HDAC2 (Histone deacetylase 2): A critical factor in environmental enrichment-mediated stroke recovery
| Autor: | Xiao-Lin Kou, Hai-Yin Wu, Dong-Ya Zhu, Yu-Hui Lin, Lei Chang, Meng-Cheng Yao, Chun-Xia Luo, Jian Dong, Huan-Yu Ni |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male medicine.medical_treatment Histone Deacetylase 2 Mice Transgenic Environment Biochemistry 03 medical and health sciences Cellular and Molecular Neuroscience Mice 0302 clinical medicine Neuroplasticity Medicine Animals Stroke Gene knockdown Environmental enrichment biology Histone deacetylase 2 business.industry Recovery of Function medicine.disease Mice Inbred C57BL 030104 developmental biology Corticospinal tract biology.protein business Stroke recovery Neuroscience 030217 neurology & neurosurgery Neurotrophin |
| Zdroj: | Journal of neurochemistryREFERENCES. 155(6) |
| ISSN: | 1471-4159 |
| Popis: | Environmental enrichment (EE) is a generally accepted strategy to promote stroke recovery and its beneficial effect is positively correlated with neuroplasticity. However, the mechanisms underlying it remain elusive. Histone deacetylase 2 (HDAC2), a negative regulator of neuroplasticity, is up-regulated after stroke. Thus, we hypothesized that HDAC2 may participate in EE-mediated stroke recovery. In this study, focal stroke was induced by photothrombosis in male mice exposing to EE or standard housing (SH) conditions. Recombinant virus vectors, including Ad-HDAC2-Flag, AAV-CAG-EGFP-Cre, LV-shHDAC2, or their controls were microinjected into the motor cortex at 3 days before stroke. Grid-walking and cylinder tasks were conducted to assess motor function. Western blot and immunostaining were used to uncover the mechanisms underlying EE-mediated stroke recovery. We found that EE exposure reversed stroke-induced HDAC2 up-regulation, implicating HDAC2 in EE-mediated functional recovery. Importantly, EE-dependent stroke recovery was counteracted by over-expressing HDAC2, and HDAC2 knockdown promoted functional recovery from stroke to the similar extent as EE exposure. Moreover, the knockdown of HDAC2 epigenetically enhanced expressions of neurotrophins and neuroplasticity-related proteins, with similar effects as EE, and consequently, whole brain and corticospinal tract (CST) rewiring. Together, our findings indicate that HDAC2 is critical for EE-dependent functional restoration. Precisely targeting HDAC2 may mimic EE and serve as a novel therapeutic strategy for stroke recovery. |
| Databáze: | OpenAIRE |
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