The disruption of CREB/BDNF/TrkB signaling. Dynamic changes induced by zinc deficiency

Abstract

Background Our previous studies indicated that expression of several proteins involved in numerous aspects of plasticity in the central nervous system (CNS) is modulated by four-week dietary deprivation of trace element zinc. The levels of the phosphorylated forms of transcription factor cyclic AMP response-element binding (pCREB) protein, neurotrophin brain derived neurotrophic factor (BDNF) protein and high-affinity tropomyosine-related kinase B receptor (TrkB) protein were significantly decreased in the hippocampus of rats fed a zinc-deficient diet for four weeks. However, no changes of these proteins between rats subjected to four-week zinc restriction and the control animals were found in the prefrontal cortex. Aims Here we examined whether six-week dietary zinc deprivation induces changes in the protein levels of pCREB, BDNF and TrkB in the prefrontal cortex and hippocampus of rats. Methods Male Sprague Dowley rats (5-week-old) were fed a 50 mg Zn/kg (control group) or a 3 mg Zn/kg (zinc deficient group) diet for six weeks. The protein levels of pCREB, BDNF and TrkB were measured using western blotting. Results The levels of pCREB and BDNF proteins were significantly decreased (by 46% and 52%) in the prefrontal cortex and (by 44% and 54%) in the hippocampus of rats subjected to six-week zinc-deficient diet when compared with that of the control animals. Interestingly, at the same time point an increase (by 153%) in TrkB protein was observed in the prefrontal cortex of group fed zinc-deficient diet for six weeks compared to the control group. Conclusions The present data reports that six-week dietary zinc deprivation, unlike four-week zinc restriction, influences not only the hippocampus, but also the prefrontal cortex of rats. One can assume that CREB/ BDNF/TrkB proteins levels changes are dynamic in response to zinc deprivation and vary not only across brain regions but also in the course of time.