Mechanistic Link of ER Stress and Neuroinflammation Following Pyrethroid Exposure

NIH RePORTER · NIH · R01 · $18,143 · view on reporter.nih.gov ↗

Abstract

Endoplasmic reticulum (ER) stress and neuroinflammation have been involved in the pathogenesis of neurodegeneration and cognitive dysfunctions in aging and neurodegenerative diseases. When robust, sustained levels of ER stress are sensed by cells, UPR function is impaired and activation of inflammatory and apoptotic pathways are triggered, which consequently leads to chronic and persistent neurodegeneration and impairment of adult neurogenesis. Exposure to environmental toxicants, including pesticides have been shown as causative agents of ER stress, and neuroinflammation associated with neurodegeneration and neurological diseases. Pyrethroids are the most widely employed group of insecticides to control pests in public health, agriculture, and residential settings. Importantly, cognitive impairment has been reported in adults occupationally exposed to pyrethroids. In previous studies, we have shown that repeated pyrethroid exposure induced ER stress, apoptotic cell death, disruption of hippocampal neurogenesis, and learning and cognitive deficits in adult mice. Recently, we reported that pyrethroid insecticides activate microglia and increase production of major inflammatory mediators TNF-α and ROS in microglial cells and that repeated adult exposure to deltamethrin causes oxidative stress and neuroinflammation in the hippocampus of adult mice. These results suggest that ER stress-mediated neuroinflammation may be a primary mechanism by which deltamethrin impaired hippocampal neurogenesis and cognitive dysfunction following deltamethrin exposure. Here, we will determine the weather inhibition of ER stress attenuates neuroinflammation in the hippocampus in mice following deltamethrin exposure.

Key facts

NIH application ID
10772236
Project number
3R01ES027481-06S2
Recipient
FLORIDA INTERNATIONAL UNIVERSITY
Principal Investigator
Muhammad M Hossain
Activity code
R01
Funding institute
NIH
Fiscal year
2023
Award amount
$18,143
Award type
3
Project period
2023-04-25 → 2023-07-31