Chronic AdipoRon Treatment Mimics the Effects of Physical Exercise on Restoring Hippocampal Neuroplasticity in Diabetic Mice.
Chronic AdipoRon Treatment Mimics the Effects of Physical Exercise on Restoring Hippocampal Neuroplasticity in Diabetic Mice.
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慢性 AdipoRon 治疗模拟体育锻炼对恢复糖尿病小鼠海马神经可塑性的影响
DOI：
10.1007/s12035-021-02441-7
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发表时间：
2021-09
影响因子：
5.1
通讯作者：
Yau SY
中科院分区：
文献类型：
--
作者：
Lee TH;Ahadullah;Christie BR;Lin K;Siu PM;Zhang L;Yuan TF;Komal P;Xu A;So KF;Yau SY
运动模拟药物的管理可能是一种新的治疗方法来对抗共病性神经变性和代谢综合征。脂联素是一种脂肪细胞分泌的激素。除了其抗糖尿病作用外，脂联素还介导与成人海马神经发生相关的体育锻炼的抗抑郁作用。脂联素受体激动剂AdipoRon的降糖作用已被证实，但其在糖尿病条件下海马的潜在促认知和神经营养作用尚不清楚。本研究报道慢性AdipoRon治疗2周可改善链脲佐菌素诱导的糖尿病小鼠海马依赖的空间识别记忆。此外，AdipoRon处理可增加糖尿病小鼠海马齿状回（DG）祖细胞增殖和神经元分化。此外，AdipoRon处理显著增加了糖尿病小鼠齿状区树突复杂性、脊柱密度和n -甲基-d -天冬氨酸受体依赖的长期增强（LTP），并增加了DG中的BDNF水平。AdipoRon处理激活了DG中的AMPK/PGC-1α信号传导，而当PGC-1α信号被药物抑制时，细胞增殖和LTP未见增加。总之，慢性AdipoRon治疗部分模仿体育锻炼对糖尿病大脑学习记忆和海马神经可塑性的益处。结果表明，AdipoRon可能是一种潜在的体育运动模拟物，可以改善海马的可塑性，从而挽救典型的糖尿病相关的学习和记忆障碍。
Administration of exercise mimetic drugs could be a novel therapeutic approach to combat comorbid neurodegeneration and metabolic syndromes. Adiponectin is an adipocyte-secreted hormone. In addition to its antidiabetic effect, adiponectin mediates the antidepressant effect of physical exercise associated with adult hippocampal neurogenesis. The antidiabetic effect of the adiponectin receptor agonist AdipoRon has been demonstrated, but its potential pro-cognitive and neurotrophic effects in the hippocampus under diabetic condition are still unclear. This study reported that chronic AdipoRon treatment for 2 weeks improved hippocampal-dependent spatial recognition memory in streptozotocin-induced diabetic mice. Besides, AdipoRon treatment increased progenitor cell proliferation and neuronal differentiation in the hippocampal dentate gyrus (DG) of diabetic mice. Furthermore, AdipoRon treatment significantly increased dendritic complexity, spine density, andN-methyl-D-aspartate receptor-dependent long-term potentiation (LTP) in the dentate region, and increased BDNF levels in the DG of diabetic mice. AdipoRon treatment activated AMPK/PGC-1α signalling in the DG, whereas increases in cell proliferation and LTP were not observed when PGC-1α signalling was pharmacologically inhibited. In sum, chronic AdipoRon treatment partially mimics the benefits of physical exercise for learning and memory and hippocampal neuroplasticity in the diabetic brain. The results suggested that AdipoRon could be a potential physical exercise mimetic to improve hippocampal plasticity and hence rescue learning and memory impairment typically associated with diabetes.
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影响因子：
11.8
作者：
Dasgupta, Biplab;Milbrandt, Jeffrey
通讯作者：
Milbrandt, Jeffrey
影响因子：
3.5
作者：
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通讯作者：
Manahan-Vaughan, Denise
影响因子：
3.2
作者：
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通讯作者：
Timar, Bogdan
影响因子：
16.2
作者：
Gregg, EW;Breckles, GLA;Narayan, KMV
通讯作者：
Narayan, KMV
影响因子：
1.8
作者：
Fei, L.;Yong-Jun, H.;Jun, L.
通讯作者：
Jun, L.