Huperzine A Reverses Cholinergic and Monoaminergic Dysfunction Induced by Bilateral Nucleus Basalis Magnocellularis Injection of β-Amyloid Peptide (1–40) in Rats

Abstract

(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.

The effects of huperzine A and IDRA 21 on visual recognition memory in young macaques

“…Both of these agents have been shown to attenuate cognitive deficits caused by various experimental interventions in animal models. Huperzine A, a drug that augments cholinergic function by blocking acetylcholinesterase (AChE) activity, has been tested in clinical trials for dementia (Wang et al, 2009) and in animal models of cognitive impairment caused by blockade or loss of cholinergic neurons (Liang et al 2008; Xiong, 1998), age (Ye et al, 2000) or ischemia (Wang et al, 2002; Wang et al, 2006; Wang et al, 2008; Zhou et al, 2001), but has not been shown to have effect in normal animals. In contrast, IDRA 21, a drug that prevents desensitization of the AMPA subtype of glutamate receptor, has been demonstrated to augment spatial memory in normal rats (Zivkovic et al, 1995), and to improve performance on a visual recognition memory task in young adult rhesus monkeys (Buccafusco et al, 2004).…”

Disease-Modifying Activity of Huperzine A on Alzheimer’s Disease: Evidence from Preclinical Studies on Rodent Models

“…The expression of BACE and APP mRNA also greatly decreased. Liang Y. Q. et al [ 28 ] injected Aβ peptide into nucleus basalis magnocellularis of rats to model AD and amyloid immunoreactivity indicated the enhancement of Aβ clearance by Huperzine A treatment. Turkseven C. H. et al [ 32 ] reported the reduction of Aβ expression in the cortex of rats which experienced long-term administration of D-galactose after forming menopause.…”

“…Huperzine A was well known for its activity in inhibiting AChE specifically [ 41 ]. Among the included articles, seven studies mentioned the cholinesterase inhibitors (ChEI) efficacy of Huperzine A. Liang Y. Q. et al [ 28 ] injected Aβ peptide into nucleus basalis magnocellularis of rats to test Huperzine A’s effects on cholinergic and monoaminergic dysfunction. They observed greater relief of acetylcholine, dopamine, norepinephrine, and 5-hydroxytryptamine deficit in Aβ injected rats’ cerebral cortex after Huperzine A treatment.…”