Aging and in vivo norepinephrine-uptake in mammalian brain

Abstract

In order to examine the cellular effect of aging in the central nervous system, the regional distribution and the dynamic aspects of catecholamine metabolism in the brain were investigated. Results indicated that the endogenous norepinephrine (NE) content is lower in hypothalamus and brain stem of older rats (25 mo. n = 6) than younger rats (12 mo. n = 6). We have also observed in these animals that the age pigments were apparently absent in the brain tissue of young rats but become a very distinct feature for the old rats and that the catecholamine strong vesicles appear to be less dense in the nerve terminals of old as compared with the young ones. 3H-NE was administered intracerebrally to mice of different age groups (4, 8, 12, 21 and 24 months) and the NE-uptake activity was examined by measuring the radioactive NE inside the isolated synaptosomes 5 min after 3H-NE injection. The result indicated that the young group (4 mo) has highest uptake activity. The uptake activity decrease with the older mice and reached the lowest in the age group of 21-24 mo. The decrease in NE-uptake activity may be related to the deterioration of synaptosomal membranes.

Functional Implications of Changes in the Senescent Brain: A Review

“…Another anabolic process which deteriorates with aging is that of the synthesis, release, and uptake of neurotransmitters. Old brains experience 25% slower rate and 50% reduced volume of axonal transport of substances essential for transmitter production (Geinisman et al, 1977a(Geinisman et al, , 1977b, a shortage of the enzymes necessary for transmitter synthesis (McGreer et al, 1977;Spillane et al, 1977;Vijayan, 1977), an impairment of waste reducing uptake of unused neurotransmitter (Jonec and Finch, 1975;Sun, 1976), fewer transmitter receptor binding sites (White et al, 418-NOVEMBER 1978 The Senescent Brain 1977), reduced number of neurotransmitter storage vesicles (Sun, 1976), and lowered sensitivity of the chemical response of the receiving neuron to delivered neurotransmitter (Govoni et al, 1977, Spano et al, 1975.…”

Elevated Neutrophil to Lymphocyte Ratio in Older Adults with Cocaine Use Disorder as a Marker of Chronic Inflammation

“…Immunosenescence changes include involution of the thymus [55], decline in T and B cell functioning [56], decrease in IL-2 production [57] and alterations of neutrophil phagocytic capability [58]. Human aging is also associated with elevated activation of the sympathetic nervous system and stress response [59], primarily through decreased norepinephrine reuptake [60,61]. For instance, as a robust modulator of monoamine transmission, cocaine also alters both central and peripheral norepinephrine function [13,62,63].…”

Abnormalities of Cerebral Oxidative Metabolism with Aging and Their Relation to the Central Noradrenergic System

“…Blood gas values for 3-month-old rats, average (range) were: pOi, 108 (92-129) mm Hg; pCO:. 39 (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43) rather than oxidative shifts as expected, were recorded in aged brains under the intense metabolic demand associated with spreading cortical depression [46], Since reductive shifts of mitochondrial components indicate oxygen insufficiency to meet metabolic de mands [2,19], it was evident that metabolic functioning was adequate for 'resting' but not intensely active conditions in the aged cere bral cortex.…”

“…There is also evidence that central cate cholamine mechanisms may be impaired with aging [1,8,9,26], For example, regional activities of tyrosine hydroxylase and aro matic L-amino acid decarboxylase, as well as tissue concentration of brain catecholamines, were decreased in senescence [8,26], Also, the high-affinity uptake of catecholamines [43] and the mechanisms that control the density of adrenoceptor binding sites [10] may be altered with age. Thus far, however, relationships among the age-related changes in cerebral blood flow, cerebral oxidative me tabolism and activity of the central noradren ergic system have not been established.…”