Showing papers on "Aging brain published in 2001"

ROS generation, lipid peroxidation and antioxidant enzyme activities in the aging brain

Abstract: The objective of this study was to determine the specific relationship between brain aging and changes in the level of oxidative stress, lipid peroxidation (LPO) and in the activities of antioxidant enzymes. We used four different age groups (2-3 months, 10-11 months, 16-17 months and 20-21 months) which represented young adults, adults, beginning senescence and senescence, respectively. Basal levels of LPO products measured as malondialdehyde increased gradually with age in mouse brain homogenate. The extent of stimulated LPO products, however, was clearly decreased in the brain of adult mice compared to young mice but increased again in the brain of senescent mice. We could not detect any appreciable age-related changes in the basal as well as in stimulated levels of ROS measured with the fluorescent dyes dichlorofluorescein and dihydrorhodamine123. Nevertheless, there was a significant delay in the time course of ROS-generation in brain cells from old mice. The activities of the antioxidant enzymes CuZn-superoxide dismutase and glutathione reductase increased with age whereas glutathione peroxidase remained unchanged. On the basis of our present findings, we envisage a potential model that integrates several divergent findings described in the literature about the role of oxidative stress in brain aging.

Functional neurobiology of aging

Abstract: Contributors. Foreword. Preface. Overview: Introduction to Concepts in Aging Research: Age-Specific Rates of Neurological Disease, J.E. Riggs. Nature versus Nurture in the Aging Brain, C.V. Mobbs and J.W. Rowe. Neurochemistry of Receptor Dynamics in the Aging Brain, B.J. Keck and J.M. Lakoski. Epidemiology of Neural Aging: Demography and Epidemiology of Age-Associated Neuronal Impairment, C.K. Cassel and K. Ek. Memory: Neocortical and Hippocampal Functions: Neuropsychology of Human Aging. Memory Changes with Aging and Dementia, P.D. Harvey and R.C. Mohs. Histology of Age-Related Cortical Changes in Humans: Types of Age-Related Brain Lesions and Relationship to Neuropathological Diagnostic Systems of Alzheimer's Disease, P. Giannakopoulos, E. Kovari, G. Gold, P.R. Hof, and C. Bouras. Morphological changes in Human Cerebral Cortex during Normal Aging, T. Bussiere and P.R. Hof. Longevity and Brain Aging: The Paradigm of Centenarians, C. Bouras, P.G. Vallet, E. Kovari, J.-P. Michel, F.R. Herrmann, P.R. Hof, and P. Giannakopoulos . Alzheimer's Disease: Regional and Laminar Patterns of Selective Neuronal Vulnerability in Alzheimer's Disease, P.R. Hof. Patterns of Cortical Neurodegeneration in Alzheimer's Disease: Subgroups, Subtypes, and Implications for Staging Strategies, B.A. Vogt, L.J. Vogt, and P.R. Hof. Non-Alzheimer Age-Associated Dementing Disorders: Vascular Dementia, G. Gold, C. Bouras, J.-P. Michel, P.R. Hof, and P. Giannakopoulos. Frontotemporal Dementias: From Classification Problems to Pathogenetic Uncertainties, P. Giannakopoulos, E. Kovari, G. Gold, P.R. Hof and C. Bouras. Progressive Supranuclear Palsy and Corticobasal Degeneration, D.W. Dickson. Neurobiology of Disorders with Lewy Bodies, L. Hansen and E. Masliah. Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex of Guam, D.P. Perl. In Vivo Imaging of Aging Brain: Brain Energy Metabolism: Cellular Aspects and Relevance to Functional Brain Imaging, P.J. Magistretti, S. Joray, and L. Pellerin. Functional Imaging in Cognitively Intact Aged People, N.D. Anderson and C.L. Grady. Functional Brain Studies of the Neurometabolic Bases of Cognitive and Behavioral Changes in Alzheimer's Disease, P. Pietrini, M.L. Furey, M. Guazzelli, and G.E. Alexander. Biochemical Correlates of Memory Impairments: Cholinergic Basal Forebrain Systems in the Primate Central Nervous System: Anatomy, Connectivity, Neurochemistry, Aging, Dementia, and Experimental Therapeutics, E.J. Mufson and J.H. Kordower. Glutamate Receptors in Aging and Alzheimer's Disease, A. Mishizen, M. Ikonomovic, and D.M. Armstrong. Tau Phosphorylation, L. Buee and A. Delacourte. Hereditary Basis of Alzheimer's Disease and Related Dementias: Etiology, Genetics, and Pathogenesis of Alzheimer's Disease, C. McKeon-O'Malley