S100beta upregulation: a possible mechanism of deltamethrin toxicity and motor coordination deficits

Deltamethrin (DLT) is a type II synthetic pyrethroid with insecticidal properties. It has been considered safe to humans. Excessive exposure of DLT is being variously reported, recently, to cause potential neurotoxicity in adults, as characterized by ataxia, loss of coordination, hyperexcitability, convulsions and paralysis. However, limited information is available on its impact at lower/safe to human doses during development. The present study was designed to assess the postnatal (P) exposure of DLT (as low as 0.7 mg/kg, i.p.) on S-100beta expression in developing rat cerebellum and its impact on Purkinje cell morphogenesis and dendritogenesis, and subsequent spontaneous motor activity (SMA) deficits. Wistar rat pups born to healthy mothers were injected with DLT (Sigma) at a dosage of 0.7 mg/kg body wt., i.p. dissolved in DMSO (Sigma) during P0-7th (DLT-I) and P9-13th day (DLT-II). The control pups were injected with equivalent volumes of DMSO. The pups of both the groups were used to assess the spontaneous motor activity P21 onwards. The cryocut sections (30 microm) of the cerebella were used for anti-S-100beta antibody labeling using streptavidin biotin HRP method. An upregulation of S-100beta expression in Bergmann glial fibers was recorded at P12 and P15 day preparations in both DLT-I and DLT-II treated groups. However, such upregulation of S-100beta was more prominent in DLT-II treated group animals with a large number of strongly S-100beta immunopositive astrocytes flanking around the Purkinje neurons. In Golgi preparation the Purkinje neurons in DLT treated groups had reduced dendritic arbor with short primary dendrites and much reduced dendritic branches which appeared stumpy and hypertrophied. The granule cell proliferation and migration as well as Purkinje cell morphogenesis and dendritogenesis are affected following DLT exposure in the present investigation. This may also affect the mossy fiber-granule cell-parallel pathway formation which in turn may decrease the firing of Purkinje cells (GABAergic inhibitory projections) and thus an increase in the output of the neurons in the deep cerebellar nuclei neurons and disturbed motor coordination.