexpresses the protein isoform munc18-1a in the brain was characterized. This animal displays several schizophrenia-related behaviors, supersensitivity to hallucinogenic drugs and deficits in prepulse inhibition that reverse afte...

  18. Gender and age related expression of Oct-6--a POU III domain transcription factor, in the adult mouse brain.

    Science.gov (United States)

    Ilia, Maria; Sugiyama, Yuka; Price, Jack

    2003-06-26

    Oct-6 is a POU III domain transcription factor whose primary role is thought to be developmental. It is expressed in embryonic stem cells, Schwann cells, and in neuronal subpopulations during telencephalic development. Its best characterised role is in Schwann cells where it is thought to regulate myelin specific gene expression. Expression of Oct-6 was recently discovered in neurons in post-mortem human schizophrenic specimens while being undetectable in matched controls. This study of human tissue contrasted in a number of regards with earlier studies of rodent brain, and questioned what we can consider to be normal adult expression of this gene. In this study, we have investigated Oct-6 expression via in situ hybridisation and Western blot analysis in normal adult female mice of different ages. We show that both RNA and protein levels of Oct-6 expression are highly sustained in the adult and aging cerebellum, whereas they are attenuated in the telencephalon by PW30 (postnatal week 30). These observations suggest that Oct-6 expression takes place in a sex and age dependent way. PMID:12782346

  19. 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

  20. The use of bone age for bone mineral density interpretation in a cohort of pediatric brain tumor patients

    International Nuclear Information System (INIS)

    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.)