2. Academic Validation
  3. Lactylation of histone by BRD4 regulates astrocyte polarization after experimental subarachnoid hemorrhage

Lactylation of histone by BRD4 regulates astrocyte polarization after experimental subarachnoid hemorrhage

  • J Neuroinflammation. 2024 Jul 30;21(1):186. doi: 10.1186/s12974-024-03185-6.
Fan Zhang # 1 2,  Jian Zhou # 1 2,  Peng Lu # 1 2,  Xianhui Zhang 2,  Lei Yang 1 2,  Jinpeng Wu 1 2,  Lihan Zhang 2,  Lifang Zhang 3,  Jinwei Pang 1,  Huangfan Xie 2 4,  Bingqing Xie 2 4,  Yong Jiang 5 6 7 8,  Jianhua Peng 9 10 11
Affiliations

Affiliations

  • 1 Department of Neurosurgery, The Affiliated Hospital, Southwest Medical University, NO. 25 of Taiping Street, Luzhou, Sichuan, 646000, China.
  • 2 Laboratory of Neurological Diseases and Brain Function, The Affiliated Hospital, Southwest Medical University, Luzhou, China.
  • 3 Sichuan Clinical Research Center for Neurosurgery, The Affiliated Hospital, Southwest Medical University, Luzhou, China.
  • 4 Institute of Brain Science, Southwest Medical University, Luzhou, China.
  • 5 Department of Neurosurgery, The Affiliated Hospital, Southwest Medical University, NO. 25 of Taiping Street, Luzhou, Sichuan, 646000, China. jiangyong@swmu.edu.cn.
  • 6 Laboratory of Neurological Diseases and Brain Function, The Affiliated Hospital, Southwest Medical University, Luzhou, China. jiangyong@swmu.edu.cn.
  • 7 Institute of Brain Science, Southwest Medical University, Luzhou, China. jiangyong@swmu.edu.cn.
  • 8 Sichuan Clinical Research Center for Neurosurgery, The Affiliated Hospital, Southwest Medical University, Luzhou, China. jiangyong@swmu.edu.cn.
  • 9 Department of Neurosurgery, The Affiliated Hospital, Southwest Medical University, NO. 25 of Taiping Street, Luzhou, Sichuan, 646000, China. pengjianhua@swmu.edu.cn.
  • 10 Laboratory of Neurological Diseases and Brain Function, The Affiliated Hospital, Southwest Medical University, Luzhou, China. pengjianhua@swmu.edu.cn.
  • 11 Academician (Expert) Workstation of Sichuan Province, The Affiliated Hospital, Southwest Medical University, Luzhou, China. pengjianhua@swmu.edu.cn.
  • # Contributed equally.
PMID: 39080649 DOI: 10.1186/s12974-024-03185-6
Abstract

Under subarachnoid hemorrhage (SAH) conditions, astrocytes undergo a marked intensification of glycolytic activity, resulting in the generation of substantial amounts of lactate to maintain the energy demand for neurons and Other brain cells. Lactate has garnered increasing attention in recent years because of its emerging role in critical biological processes such as inflammation regulation and neuroprotection, particularly through its histone lactylation. Bromodomain-containing protein 4 (BRD4) plays a crucial role in maintaining neural development and promoting memory formation in the central nervous system. Nonetheless, the function and regulatory mechanism of BRD4 and histone lactylation in astrocytes following SAH remain elusive. Our findings indicate that BRD4, a crucial epigenetic regulator, plays a definitive role in histone lactylation. Both in vitro and in vivo, these results demonstrated that targeted silencing of BRD4 in astrocytes can significantly reduce H4K8la lactylation, thereby aggravating the A1 polarization of astrocytes and ultimately affecting the recovery of neural function and prognosis in mice after SAH. In summary, BRD4 plays a pivotal role in modulating astrocyte polarization following SAH via histone lactylation. Targeting this mechanism might offer an efficient therapeutic strategy for SAH.

Keywords

Astrocytic polarization; Bromodomain-containing protein 4; Histone lactylation; Subarachnoid hemorrhage.

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