The Effect of Ghrelin on Apoptosis, Necroptosis and Autophagy Programmed Cell Death Pathways in the Hippocampal Neurons of Amyloid-β 1–42-Induced Rat Model of Alzheimer’s Disease

Alzheimer's disease (AD) is a common progressive and irreversible neurodegenerative disorder. Neuronal loss in the brain is one of the important characteristic features of AD, which is along with memory and cognitive dysfunction. Activation of programmed cell deaths, especially apoptosis and necroptosis, and autophagy failure play critical roles in the pathogenesis of AD. Ghrelin, an appetite-related hormone, exerts neuroprotective effects via the stimulation of growth hormone secretagogue receptor type 1a in the central nervous system. In this study, rats' cognitive impairments were induced by intra-hippocampal Cornu Ammonis 3 administration of amyloid-beta 1-42 (Aβ 1-42). Then, animals were treated with ghrelin 80 μg/kg via intraperitoneal injection for 10 consecutive days. The Morris water maze and passive avoidance learning test were used to evaluate the effect of ghrelin on learning and memory performance. After that, a histopathological study on rat’s hippocampi was done, and the expressions of pro-apoptotic protein Bax, anti-apoptotic protein Bcl-2, necroptotic proteins RIP1K and RIP3K and autophagic marker Beclin-1 were assessed, using western blotting method. Our findings show that ghrelin improves memory impairment in Aβ 1-42-induced rats and reduces Bax, RIP1K, and RIP3K expressions and also Bax/Bcl-2 ratio, as well as Beclin-1 expressions. In conclusion, our study suggests that ghrelin can provide neuroprotection via inhibition of apoptosis and necroptosis and autophagy promotion in Aβ 1-42-induced model of Alzheimer's disease.