Abstract
Neonicotinoids, a new class of insecticide, mimic the chemical structure of nicotine to bind to the nicotinic acetylcholine receptor (nAChR) to provide highly systemic insecticidal effects. Due to the difference of nAChR sensitivities between insects and mammal, neonicotinoids have been seen as safer insecticides than organophosphate compounds; however, recently, some reports suggest the developmental neurotoxicity of neonicotinoids.
In this study, we exposed Acetamiprid (ACE), a type of neonicotinoid, in different dosages to rat embryo, and observed cerebellar development in the offspring. 20 mg/kg-, 40 mg/kg-, or 60 mg/kg-ACE were orally administered to Wistar rats on the 15th day of gestation (G15). The male pups underwent perfusion fixation 14 days after birth (P14). The cerebellar slices immunochemistry stained with anti-Calbindin D-28k / Iba1 were observed with a confocal microscope. Then, the samples were subjected to Hematoxylin and Eosin (HE) staining to observe the entire image of the cerebellar vermis with a light microscope.
In ACE 40 mg/kg pups, the alignment of Purkinje Cell (PC) significantly misaligned, and in ACE 60 mg/kg pups, slight misalignment. Some PCs distributed the region under the standard Purkinje layer to be surrounded into the granular layer. ACE 20 mg/kg pups showed no misalignment of PC. In addition, ACE 40 mg/kg- and ACE 60 mg/kg-pups showed the higher cerebellar lobule folding between lobule V and VI in vermis than the control rats, whereas ACE 20 mg/kg-pups was almost as same as the control rats. The folding rates of ACE 40 mg/kg and 60 mg/kg were similar to the cerebellum treated with valproate, which is a well-known HDAC inhibitor and ASD-inducer.
These studies suggest that fetal exposure to high-dose ACE might affect cerebellar development and PC alinement. ACE 40 mg/kg dosage would not induce neuronal overkill but malformation in developing cerebellum, although ACE 60 mg/kg dosage would induce neuronal overkill. It might be related to the degree of microglia activation.
