Zinc deficiency in rats is associated with up-regulation of hippocampal NMDA receptor

• Zinc deficiency induces anhedonia and impairs social behavior in rats.
• Zinc deficiency increases GluN2A and GluN2B protein levels in the rat hippocampus.
• Zinc deficiency increases GluN2A protein level in the rat prefrontal cortex.
• Zinc deficiency decreases PSD-95, p-CREB and BDNF protein levels in the rat hippocampus.

RationaleData indicated that zinc deficiency may contribute to the development of depression; however changes induced by zinc deficiency are not fully described.ObjectivesIn the present paper we tested whether the dietary zinc restriction in rats causes alterations in N-methyl-D-aspartate receptor (NMDAR) subunits in brain regions that are relevant to depression.MethodsMale Sprague Dawley rats were fed a zinc adequate diet (ZnA, 50 mg Zn/kg) or a zinc deficient diet (ZnD, 3 mg Zn/kg) for 4 or 6 weeks. Then, the behavior of the rats was examined in the forced swim test, sucrose intake test and social interaction test. Western blot assays were used to study the alterations in NMDAR subunits GluN2A and GluN2B and proteins associated with NMDAR signaling in the hippocampus (Hp) and prefrontal cortex (PFC).ResultsFollowing 4 or 6 weeks of zinc restriction, behavioral despair, anhedonia and a reduction of social behavior occurred in rats with concomitant increased expression of GluN2A and GluN2B and decreased expression of the PSD-95, p-CREB and BDNF protein levels in the Hp. The up-regulation of GluN2A protein was also found in the PFC, but only after prolonged (6 weeks) zinc deprivation.ConclusionsThe procedure of zinc restriction in rats causes behavioral changes that share some similarities to the pathophysiology of depression. Obtained data indicated that depressive-like behavior induced by zinc deficiency is associated with the changes in NMDAR signaling pathway.

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