Enriched environment causes epigenetic changes in hippocampus and improves long-term cognitive function in sepsis

Area of Science:

• Neuroscience
• Molecular Biology
• Pathophysiology

Background:

• Sepsis causes life-threatening organ dysfunction due to an inappropriate host response to infection.
• Oxidative stress and inflammation in sepsis lead to dysregulated gene expression and hyperinflammation.
• Environmental conditions influence disease pathology; enriched environments (EE) improve cognition and modulate epigenetic enzymes.

Purpose of the Study:

• To evaluate epigenetic alterations in the brain following sepsis.
• To investigate the effects of environmental enrichment (EE) on sepsis-induced brain changes and cognitive deficits.

Main Methods:

• Male Wistar rats underwent cecal ligation and perforation (CLP) to induce sepsis or sham surgery.
• Animals were assessed at various time points (24h to 30 days) post-sepsis or maintained in standard (SE) or enriched environments (EE).
• Evaluated behavioral tests, epigenetic enzyme activities (HAT, HDAC, DNMT), biochemical markers, and synaptic plasticity.

Main Results:

• Sepsis led to increased histone deacetylase (HDAC) and DNA methyltransferase (DNMT) activities, correlating with cognitive impairment.
• Environmental enrichment (EE) reduced HDAC and DNMT activity in septic animals.
• EE reversed cognitive deficits, decreased IL1-β levels, and increased PSD-95 levels in the hippocampus.

Conclusions:

• Environmental conditions significantly modulate long-term cognitive consequences of sepsis.
• Environmental enrichment (EE) shows potential benefits in mitigating sepsis-induced brain dysfunction and cognitive impairment.
• EE offers a promising non-pharmacological intervention strategy for sepsis recovery.