Huperzine A reverses cholinergic and monoaminergic dysfunction induced by bilateral nucleus basalis magnocellularis injection of beta-amyloid peptide (1-40) in rats.
(1) Huperzine A, a promising therapeutic agent for Alzheimer's disease (AD), was tested for its effects on cholinergic and monoaminergic dysfunction induced by injecting beta-amyloid peptide-(1-40) into nucleus basalis magnocellularis of the rat. (2) Bilateral injection of 10 microg beta-amyloid peptide-(1-40) into nucleus basalis magnocellularis produced local deposits of amyloid plaque and functional abnormalities detected by microdialysis. In medial prefrontal cortex, reductions in the basal levels and stimulated release of acetylcholine, dopamine, norepinephrine, and 5-hydroxytryptamine were observed. However, oral huperzine A (0.18 mg/kg, once daily for 21 consecutive days) markedly reduced morphologic abnormalities at the injection site in rats infused with beta-amyloid peptide-(1-40). Likewise, this treatment ameliorated the beta-amyloid peptide-(1-40)-induced deficits in extracellular acetylcholine, dopamine, and norepinephrine (though not 5-hydroxytryptamine) in medial prefrontal cortex, and lessened the reduction in nicotine or methoctramine-stimulated release of acetylcholine and K(+)-evoked releases of acetylcholine and dopamine. (3) The present results provide the first direct evidence that huperzine A acts to oppose neurotoxic effects of beta-amyloid peptide on cholinergic, dopaminergic, and noradrenergic systems of the rat forebrain.
Liang
Yan Qi
YQ
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhangjiang Hi-Tech Park, Shanghai, 201203, P.R. China.
Huang
Xiao Tian
XT
Tang
Xi Can
XC
D000109:Acetylcholine / Q000378:metabolism; D000470:Alkaloids; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D020532:Basal Nucleus of Meynert / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D015306:Biogenic Monoamines / Q000378:metabolism*; D002794:Choline / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D007267:Injections; D018377:Neurotransmitter Agents / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D010455:Peptides / Q000008:administration & dosage / Q000633:toxicity*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000494:pharmacology*
D000470:Alkaloids; D016229:Amyloid beta-Peptides; D015306:Biogenic Monoamines; D018377:Neurotransmitter Agents; D010455:Peptides; D012717:Sesquiterpenes; C050426:huperzine A; D002794:Choline; D000109:Acetylcholine; D004298:Dopamine; D009638:Norepinephrine