Cypermethrin Impairs Hippocampal Neurogenesis and Cognitive Functions by Altering Neural Fate Decisions in the Rat Brain
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Cypermethrin Impairs Hippocampal Neurogenesis and Cognitive Functions by Altering Neural Fate Decisions in the Rat Brain Anuradha Yadav 1,2 & Ankit Tandon 1,3 & Brashket Seth 1,2 & Shweta Goyal 1,2 & Sangh Jyoti Singh 1,2 & Shashi Kant Tiwari 1,2,4 & Swati Agarwal 1,2,5 & Saumya Nair 1 & Rajnish Kumar Chaturvedi 1,2 Received: 7 February 2020 / Accepted: 28 August 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
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 . Neural stem cells . Hippocampus . Neurodegeneration . Neurogenesis
Introduction Anuradha Yadav, Ankit Tandon and Brashket Seth contributed equally to this work. * Rajnish Kumar Chaturvedi [email protected] 1
Developmental Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhavan, 31 Mahatma Gandhi Marg, Lucknow, Uttar Pradesh 226001, India
2
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
3
Department of Biochemistry, School of Dental Sciences, Babu Banarasi Das University, BBD City, Faizabad Road, Lucknow, Uttar Pradesh 226028, India
4
Present address: University of California San Diego, La Jolla, CA 92093, USA
5
Present address: Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Neurogenesis is a develo
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