Showing papers on "Aging brain published in 1999"

Corticosteroids, the Aging Brain and Cognition.

Abstract: The hippocampal region of the brain is a useful model system for understanding the plasticity and resilience of brain cells to stress hormone action and aging. Hippocampal neurons show both structural and functional plasticity, and individual differences in hippocampal function are shaped by early life experiences. For human brain aging, there are new non-invasive imaging tools to relate to the animal models, and these can help to assess the vulnerability of the aging hippocampus in relation to stress and Alzheimer's disease.

Piracetam improves cognitive performance by restoring neurochemical deficits of the aged rat brain.

Abstract: In order to test the hypothesis that piracetam improves cognitive functions by restoring biochemical deficits of the aging brain, we investigated the effects of piracetam treatment (300 mg/kg daily for 6 weeks) on the active avoidance performance of young and aged rats. After testing, the rats were killed and membrane fluidity and NMDA as well muscarinic cholinergic receptor densities were determined in the frontal cortex, the hippocampus, the striatum, as well as the cerebellum. Piracetam treatment improved active avoidance learning in the aged rats only and elevated membrane fluidity in all brain regions except the cerebellum in the aged animals. Moreover, we observed a positive effect of piracetam treatment on NMDA receptor density in the hippocampus and on muscarinic cholinergic receptor densities in the frontal cortex and the striatum and to a lesser extent in the hippocampus. Again, these effects were only observed in aged animals. Discrimination analysis indicated that piracetam effects on membrane fluidity in the frontal cortex, the hippocampus, and the striatum and its effects on NMDA densities in the hippocampus might be involved in its positive effects on cognitive performance.

Manganese uptake into rat brain during development and aging.

Abstract: Manganese (Mn) is an essential metal and plays an important role in the brain. To evaluate Mn uptake into the brain during development and aging, 54Mn concentrations in the brain of rats aged from 5 days to 95 weeks were measured after injection of 54MnCl2. 54Mn concentration in the brain of 5-day-old rats was the highest of all age groups tested. The liver and blood of 5-day-old rats also showed the highest 54Mn concentrations among the age groups. These results suggest that Mn is required in a high amount during infancy and that a sufficient Mn supply is critical for normal brain development. The high uptake of Mn into the brain of neonatal rats may be due to high levels of Mn in the blood, which may be supplied from the liver. In the 5-day-old brain, 54Mn was relatively concentrated in the hippocampal CA3 and dentate gyrus and the pons. In the aging brain, 54Mn was relatively concentrated in the inferior colliculi, olivary nuclei and red nuclei.

Corticosterone regulation of serotonin transporter and 5-HT1A receptor expression in the aging brain

Abstract: Hypercortisolemia is often observed in patients suffering from major depression. As the serotonergic (5-hydroxytryptamine; 5-HT) system plays a major role in the etiology of depression, a loss of endocrine and neurotransmitter system interactions, including corticosterone regulation of 5-HT transporter (5-HTT) and 5-HT receptor expression, may underlie age-related deficits in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis and correlate with an increased incidence of depression with advancing age. In this study, female Fischer 344 rats, ages 3, 13, and 18 months, were bilaterally adrenalectomized and supplemented for 3 weeks with corticosterone (0, 200, or 600 mg; LC, MC, or HC, respectively) containing 21 day sustained-release pellets implanted subcutaneously. Quantitative autoradiography of hippocampal and cortical regions using [3H]citalopram revealed a significant decrease in hippocampal 5-HTT binding in the 3-month HC treatment group compared to age-matched MC and LC groups; this loss was not present in the 13- or 18-month groups. Similarly, quantitative autoradiography using the radiolabeled 5-HT1A receptor agonist 8-hydroxy-2-(di-N-propylamino) tetralin demonstrated a significant decline in receptor density in 3- and 13-month MC and HC groups as compared to age-matched LC groups in the hippocampus. These hormone treatments (MC or HC), however, failed to alter hippocampal 5-HT1A binding site density in the 18-month groups as compared to the age-matched LC group. The 5-HT2A receptor was also evaluated using [3H]ketanserin and showed no age- or corticosterone-related changes in the cortex. Overall, an age-associated deficit in the regulation of the hippocampal serotonergic system by varied corticosterone treatment was revealed in the present study, which may underlie the increased incidence of depression and hypercortisolemia found with advancing age. Synapse 32:58–66, 1999. © 1999 Wiley-Liss, Inc.

