Tissue specific differential response in metabolic activities of cerebrum, cerebellum, pons and medulla associated with thyroid dysfunction in sub-acute fluoride toxicity

Abstract

Objectives: In this present in vivo study, we are trying to explore differential effects of fluoride on metabolic functions of four discrete regions of rat brain associated with thyroidal insufficiency. Methods: Male rats of Wistar strain (N=6) were orally fed with 20 mg/kg/day fluoride for 30 days. Results: The results showed that following fluoride exposure, total protein content depleted more significantly in cerebrum and medulla in comparison to cerebellum and pons. Due to less availability of protein in all those tissues especially in medulla the proleolytic enzyme activity was severely affected by fluoride. Change in acidic protein content after fluoride exposure was more in cerebrum than in medulla, pons and cerebellum, whereas basic protein reduced markedly in medulla followed by pons, cerebellum and cerebrum. Additionally, neutral protein depleted more adversely in cerebellum and medulla in comparison with pons and cerebrum. Both DNA and RNA contents were markedly reduced in medulla and pons as compared with cerebrum and cerebellum. Increased RNase activity may be a causative factor for decreased RNA content in those tissues after fluoride treatment. Additionally, protein carbonylation is pronounced in cerebrum as compared with other tissue which may be responsible for depleting acidic proteins in that region. The neurotransmitter level was markedly reduced in cerebellum followed by medulla, pons and cerebrum. Conclusion: Thus, it is suggested that fluoride altered metabolic homeostasis in cerebrum, cerebellum, pons, medulla and thyroid in a tissue specific manner. Moreover, it is further observed that among the studied brain regions medulla and pons were adversely affected in terms of their protein and nucleic acid metabolism, whereas cerebellum was severely depressed to synthesize neurotransmitters following fluoride exposure.