Showing papers on "Aging brain published in 1996"

Growth hormone induces somatostatin and insulin-like growth factor I gene expression in the cerebral hemispheres of aging rats.

Abstract: The neuropeptide somatostatin (SS) plays a role as a modulator of cognitive functions and as a potential tropic factor in the central nervous system. A reduction in SS levels has been demonstrated in the aging brain and in dementia. In addition, insulin-like growth factor I (IGF-I) acts as a paracrine factor in multiple GH actions and is also found in the cerebral hemispheres, where it exerts neurotropic effects. We used aging rats as an in vivo model of GH deficiency to study the possible participation of exogenous GH in the modulation of the cerebral hemispheric SS and IGF-I. Two sets of experiments were carried out. In the first set, the age-related patterns of GH, IGF-I, and SS in the serum, pituitary, and cerebral hemispheres were established. In the second experimental set, 90-day-old (adult) and 2-yr-old (aging) male rats received recombinant human GH (200 μg/sc · day) or vehicle for 7 consecutive days. The serum levels of rat GH and IGF-I as well as pituitary GH messenger RNA decreased in 2-yr-old rats compared with those in adult rats. After GH treatment, pituitary GH messenger RNA levels decreased markedly in the 90-day-old and 2-yr-old rats. Serum immunoreactive GH decreased in the adult animals, whereas it remained unaffected in the aging ones, whereas serum IGF-I levels were not altered by GH treatment in either group. Immunoreactive levels and messenger RNA of both SS and IGF-I were low in the cerebral hemispheres of aging rats, but were restored to the levels found in adult rats after GH treatment. As treatment did not induce changes in the serum IGF-I levels, these results provide evidence of a stimulatory action of peripherally administered GH on the regulation of SS and IGF-I genes in the aging rat in the central nervous system. These data also show a new target action for GH and could provide a molecular basis for the improvement of some symptoms of GH deficiency that occurs after recombinant human GH treatment.

Age-related changes in cortical blood flow activation during perception and memory.

Abstract: Although many cognitive functions are affected by age, some are relatively maintained. There also are numerous age-related changes in brain structure, but not much is known about how these changes impact upon the alterations seen in cognition. In order to understand the basis for the reductions and sparings of cognitive function in the aged, experiments were carried out to compare regional cerebral blood flow (rCBF) and performance in young and old subjects on visual perceptual and memory tasks. In the first experiment, which examined the perception of faces and spatial locations, old subjects were as accurate as young subjects, and both groups had rCBF activation in fusiform gyrus during face matching and in superior parietal cortex during location matching. However, old subjects had less activation of prestriate cortex and more activation of frontal and lateral temporal cortex than did young subjects. The second experiment tested recognition memory for faces, a task on which old subjects were impaired. Young subjects had rCBF activation in left prefrontal and inferior temporal cortex and in right hippocampus during encoding of the faces, and in right prefrontal and parietal cortex during recognition. Old subjects showed no significant activation of the areas involved in encoding, but did have increased rCBF in right prefrontal cortex during recognition. These results suggest that the aging brain can demonstrate alterations of the functional systems involved in some cognitive processes, such as perception, that may serve as a compensatory mechanism to maintain performance. Failure to show such compensation, coupled with dysfunction of the areas primarily involved in processing may lead to more marked deficits in performance.

Human aging brain disorders: role of antioxidant enzymes.

Abstract: In order to investigate the role of two free radical detoxificant enzymes in patients with aging brain disorders, superoxide dismutase (SOD) and catalase (CAT) activities have been measured in blood from male and female human patients of different ages with several types of aging brain disorders. When compared with activities in the normal population, we have detected: 1) SOD and CAT activities are decreased in patients with Parkinson disease. 2) SOD activity seems to be normal and CAT activity is decreased in patients with dementia. 3) In the patients with stroke, SOD activity is normal, while CAT activity is decreased. SOD activity was measured in red blood cells using the Minami and Yoshikawa method. CAT activity was measured in hemolysates by the method of Aebi. We can conclude that SOD and CAT activities in patients with Parkinson disease are decreased.

