Showing papers on "Aging brain published in 1997"

Life and Death of Neurons in the Aging Brain

Abstract: Neurodegenerative disorders are characterized by extensive neuron death that leads to functional decline, but the neurobiological correlates of functional decline in normal aging are less well defined. For decades, it has been a commonly held notion that widespread neuron death in the neocortex and hippocampus is an inevitable concomitant of brain aging, but recent quantitative studies suggest that neuron death is restricted in normal aging and unlikely to account for age-related impairment of neocortical and hippocampal functions. In this article, the qualitative and quantitative differences between aging and Alzheimer's disease with respect to neuron loss are discussed, and age-related changes in functional and biochemical attributes of hippocampal circuits that might mediate functional decline in the absence of neuron death are explored. When these data are viewed comprehensively, it appears that the primary neurobiological substrates for functional impairment in aging differ in important ways from those in neurodegenerative disorders such as Alzheimer's disease.

Chapter 7 Protein Oxidation Processes in Aging Brain

Abstract: Publisher Summary Aging and age-related neurological disorders, especially Alzheimer's disease (AD) and stroke, affect millions of people worldwide. Free radical-associated protein oxidation in these brain disorders appears fundamental to the pathogenesis and etiology, and, hence, treatment of each. Other neurological disorders of the brain are associated with free radical oxidative stress, for example, Parkinson's disease, amyotrophic lateral sclerosis, Wilson's disease, and traumatic brain injury. Hence, greater understanding of free radical processes and their treatment and prevention in AD and stroke likely will provide insight into the basis of and treatment for other neurological disorders of oxidative stress. Membrane and cytosolic proteins, along with bilayer lipids, are primary targets for free radical oxidation in brain cells. This chapter summarizes some of the studies on protein oxidation and its involvement in aging, AD, and stroke. Several methods are widely used to assess the role of protein oxidation in oxidative stress in various diseases and in aging. The formation of cross-linked protein aggregates is of particular significance in the accumulation of reactive oxygen species (ROS)-mediated protein damage during aging and oxidative stress because such aggregates are resistant to degradation by proteases that preferentially degrade the oxidized forms of proteins.

Mitochondrial membrane fluidity and oxidative damage to mitochondrial DNA in aged and AD human brain.

Abstract: Oxidative damage on biological molecules has been proposed as a major cause of alterations observed in aging brain as well as in neurodegenerative diseases. In this study, we measured membrane fluidity in mitochondria extracted from three cerebral regions and cerebellum of Alzheimer disease (AD) patients and age-matched controls by means of fluorescence polarization technique. A significant reduction of mitochondrial membrane fluidity was found in AD, except in cerebellum. In controls, a decrease of membrane fluidity was observed along with age, and it was also related to the content of the oxidized nucleoside 8-hydroxy-2'-deoxyguanosine (OH8dG) in mitochondrial DNA (mtDNA). Alteration in membrane fluidity seems to be a result of lipid peroxidation, since it dramatically decreased when mitochondria were exposed to FeCl2 and H2O2. The parallel increase of viscosity in mitochondrial membrane and the amount of OH8dG in mtDNA is suggestive of a relationship between these biological markers of oxidative stress. These results provide further evidence that oxidative stress may play a role in the pathogenesis of AD.

Light Microscopic Quantification of Morphological Changes During Aging in Neurons and Glia of the Rat Parietal Cortex

Abstract: Background:Different changes in neuronal and glial popu- lation of the aging brain have been described; however, the degree and extent of these changes are controversial. This study evaluates the quantitative and cytomorphometric effects of aging on neuronal and glial populations in the parietal cortex of the rat. Methods: The study was performed in two groups of rats aged 4-6 and 30-32 months. Cortical volume, neuronal density, glial density, and neuro- nal area, and shapes of the soma and nucleus were analyzed in cortical layers I, II-IV, V, and VI using serial sections stained with cresyl-fast- violet, and quantitative morphometric techniques. Results: No changes with age were found in volume of the cortex or neuronal density. Glial density increased significantly (mean for all layers 17%) in older rats. Layers II-IV, V, and VI showed an age-related decrease in the area of the neuronal soma. Neuronal shape, as revealed by the major/minor diameter ratio, also showed a decrease in old rats but only in layer II-IV. Nuclear area decreased with age only in layer VI. Conclusions: The stability of neuronal density together with the in- creased number of glial cells and the changes in neuronal soma size suggest that aged-related cognitive impairment could be a consequence of neuronal dysfunction rather than actual neuronal losses. Anat. Rec. 247:

