Heat stroke-induced cerebral cortex nerve injury by mitochondrial dysfunction: A comprehensive multi-omics profiling...

Area of Science:

• Neuroscience
• Environmental Health
• Biochemistry

Background:

• Global warming contributes to frequent extreme summer temperatures, increasing heat stroke risk.
• Heat stroke poses severe health risks, particularly to the brain, but its pathogenesis is not fully understood.

Purpose of the Study:

• To investigate the molecular mechanisms of heat stroke-induced brain damage using a mouse model.
• To identify specific brain regions and molecular pathways affected by heat stroke.

Main Methods:

• Constructed a mouse model of heat stroke by exposing mice to 42°C and 50% humidity.
• Utilized cFos protein localization to identify damaged brain regions.
• Performed multi-omics analyses (metabolomics, transcriptomics, proteomics) on the cerebral cortex.

Main Results:

• Identified the cerebral cortex, particularly the anterior cingulate cortex, as the most affected brain region.
• Revealed significant alterations in neurotransmitter systems, mitochondrial dysfunction, histidine and pentose phosphate pathways, and oxidative stress.
• Observed increased Reactive Oxygen Species (ROS) production and downregulation of Tomm40 and mitochondrial permeability transition pore, indicating severe mitochondrial dysfunction.

Conclusions:

• Heat stroke-induced mitochondrial dysfunction in the cerebral cortex is a primary cause of neural impairment.
• This multi-omics study provides a comprehensive understanding of heat stroke's molecular impact on the brain.
• Findings offer new avenues for heat stroke prevention, treatment, and environmental policy development.