Coenzyme Q10 and vitamin E alleviate heat stress-induced mood disturbances in male mice: Modulation of inflammatory pathways and the HPA axis

Behav Brain Res. 2025 Jan 5:476:115259. doi: 10.1016/j.bbr.2024.115259. Epub 2024 Sep 18.

Abstract

Heat stress, as an environmental stressor, can lead to temperature dysregulation and neuroinflammation, causing depression and anxiety by disrupting brain physiology and functional connectivity. This study looked at how co-enzyme Q10 (Q10) and vitamin E (Vit E), alone and together, affected heat stress-caused anxiety and depression symptoms and inflammation in male mice. Five groups were utilized in the study: control, heat stress (NS), Q10, Vit E, and the combination group (Q10+Vit E). The mice were subjected for 15 min/day to a temperature of 43°C for 14 consecutive days, followed by daily treatments for two weeks with either normal saline, Q10 (500 mg/kg), Vit E (250 mg/kg), or their combination. The forced swimming test (FST) and tail suspension test (TST) were employed to evaluate despair behavior, whereas the elevated plus maze (EPM) and open field test (OFT) were used to assess anxious behaviors. Subsequently, the animals were sacrificed, and serum corticosterone levels, protein expression of inflammasome-related proteins, and hsp70 gene expression were evaluated in the prefrontal cortex (PFC). The study revealed that treatment with Vit E and Q10, alone or together, provided anxiolytic and antidepressant effects in the heat-stress-subjected animals. Also, giving Vit E and Q10 alone or together greatly lowered serum corticosterone levels. In the PFC, they also lowered the levels of hsp70 mRNA and NF-κB, caspase 1, NLRP3, and IL-1β proteins. It is speculated that treatment with Q10 and Vit E can attenuate heat stress-associated anxious and depressive responses by inhibiting the inflammatory pathways and modulating the hypothalamus-pituitary-adrenal axis.

Keywords: Anxiety; Corticosterone; Depression; Inflammation; Thermal stress.

MeSH terms

  • Animals
  • Anxiety* / drug therapy
  • Anxiety* / etiology
  • Anxiety* / metabolism
  • Behavior, Animal / drug effects
  • Corticosterone / blood
  • Depression* / drug therapy
  • Depression* / etiology
  • Depression* / metabolism
  • Disease Models, Animal
  • HSP70 Heat-Shock Proteins / metabolism
  • Heat Stress Disorders / drug therapy
  • Heat Stress Disorders / metabolism
  • Hypothalamo-Hypophyseal System* / drug effects
  • Hypothalamo-Hypophyseal System* / metabolism
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Male
  • Mice
  • Mood Disorders / drug therapy
  • Mood Disorders / etiology
  • Neuroinflammatory Diseases / drug therapy
  • Neuroinflammatory Diseases / metabolism
  • Pituitary-Adrenal System* / drug effects
  • Pituitary-Adrenal System* / metabolism
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / metabolism
  • Ubiquinone* / administration & dosage
  • Ubiquinone* / analogs & derivatives
  • Ubiquinone* / pharmacology
  • Vitamin E* / administration & dosage
  • Vitamin E* / pharmacology

Substances

  • coenzyme Q10
  • Ubiquinone
  • Vitamin E
  • Corticosterone
  • HSP70 Heat-Shock Proteins