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

Zhang,Xiao  Qian; Mu,Jing  Wei; Wang,Hui  Bin; Jolkkonen,Jukka; Liu,Ting  Ting; Xiao,Ting; Zhao,Mei; Zhang,Chao  Dong; Zhao,Chuan  Sheng

doi:10.3892/mmr.2016.5470

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

Authors:
- Xiao Qian Zhang
- Jing Wei Mu
- Hui Bin Wang
- Jukka Jolkkonen
- Ting Ting Liu
- Ting Xiao
- Mei Zhao
- Chao Dong Zhang
- Chuan Sheng Zhao
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Affiliations: Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China, Department of Neurology, The People's Hospital of Liaoning, Shenyang, Liaoning 110016, P.R. China, Institute of Clinical Medicine‑Neurology, University of Eastern Finland, 70211 Kuopio, Finland, Department of Dermatology, The First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, P.R. China, Department of Cardiology, The Shengjing Affiliated Hospital, China Medical University, Shenyang, Liaoning 110004, P.R. China
Published online on: July 6, 2016 https://doi.org/10.3892/mmr.2016.5470
Pages: 2231-2237

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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.

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