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  3. Peroxisome proliferator-activated receptor-γ ameliorates neuronal ferroptosis after traumatic brain injury in mice by inhibiting cyclooxygenase-2

Peroxisome proliferator-activated receptor-γ ameliorates neuronal ferroptosis after traumatic brain injury in mice by inhibiting cyclooxygenase-2

  • Exp Neurol. 2022 Aug;354:114100. doi: 10.1016/j.expneurol.2022.114100.
Hui Liang 1,  Ting Tang 1,  Hanyu Huang 2,  Tao Li 2,  Chaochao Gao 2,  Yanling Han 3,  Bin Yuan 2,  Shengqing Gao 1,  Handong Wang 4,  Meng-Liang Zhou 5
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, PR China.
  • 2 Department of Neurosurgery, Affiliated Jinling Hospital, Nanjing Medical University, Nanjing, PR China.
  • 3 Department of Neurosurgery, Jinling Hospital, Nanjing, PR China.
  • 4 Department of Neurosurgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, PR China. Electronic address: njhdwang@hotmail.com.
  • 5 Department of Neurosurgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, PR China. Electronic address: mengliangzhou@yahoo.com.
PMID: 35490721 DOI: 10.1016/j.expneurol.2022.114100
Abstract

Among the multiple kinds of neuronal cell death triggered by traumatic brain injury (TBI), Ferroptosis, an iron-dependent lipid peroxidative regulatory cell death, has a critical role. Peroxisome proliferator-activated receptor-γ (PPARγ) is a nuclear transcription factor that regulates lipid metabolism and suppresses neuronal inflammation. However, the role of PPARγ in neuronal Ferroptosis induced by TBI remains unclear. Here, we investigated the regulatory effect of PPARγ on neuronal Ferroptosis in a weight-drop TBI model in vivo and an RAS-selective lethal 3 (RSL3)-activated ferroptotic neuronal model in vitro. PPARγ was mainly localized in the nucleus of neurons and was decreased in both the in vivo TBI model and the in vitro ferroptotic neuronal model. The addition of a specific agonist, pioglitazone, activated PPARγ, which protected neuronal function post-TBI in vivo and increased the viability of ferroptotic neurons in vitro. Further investigation suggested that PPARγ probably attenuates neuronal Ferroptosis by downregulating cyclooxygenase-2 (COX2) protein expression levels in vivo and in vitro. This study revealed the relationship among PPARγ, Ferroptosis and TBI and identified a potential target for comprehensive TBI treatment.

Keywords

COX2; Ferroptosis; Neurons; PPARγ; Traumatic brain injury.

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