Nerve growth factor binding in aged rat central nervous system: Effect of acetyl‐l‐carnitine

Abstract

The nerve growth factor protein (NGF) has been demonstrated to affect neuronal development and maintenance of the differentiated state in certain neurons of the peripheral and central nervous system (CNS) of mammals. In the CNS, NGF has sparing effects on cholinergic neurons of the rodent basal forebrain (BF) following lesions where it selectively induces choline acetyltransferase (ChAT). NGF also induces ChAT in the areas to which BF provides afferents. In aged rats, there is a reduction in the NGF-binding capacity of sympathetic ganglia. Here, we wish to report that there is a decrease in the NGF-binding capacity of the hippocampus and basal forebrain of aged (26-month-old) rats as compared to 4-month-old controls but no change in NGF binding in cerebellum. In all instances, equilibrium binding dissociation constants did not differ significantly. Treatment of rats with acetyl-L-carnitine, reported to improve cognitive performance of aged rats, ameliorates these age-related deficits.

Acetyl-L-carnitine physical-chemical, metabolic, and therapeutic properties: relevance for its mode of action in Alzheimer's disease and geriatric depression

“…ALCARtreated aged rats have improvement of age-related reduction in NGF-binding capacity found in hippocampus and basal forebrain areas 40 and ALCAR increases choline acetyltransferase activity and NGF receptor expression in the developing rat striatum. 41 Taglialatela et al 42 reported that ALCAR: (1) enhances the response of PC12 cells to NGF suggesting that ALCAR may increase the response of aged neurons to neurotrophic factors within the CNS; (2) stimulates NGF receptors and neurite growth in PC12 cells; 43,44 and (3) increases NGF levels and choline acetyltransferase activity in rat CNS.…”

“…81 ALCAR restores choline acetyltransferase activity in the hippocampus of rats with partial unilateral fimbriafornix transection which produces degeneration of cholinergic pathways. 82 Prickaerts et al 83 demonstrated that chronic ALCAR administration to streptozotocintreated rats attenuated choline acetyltransferase activity and the spatial memory impairment of these rats, and Taglialatela et al 40 reported that ALCAR treatment increases choline acetyltransferase activity in the CNS system of aged rats and this was associated with increased NGF levels. ALCAR can counteract the agedependent reduction of several CNS receptor systems, including NMDA receptors, NGF receptors, and glucocorticoid receptors 84 and ALCAR prevents age-related NMDA receptor loss in hippocampus, striatum, and frontal cortex of rats.…”

L-Acetylcarnitine: A Proposed Therapeutic Agent for Painful Peripheral Neuropathies

“…Aside from its role in fatty acid -oxidation, many other functions have been attributed to L-acetylcarnitine. It has been reported that L-acetylcarnitine modulates the activity of nerve growth factor (NGF) in the nervous system in rats [1,40,52], increases the activity of choline acetyltransferase, enhances the expression of NGF receptors in the striatum and hippocampus of rats during development [10] and modulates different neurotransmitter systems including the cholinergic and dopaminergic system [24,20]. Additionally L-acetylcarnitine functions as a donor of acetyl groups in oxidative glycolysis [4] and can also have important biological function due to its ability to contribute to acetylation of -OH or -NH 2 functional groups on amino acids and Nterminal groups in proteins and peptides [39].…”

Effect of Different Chronic Intermittent Stressors and Acetyl-/-Carnitine on Hypothalamic β-Endorphin and GnRH and on Plasma Testosterone Levels in Male Rats

“…ALC is known as a neurotropic drug which acts on central nervous sys tem function by cholinergic and serotoninergic pathways [29] and/or by activation of the GABA transport system [30,31 ]. Effects on glucocorticoid or nerve growth factor receptors in the hippocampus or on hypothalamic |5-EP have been shown [32][33][34]. At the same time, ALC was described as a physiologically important substrate for ma turing sperm cells [35].…”