Embryonic exposure to acetamiprid insecticide induces CD68-positive microglia and Purkinje cell arrangement abnormalities in the cerebellum of neonatal rats.

Abstract

Concerns have been raised regarding acetamiprid (ACE), a neonicotinoid insecticide, due to its potential neurodevelopmental toxicity. ACE, which is structurally similar to nicotine, acts as an agonist of nicotinic acetylcholine receptors (nAChRs) and resists degradation by acetylcholinesterase. Furthermore, ACE has been reported to disrupt neuronal transmission and induce developmental neurotoxicity and ataxia in animal models. However, the prenatal ACE exposure and its pathological changes, including impacts on motor control, remains unclear. In this study, we investigated the effects of ACE exposure, focusing on the development of cerebellar neurons and glia, which are linked to motor impairment. ACE at doses of 20, 40-, and 60 mg/kg body weight was administered to Pregnant Wistar rats via feed on gestational day (G) 15. The developing cerebellum of the pups was examined on postnatal days (P) 7, 14, and 18, corresponding to the critical periods of cerebellar maturation in rodents. Our data revealed that ACE exposure at 40 and 60 mg/kg induced abnormal neuronal alignment on P14, and neuronal cell loss on P18. Additionally, ACE altered microglial behavior, with an increase in the number of CD68-positive microglia, suggesting that the exposure results in an increase in phagocytic microglia in response to neuronal abnormalities, ultimately leading to neuronal cell loss. Pups exposed to 60 mg/kg ACE exhibited hindlimb clasping during the hindlimb suspension test, indicating motor impairment. These findings suggest that ACE exposure causes neuronal cell loss of developing Purkinje cells and promotes a phase shift to the activate mode of microglia. This study further highlights the crucial role of neuron-glia interactions in ACE-induced motor impairment, thus contributing to our understanding of the potential risks associated with prenatal ACE exposure.