Selenium-containing peptides attenuating Pb-induced memory impairment through microRNA-mediated signaling

Area of Science:

• Neuroscience
• Toxicology
• Molecular Biology

Background:

• Lead (Pb) accumulation in the hippocampus causes oxidative stress and memory impairments.
• Selenium-containing peptides show potential in mitigating Pb-induced neurotoxicity.
• Understanding the role of microRNAs in peptide-mediated memory protection is crucial.

Purpose of the Study:

• To investigate the neuroprotective effects of selenium peptides TSeMMM and SeMDPGQQ against lead acetate-induced memory deficits.
• To explore the involvement of microRNAs in the memory protection mechanisms of these peptides.
• To elucidate the impact on hippocampal oxidative stress and neuronal morphology.

Main Methods:

• Mouse models of memory impairment induced by lead acetate administration.
• Assessment of Pb accumulation, oxidative stress markers, and hippocampal neuron morphology.
• Analysis of Brain-Derived Neurotrophic Factor (BDNF) expression and the Keap1/Nrf2 pathway.
• MicroRNA sequencing to identify differentially expressed microRNAs.

Main Results:

• TSeMMM and SeMDPGQQ treatments reversed lead accumulation and oxidative stress in the hippocampus.
• Improved hippocampal neuron morphology and regulated BDNF expression and Keap1/Nrf2 pathway were observed.
• Lead administration altered 26 microRNAs; high-dose TSeMMM and low-dose SeMDPGQQ restored 4 of them.

Conclusions:

• Selenium peptides TSeMMM and SeMDPGQQ effectively alleviate lead-induced neurotoxicity and memory impairments.
• These peptides modulate hippocampal oxidative stress, neuronal morphology, and specific microRNA expression.
• The findings highlight selenium-enriched factors as promising therapeutic agents for lead neurotoxicity.