Ghrelin Ameliorates Cognitive Dysfunction and Neurodegeneration in Intrahippocampal Amyloid-beta(1-42) Oligomer-Injected Mice

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by cognitive deficits, neuroinflammation, and loss of neurons. Recently, it has been shown that ghrelin, a 28 amino acid peptide hormone produced from the stomach and hypothalamus, has been reported as a potential therapeutic agent for several neurological disorders, including Parkinson's disease (PD), stroke, epilepsy, multiple sclerosis, and spinal cord injury. Here we determined the effects of ghrelin on memory impairments and neuropathological changes in an AD mouse model induced by intrahippocampal injection of amyloid-beta oligomers (A beta O). We report that ghrelin: 1) rescues memory deficits in mice injected with A beta O in the hippocampus; 2) decreases A beta O-induced microgliosis in hippocampus; 3) attenuates hippocampal neuronal loss mediated by A beta O; 4) prevents A beta O-associated synaptic degeneration including cholinergic fiber loss. Taken together, our findings demonstrate that ghrelin can ameliorate A beta O-induced cognitive impairment associated with neuroinflammation and neuronal loss. These results suggest that ghrelin may be a promising therapeutic agent for the treatment of AD.