Hippocampal MCT4 as a key regulator in excessive exercise-induced cognitive impairment: involvement of neuroinflammation

Abstract

Background: As human life expectancy increases, maintaining a healthy lifestyle has become crucial. However, excessive exercise (EE) can lead to negative consequences such as muscle damage and exercise addiction. Recently, numerous reports have indicated that EE negatively impacts cognitive performance, although the exact mechanism remains unclear.

Objective: This study aimed to investigate the specific mechanisms underlying cognitive alterations induced by EE.

Methods: We conducted the Y-maze, Barnes maze, and Novel Object Recognition Test to assess both short-term and long-term memory, as well as object recognition ability. We then validated our findings using qRT-PCR to elucidate the underlying mechanisms. Additionally, Diclofenac (Dic), an anti-inflammatory drug, was administered to evaluate its effects on cognitive function and the results of the molecular experiments.

Results: EE-induced mice exhibited cognitive impairments, along with elevated expression of inflammatory cytokines such as tumor necrosis factor-α, interleukin (IL) -6, and IL-1β, and downregulated monocarboxylate transporters (MCTs) like MCT4. However, animals pre-treated with Dic regained cognitive function, alongside restored levels of IL-6, IL-1β, and MCT4.

Conclusion: MCT4 plays may play a crucial role in EE-induced cognitive impairments.

Keywords: Cognitive; Excessive exercise; Monocarboxylate transporter; Neuroinflammation.