Neurobehavioral toxicity of cypermethrin in association with oxidative, inflammatory and neurotrophic changes in the hippocampus of rats

Pyrethroid pesticides can induce neurotoxicity in target and non-target organisms. We examined the effects of sub-chronic exposure to cypermethrin on anxiety-like behaviors, memory function and molecular changes in the hippocampus of rats. Twenty-four male Wistar rats (weighing 200-250 g) were randomly divided into three groups (<i>n</i> = 8) and received orally corn oil, cypermethrin 2 and cypermethrin 4 mg/kg/day, for 30 days. The elevated plus maze (EPM), open field maze (OFM) and novel object recognition memory (NORM) tests were conducted. At the end, brain derived neurotrophic factor (BDNF), glycogen synthase kinase-3 β (GSK-3β), cholinesterase activity, oxidative stress markers and inflammatory mediators were evaluated in the hippocampus. The results of OFM and EPM indicated higher level of anxiety and motor activity alterations in the cypermethrin treated rats. NORM test revealed impairment of cognitive memory and decreased discrimination ratio in cypermethrin treated rats. Cypermethrin decreased BDNF and increased GSK-3β, oxidative stress and mRNA expression of IL-1β and TNF-α and NF-κB in the hippocampus. The activity of cholinesterase enzyme was not changed. Cypermethrin can impair learning and memory along with provoking oxidative stress and inflammation, and dysregulation of BDNF and GSK-3β pathway may be involved in neurocognitive and neurobehavioral disorders due to long-time exposures.