and R. Tanzi. Nonhereditary Mechanisms of Alzheimer's Disease: Inflammation, Free Radicals, Glycation, Metabolism and Apoptosis, and Heavy Metals, M.P. Mattson. Rodent Models of Age-Related Memory Impairments: Rodent Models of Age-Related Memory Impairments, D.K. Ingram. Genetically Engineered Models of Human Age-Related Neurogenerative Diseases, J.C. Vickers. Nonhuman Primate and Other Vertebrate Models of Brain Aging: Cognitive Aging in Nonhuman Primates, M.G. Baxter. Brain Aging in Strepsirhine Primates, E.P. Gilissen, M. Dhenain, and J.M. Allman. Age-Related Morphologic Alterations in the Brain of Old World and New World Anthropoid Monkeys, P.R. Hof and H. Duan. The Study of Brain Aging in Great Apes, J.M. Erwin, E.A. Nimchinsky, P.J. Gannon, D.P. Perl, and P.R. Hof. Neurobiological Models of Aging in the Dog and Other Vertebrate Species, E. Head, N.W. Milgram, and C.W. Cotman. Interventions: Estrogens and Alzheimer's Disease, N.D. Tsopelas and D.B. Marin. Cholinergic Treatments of Alzheimer's Disease, N.D. Tsopelas and D.B. Marin. Anti-Inflammatory and Antioxidant Therapies in Alzheimer's Disease, P.S. Aisen and G.M. Pasinetti. Senses: Sensory Cortices and Primary Afferent Functions: Vision: The Retina in Aging and in Alzheimer's Disease, R.O. Kuljis. Pathogenesis of Glaucomatous Optic Neuropathy, M.R. Hernandez and A.H. Neufeld. Color Vision, Object Recognition, and Spatial Localization in Aging and Alzheimer's Disease, A. Cronin-Golomb. Hearing: Anatomical and Neurochemical Bases of Presbycusis, R.D. Frisina, Jr. Age, Noise, and Ototoxic Agents, R.J. Salvi, D. Ding, A.C. Eddins, S.L. McFadden, and D. Henderson. Auditory Temporal Processing during Aging, D.R. Frisinia, R.D. Frisinia, Jr., K.B. Snell, R. Burkard, J.P. Walton, and J.R. Ison. Neurophysiological Manifestations of Aging in the Peripheral and Central Auditory Nervous System, J.P. Walton and R. Burkard. Genetics and Age-Related Hearing Loss, S.L. McFadden. Animal Models of Presbycusis and the Aging Auditory System, J.F. Willott. The Development of Animal Models for the Study of Presbycusis: Building a Behavioral Link between Perception and Physiology, J.R. Ison. Rehabilitation for Presbycusis, D.G. Sims and R. Burkard. Chemical Senses: Olfaction and Gustation in Normal Aging and Alzheimer's Disease, R.L. Doty. Locomotion: Basal Ganglia and Muscular Functions: Functional Impairments in Humans: Aging Effects on Muscle Properties and Human Performance, S.A. Jubrias and K.E. Conley. Parkinson's Disease: Symptoms and Age Dependency, S.A. Eshuis and K.L. Leenders. Pathology and Biochemistry of Aging and Disease of Basal Ganglia: The Basal Ganglia Dopaminergic Systems in Normal Aging and Parkinson's Disease, J.N. Joyce. Huntington's Disease, S.E. Browne and M.F. Beal. Animal Models: Biochemical and Anatomical Changes in Basal Ganglia of Aging Animals, J.A. Stanford, M.A. Hebert, and G.A. Gerhardt. Homeostasis: Hypothalamus and Related Systems: Reproduction and the Aging Brain: Male Sexual Behavior during Aging, H. Kuno, M. Godschalk, and T. Mulligan. Sexual Behavior in Aging Women, N.E. Avis. Factors Influencing the Onset of Female Reproductive Senescence, P.S. LaPolt and J.K.H. Lu. Female Sexuality during Aging, N.L. McCoy. Hypothalamic Neuropeptide Gene Expression in Postmenopausal Women, N.E. Rance and T.W. Abel. Neuroendocrine Aspects of Female Reproductive Aging, P.M. Wise and M.J. Smith. Hypothalamic Changes Relevant to Reproduction in Aging Male Rodents, D.A. Gruenewald and A.M. Matsumoto. Metabolism and the Aging Brain: Regulation of Energy Intake in Old Age, S.B. Roberts and N.P. Hays. Thermoregulation during Aging, B.A. Horwitz, A.M. Gabaldon, and R.B. McDonald. Biological Rhythms and the Aging Brain: Sleep and Hormonal Rhythms in Humans, G. Copinschi, R. Leproult, and E. Van Cauter. Circadian Rhythms and Sleep in Aging Rodents, D.E. Kolker and F.W. Turek. Glucocorticoid Secretion and the Aging Brain: Clucocorticoids and the Aging Brain: Cause or Consequence? P.J. Lucassen and E.R. De Kloet. Growth Hormone, Insulin-like Growth Factor-1, and the Aging Brain, P.L. Thornton and W.E. Sonntag. Automatic Nervous System and the Aging Brain: The Aged Sympathetic Nervous System, G.A. Kuchel and T. Cowen. Appendix. Basic Genetic Concepts.

