2. Academic Validation
  3. Pramipexole improves depression-like behavior in diabetes mellitus with depression rats by inhibiting NLRP3 inflammasome-mediated neuroinflammation and preventing impaired neuroplasticity

Pramipexole improves depression-like behavior in diabetes mellitus with depression rats by inhibiting NLRP3 inflammasome-mediated neuroinflammation and preventing impaired neuroplasticity

  • J Affect Disord. 2024 Jul 1:356:586-596. doi: 10.1016/j.jad.2024.04.073.
Ping Li 1,  Tingting Wang 1,  Haipeng Guo 1,  Yingxi Liu 1,  Hongqing Zhao 2,  Tingting Ren 1,  Yingjuan Tang 1,  Yuhong Wang 3,  Manshu Zou 4
Affiliations

Affiliations

  • 1 Hunan University of Chinese Medicine, Changsha 410208, Hunan, China.
  • 2 Hunan University of Chinese Medicine, Changsha 410208, Hunan, China; Hunan Provincial Key Laboratory of Prevention and Treatment of Depressive Diseases with Traditional Chinese Medicine, Changsha 410208, Hunan, China.
  • 3 Hunan University of Chinese Medicine, Changsha 410208, Hunan, China; Hunan Provincial Key Laboratory of Prevention and Treatment of Depressive Diseases with Traditional Chinese Medicine, Changsha 410208, Hunan, China. Electronic address: [email protected].
  • 4 Hunan University of Chinese Medicine, Changsha 410208, Hunan, China; Hunan Provincial Key Laboratory of Prevention and Treatment of Depressive Diseases with Traditional Chinese Medicine, Changsha 410208, Hunan, China. Electronic address: [email protected].
PMID: 38657764 DOI: 10.1016/j.jad.2024.04.073
Abstract

Background: 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.

Methods: 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).

Results: 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.

Limitation: 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.

Conclusions: 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.

Keywords

Depression; Diabetes mellitus; Dopamine receptors; Neuroinflammation; Neuroplasticity; Pramipexole.

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