Increased protein expression levels of pCREB, BDNF and SDF-1/CXCR4 in the hippocampus may be associated with enhanced neurogenesis induced by environmental enrichment

Abstract

Brain plasticity is very sensitive to the environment. Certain neurotrophic factors and neurotransmitter receptors, including brain-derived neurotrophic factor (BDNF), cyclic adenosine monophosphate response element‑binding protein (CREB), stromal cell‑derived factor‑1 (SDF‑1) and its specific receptor, C-X-C motif chemokine receptor 4 (CXCR4), are important in neurogenesis in adult animals. In the present study, the effects of environmental enrichment (EE) on neurogenesis in the dentate gyrus (DG) and subventricular zone (SVZ), and the protein expression levels of BDNF, CREB, SDF‑1 and CXCR4 were investigated. Adult rats were randomly assigned as controls or underwent EE for 30 days. Subsequently, immunofluorescence staining was used to analyze cell proliferation in the DG and SVZ, and the differentiation and survival of newly‑formed cells in the hippocampus. The protein expression levels of BDNF, phosphorylated CREB (pCREB), protein kinase A catalytic subunit α, SDF‑1 and CXCR4 in the hippocampus were assayed by western blotting. Cognitive function was assessed in a Morris water maze. EE improved cognitive function, and increased the proliferation, differentiation and survival of newly‑formed neurons in the DG of adult rats; however, EE did not activate neurogenesis in the SVZ. Furthermore, EE enhanced the protein expression levels of BDNF, pCREB, SDF-1 and CXCR4 in the hippocampus. These results provide a theoretical basis to explain the beneficial effects of EE on healthy, adult rats.

Can the effects of environmental enrichment modulate BDNF expression in hippocampal plasticity? A systematic review of animal studies

“…Thus, it has been reported that the increase in the neurogenesis that occurs due to exposure to EE results from the integration of new functional circuits of generated neurons and an increase in the number of synapses in the perforating fiber pathway of the DG and CA3‐CA1 region (Madronal et al, ). It is now clear that the exposure of adult rats to EE and exercise induces neurogenesis in the DG and may be correlated with an elevation in hippocampal BDNF levels (Choi et al, ; Mosaferi, Babri, Mohaddes, Khamnei, & Mesgari, ; Zhang et al, ).…”

Brain-derived neurotrophic factor promotes human granulosa-like tumor cell steroidogenesis and proliferation by activating the FSH receptor-mediated signaling pathway

“…BDNF was shown to stimulate the differentiation of neural progenitor cells, regulating neurogenesis 39 . Moreover, BDNF administration or its increased expression promotes hippocampal neurogenesis and increases neuronal activity 40, 41 . Therefore, BDNF not only regulates the neurons, but also promotes growth and physiological functions (steroidogenesis) in granulosa cells.…”

The Impact of CXCR4 Blockade on the Survival of Rat Brain Cortical Neurons

“…However, available data about the CXCR4 receptor behavior are contradictory. Whereas some authors, using different models, have demonstrated that CXCR4 activation may promote reversion of cellular damage induced by several insults [6,11,34], other authors have reported the opposite [15,16,17]. In fact, the activation of CXCR4 chemokine receptor led to detrimental effects in these recent studies [14,15,16,17].…”

“…Exposure to SDF-1α rescues these cells from apoptosis and induces a time-dependent increase of total Rb expression [6]. Increased expression of SDF-1α/CXCR4 in the hippocampus may be associated with enhanced neurogenesis induced by environmental enrichment [11]. AMD3100 reversed the neurogenesis and behavioral recovery promoted by forced limb-use in rats subjected to stroke [12].…”