Showing papers on "Aging brain published in 1989"

The role of calcium regulation in brain aging: reexamination of a hypothesis.

Abstract: Studies of the central nervous system have a long history; however, it is only recently that we have begun to understand brain function in health and disease states. And, the topic of the aging brain has become a subject of intense study for a short period. At present, the process of normal aging is relatively poorly understood. Although there are a number of theories of aging, no single theory appears to account for most age-dependent brain changes. This review provides a re-evaluation of the "Calcium Hypothesis of Brain Aging" in light of new evidence which supports the proposition that cellular mechanisms, which maintain the homeostasis of cytosol Ca2+ concentration, play a key role in brain aging; and that sustained changes in [Ca2+]i homeostasis provide the final common pathway for age-associated brain changes. This revision of the calcium hypothesis suggests that there is a complex interaction between the amount of [Ca2+]i perturbation and the duration of such deregulation of Ca2+ homeostasis and it proposes that a small disturbance in Ca2+ homeostasis with a sustained increase in [Ca+]i over a long period has similar cell injuring consequences as that produced by a large increase in [Ca2+]i over a shorter period. Although there are several alternative mechanisms through which the regulation of cytosol [Ca2+]i can be disrupted (such as changes in ion channels, extrusion pumps, and sequestration), this review focuses on disruptions in energy metabolism and changes in the structure and function of membranes as the most likely antecedent events which lead to disruption of Ca2+ homeostasis. The principle purpose of this review is to identify scientific opportunities and stimulate further research into cellular mechanisms of brain aging.

The effect of aging on glutathione and cysteine levels in different regions of the mouse brain.

Abstract: A general glutathione (GSH) deficiency occurs in many tissues of the aging mouse. However, there is no information on GSH in the aging brain even though it has been involved in a number of neurobiologic reactions. To this end, C57BL/6 mice, 3-31 months old, representing the growth, maturation, and aging periods of the life-span were studied. Brain cortex, hippocampus, and stem samples were dissected, processed, and analyzed specifically for reduced and oxidized glutathione (GSH, GSSG) and cyst(e)ine using high performance liquid chromatography with dual electrochemical detection. The GSH content of each brain region varied in the order brain cortex > brain hippocampus > brainstem. However, the GSH profiles of all regions were the same through the life-span, namely, high values during growth dropping to a maturation plateau and then decreasing 30% during aging. In contrast to GSH, the order of cysteine levels was brain cortex c brain hippocampus e brainstem and no life-span changes occurred in any region. In addition, the brain GSSG and cystine contents of all regions were very low and did not change during the life-span. Thus, the GSH loss was not accountable by oxidation to GSSG or degradation to cyst(e)ine. Altogether these results demonstrated a GSH deficiency in brain tissues of aging mice like that found previously in other tissues. These findings suggest an increased susceptibility of the aging brain to oxidative damage. (P.S.E.B.M. 1989, Vol 1901

The aging brain. A normal phenomenon with not-so-normal arachidonic acid metabolism.

Abstract: Aging is a property of any multicellular organism and is characterized by a measurable decline of physiological functions. The brain, which is composed of postmitotic nonrenewable cells, is a particularly strong candidate for an organ that plays a crucial role in biological aging. Even if the causes of this decline a re still unknown, several hypotheses have been advanced in the attempt to explain the gradual loss of this organ’s ability to adapt to the environment. Among these, the membrane deterioration theory is considered one of the most important factors in explaining the aging phenomena. Membranes are made up of a bimolecular leaflet of phospholipids and cholesterol interacting with proteins through ionic and hydrophobic forces.’ Protein-lipid interaction may play an important role in regulating some of the membrane functions, and, in addiction, the acyl groups of membrane phospholipids are also important to the activity of membrane-bound enzymes. The degree of unsaturation, the cholesterol content, and membrane lipid asymmetry are thought to be important in maintaining membrane fluidity in highly functional membranes; and any modification of these parameters leads to a variation of the membrane functions. Modifications of membrane functions related to the alterations of these parameters in aged animal models have been described. ’-’ Among other parameters, a high degree of unsaturation is important in order to maintain a liquid crystalline state of the membrane, while the presence of polyunsaturated fatty acids in the membrane is undesiderable due to the liability of these molecules to oxidation and free radical attack: which may facilitate the aging process. The “free radical theory of aging” was proposed by Harman in 1956’; it states that a major contributor to the aging processes is the continuous production of oxygen radicals. One of the most evident consequences of lipid peroxidation started by radicals is the accumulation of lipofuscin with age.8 The above findings lead one to expect that age induces a modification of the phospholipid polyunsaturated fatty acid profile. The first report on this field was that of O’Brien and Sampson, who in 1965 determined the fatty acid composition of lipids

Brain cytochrome oxidase activity of synaptic and nonsynaptic mitochondria during aging.

Abstract: The activity of cytochrome c oxidase was studied in aging brain on non-synaptic and intra-synaptic mitochondria from frontal cerebral cortex, hippocampus and striatum of 4, 8, 12, 16, 20 and 24 month-old Sprague-Dawley rats. Specific activities of cytochrome oxidase were significantly higher in light synaptic mitochondria than in non-synaptic or heavy ones at all the ages examined. However, enzyme activity in light mitochondria from cerebral cortex remains unchanged during aging, being increased in hippocampus and striatum. These results indicate that aging affected not only the various cerebral area (macroheterogeneity), but also the different mitochondrial populations (subcellular heterogeneity).

Excitotoxin Mediated Neuronal Loss and the Regulation of Excitatory Amino Acid Release in the Aging Brain

Abstract: The aging brain is characterized by a decrease in weight and concomitant loss of neurons1,2. The exact causes and mechanisms for neuronal loss in aging and age-related neurodegenerative diseases are largely unknown. Recent studies have shown that in ischemic, hypoxic and hypoglycemic-induced neuronal loss, the necrotic changes are due to an excess release of excitatory amino acids (glutamate, GLU: aspartate, ASP: etc.)3,4,5. The ability of competitive and noncompetitive antagonists to block or ameliorate neuronal cell death induced by excitatory amino acids has further served to confirm the specificity and importance of receptor-mediated excitotoxicity6,7,8. Therefore, in the central nervous system excessive or unregulated release of excitatory amino acids appears to be a predominate mechanism mediating neuronal death.

Problems in CT diagnosis of the aging brain

Abstract: 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 multi-infarct dementia are shown. The significance of CT studies in senile depression is discussed. The problem of vascular encephalopathy (leuko-araiosis) 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.