Melatonin reverses the profibrillogenic activity of apolipoprotein E4 on the alzheimer amyloid Aβ peptidet

Abstract: Inheritance of apoE4 is a strong risk factor for the development of late-onset sporadic Alzheimer's disease (AD). Several lines of evidence suggest that apoE4 binds to the Alzheimer Abeta protein and, under certain experimental conditions, promotes formation of beta-sheet structures and amyloid fibrils. Deposition of amyloid fibrils is a critical step in the development of AD. We report here that addition of melatonin to Abeta in the presence of apoE resulted in a potent isoform-specific inhibition of fibril formation, the extent of which was far greater than that of the inhibition produced by melatonin alone. This effect was structure-dependent and unrelated to the antioxidant properties of melatonin, since it could be reproduced neither with the structurally related indole N-acetyl-5-hydroxytryptamine nor with the antioxidants ascorbate, alpha-tocophenol, and PBN. The enhanced inhibitory effects of melatonin and apoE were lost when bovine serum albumin was substituted for apoE. In addition, Abeta in combination with apoE was highly neurotoxic (apoE4 > apoE3) to neuronal cells in culture, and this activity was also prevented by melatonin. These findings suggest that reductions in brain melatonin, which occur during aging, may contribute to a proamyloidogenic microenvironment in the aging brain.

Do glucocorticoids contribute to brain aging

Abstract: The hippocampus, an area with abundant glucocorticoid receptors, continues to be the focus of research on effects of glucocorticoids on the aging brain. Based on recent studies, the primary structural change found during aging is synaptic loss, rather than neuronal loss. High levels of glucocorticoids are associated with synaptic loss in the hippocampus, hippocampal atrophy, and cognitive decline during aging in some individuals. However, increasing levels of glucocorticoid are not always found since early experiences can alter sensitivity to negative feedback and the level of activation of the hypothalamic–pituitary–adrenal axis in aged individuals. New ways in which glucocorticoids may contribute to brain aging are discussed, including decreased responses to glucocorticoids possibly as a result of decreased glucocorticoid receptors and also altered regulation of neuronal turnover in the dentate gyrus. Decreased responsiveness of glial fibrillary acidic protein to glucocorticoids during aging could facilitate reactive gliosis and loss of synapses by altering neuron–astrocyte interactions. Neuronal turnover is regulated by glucocorticoids in the dentate gyrus where ongoing neurogenesis may be important for hippocampal-based memory formation in adulthood. Although the age-related decline in neurogenesis can be reversed by removal of adrenal steroids, the death of dentate granule neurons is also greatly increased by this treatment. Recent studies show age-related resistance to induced apoptosis and neurogenesis in the dentate gyrus following adrenalectomy, which is associated with increased expression of transforming growth factor-β1. Therefore, the contribution of glucocorticoids to brain aging depends on the physiological and cellular context and some of these effects are reversible.

