Role of mitochondrial biogenesis in methanol-induced neurobehavioral changes in rats

This study aimed to explore the role of mitochondrial biogenesis in methanol-induced neurobehavioral impairments in rats and elucidate the potential neurotoxic mechanisms of methanol exposure.

Forty-eight healthy Sprague-Dawley rats (200 ± 20 g), equally stratified by sex, were randomized into four groups: a control group (0 g/m³) and low- (25.344 g/m³), medium- (50.688 g/m³), and high-dose (101.376 g/m³) methanol exposure groups. Rats were exposed via inhalation for 2 h/day, 7 days/week for 4 weeks. Neurobehavioral changes were evaluated using the Morris water maze (MWM) and open field test (OFT). Cortical histopathology was examined via H&E staining. Mitochondrial DNA (mtDNA) content was quantified by qPCR, and ATP levels were measured using a commercial assay kit. Western blotting was performed to assess the expression of mitochondrial biogenesis-related proteins (COX IV, PGC-1α, NRF1, and TFAM).

Methanol-exposed rats exhibited significantly prolonged escape latency and fewer platform crossings in the MWM (P < 0.05). OFT results demonstrated reduced central zone activity duration, total distance traveled, and central zone entries (P < 0.05). H&E staining revealed neuronal loss and structural disorganization in the cortex. Additionally, mtDNA content and ATP levels were significantly decreased in medium- and high-dose groups (P < 0.05). Western blot analysis confirmed downregulation of COX IV, PGC-1α, NRF1, and TFAM (P < 0.05), indicating suppressed mitochondrial biogenesis.

Methanol exposure disrupts mitochondrial biogenesis in rat cortical neurons, leading to reduced mitochondrial content and ATP production, which may contribute to the observed neurobehavioral deficits. These findings provide mechanistic insights into methanol-induced neurotoxicity.