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.
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Studies in animal models report an increase in brain BDNF levels when aged animals are submitted to protocols such as long-term environmental enrichment or physical activity.
“Studies in animal models report an increase in brain BDNF levels when aged animals are submitted to protocols such as long-term environmental enrichment [47–49] or physical activity [50, 51].”
From Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation (2019) · cites this paper as [48]
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Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation
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- Authors
- Cao, W., Duan, J., Wang, X., Zhong, X., Hu, Z., Huang, F., Wang, H., Zhang, J., Li, F., Zhang, J., Luo, X., & Li, C.-Q.
- Affiliations
- Central South University (CN)
- Corresponding author
- Li, Fang
- Li, Chang-Qi
- Venue
- Behavioural Brain Research
- Publisher
- Elsevier BV
- Published
- 2014-05
- Volume
- 265
- Pages
- 76-83
- ISSN
- 0166-4328 (ISSN-L)
- OpenAlex
- W1967265074
- Cited by
- 116
- References
- 35
- Citations by year
- 2026: 7 · 2025: 3 · 2024: 3 · 2023: 8 · 2022: 9 · 2021: 5 · 2020: 12 · 2019: 13 · 2018: 12 · 2017: 14 · 2016: 14 · 2015: 7 · 2014: 9
- FWCI
- 6.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Behavioural Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China
- Central South University
- Graduate Research and Innovation Projects of Jiangsu Province
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- environmental enrichment, proBDNF, brain-derived neurotrophic factor, hippocampus, MMP-9, proteolytic cleavage, synaptic plasticity, NR1, NR2A, anxiety-like behavior, sucrose preference, neurotrophins, early life experience
- MeSH terms
- Animals, Animals, Newborn, Environment, Exploratory Behavior, Food Preferences, Gene Expression Regulation, Hippocampus, Male, Motor Activity, Protein Precursors, RNA, Messenger, Sucrose, Sweetening Agents, Swimming, Receptors, N-Methyl-D-Aspartate, Rats, Wistar, Maze Learning, Brain-Derived Neurotrophic Factor, Matrix Metalloproteinase 9, Rats
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