Ghrelin-AMPK signaling mediates the neuroprotective effects of calorie restriction in Parkinson's Disease
Journal article
Bayliss, Jacqueline A., Lemus, Moyra B., Stark, Romana, Santos, Vanessa V., Thompson, Aiysha, Rees, Daniel J., Galic, Sandra, Elsworth, John D., Kemp, Bruce Ernest, Davies, Jeffrey S. and Andrews, Zane B.. (2016). Ghrelin-AMPK signaling mediates the neuroprotective effects of calorie restriction in Parkinson's Disease. Journal of Neuroscience. 36(10), pp. 3049 - 3063. https://doi.org/10.1523/JNEUROSCI.4373-15.2016
Authors | Bayliss, Jacqueline A., Lemus, Moyra B., Stark, Romana, Santos, Vanessa V., Thompson, Aiysha, Rees, Daniel J., Galic, Sandra, Elsworth, John D., Kemp, Bruce Ernest, Davies, Jeffrey S. and Andrews, Zane B. |
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Abstract | Calorie restriction (CR) is neuroprotective in Parkinson's disease (PD) although the mechanisms are unknown. In this study we hypothesized that elevated ghrelin, a gut hormone with neuroprotective properties, during CR prevents neurodegeneration in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD. CR attenuated the MPTP-induced loss of substantia nigra (SN) dopamine neurons and striatal dopamine turnover in ghrelin WT but not KO mice, demonstrating that ghrelin mediates CR's neuroprotective effect. CR elevated phosphorylated AMPK and ACC levels in the striatum of WT but not KO mice suggesting that AMPK is a target for ghrelin-induced neuroprotection. Indeed, exogenous ghrelin significantly increased pAMPK in the SN. Genetic deletion of AMPKβ1 and 2 subunits only in dopamine neurons prevented ghrelin-induced AMPK phosphorylation and neuroprotection. Hence, ghrelin signaling through AMPK in SN dopamine neurons mediates CR's neuroprotective effects. We consider targeting AMPK in dopamine neurons may recapitulate neuroprotective effects of CR without requiring dietary intervention. |
Keywords | ampk calorie restriction; ghrelin; stereology; substantia nigra |
Year | 2016 |
Journal | Journal of Neuroscience |
Journal citation | 36 (10), pp. 3049 - 3063 |
Publisher | Society for Neuroscience |
ISSN | 0270-6474 |
Digital Object Identifier (DOI) | https://doi.org/10.1523/JNEUROSCI.4373-15.2016 |
Scopus EID | 2-s2.0-84960390578 |
Open access | Open access |
Page range | 3049 - 3063 |
Research Group | Mary MacKillop Institute for Health Research |
Publisher's version | |
Place of publication | United States |
https://acuresearchbank.acu.edu.au/item/89314/ghrelin-ampk-signaling-mediates-the-neuroprotective-effects-of-calorie-restriction-in-parkinson-s-disease
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