Where do Alzheimer's plaques and tangles come from? Aging-induced protein degradation inefficiency.

Abstract: Amyloid plaques and neurofibrillary tangles are prominent lesions in the aging brain and they may be responsible for cell death in Alzheimer's disease. But a basic question has not been answered: why and how are plaques and tangles formed during aging? In this study, we approach this question by first examining what happens in the aging body. Plaques and tangles do not come alone, but together with many other aging markers in the body (cholesterol deposition, gallstones, hair graying, and bone loss, etc.). Because these aging markers occur to a certain extent in all elderly and at about the same time in life, it is reasonable to conceive that they originate from a common cause, that is, aging-induced metabolic inefficiency. If cholesterol and gallstone depositions are the results of inefficient degradation/clearance of lipids and minerals, then similarly plaque and tangle formation in most people would be the results of inefficient normal degradation of ?-amyloid precursor protein (APP) and tau, respectively. By this view, our studies should focus on the enzymes responsible for APP and tau normal degradation and their natural changes in aging, rather than on presumed pathological factors. Whatever precise mechanisms underlying their depositions, plaques and tangles are the natural products of aging, thus fundamentally different from pathological events such as cancer growth in concept.

Neuroglia in the aging brain

Abstract: Part I. Cellular and Molecular Changes of Aged and Reactive Astrocytes Neuromorphological Changes in Neuronal and Neuroglial Populations of the Cerebral Cortex in the Aging Rat: Neurochemical Correlations Maria Angeles Peinado, Manuel Martinez, Maria Jesus Ramirez, Adoracion Quesada, Juan Angel Pedrosa, Concepcion Iribar, and Jose Maria Peinado Diversity in Reactive Astrocytes Sudarshan K. Malhotra and Theodor K. Shnitka Astrocytic Reaction After Traumatic Brain Injury Jesus Boya, J. L. Calvo, Angel Lopez-Carbonell, and Jose E. Garcia-Maurino Part II. Neuron-Glia Intercommunication Astrocytes In Situ Exhibit Functional Neurotransmitter Receptors Marilee K. Shelton and Ken D. McCarthy Glia and Extracellular Space Diffusion Parameters in the Injured and Aging Brain Eva Sykova Intercellular Diffusional Coupling between Glial Cells in Slices from the Striatum Brigitte Hamon, Jacques Glowinski, and Christian Giaume Glial Cell Involvement in Brain Repair and the Effects of Aging Elizabeth A. Howes and Peter J. S. Smith ATP Signaling in Schwann Cells Thierry Amedee, Aurore Colomar, and Jonathan A. Coles Part III. Neurotrophins, Growth Factors, and Neurohormones in Aging and Regeneration Gliosis Growth Factors in the Adult and Aging Rat Brain Gerard Labourdette and Francoise Eclancher Role of Fibroblast Growth Factor-2 in Astrogliosis John F. Reilly Trophins as Mediators of Astrocyte Effects in the Aging and Regenerating Brain Judith Lackland and Cheryl F. Dreyfus Responses in the Basal Forebrain Cholinergic System to Aging Zezong Gu and J. Regino Perez-Polo Effects of Estrogens and Thyroid Hormone on Development and Aging of Astrocytes and Oligodendrocytes Kevin Higashigawa, Alisa Seo, Nayan Sheth, Giorgios Tsianos, Hogan Shy, LathaMalaiyandi, and Paola S. Timiras Part IV. Metabolic Changes Neurotoxic Injury and Astrocytes Michael Aschner and Richard M. LoPachin Ammonium Ion Transport in Astrocytes: Functional Implications Neville Brookes Part V. Astrocytes and the Blood-Brain Barrier in Aging Molecular Anatomy of the Blood-Brain Barrier in Development and Aging Dorothee Krause, Pedro M. Faustmann, and Rolf Dermietzel The Blood-Brain Barrier in the Aging Brain Gesa Rascher and Hartwig Wolburg Astrocytes and Barrier-provided Microvasculature in the Developing Brain Luisa Roncali Part VI. Astrocytes in Neurodegenerative Diseases Microglial and Astrocytic Reactions in Alzheimer's Disease Douglas G. Walker and Thomas G. Beach Activated Neuroglia in Alzheimer's Disease Kurt R. Brunden and Robert C. A. Frederickson Reactive Astroglia in the Ataxic Form of Creutzfeldt-Jakob Disease: Cytology and Organization in the Cerebellar Cortex Miguel Lafarga, Nuria T. Villagra, and Maria T. Berciano Ischemic Injury, Astrocytes, and the Aging Brain Robert Fern Glial-Neuronal Interactions during Oxidative Stress: Implications for Parkinson's Disease Catherine Mytilineou Astrocytic Changes Associated with Epileptic Seizures Angelique Bordey and Harald Sontheimer Synaptic and Neuroglial Pathobiology in Acute and Chronic Neurological Disorders Lee J. Martin Astrocytes and Ammonia in Hepatic Encephalopathy Michael D. Norenberg

