Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 140, Issue -, Pages -Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2021.111734
Keywords
Astrocyte; Antidepressant; Diabetes; Obesity; Thiazolidinedione
Funding
- Ministry of Science and Technology, Taiwan [MOST 106-2320-B-006-058-MY3, MOST 109-2320-B-006-041MY3]
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Pioglitazone may be a potential therapeutic agent for metabolic disorders and associated depression, as it alleviated glucose metabolic dysfunctions and depressive phenotypes in mice.
The treatment of pioglitazone reduced depression-like behaviors and astrocytic activation induced by a high-fat diet.
Pioglitazone treatment had no effect on anxiety-like behaviors or hippocampus-related learning and memory in mice.
The prevalence of diabetes is rapidly increasing worldwide and is highly associated with the incidence of depression. Pioglitazone, a Peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonist, is widely used for treating patients with type 2 diabetes. However, whether pioglitazone alleviates metabolic disorder-related depression and astrocytic deficits remains unclear. Here we showed that 12 weeks of high-fat diet (HFD) feeding (from 8- to 20-week-old) induced not only obesity and insulin resistance, but also depression-like behaviors in mice. Astrocytic activation, a sign closely associated with depression, was also evident in the ventral hippocampus. Four weeks of pioglitazone (10 or 20 mg/kg, daily, from 20- to 24-week-old) treatment alleviated the HFD-induced glucose-metabolic dysfunctions, upregulation of ventral hippocampal GFAP, reduction of the total process lengths and the number of branch points of the ventral hippocampal CA1 GFAP-immunoreactive astrocytes and depressive phenotypes but had no effect on anxiety-like behaviors or hippocampus-related learning and memory in mice. These findings suggest that pioglitazone could be a potential therapeutic agent for metabolic disorders and associated depression.
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