Chrono-neuroendocrine markers of the aging brain

Abstract: The study of the neuroendocrine changes occurring in aging may give information about the CNS functions, and also explain the impaired plasticity of the aged organism. In 16 elderly women and in 14 young controls, the circadian rhythms of plasma melatonin, GH, PRL, ACTH and cortisol, and of oral temperature were simultaneously studied. The plasma cortisol circadian rhythm was also evaluated after DXM administration (1 mg orally at 23:00). The circadian profile of all the bioperiodic functions evaluated was clearly flattened in elderly subjects, and an impairment of the hormonal nocturnal secretion of GH, PRL and melatonin was apparent in elderly subjects when compared to young controls. The plasma ACTH levels throughout the 24-hour cycle were significantly higher in elderly than in young subjects. The cortisol circadian profile exhibited significantly higher values in the evening- and night-time in elderly subjects, compared to young controls; the cortisol nadir values were significantly age-related. A reduction of the sensitivity to DXM inhibition occurred in the elderly group. Both the selective impairment of nocturnal melatonin secretion, and the reduction of hypothalamo-pituitary-adrenal (HPA) sensitivity to steroid feedback might be considered as markers of aging brain. The neuroendocrine alterations of physiological aging may be ascribable to both the structural and neurochemical changes occurring in the CNS.

Alterations in calcium antagonist receptors and calcium content in senescent brain and attenuation by nimodipine and nicardipine.

Abstract: Characteristics of L- and N-type calcium (Ca++) channel antagonist receptors in brains of senescence-accelerated prone mouse (SAMP8) showing age-related deterioration of learning and memory were examined by using (+)-[3H]PN 200-110 and [125I]omega-conotoxin GVIA as radioligands. There was a tendency toward consistent decrease in Bmax for both radioligands in seven brain regions of SAMP8 compared with the control mouse. The reduction in (+)-[3H]Pn 200-110 binding sites was statistically significant in the hippocampus, midbrain and pons/medulla oblongata, and that in [125I]omega-conotoxin binding sites was significant in the cerebral cortex, corpus striatum and pons/medulla oblongata. On the other hand, there was a marked elevation in Ca++ content in the brain of SAMP8. Chronic p.o. administration (0.3, 1 and 3 mg/kg/day for 3 weeks) of nimodipine and nicardipine to SAMP8 caused a significant increase in the Bmax values of (+)-[3H]PN 200-110 binding in the cerebral cortex and hippocampus. This may reflect up-regulation of brain Ca++ channel antagonist receptors as a result of the prolonged blockade by nimodipine and nicardipine. On the other hand, similar administration of amlodipine and nilvadipine failed to produce an enhancement of Bmax values of (+)-[3H]PN 200-110 binding, whereas both drugs at high doses evoked a significant increase in the apparent dissociation constant. Furthermore, the brain Ca++ content in SAMP8 was markedly reduced by chronic p.o. administration of Ca++ channel antagonists, and the decrease was equivalently observed for all of four 1,4-dihydropyridine antagonists in spite of the difference in the effect on brain receptors. In conclusion, the present study suggests that there is an altered Ca++ homeostasis in the SAMP8 brain that is effectively attenuated by chronic administration of nimodipine and nicardipine. Hence SAMP8 may be a suitable animal model for evaluating the therapeutic effects of Ca++ channel antagonists on neurological disorders associated with the aging brain.