Glutamate Receptors in Aging and Alzheimer's Disease

Abstract: The discovery that the stimulation of ionotropic glutamate receptors mediates not only the physiological action of glutamate but also a neurotoxic response provided the impetus for numerous investigations that sought to determine the role of glutamate in the pathophysiology of a number of neurodegenerative diseases, including Alzheimer's disease (AD). To date, nearly 200 articles have been published that specifically focus on the integrity and/or functional properties of the glutamate receptors in aging and AD. This chapter attempts to synthesize the results of these many studies and present them in as unbiased manner as possible. The chapter is divided into four main sections: (i) overview of the glutamate receptors, (ii) glutamate receptors in the aging (rodent) brain, (iii) glutamate receptors in the AD brain, and (iv) current topics of glutamate toxicity in AD. What will become obvious following the reading of this chapter is that data are at times inconsistent, with some investigators reporting that glutamate receptors are highly vulnerable in the aged and AD brain, whereas others state that these receptors are intact or even hyperfunctional. Contributing to these inconsistencies are a host of technical issues. To address this matter, the details of a number of studies (i.e., strain, species, age, brain region investigated, postmortem interval, when applicable) are presented in tabular form ( TABLE 20.1 , TABLE 20.2 , TABLE 20.3 , TABLE 20.4 , TABLE 20.5 , TABLE 20.6 , TABLE 20.7 , TABLE 20.8 , TABLE 20.9 , TABLE 20.10 , TABLE 20.11 , TABLE 20.12 , TABLE 20.13 , TABLE 20.14 ). By providing this information, it is our goal that the reader will be able to make some personal assessment of the extent to which technical details, may or may not, confound the biological relevance of the findings. It is also important to bear in mind that much of our knowledge of glutamate receptors in aging and AD has come about through studies employing autoradiographic techniques to investigate the anatomical distribution and density of various ligand-specific binding sites. Although these studies have been of considerable value in defining the role of glutamate in the aging brain and AD, it is clear from our knowledge of the molecular biology of the glutamate receptor that specific techniques are required allowing for the identification of individual glutamate receptor subtypes. Studies employing these latter techniques are currently underway in several laboratories and while much of the data remain unpublished it is clear that these works will play a critical role in the future in defining glutamates participation as an excitotoxic agent in the aging brain and AD.

Glucocorticoids and the aging brain; cause or consequence?

