Acetyl-L-carnitine treatment increases nerve growth factor levels and choline acetyltransferase activity in the central nervous system of aged rats.
The hypothesis that some neurodegenerative events associated with ageing of the central nervous system (CNS) may be due to a lack of neurotrophic support to neurons is suggestive of a possible reparative pharmacological strategy intended to enhance the activity of endogenous neurotrophic agents. Here we report that treatment with acetyl-l-carnitine (ALCAR), a substance which has been shown to prevent some impairments of the aged CNS in experimental animals as well as in patients, is able to increase the levels and utilization of nerve growth factor (NGF) in the CNS of old rats. The stimulation of NGF levels in the CNS can be attained when ALCAR is given either for long or short periods to senescent animals of various ages, thus indicating a direct effect of the substance on the NGF system which is independent of the actual degenerative stage of the neurons. Furthermore, long-term treatment with ALCAR completely prevents the loss of choline acetyltransferase (ChAT) activity in the CNS of aged rats, suggesting that ALCAR may rescue cholinergic pathways from age-associated degeneration due to lack of retrogradely transported NGF.
Taglialatela
G
G
Institute for Research on Senescence Sigma-Tau, Pomezia, Italy.
Navarra
D
D
Cruciani
R
R
Ramacci
M T
MT
Alemà
G S
GS
Angelucci
L
L
D000108:Acetylcarnitine / Q000494:pharmacology*; D000375:Aging / Q000378:metabolism*; D000818:Animals; D002795:Choline O-Acetyltransferase / Q000096:biosynthesis* / Q000235:genetics; D003345:Corticosterone / Q000097:blood; D004790:Enzyme Induction / Q000187:drug effects; D005625:Frontal Lobe / Q000166:cytology / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D009410:Nerve Degeneration / Q000187:drug effects; D009414:Nerve Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D016548:Prosencephalon / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical
D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D000108:Acetylcarnitine; D002795:Choline O-Acetyltransferase; D003345:Corticosterone