Cyclosporine-A enhances choline acetyltransferase immunoreactivity in the septal region of adult rats.
Cyclosporine-A (CsA) is the primary anti-rejection drug used for organ and neural transplantation therapy. In addition to its immunosuppressive action, CsA has been recently shown to exert neuroprotective and neurotrophic effects in the central nervous system when able to cross the blood-brain barrier. Postulated mechanisms for these CsA-induced beneficial effects include the drug's powerful inhibition of the calcium-dependent phosphatase calcineurin (CN) and blockade of the assembly of the mitochondrial permeability transition pore. We report here, for the first time, that adult Wistar rats treated with CsA (10 mg/kg per day, i.p. for 9 days) displayed significantly reduced septal CN expression in combination with enhanced levels of septal choline acetyltransferase (ChAT) immunoreactivity as compared to controls. The observed enhancement of septal ChAT immunoreactivity suggests potential therapeutic utility of CsA for brain disorders characterized by alterations of the cholinergic system.
Borlongan
C V
CV
National Institutes of Health, National Institute on Drug Abuse Intramural Research Program, Cellular Neurobiology, Baltimore, MD 21224, USA. cborlong@intra.nida.nih.gov
Stahl
C E
CE
Keep
M F
MF
Elmér
E
E
Watanabe
S
S
D000818:Animals; D002795:Choline O-Acetyltransferase / Q000187:drug effects / Q000378:metabolism*; D016572:Cyclosporine / Q000494:pharmacology*; D005260:Female; D007150:Immunohistochemistry; D051381:Rats; D017208:Rats, Wistar; D020665:Septum of Brain / Q000201:enzymology*
D016572:Cyclosporine; D002795:Choline O-Acetyltransferase