Pioglitazone reduces mortality, prevents depressive-like behavior, and impacts hippocampal neurogenesis in the 6-OHDA model of Parkinson's disease in rats
Pioglitazone reduces mortality, prevents depressive-like behavior, and impacts hippocampal neurogenesis in the 6-OHDA model of Parkinson's disease in rats
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DOI：
10.1016/j.expneurol.2017.11.009
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发表时间：
2018-02-01
影响因子：
5.3
通讯作者：
Weffort de Oliveira, Rubia Maria
中科院分区：
文献类型：
--
作者：
Bonato, Jessica Mendes;Bassani, Taysa Bervian;Weffort de Oliveira, Rubia Maria
成人海马神经发生缺陷被认为是帕金森病 (PD) 患者经常观察到的抑郁症状的潜在病理生理机制。吡格列酮是一种选择性过氧化物酶体增殖物激活受体 γ (PPAR-γ) 激动剂，已被证明具有抗炎和抗抑郁作用，并可调节多种神经退行性疾病中的神经可塑性。本研究调查了吡格列酮对 PD 大鼠模型抑郁表型和成年海马神经发生的影响，该模型是通过双侧黑质致密部 (SNpc) 输注 6-羟基多巴胺 (6-0HDA) 诱导的。患有 SNpc 和腹侧被盖区 (VTA) 神经变性的大鼠表现出类似绝望的行为，同时海马中的小胶质细胞持续激活。吡格列酮可降低 6-OHDA 诱导的黑质病变早期的死亡率并减弱小胶质细胞的活化。吡格列酮发挥抗抑郁样作用，并增加黑质病变大鼠海马神经元的存活率。这些结果表明，吡格列酮通过促进 6-OHDA 损伤大鼠海马神经发生来发挥神经保护作用，这可能有助于其抗抑郁样作用。
Deficiencies in adult hippocampal neurogenesis have been suggested to be a possible pathophysiological mechanism that underlies depressive symptoms that are often observed in patients with Parkinson's disease (PD). Pioglitazone, a selective peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonist, has been shown to exert antiinflammatory and antidepressant effects and modulate neural plasticity in several neurodegenerative disorders. The present study investigated the effects of pioglitazone on depressive phenotypes and adult hippocampal neurogenesis in a rat model of PD that was induced by bilateral 6-hydroxydopamine (6-0HDA) infusions in the substantia nigra pars compact (SNpc). Rats with SNpc and ventral tegmental area (VTA) neurodegeneration exhibited despair-like behavior, concomitant with persistent microglial activation in the hippocampus. Pioglitazone reduced the rate of mortality and attenuated microglial activation in the early phase of 6-OHDA-induced nigral lesions. Pioglitazone exerted antidepressant-like effects and increased the survival of neurons in the hippocampus in rats with nigral lesions. These results indicate that pioglitazone exerts neuroprotective effects by facilitating hippocampal neurogenesis in 6-OHDA-lesioned rats, which might contribute to its antidepressant-like effect.