Primary Cultures of Rat Cerebellar Granule Cells as a Model to Study Neuronal 5‐Lipoxygenase and FLAP Gene Expression

Abstract: Aging is associated with chronic neurodegenerative diseases and increased brain vulnerability that may lead to a worse outcome from brain insults in elderly than in young subjects. Inflammation is one of the patholphysiological mechanisms of both chronic and acute neurodegeneration. Leukotrienes are inflammatory lipid mediators whose formation from arachidonic acid is initiated by 5-lipoxygenase (5-LO). 5-LO is also expressed in neurons and can be activated by brain injuries, whereas 5-LO inhibitors can provide neuroprotection. The expression of the 5-LO gene appears to be inhibited by the pineal hormone, melatonin, and stimulated by stress hormone glucocorticoids (e.g., corticosterone and the synthetic glucocorticoid dexamethasone). Melatonin deficiency and hyperglucocorticoidemia frequently develop with aging. We found that old or pinealectomized, i.e., melatonin-deficient rats are more susceptible to kainate-triggered excitotoxic limbic brain injury than the corresponding young or sham-pinealectomized controls, and that pinealectomy, aging, or glucocorticoid treatment result in an enhanced expression of 5-LO in limbic structures. We hypothesize that an aging brain is at a higher risk of neurodegeneration via aging-suppressed melatonin secretion and/or aging-increased glucocorticoid secretion and the resultant upregulation of 5-LO expression. Furthermore, we propose that suppressing the 5-LO expression and/or activity will increase the brain's resistance to injury. The results of our ongoing research are expected to elucidate the role of 5-LO in aging and neurodegeneration and to indicate neuroprotective therapies that would target the 5-LO pathway.

Neuropharmacology and receptor studies in the elderly.

Abstract: Functional brain imaging has provided unique and exciting opportunities to strengthen our knowledge of the biologic substrate of the aging brain and neuropsychiatric disorders. Positron emission tomography (PET) is a particularly powerful tool for quantifying the neurobiologic correlates of cognition, mood, and behavior. Initial PET studies of aging, psychiatric disorders, and neurodegenerative disease focused primarily on generalized physiologic parameters such as cerebral blood flow and metabolism, and early neuroreceptor imaging studies relied on relatively nonselective markers. New, selective receptor radioligands now offer a previously inaccessible means to investigate the dynamic relationships among neurochemistry, aging, and psychopathology in vivo. This approach has substantial advantages over peripheral (platelet and cerebrospinal fluid) markers, neuroendocrine challenge studies, animal models, and postmortem receptor binding assays. Advances in tracer kinetic modeling, magnetic resonance imaging facilitated PET image analysis, radiochemistry techniques, instrumentation, and image processing have helped pave the way for increased emphasis on functional imaging studies of neuropsychiatric disorders. The capability to correct PET image data for the confounding effect of cerebral atrophy permits relationships among age-related brain changes and neurobiologic disease mechanisms to be more accurately examined in the elderly.

Genetic aberrancies and neurodegenerative disorders

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.

Estrogen and Brain Aging

Abstract: Recent research findings have made it clear that the female sex-steroid hormone estrogen has several functions other than regulation of sexual and reproductive behavior. In addition to this hormone's well-known influence on bone and the heart, this hormone exerts a wide variety of effects on the brain, including both development and function. The current interest in aging of the brain derives, in part, from the enormous and global increase in the proportion of elderly people. Old age is associated with several health problems including a general decline in mental function, especially in dementia, and specifically Alzheimer's dementia (AD). To focus on this issue, it is essential to understand the changes taking place in the aging brain and the role that estrogen plays in this process. This article reviews the data on the involvement of estrogen in the aging brain and discusses the potential consequences of estrogen replacement therapy.

Estrogen and Brain Function: Implications for Aging and Dementia

Abstract: Estrogen is involved in a multitude of processes throughout the lifespan in the brains of both females and males. For example, this steroid hormone affects critical developmental events such as neuronal differentiation, growth and synaptogenesis, which ultimately leads to the establishment of the sexually differentiated brain (McEwen et al. 1977; Maclusky et al. 1987; Toaran Allerland 1991). In the adult CNS, estrogen, together with progesterone, orchestrate rapid and continuous neuroplastic events, including the cyclic synaptic turnover which occurs throughout the rat estrus cycle (Wooley and McEwen, 1993). The aging brain is associated with declines in many neural systems, often resulting in functional deficits; recent evidence suggests that estrogen replacement can decrease the risk of neurodegenerative disorders, such as Alzheimer's disease, and alleviate some of the cognitive deficits in afflicted women (Paganin-Hill and Henderson 1994;Henderson et al. 1994; Tang et al. 1996). Considering these few examples, it becomes apparent that the brain systems targeted by estrogen are many, encompassing both reproductive and non-reproductive circuitries. In this chapter, we will review evidence for estrogen regulation of specific brain-cell phenotypes in an attempt to understand estrogen's influence on brain function. First, we will briefly consider the various means by which estrogen is believed to interact with target cells.