Inhibition of Orexin/Hypocretin Neurons Ameliorates Elevated Physical Activity and Energy Expenditure in the A53T Mouse Model of Parkinson's Disease.
Inhibition of Orexin/Hypocretin Neurons Ameliorates Elevated Physical Activity and Energy Expenditure in the A53T Mouse Model of Parkinson's Disease.
复制标题
抑制增食欲素/下丘脑神经元能改善A53T帕金森病小鼠模型中增加的体力活动和能量消耗。
DOI：
10.3390/ijms22020795
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发表时间：
2021-01-14
影响因子：
5.6
通讯作者：
Kotz CM
中科院分区：
文献类型：
--
作者：
Stanojlovic M;Pallais JP;Kotz CM
除了经典的运动症状外，帕金森病还具有各种非经典症状。有趣的是，参与探索性运动、自发性身体活动和能量消耗调节的食欲素神经元在帕金森氏症中受到影响。在这项研究中，我们假设帕金森病相关的病理影响食欲素神经元，因此损害了它们调节的功能。为了测试这一点，我们使用了帕金森氏症的转基因动物模型，A53 T小鼠。我们测量了身体成分，探索性运动，自发性体力活动和能量消耗。此外，我们评估了α-突触核蛋白积聚、炎症和星形胶质细胞增生。最后，我们假设食欲素神经元的化学发生抑制将改善A53 T小鼠中观察到的损伤。我们发现，A53 T小鼠的衰老伴随着脂肪量的减少和探索运动、自发体力活动和能量消耗的增加。我们检测到食欲素神经元中存在α-突触核蛋白积聚，星形胶质细胞增生增加和小胶质细胞活化。此外，在A53 T小鼠中观察到抑制性突触前末梢的损失和食欲素细胞数量的减少。正如假设的那样，这种化学遗传干预减轻了帕金森病病理学引起的行为障碍。这项研究暗示了食欲素参与早期帕金森病相关的下丘脑调节的生理功能障碍，并强调了食欲素神经元在帕金森病病理学中的重要性。
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.
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影响因子：
12.7
作者：
Bengoa-Vergniory N;Roberts RF;Wade-Martins R;Alegre-Abarrategui J
通讯作者：
Alegre-Abarrategui J
影响因子：
7.1
作者：
Arawaka S;Sato H;Sasaki A;Koyama S;Kato T
通讯作者：
Kato T
影响因子：
5.6
作者：
de Lecea L;Huerta R
通讯作者：
Huerta R
DOI：
10.1038/ijo.2017.92
发表时间：
2017-08
期刊：
International journal of obesity (2005)
影响因子：
--
作者：
Coborn JE;DePorter DP;Mavanji V;Sinton CM;Kotz CM;Billington CJ;Teske JA
通讯作者：
Teske JA
影响因子：
3.8
作者：
Anandhan A;Jacome MS;Lei S;Hernandez-Franco P;Pappa A;Panayiotidis MI;Powers R;Franco R
通讯作者：
Franco R