Abstract: In this review we discuss if changes in corticosteroid levels are the cause or consequence of the aging process and age-related brain pathology. Accumulating evidence suggests that corticosteroid levels are not consistently elevated in aging. However, if corticosteroid levels circulate in aberrant concentrations, they do increase the vulnerability to cognitive decline and disease, rather than aging per se. Corticosteroid hormone action is mediated through mineralocorticoid (MR) and glucocorticoid receptors (GR) that are colocalized in hippocampal neurons. The high-affinity MR operates in a proactive mode, limiting homeostatic disturbance and promoting neuronal stability. The low-affinity GR on the other hand, facilitates, in a reactive manner, the recovery of homeostasis following perturbation by stress. Together, steroid hormone-mediated MR and GR actions involve the expression of specific target genes that control brain processes like neuronal excitability, calcium homeostasis, energy metabolism, and cell division in discrete hippocampal regions. Given this capacity, MR and GR are critical for the set point regulation of many homeostatic processes during aging. Depending on additional environmental and genetic factors, an imbalance in their actions can therefore result in altered stress regulation, cognitive decline, and impaired behavioral adaptation, through dysregulation of the same genes that are otherwise essential for maintaining neuronal homeostasis and health. Corticosteroid receptors and their responsive genes are thus not only critical for successful aging, they form at the same time excellent drug targets, through which homeostasis can be reestablished and the restorative capacity still present within the diseased aging brain, promoted. © 2001 Academic Press.

Changes of the brain synapses during aging. New aspects.

Abstract: The process of brain aging is an interaction of age-related losses and compensatory mechanisms. This review is focused on the changes of the synaptic number and structure, their functional implications, regarding neurotransmission, as well as the electrical activity of neuronal circuits. Moreover, the importance of calcium homeostasis is strongly emphasized. It is also suggested that many neuronal properties are preserved, as a result of adaptive mechanisms, and that a series of interdependent factors regulate brain aging. The "new frontier" in research is the challenge of understanding the effects of aging, both to prevent degenerative diseases and reduce their consequences. New aspects are considered a) the role of nitric oxide, b) free radicals and apoptosis, c) impaired cerebral microcirculation, d) metabolic features of aging brain, e) the possible neuroprotective role of insulin-like growth factor-1 (IGF-1) and ovarian steroids and e) stress and aging. These numerous multifactorial approaches are essential to understand the process of aging. The more we learn about it, the more we realize how to achieve "successful" aging.

3 – Neurochemistry of Receptor Dynamics in the Aging Brain

Abstract: This chapter discusses the neurochemistry of changes that usually occur in various receptor systems in an aging brain. Numerous investigations have been conducted to identify changes in synaptic processes, which are associated with specific age-related disorders. There are researchers who provide a clear overview of the decline in striatal noradrenaline, dopamine, and serotonin concentrations occurring with old age and at the same time suggest that these changes correspond to different alterations in cognitive function. In addition, different studies—which use aged nonhuman primates—have demonstrated reductions in a variety of neurotransmitters, which include acetylcholine and serotonin. The chapter also describes the neurotransmitter system throughout to exemplify various facets of receptor-related changes in an aging brain. The enhancements in image resolution that can be obtained in vivo provide the first steps toward successful monitoring receptors in an organism on a continual basis throughout a health span. The temporal limitation of the current approach holds a greater promise for resolution in the future.

Brain aging research at the close of the 20th century: from bench to bedside.

Abstract: Remarkable and continued growth in the field of brain aging research has been fueled by a confluence of factors. Developments in molecular biology, imaging, and genetics coupled with the imperative caused by the aging of the population has created fertile ground for improved understanding of the interaction between brain function and behavior. Aging changes in neurochemical systems may account for the spectrum of cognitive and behavioral states of successfully aged pen sons, but may also contribute to enhanced vulnerability to depressive or dementing illness. In particular, the refinement of in vivo imaging approaches to investigating the structure and function of the aging brain has provided the opportunity to strengthen our knowledge of the biological substrate of the aging brain and neuropsychiatrie disorders, and translate these into therapeutics.