Embelin Improves the Spatial Memory and Hippocampal Long-Term Potentiation in a Rat Model of Chronic Cerebral Hypoperfusion

Saatheeyavaane Bhuvanendran,Yatinesh Kumari,Siti Najmi Syuhadaa Bakar,Zurina Hassan,Mohd. Farooq Shaikh,Iekhsan Othman

doi:10.1038/s41598-019-50954-y

Saatheeyavaane Bhuvanendran, Yatinesh Kumari + Show 4 more

Open Access

https://doi.org/10.1038/s41598-019-50954-y

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Abstract

Alzheimer’s disease (AD) is the second most occurring neurological disorder after stroke and is associated with cerebral hypoperfusion, possibly contributing to cognitive impairment. In the present study, neuroprotective and anti-AD effects of embelin were evaluated in chronic cerebral hypoperfusion (CCH) rat model using permanent bilateral common carotid artery occlusion (BCCAO) method. Rats were administered with embelin at doses of 0.3, 0.6 or 1.2 mg/kg (i.p) on day 14 post-surgery and tested in Morris water maze (MWM) followed by electrophysiological recordings to access cognitive abilities and synaptic plasticity. The hippocampal brain regions were extracted for gene expression and neurotransmitters analysis. Treatment with embelin at the doses of 0.3 and 0.6 mg/kg significantly reversed the spatial memory impairment induced by CCH in rats. Embelin treatment has significantly protected synaptic plasticity impairment as assessed by hippocampal long-term potentiation (LTP) test. The mechanism of this study demonstrated that embelin treatment alleviated the decreased expression of BDNF, CREB1, APP, Mapt, SOD1 and NFκB mRNA levels caused by CCH rats. Furthermore, treatment with embelin demonstrated neuromodulatory activity by its ability to restore hippocampal neurotransmitters. Overall these data suggest that embelin improve memory and synaptic plasticity impairment in CCH rats and can be a potential drug candidate for neurodegenerative disease-related cognitive disorders.

Highlights

Synaptic integrity and plasticity are crucial for a healthy brain function especially in learning and memory[11]
The Morris water maze (MWM) test was used in this study to evaluate the effects of embelin on the spatial memory impairment induced by chronic cerebral hypoperfusion (CCH) rats
The results indicated reduced long-term potentiation (LTP) in the bilateral common carotid artery occlusion (BCCAO) group treated with vehicle alone compared to that of the sham group (p < 0.0001) with enhanced LTP in the BCCAO rats treated with embelin 0.3 and 0.6 mg/kg groups (p < 0.0001)

Summary

Introduction

Synaptic integrity and plasticity are crucial for a healthy brain function especially in learning and memory[11]. Cognitive decline symptoms in neurological disorders including AD and dementia have been associated with synaptic plasticity impairment[12] by evidence of loss of synapse numbers and functions in the hippocampus[13,14]. The neuroprotective effect of embelin in Alzheimer’s disease-like condition model has been reported[17,20], but specific neuroprotective mechanism of action against memory impairments in CCH-induced BCCAO rats remain elusive. LTP of embelin in this study is the first to be reported, which may reveal the synaptic plasticity properties of this yellowish-orange compound as a potential therapy for Alzheimer’s disease-like conditions. The last part of this experiment involved the extraction of rat’s brain for studying their gene expression and neurotransmitter to aid in determining the potential mechanism responsible for the neuroprotective effect of embelin in vascular cognitive impairment and dementia conditions

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