title: Early enriched environment induces an increased conversion of proBDNF to BDNF in the adult rat's hippocampus.
abstract: An enriched environment has been shown to influence brain plasticity and function by involving the action of brain-derived neurotrophic factor (BDNF). BDNF, which is synthesized as a precursor molecule (proBDNF) that undergoes proteolytic cleavage, plays an important role in synaptic plasticity and contributes to several brain functions such as memory, learning, and behavior. The neurotrophins and proneurotrophins often play opposite roles in the brain, suggesting that proteolytic cleavage of proneurotrophins controls the action of neurotrophins. However, few studies have focused on the expression and cleavage of proBDNF after exposure to an enriched environment. Our study aimed to explore the effects of an early-enriched environment on the conversion of proBDNF to BDNF in the adult rats' hippocampus. We found that there was no difference in the expression of proBDNF in the hippocampus between the SE (standard environment) and EE (enriched environment) rats, but a significantly increased BDNF protein level was found in the EE rats. Thus, a remarkably enhanced ratio of BDNF to proBDNF (BDNF/proBDNF) was observed in the EE rats. In addition, the EE resulted in a remarkably up-regulated matrix metalloproteinase-9 (MMP-9) in the hippocampus, which played a key role in converting proBDNF to BDNF in the extracellular space. Furthermore, the expression of synapse-related proteins (NR1 and NR2A) was analyzed, and the results indicated that EE could significantly increase the expression of NR1 and NR2A in the hippocampus. In addition, the behavioral results showed that EE reduced anxiety-like behavior in the elevated-plus maze test and reduced immobility time in the forced swimming test. Moreover, the EE resulted in an increased preference for sucrose compared to the SE. These results suggested that the EE up-regulated MMP-9 levels within the hippocampus, which might facilitate the conversion of proBDNF to BDNF, thereby contributing to the long lasting alterations of synaptic plasticity and behavior.
authors.affiliation: Department of Anatomy and Neurobiology, XiangYa School of Medicine, Central South University, Tongzipo Road 172, Changsha, Hunan, PR China.
authors.forename: Wenyu
authors.initials: W
authors.lastname: Cao
authors.affiliation: Department of Anatomy and Neurobiology, XiangYa School of Medicine, Central South University, Tongzipo Road 172, Changsha, Hunan, PR China.
authors.forename: Juan
authors.initials: J
authors.lastname: Duan
authors.affiliation: Department of Anatomy and Neurobiology, XiangYa School of Medicine, Central South University, Tongzipo Road 172, Changsha, Hunan, PR China.
authors.forename: Xueqin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Anatomy and Neurobiology, XiangYa School of Medicine, Central South University, Tongzipo Road 172, Changsha, Hunan, PR China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Zhong
authors.affiliation: Department of Anatomy and Neurobiology, XiangYa School of Medicine, Central South University, Tongzipo Road 172, Changsha, Hunan, PR China.
authors.forename: Zhaolan
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Anatomy and Neurobiology, XiangYa School of Medicine, Central South University, Tongzipo Road 172, Changsha, Hunan, PR China.
authors.forename: Fulian
authors.initials: F
authors.lastname: Huang
authors.affiliation: Department of Anatomy and Neurobiology, XiangYa School of Medicine, Central South University, Tongzipo Road 172, Changsha, Hunan, PR China.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Anatomy and Neurobiology, XiangYa School of Medicine, Central South University, Tongzipo Road 172, Changsha, Hunan, PR China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Anatomy and Neurobiology, XiangYa School of Medicine, Central South University, Tongzipo Road 172, Changsha, Hunan, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Anatomy and Neurobiology, XiangYa School of Medicine, Central South University, Tongzipo Road 172, Changsha, Hunan, PR China.
authors.forename: Jianyi
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Anatomy and Neurobiology, XiangYa School of Medicine, Central South University, Tongzipo Road 172, Changsha, Hunan, PR China.
authors.forename: Xuegang
authors.initials: X
authors.lastname: Luo
authors.affiliation: Department of Anatomy and Neurobiology, XiangYa School of Medicine, Central South University, Tongzipo Road 172, Changsha, Hunan, PR China. Electronic address: changqili@csu.edu.cn.
authors.forename: Chang-Qi
authors.initials: CQ
authors.lastname: Li
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D004777:Environment; D005106:Exploratory Behavior; D005518:Food Preferences; D005786:Gene Expression Regulation / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D018782:Maze Learning; D009043:Motor Activity / Q000502:physiology; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D013395:Sucrose / Q000008:administration & dosage; D013549:Sweetening Agents / Q000008:administration & dosage; D013550:Swimming / Q000523:psychology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C409466:NR1 NMDA receptor; C120997:NR2A NMDA receptor; D011498:Protein Precursors; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D013549:Sweetening Agents; D013395:Sucrose; D020780:Matrix Metalloproteinase 9
keywords: Brain-derived neurotrophic factor; Enriched environment; Hippocampus; Matrix metalloproteinase-9; Pro-brain-derived neurotrophic factor