Principles of neural aging

Abstract: Contents in Brief: Preface. Acknowledgements. Contributors. Section I: General Theories of Aging: Part I: General Theories of Aging. Mechanisms of aging (S.U. Dani). Biophysical principles of aging (S.U. Dani). Mutation, evolution and aging (S.U. Dani, A.J.G. Simpson). General theories of aging: unification and synthesis (J.L. Graves). Part II: Proximate Mechanisms of Neural Aging. Structural regulation of gene expression: chromatin reorganization (A. Macieira-Coelho). Deletions of the mitochondrial genome and neurodegenerative diseases (S. Zullo, C.R. Merril). Molecular turnover and aging (S.U. Dani). The molecular biology of A|A deposition in Alzheimer disease (A.I. Bush, R.E. Tanzi). Internal disintegration of neurons by amyloid |A protein precursors (K. Yoshikawa). Section II: Ontogeny, Evolution and Neural Aging. Cell differentiation and ontogeny of the nervous system (S. Fujita). Ontogeny and evolution of the vertebrate central nervous system (S. Fujita). Evolution of brain size, morphological restructuring and longevity in early hominids (P.V. Tobias). Development of the human central nervous system (F. M 'ller, R. O'Rahilly). The limbic system as a model of cytoarchitectonical changes in the developing brain (I.N. Bogolepova). The metabolic basis of encephalization, prolonged life span, and the evolution of longevity (S.U. Dani). Evolution, secular changes and aging: how old is our brain? (S.U. Dani). Section III: Tissue and Cellular Changes. Neuron death: a developmental perspective (R. Linden). The aging human cerebral cortex: morphometry of areal differences and their functional meaning (H. Haug). Histological markers of neuronal aging and their meaning (S.U. Dani). Clinico-neuropathologic integration of dementia and Parkinson syndrome (neurofibrillary tangles and lewy bodies) (A. Hori). Changes in the white matter (J.E.H. Pittella). Nerve cell loss in the myenteric plexus (R.R. de Souza). Changes in the peripheral nervous system (T. Maisonobe, J-J. Hauw). Neoplasia as a model of neural aging (G.F. Walter). Dysregulation of glial cell apoptosis in the basis of neoplasia (D. Schiffer). Glial degeneration (K. Ikeda). Vascular changes (J.R.E. Bohl, A. Hori). Imaging the aging brain (H. Becker). Neuroimaging in the in vivo measurement of regional function in the aging brain (A.B. Newberg, A. Alavi). Aging in childhood (A. Hori). Section IV: Neural Aging, From Perception to Behavior. Geriatric psychiatry: the impact of neural science on mental health care of the aged (A. Meyer-Lindenberg, B. Gallhofer). Movement disorders (F. Blandini, C.Tassorelli, J.T. Greenamyre)

Selective Impairments of Mitochondrial Respiratory Chain Activity During Aging and Ischemic Brain Damage

Abstract: Cumulative oxidative damage to mitochondrial deoxyribonucleic acid (DNA) with subsequent defects in oxidative phosphorylation may reduce the capacity of the aging brain to cope with metabolic stress. This may contribute to the age related increase in cerebral infarct size that has been documented following permanent middle cerebral artery occlusion (MCAO) in the rat. This hypothesis was evaluated by assessing mitochondrial respiratory chain complex activity in both ischemic and non ischemic brain tissue of adult (10 month) and aged (28 month) male Wistar rats, six hours after occlusion of the left middle cerebral artery. Aging was associated with a significant decline in cerebral mitochondrial function with impairment of the activities of complexes I, II and IV. The individual respiratory chain complexes also exhibited selective vulnerability to a focal cerebral ischemic lesion, with significant impairment of complex I activity in the lesioned hemisphere of both age groups. The age related decline in complex I activity may be important in the enhanced susceptibility of the aging brain to ischemic neuronal damage.

Chapter 11 Neurotrophic Factors and the Aging Brain

Abstract: Publisher Summary Neurons in the brain are intricately connected in cell circuits in which intercellular communication is mediated by a variety of signaling molecules. One class of signaling molecules that appears to play a particularly prominent role in promoting the survival and growth of neurons is neurotrophic factors (NTFs). NTFs appear to represent prototypical anti-oxidation intercellular messengers in the brain. This chapter considers data concerning: the expression of NTFs and their cellular receptors in the normal adult and aging brain; roles of NTFs in regulating survival and plasticity of neurons; the signal transduction pathways that mediate cellular responses to NTFs; and the ability of NTFs to protect neurons against insults relevant to the pathogenesis of several age-related neurodegenerative disorders including, Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and stroke. Two general mechanisms whereby NTFs protect neurons against insults relevant to the aging brain are by suppressing free radical production and by stabilizing cellular ion homeostasis. The specific molecular events involved in the signal transduction mechanisms of NTF are rapidly emerging, and are providing targets for the development of drugs aimed at preventing age- and disease-related neuron degeneration.

