β-Hexachlorocyclohexane triggers neuroinflammatory activity, epigenetic histone post-translational modifications and...

Area of Science:

• Environmental toxicology
• Neuroscience
• Epigenetics

Background:

• Persistent organic pollutants (POPs) are global environmental contaminants.
• Beta-hexachlorocyclohexane (β-HCH) is a stable, illegally dumped organochlorine pesticide with known pathogenetic mechanisms.
• Neurotoxic effects of β-HCH exposure require further investigation.

Purpose of the Study:

• To investigate the neurotoxic effects of β-HCH exposure.
• To explore epigenetic modifications induced by β-HCH.
• To assess the impact of β-HCH on cognitive functions.

Main Methods:

• Utilized neuronal cells (N2a), microglia (BV-2), and C57BL/6 mice models.
• Employed western blot, qPCR, and proteomic analyses.
• Conducted behavioral tests including Novel Object Recognition Test (NORT) and Object Place Recognition Task (OPRT).

Main Results:

• β-HCH exposure modulated NF-κB and induced epigenetic modifications in H3 histone acetylation (H3K9, H3K27) differently across cell types and brain regions.
• Cognitive impairment was observed, evidenced by deficits in recognition memory and spatial navigation.
• Decreased expression of BDNF and SNAP-25 genes, crucial for synaptic function, was linked to cognitive deficits.

Conclusions:

• β-HCH exposure induces neurotoxicity and cognitive impairment through epigenetic alterations and reduced expression of synaptic genes.
• Findings highlight β-HCH's role in neurological disease pathogenesis.
• Recommendations for regulatory action against illicit β-HCH use to protect human and animal health.