Cypermethrin Impairs Hippocampal Neurogenesis and Cognitive Functions by Altering Neural Fate Decisions in the Rat Brain

Abstract

Neurogenesis is a developmental process that involves fine-tuned coordination between self-renewal, proliferation, and differentiation of neural stem cells (NSCs) into neurons. However, early-life assault with environmental toxicants interferes with the regular function of genes, proteins, and other molecules that build brain architecture resulting in attenuated neurogenesis. Cypermethrin is a class II synthetic pyrethroid pesticide extensively used in agriculture, veterinary, and residential applications due to its low mammalian toxicity, high bio-efficacy, and enhanced stability. Despite reports on cypermethrin-mediated behavioral and biochemical alterations, till now, no study implicates whether cypermethrin exposure has any effect on neurogenesis. Therefore, the present study was undertaken to comprehend the effects of cypermethrin treatment on embryonic and adult neurogenesis. We found that cypermethrin exposure led to a considerable decrease in the BrdU/Sox-2⁺, BrdU/Dcx⁺, and BrdU/NeuN⁺ co-labeled cells indicating that cypermethrin treatment decreases NSC proliferation and generation of mature and functional neurons. On the contrary, the generation of BrdU/S100β⁺ glial cells was increased resulting in neurogliogenesis imbalance in the hippocampus. Further, cypermethrin treatment also led to an increased number of BrdU/cleaved caspase-3⁺ and Fluoro-Jade B⁺ cells suggesting an induction of apoptosis in NSCs and increased degeneration of neurons in the hippocampus. Overall, these results explicate that cypermethrin exposure not only reduces the NSC pool but also disturbs the neuron-astrocyte ratio and potentiates neurodegeneration in the hippocampus, leading to cognitive dysfunctions in rats.

Keywords: Cypermethrin; Hippocampus; Neural stem cells; Neurodegeneration; Neurogenesis.