The Effect of Non-Competitive N-Methyl-D-Aspartate Receptor Antagonism on Cerebral Oedema and Cerebral Infarct Size in the Aging Ischaemic Brain

Abstract: Although vulnerability to ischemic neuronal injury is enhanced with age, the aging brain may be less amenable to neuroprotection as a result of quantitative and qualitative changes in the NMDA receptor. In addition, the elderly may be less tolerant of adverse effects of neuroprotective drugs and this might ultimately limit therapeutic potential in human stroke. However, antagonism of the excitotoxic effects of glutamate by parenteral administration of the non competitive NMDA antagonist magnesium has been well tolerated and has shown to be neuroprotective in young animal models of stroke and head injury. We therefore evaluated the potential of magnesium chloride to reduce ischemic neuronal injury in aged rodents subjected to permanent occlusion of the middle cerebral artery.

Chapter 4 Cerebrovascular Changes in the Aging Brain

Abstract: Publisher Summary This chapter examines how “normal” or “abnormal” aging may affect the cerebrovasculature and internal neurosystems that depend on optimal cerebral blood flow delivery. The collective evidence of the effect of aging on the cerebrovasculature is often in disagreement with respect to progressive changes that may affect brain function. Aging apparently reduces the cerebral metabolic rate for oxygen (CMRO2) but its effect on cerebral metabolic rate of glucose (CMRglu) is less clear. Cerebrovascular disease may be related to aging only because the older we become, the more susceptible the system becomes over a longer exposure to an array of risk factors, such as hypertension, hyperlipidemia, and smoking. Many of these risk factors also predispose the cerebral vessels to stiffen and lose much of their distensibility, a phenomenon that may lead to structural vessel deformities and changes in the hemodynamics and perfusion pressure of the brain. Structural vessel deformities during aging may cause blood-brain barrier changes and allow substances that are normally kept out of the brain to enter and possibly damage the CNS. It would appear that endocrine hormones, particularly estrogen, may exert some protection from cerebral ischemia and hypoxia in pre-menopausal women and that such protection may continue to some degree with estrogen replacement therapy in post-menopausal individuals.

The aging brain

Abstract: Contents. List of Contributors. Preface (M.P. Mattson and J.W. Geddes). Toward a Cognitive Neuroscience of Normal Aging (P.R. Rapp and M. Gallagher). The Neuronal Cytoskeleton: Changes Associated with Age, Neurodegenerative Disease, and Neuronal Insult (J.W. Geddes and A.I. Matus). Structural Changes in the Aged Brain (D.W. Dickson). Cerebrovascular Changes in the Aging Brain (J.C. de la Torre). Metabolism of the Aging Brain (J.P. Blass, G.E. Gibson, and S. Hoyer). Contribution of Mitochondrial Alterations to Brain Aging (G. Benzi and A. Moretti). Protein Oxidation Processes in Aging Brain (D.A. Butterfield and E.R. Stadtman). Neuroendocrine Aspects of the Aging Brain (P.M. Wise, J.P. Herman, and P.W. Landfield). Changes in Neurotransmitter Signal Transduction Pathways in the Aging Brain (J.F. Kelly and G.S. Roth). Food Restriction and Brain Aging (C.E. Finch and T.E. Morgan). Neurotrophic Factors and the Aging Brain (M.P. Mattson and O. Lindvall). Index.

Chapter 9 Changes in Neurotransmitter Signal Transduction Pathways in the Aging Brain

Abstract: Publisher Summary Cell to cell signaling in the brain propagates by ion flux-mediated electrical conduction and chemical stimulation of cell surface receptors. Chemical signaling by neurotransmitters represents the commonest mode of communication between nerve cells. A number of investigators have hypothesized that deficits in neurotransmission may underlie age-related changes in learning and memory and motor function and that these changes as well as other molecular and cellular alterations may promote or contribute to the development of age-related neurodegenerative diseases, including Alzheimer's Disease and Parkinson's Disease. This chapter discusses recent data from rodent, primate, and human studies that investigate age-related changes in interneuronal signaling by the classical neurotransmitters, acetylcholine, dopamine, norepinephrine, serotonin, glutamate, and GABA. It summarizes current research in this field as well as suggests future directions for investigation. The chapter discusses evidence that supports the presence of defective muscarinic cholinergic receptor G protein coupling in rat and human striata. In addition, it discusses evidence that suggests that age-related changes in neuronal membrane composition and structure contribute to changes in neurotransmitter signal conduction.