Neuroanatomy of the Aging Brain Observed in Vivo

Abstract: There is little doubt that aging is accompanied by significant changes in brain structure. The question is whether the brain ages as a uniform whole or as a system of differentially vulnerable components. As neuropathologists investigating the aged human brain are “often struck by the focal nature of... cortical atrophy” (Katzman & Terry, 1983, p. 35), it seems that brain aging is, at least in its early stages, localized and selective. Cumulative evidence from autopsy studies suggests that in addition to diffuse changes in cerebral structure associated with old age, intensified regional cerebral atrophy is observed in humans and other mammals (see Coleman & Flood, 1987; Flood & Coleman, 1988; and Kemper, 1994, for comprehensive reviews). Postmortem findings indicate that certain brain regions such as the prefrontal, inferior pariet al, and entorhinal cortices, as well as the hippocampal formation, are especially susceptible to aging (Arriagada & Hyman, 1990; Haug, 1985; Mani, Lohr, & Jeste, 1986; Terry, De Teresa, & Hansen, 1987). The results of neuroanatomical studies in nonhuman primates suggest that the visual and motor cortices are virtually unaffected by aging (Vincent, Peters, & Tigges, 1989; Tigges, Herndon, & Peters, 1990), although some human postmortem data reveal age-related atrophy in the macular projection area of the striate cortex (Devaney & Johnson, 1980). In rodents, frontal lobes, amygdala, caudate-putamen complex, entorhinal cortex, and cerebellar hemispheres are also know as atrophy-prone areas (Shimada, Hosokawa, Ohta, Akiguchi, & Takeda, 1994). Selective vulnerability of brain tissue to aging is consistent with the notion of pathoclisis proposed more than 40 years ago by Vogt and Vogt (1951), who argued that some gray matter structures (grisea) exhibited increased susceptibility to pathogens.

Expression and distribution of amyloid precursor protein-like protein-2 in Alzheimer's disease and in normal brain.

Abstract: Amyloid precursor-like protein-2 (APLP-2) belongs to a family of homologous amyloid precursor-like proteins. In the present study we report on the expression and distribution of APLP-2 in fetal and adult human brain and in brains of patients with Alzheimer's disease. We demonstrate that APLP-2 mRNAs encoding isoforms predicted to undergo post-translational modification by chondroitin sulfate glycosaminoglycans are elevated in fetal and aging brains relative to the brains of young adults. Immunocytochemical labeling with APLP-2-specific antibodies demonstrates APLP-2 immunoreactivity in cytoplasmic compartments in neurons and astrocytes, in large part overlapping the distribution of the amyloid precursor protein. In Alzheimer's disease brain, APLP-2 antibodies also label a subset of neuritic plaques. APLP-2 immunoreactivity is particularly conspicuous in large dystrophic neurites that also label with antibodies specific for APP and chromogranin A. In view of the age-dependent increase in levels of chondroitin sulfate glycosaminoglycan-modified forms of APLP-2 in aging brain and the accumulation of APLP-2 in dystrophic presynaptic elements, we suggest that APLP-2 may play roles in neuronal sprouting or in the aggregation, deposition, and/or persistence of beta-amyloid deposits.

Chapter 6 Neuronal Calcium Regulation in Aging Brain

Abstract: Publisher Summary This chapter discusses the major elements of the Ca 2+ hypothesis, followed by an overview of the principal neuronal systems responsible for regulating intracellular Ca 2+ and reviews the experimental observations that have been reported with regard to altered Ca 2+ homeostasis in aging neurons. It is suggested that aging-related alterations in Ca 2+ handling mechanisms could serve to make the cells highly vulnerable to metabolic stresses such as ischemia, enhanced free radical production, head trauma, and hyperthermia and, possibly, to the abnormal processing and deposition of amyloid peptides within specific brain regions. The Ca 2+ hypothesis provides a cogent unifying concept that may help explain the cognitive decline that occurs with normal aging in many individuals and the underlying process that sets the stage for the development of late-onset Alzheimer's disease in a very large percentage of the elderly. Many more studies are needed to see if a link can indeed be demonstrated between Ca 2+ dysregulation and impaired behavioral and cognitive performance. If this link is established, it may be possible in the not too distant future to develop means of dampening the impact alterations in these systems have on optimal brain function.