Effect of Folic Acid in prenatal Pregabalin induced Cerebellar changes in the Swiss albino mice


P. Yadav, S. Shresths, R. P. Kushwaha, C. B. Jha, G. P. Rauniyar, R. Shah

Abstract:

Background: The first report that antiepileptic drugs (AEDs) may have teratogenic effects dates back over 40 years. Pregabalin(PGB) is approved as new AEDs, in July 2004. Folic acid supplementation during organogenesis is associated with a decrease in the incidence of nervous system malformations. The objective is to detect the morphomertical and histological effect of pregabalin on the early embryogenesis of the cerebellum & to detect prenatal effect of folic acid on Pregabalin induced cerebellar changes in Swiss albino mice.

Materials and Methods: 24 pregnant female mice were divided into four groups, which received folic acid, PGB and PGB with folic acid at 0.1mg; 600mg/Kg b.wt/day respectively & one control group. Mice were allowed to deliver naturally, on PND 31-34, they were sacrificed. Slides of cerebellar section were prepared & sent for histopathological examination.

Results: Sections of PGB group showed disruption of the architecture in the purkinje cell layer along with pyknotic nuclei. Mild vacuolization was seen in the Granular layer. Compression and haemorrhage was seen in focal area of white matter.

Cerebellar sections of Folic acid & PGB showed restoration of the cerebellar architecture.  Significant difference (p<0.05) is noted when the brain weight of PGB treated group is compared with PGB & Folic acid treated group. Mean diameter of Purkinje neurons of PGB treated group when compared with PGB and folic acid treated groups showed significant difference (p< 0.001)

Conclusions: Study confirmed the protective role of folic acid against cerebellar neurotoxic effects of PGB prenatal exposure.

Key words: Pregabalin, Folic acid, Cerebellum, Purkinje cells