Permethrin exposure affects neurobehavior and cellular characterization in rats' brain

Abstract

This study investigated the neurotoxic effects of permethrin on the cerebellum, hippocampus and prefrontal cortex of Wistar rats and its effects on some behavioral patterns. Fifteen adult male Wistar rats were grouped into three categories: Group A received 0.1 mL normal saline (control), and Groups B and C received mixed feed with 500 mg/kg and 1,000 mg/kg of 0.6% permethrin, respectively, for 14 days. The animals were assessed for memory, anxiety and exploratory locomotion and thereafter anesthetized and transcardially perfused with normal saline and 4% paraformaldehyde (PFA). Cerebellum, hippocampus and prefrontal cortex were excised from the whole brain and processed for tissue histology, histochemistry and immunohistochemistry. Oxidative status and lipid peroxidation were also assessed using catalase, glutathione peroxidase, superoxide dismutase and malondialdehyde as biomarkers. Results revealed dosedependent decrease in body weights but increase in cerebellar and prefrontal weights, depletion of endogenous antioxidant markers, cognitive deficits, reduced locomotor activities, degenerative changes in the microarchitecture at high doses and presence of chromatolytic cells at both low and high doses of permethrin. Astrocytes were activated while synaptophysin expression was downregulated. Permethrin causes dose-dependent neurotoxicity on the morphology, neurochemistry and oxidative status of different brain regions, and these could affect behavioral performance and other neurologic functions.

Exposure to Sub-Lethal Doses of Permethrin Is Associated with Neurotoxicity: Changes in Bioenergetics, Redox Markers, Neuroinflammation and Morphology

“…Parihar associated hippocampal pathology with decreased neurogenesis, loss of principal neurons, and inflammation as well as a dysfunction of mood and cognition in a model of Gulf-War illness using rats [28]. Our data showed that PERM exposure can compromise hippocampal structural integrity, which in turn could affect vital neurological functions of this brain region, causing alterations such as motor deficits or dysfunctions in learning and memory, as has been described by Omotoso and co-workers (2020) [56] and Abdel-Rahman and co-workers (2001) [79]. However, a more detailed study of the changes induced by PERM exposure is needed to better understand the effects of this pyrethroid on brain integrity.…”

“…Several studies have reported changes in the activity of SOD and GPx as well as a decay in GSH levels in the brain and peripherical blood after exposure to high doses of PERM [49,54,55]. Omotoso and co-workers explored SOD, CAT and GPx activities after PERM exposure in the prefrontal cortex, hippocampus and cerebellum correlated with lipoperoxidation using doses of 500 and 1000 mg/kg [56]. They found a general decrease in enzyme activity and a rise in lipoperoxidation levels.…”

Animal models of Parkinson’s disease: a guide to selecting the optimal model for your research

“…A lot of the early pivotal studies using MPTP in NHPs showed that exposure to this toxin impacts cognitive function [143,185,[203][204][205][206]. Since then, rodent studies have reported similar deficits with MPTP as well as other toxins (paraquat, permethrin, 6-OHDA, rotenone and LPS) [53,114,[207][208][209].…”

“…Permethrin on the other hand fails to exhibit anxiety-like behaviour [207] and paraquat has only been shown to date to cause depressive-and anxiety-like behaviour when given alongside maneb, a type of fungicide [217]. When AAV--synuclein is injected into the SNpc, it too causes depressive behaviour although this occurs prior to motor deficits, unlike the clinical situation [218].…”

“…Models induced by MPTP, 6-OHDA and LPS treatment in rodents express similar anxiety-like symptoms [ 41 , 78 , 203 , 209 ], while the rotenone model only shows depressive behaviour [ 41 , 216 ]. Permethrin on the other hand fails to exhibit anxiety-like behaviour [ 207 ] and paraquat has only been shown to date to cause depression- and anxiety-like behaviour when given alongside maneb, a type of fungicide [ 217 ].…”