普拉克索
神经可塑性
萧条(经济学)
神经炎症
医学
炎症体
啮齿动物模型
糖尿病
神经科学
心理学
精神科
内科学
内分泌学
帕金森病
受体
炎症
疾病
经济
宏观经济学
作者
Ping Li,Tingting Wang,Haipeng Guo,Yingxi Liu,Huajie Zhao,Tingting Ren,Yongfu Tang,Yuhong Wang,Manshu Zou
标识
DOI:10.1016/j.jad.2024.04.073
摘要
Diabetes mellitus (DM) is frequently associated with the occurrence and development of depression, and the co-occurrence of diabetes mellitus with depression (DD) may further reduce patients' quality of life. Recent research indicates that dopamine receptors (DRs) play a crucial role in immune and metabolic regulation. Pramipexole (PPX), a D2/3R agonist, has demonstrated promising neuroprotective and immunomodulatory effects. Nevertheless, the therapeutic effects and mechanisms of action of PPX on DM-induced depression are not clear at present. Depression, DM, and DD were induced in a rat model through a combination of a high-fat diet (HFD) supplemented with streptozotocin (STZ) and chronic unpredictable mild stress (CUMS) combined with solitary cage rearing. The pathogenesis of DD and the neuroprotective effects of DRs agonists were investigated using behavioral assays, enzyme-linked immunosorbent assay (ELISA), hematoxylin-eosin (HE) staining, Nissl staining, Western blotting (WB) and immunofluorescence (IF). DD rats exhibited more severe dopaminergic, neuroinflammatory, and neuroplastic impairments and more pronounced depressive behaviors than rats with depression alone or DM. Our findings suggest that DRs agonists have significant therapeutic effects on DD rats and that PPX improved neuroplasticity and decreased neuroinflammation in the hippocampus of DD rats while also promoting DG cell growth and differentiation, ultimately mitigating depression-like behaviors. Our study is based on a rat model. Further evidence is needed to determine whether the therapeutic effects of PPX apply to patients suffering from DD. Neuroinflammation mediated by damage to the dopaminergic system is one of the key pathogenic mechanisms of DD. We provide evidence that PPX has a neuroprotective effect on the hippocampus in DD rats and the mechanism may involve the inhibition of NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation by DRs to attenuate the neuroinflammatory response and neuroplasticity damage.
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