Chapter 5 Metabolism of the Aging Brain

Abstract: Publisher Summary This chapter discusses the effects of age on the metabolism of the nervous system are described both in unusually healthy individuals (successful aging) as well as in individuals who have diseases that are very common in the elderly (usual aging). The principles of neurobiology apply to the aging brain as they do to the adult and developing brain. The nervous system is complicated and regionally specialized. Dysfunction of the nervous system can often be documented at relatively early stages of disease or other damage, for instance by neuropsychological measurements or detailed neurological examination, and can often be mapped relatively precisely to specific parts of the brain, spinal cord, or peripheral nerves. The mechanisms of aging apply to the nervous system as they do to other tissues. In humans in vivo, cerebral metabolism tends to fall with aging, although it is possible to select a group of very healthy older subjects in whom measures of cerebral metabolism (cerebral metabolic rate for glucose [CMRglu] or for oxygen [CMRO 2 ] or for cerebral blood flow [CBF]) are comparable to those in younger subjects. A number of common diseases of aging can reduce cerebral metabolic rates, including cardiac disease, hypertension, strokes and other forms of cerebrovascular disease, and Alzheimer's disease. The decreases in metabolic rate in aged brain may be due to damage by reactive oxygen species (ROS), particularly to mitochondrial DNA (mtDNA) and to the cytochromes derived from mtDNA.

Responses of aging brain to physical exercise: changes in the substrates of energy metabolism.

Abstract: Responses of aging brain to physical training was evaluated by quantifying the substrates, glucose, lactic acid, and nucleic acids in cerebral cortex (CC) and medulla oblongata (MO) of the brain in rats. Rats of 1 month (young), 6 months (adult), 12 months (middle-aged) and 18 months (old) of age were swim-trained for 30 days. Glucose content of CC and MO increased with training whereas blood glucose decreased in trained young and adult animals with middle-aged and old animals maintaining constant blood glucose. Brain lactate in these two regions decreased with training in all age groups. However, the old animals showed an elevation in blood lactic acid in trained state, while the other age groups showed a decrease. Nucleic acid content, decreased with age, especially the RNA content in MO showing a larger depletion. However, there was no discernible influence of physical exercise on these parameters. Physical training has influenced the aging brain's adaptability, as seen by increase in its glucose content in young animals and also possible utilization of lactate as an additional substrate in old animals as evidenced by an increase in blood lactic acid.

[Neuronal growth-associated proteins in neural plasticity and brain aging].

Abstract: This review summarizes current issues on neuronal structural plasticity and its molecular marker genes in the aged brain. Neuronal growth-associated proteins (nGAPs) are introduced as potential markers of neuronal structural plasticity in the brain. The expression of genes encoding nGAPs such as GAP-43, SCG10 and stathmin is increased following striatal and hippocampal neuronal deafferentation lesions in the adult rat brain. In aged brains, the magnitude of neuronal plasticity is reduced and nGAP gene induction is limited at least in part, while the kinetics of the response remains unchanged in comparison to young brains. These results suggest that nGAPs serve as molecular markers of neuronal structural plasticity in the aging brain and that neuronal plasticity decreases, at least in certain neuronal circuits, during aging. The expression of genes encoding SCG10, stathmin and GAP-43 is also altered in age-related neurodegenerative conditions such as Alzheimer's disease in humans. Thus, studies of nGAPs are important for the elucidation of the mechanisms of the reduction of neuronal structural plasticity in aged brains.

Presenilin-1 polymorphism and neuropathological lesions of aging brain and late-onset Alzheimer's disease

Abstract: In addition to missense mutations of the presenilin-1 gene, an association between a polymorphism within the intron 3’to exon 8 and late-onset sporadic Alzheimer's disease (AD) cases has been reported. This study examined the relationship between this polymorphism and the density of lesions by studying a homogeneous group of cases with different levels (normal to severely demented) of intellectual impairment. There were no differences in age and intellectual status between the groups of different genotypes. In all areas of the brain examined (frontal, temporal, calcarine, supramarginal and subicular areas), we found no difference in the density of Aβ-deposits. Only in the subicular area, a lower density of neurofibrillary tangles (NFT) was found in the 2/2 genotype group compared with those found in the combined group of 1/1 and 1/2 genotypes. This suggests that this polymorphism influences the development of NFT preferentially detected in the subiculum, where prominent AD lesions are usually observed.