Tacrine accelerates spatial long-term memory via improving impaired neural oscillations and modulating GAD isomers including neuro-receptors in the hippocampus of APP/PS1 AD mice

Abstract

Tacrine (Amino tetrahydroacridine hydrochloride hydrate) is a non-competitive and reversible inhibitor of acetylcholine esterase, and butylcholinesterase. Alzheimer's disease (AD) shows multiple types of pathological pathway in which cholinergic neuron deficiency is 95 % popular and the oldest pathological mechanism. However, the effect of tacrine on the hippocampal dependent memory is not yet known. In this study, we did verify that tacrine induced recovery of the specific pattern associated memory along with long-term memory through the improvement in the pattern of neural oscillation from deficits condition in the hippocampus of 6th month old AD mice. Our results showed that tacrine improved the performance of Morris water maze related spatial cognitive functions, and enhanced LTP in AD-TAC mice. Furthermore, our results implied that tacrine strongly improve the patterns of neural oscillations, and hippocampal synaptic plasticity in the 6th month old APP-PS1 double transgenic AD-TAC mice via changing the theta and alpha power spectra including with the improvement in theta, alpha and gamma synchronization. Moreover, tacrine generated the improvement in the theta cross spectra, theta-gamma phase-phase synchronization and theta-gamma phase-amplitude coupling. Besides, the data represented that tacrine accelerated the expression of NR2B, SYP and GAD65 while it caused deceleration on the expression of GAD67 neurotransmitter and Aβ. Thus, our results infer that tacrine works as a strong causative agent for improving the specific pattern-associated spatial long-term memory in the AD mice without showing any side effect.

Keywords: Aβ; GAD isomers; LTP; Local field potential; Neural oscillations; Tacrine.