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Article

Inhibition of Orexin/Hypocretin Neurons Ameliorates Elevated Physical Activity and Energy Expenditure in the A53T Mouse Model of Parkinson’s Disease

1
Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Bünteweg 17, 30559 Hannover, Germany
2
Integrative Biology and Physiology, University of Minnesota, Minneapolis, 321 Church St SE, Minneapolis, MN 55455, USA
3
Minneapolis VA Health Care System, GRECC, 1 Veterans Dr, Minneapolis, MN 55417, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(2), 795; https://doi.org/10.3390/ijms22020795
Received: 21 December 2020 / Revised: 6 January 2021 / Accepted: 8 January 2021 / Published: 14 January 2021
(This article belongs to the Special Issue Neuropeptides and Myopeptides)
Aside from the classical motor symptoms, Parkinson’s disease also has various non-classical symptoms. Interestingly, orexin neurons, involved in the regulation of exploratory locomotion, spontaneous physical activity, and energy expenditure, are affected in Parkinson’s. In this study, we hypothesized that Parkinson’s-disease-associated pathology affects orexin neurons and therefore impairs functions they regulate. To test this, we used a transgenic animal model of Parkinson’s, the A53T mouse. We measured body composition, exploratory locomotion, spontaneous physical activity, and energy expenditure. Further, we assessed alpha-synuclein accumulation, inflammation, and astrogliosis. Finally, we hypothesized that chemogenetic inhibition of orexin neurons would ameliorate observed impairments in the A53T mice. We showed that aging in A53T mice was accompanied by reductions in fat mass and increases in exploratory locomotion, spontaneous physical activity, and energy expenditure. We detected the presence of alpha-synuclein accumulations in orexin neurons, increased astrogliosis, and microglial activation. Moreover, loss of inhibitory pre-synaptic terminals and a reduced number of orexin cells were observed in A53T mice. As hypothesized, this chemogenetic intervention mitigated the behavioral disturbances induced by Parkinson’s disease pathology. This study implicates the involvement of orexin in early Parkinson’s-disease-associated impairment of hypothalamic-regulated physiological functions and highlights the importance of orexin neurons in Parkinson’s disease symptomology. View Full-Text
Keywords: Parkinson’s disease; orexin; neuromodulation Parkinson’s disease; orexin; neuromodulation
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MDPI and ACS Style

Stanojlovic, M.; Pallais, J.P.; Kotz, C.M. Inhibition of Orexin/Hypocretin Neurons Ameliorates Elevated Physical Activity and Energy Expenditure in the A53T Mouse Model of Parkinson’s Disease. Int. J. Mol. Sci. 2021, 22, 795. https://doi.org/10.3390/ijms22020795

AMA Style

Stanojlovic M, Pallais JP, Kotz CM. Inhibition of Orexin/Hypocretin Neurons Ameliorates Elevated Physical Activity and Energy Expenditure in the A53T Mouse Model of Parkinson’s Disease. International Journal of Molecular Sciences. 2021; 22(2):795. https://doi.org/10.3390/ijms22020795

Chicago/Turabian Style

Stanojlovic, Milos, Jean P. Pallais, and Catherine M. Kotz 2021. "Inhibition of Orexin/Hypocretin Neurons Ameliorates Elevated Physical Activity and Energy Expenditure in the A53T Mouse Model of Parkinson’s Disease" International Journal of Molecular Sciences 22, no. 2: 795. https://doi.org/10.3390/ijms22020795

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