Amelioration of impaired hippocampal cognitive performance in Alzheimer's disease via long-term intervention with ghrelin

Abstract

Introduction

Alzheimers disease (AD) is a neurodegenerative disorder characterized by loss of memory and cognitive deficits. Ghrelin is a peptide hormone which has been linked to neuroprotection, memory and learning processes.

Objectives

This study investigated the effects of ghrelin-induced memory retention on amelioration of cognitive deficits via restoration of long-term potentiation (LTP) and induction of synaptic plasticity in hippocampal CA3, using a rat model of AD induced by amyloid-β (1-42) injection.

Methods

Five groups of male rats (230–270 g) including ghrelin-treated (200 ng/rat, [ICV], daily for two weeks), Aβ1-42 injected (5 μL/rat) and Aβ1-42 plus ghrelin-treated animals were designed. Ghrelin was administered after an ICV injection of Aβ1-42. To assess cognitive performance and the motor dysfunction, passive avoidance tests and open-field were performed, respectively. Step-through latency (STL) was evaluated as learning and memory index. Intrahippocampal field potential recordings were done.

Results

Results showed that following Aβ1-42 injection, STL and induction of LTP were significantly decreased whereas ICV injection of ghrelin significantly enhanced memory retention by improvement of STL and restitution of LTP in the CA3 with increased EPSP slope and PS amplitude, suggesting the involvement of ghrelin in postsynaptic mechanisms of hippocampal LTP.

Conclusions

It was revealed that neuroprotective effects of chronic ghrelin not only can enhance but also can restore LTP in the CA3 area in Aβ-induced AD. Results suggest that ghrelin may be considered as a promising therapeutic agent to alleviate cognitive deficits of AD.

Disclosure of interest

The author has not supplied his/her declaration of competing interest.