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Delayed and Abbreviated Environmental Enrichment after Brain Trauma Promotes Motor and Cognitive Recovery That Is Not Contingent on Increased Neurogenesis.

ABSTRACT: Environmental enrichment (EE) confers motor and cognitive recovery in pre-clinical models of traumatic brain injury (TBI), and neurogenesis has been attributed to mediating the benefits. Whether that ascription is correct has not been fully investigated. Hence, the goal of the current study is to further clarify the possible role of learning-induced hippocampal neurogenesis on functional recovery after cortical impact or sham injury by utilizing two EE paradigms (i.e., early + continuous, initiated immediately after TBI and presented 24?h/day; and delayed + abbreviated, initiated 4 days after TBI for 6?h/day) and comparing them to one another as well as to standard (STD) housed controls. Motor and cognitive performance was assessed on post-operative Days 1-5 and 14-19, respectively, for the STD and early + continuous EE groups and on Days 4-8 and 17-22, for the delayed + abbreviated EE groups. Rats were injected with bromodeoxyuridine (BrdU, 500?mg/ kg; intraperitoneally) for 3 days (12?h apart) before cognitive training and sacrificed 1 week later for quantification of BrdU+ and doublecortin (DCX+) labeled cells. Both early + continuous and delayed + abbreviated EE promoted motor and cognitive recovery after TBI, relative to STD (p??0.05). However, only early + continuous EE increased DCX+ cells beyond the level of STD-housed controls (p?

SUBMITTER: Lajud N

PROVIDER: S-EPMC6387570 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Delayed and Abbreviated Environmental Enrichment after Brain Trauma Promotes Motor and Cognitive Recovery That Is Not Contingent on Increased Neurogenesis.

Lajud Naima N Díaz-Chávez Arturo A Radabaugh Hannah L HL Cheng Jeffrey P JP Rojo-Soto Georgina G Valdéz-Alarcón Juan J JJ Bondi Corina O CO Kline Anthony E AE

Journal of neurotrauma 20181128 5

Environmental enrichment (EE) confers motor and cognitive recovery in pre-clinical models of traumatic brain injury (TBI), and neurogenesis has been attributed to mediating the benefits. Whether that ascription is correct has not been fully investigated. Hence, the goal of the current study is to further clarify the possible role of learning-induced hippocampal neurogenesis on functional recovery after cortical impact or sham injury by utilizing two EE paradigms (i.e., early + continuous, initia ...[more]

PMID: 30051757

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Project description:Environmental enrichment (EE) is a therapeutic paradigm that consists of complex combinations of physical, cognitive, and social stimuli. The mechanisms underlying EE-mediated synaptic plasticity have yet to be fully elucidated. In this study, we investigated the effects of EE on synaptic vesicle-associated proteins and whether the expression of these proteins is related to behavioral outcomes. A total of 44 CD-1® (ICR) mice aged 6 weeks were randomly assigned to either standard cages or EE (N = 22 each). Rotarod and ladder walking tests were then performed to evaluate motor function. To identify the molecular mechanisms underlying the effects of EE, we assessed differentially expressed proteins (DEPs) in the striatum by proteomic analysis. Quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and immunohistochemistry were conducted to validate the expressions of these proteins. In the behavioral assessment, EE significantly enhanced performance on the rotarod and ladder walking tests. A total of 116 DEPs (54 upregulated and 62 downregulated proteins) were identified in mice exposed to EE. Gene ontology (GO) analysis demonstrated that the upregulated proteins in EE mice were primarily related to biological processes of synaptic vesicle transport and exocytosis. The GO terms for these biological processes commonly included Synaptic vesicle glycoprotein 2B (SV2B), Rabphilin-3A, and Piccolo. The qRT-PCR and western blot analyses revealed that EE increased the expression of SV2B, Rabphilin-3A and Piccolo in the striatum compared to the control group. Immunohistochemistry showed that the density of Piccolo in the vicinity of the subventricular zone was significantly increased in the EE mice compared with control mice. In conclusion, EE upregulates proteins associated with synaptic vesicle transport and exocytosis such as SV2B, Rabphilin-3A and Piccolo in the striatum. These upregulated proteins may be responsible for locomotor performance improvement, as shown in rotarod and ladder walking tests. Elucidation of these changes in synaptic protein expression provides new insights into the mechanism and potential role of EE.

Dataset Information

Delayed and Abbreviated Environmental Enrichment after Brain Trauma Promotes Motor and Cognitive Recovery That Is Not Contingent on Increased Neurogenesis.

Publications

Delayed and Abbreviated Environmental Enrichment after Brain Trauma Promotes Motor and Cognitive Recovery That Is Not Contingent on Increased Neurogenesis.

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