Affiliations: [a] Department of Biochemistry and Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea | [b] Interdisciplinary Graduate Program of Genetic Engineering, Seoul National University, Seoul, Korea | [c] Department of Oriental Pharmaceutical Science, College of Pharmacy and Kyung Hee East-West Pharmaceutical Research Institute, Kyung Hee University, Seoul, Korea
Correspondence:
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Correspondence to: Inhee Mook-Jung, Department of Biochemistry and Biomedical Sciences, Seoul National University College of Medicine, 28 Yungun-dong, Jongno-gu, Seoul 110-799, Republic of Korea. Tel.: +82 2 3668 7636; Fax: +82 2 3672 7352; E-mail: [email protected].
Abstract: 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-β oligomers (AβO). We report that ghrelin: 1) rescues memory deficits in mice injected with AβO in the hippocampus; 2) decreases AβO-induced microgliosis in hippocampus; 3) attenuates hippocampal neuronal loss mediated by AβO; 4) prevents AβO-associated synaptic degeneration including cholinergic fiber loss. Taken together, our findings demonstrate that ghrelin can ameliorate AβO-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.
