Prolong intermittent injection of human parathyroid hormone in rats modulates the expression of several proteins in the neuropil of the cerebellar cortex.

ABSTRACT

INTRODUCTION: The intermittent use of recombinant human parathyroid hormone (iPTH) alters calcium metabolism and induces osteogenesis in experimental models. However, the real effects of iPTH in excitable cells and neurons that require membrane receptors to undergo membrane depolarization/repolarization (Na+K+ATPase) to generate ATP, voltage-gated calcium channel (calcium-IP3R-calponin) as well as GABAergic (GABAA) signaling remains unclear. OBJECTIVES: In this study, the expression of IP3R, Na+K+-ATPase, GABAA and calmodulin proteins were evaluated in histological sections of the cerebellum of rats following prolonged injection of iPTH. METHODS: Twenty Wistar rats were used in this study and randomly assigned as either or control group. The test group were subcutaneously injected with 20 µg/kg of iPTH, 3×/week for 8 weeks, while the control group received 1 ml/kg of 0.9% saline solution. The rats were euthanized on the 60th day after the first administration, and their cerebellar vermis was removed and submitted to histological and immunohistochemical evaluation for detection of IP3R, Na+K+-ATPase, GABAA and calmodulin proteins. The expression of proteins was evaluated in the areas corresponding to the Purkinje cells as well as in neuropil of molecular layer of cerebellum. All results were transformed into a percentage for each area analyzed to verify significance between groups. RESULTS: Rats that received iPTH demonstrated significant reduction of IP3R, calmodulin and GABAA in Purkinje cells and neuropil of molecular layer while the expression of Na+K+-ATPase was similar. CONCLUSION: It was concluded that iPTH decreased the expression of IP3R and calmodulin while it did not alter the expression of Na+K+-ATPase. These changes insinuate the ionic activity of calcium and sodium/potassium. Yet, the iPTH alters GABAergic signaling in Purkinje cells, suggesting neurotransmission activity changes in the cerebellum.