2. Academic Validation
  3. Leptin combined with withaferin A boost posthemorrhagic neurogenesis via activation of STAT3/SOCS3 pathway

Leptin combined with withaferin A boost posthemorrhagic neurogenesis via activation of STAT3/SOCS3 pathway

  • Exp Neurol. 2024 Jul:377:114809. doi: 10.1016/j.expneurol.2024.114809.
Dongshan Ya 1,  Wenjing Xiang 1,  Yanlin Jiang 2,  Yingmei Zhang 1,  Zixian Zhou 1,  Xiaoxia Li 1,  Jungang Deng 2,  Meiling Chen 3,  Bin Yang 4,  Xiaohui Lin 5,  Rujia Liao 6
Affiliations

Affiliations

  • 1 Laboratory of Neuroscience, Affiliated Hospital of Guilin Medical University, Guilin Medical University, Guilin 541004, China; Department of Neurology, Affiliated Hospital of Guilin Medical University, Guilin Medical University, Guilin 541004, China.
  • 2 Department of Pharmacology, Affiliated Hospital of Guilin Medical University, Guilin Medical University, Guilin 541004, China.
  • 3 Department of Neurology, Affiliated Hospital of Guilin Medical University, Guilin Medical University, Guilin 541004, China.
  • 4 Guangxi Clinical Research Center for Neurological Diseases, Affiliated Hospital of Guilin Medical University, Guilin Medical University, Guilin 541004, China.
  • 5 Department of Geriatrics, Affiliated Hospital of Guilin Medical University, Guilin Medical University, Guilin 541004, China.
  • 6 Laboratory of Neuroscience, Affiliated Hospital of Guilin Medical University, Guilin Medical University, Guilin 541004, China; Department of Neurology, Affiliated Hospital of Guilin Medical University, Guilin Medical University, Guilin 541004, China. Electronic address: liaorujia@hotmail.com.
PMID: 38714285 DOI: 10.1016/j.expneurol.2024.114809
Abstract

Neurogenesis as a potential strategy to improve the consequences of intracerebral hemorrhage (ICH). The current study investigates the effects of withaferin A (WFA) in combination with Leptin (LEP) on ICH and neurogenesis mechanisms. LEP levels were dramatically reduced on days 7 and 14 following ICH insults in mice, but continuous WFA therapy significantly improved the potency of intrinsic LEP on day 14 after ICH. Furthermore, WFA combined with LEP enhances intrinsic neurogenesis and lessen motor deficits and long-term cognitive outcomes after ICH. In parallel, Leptin deficiency in ob/ob mice limits enhancement of neurogenesis following ICH in response to WFA combined with LEP treatment. Importantly, the functional recovery conferred by WFA combined with LEP after ICH was inhibited by neurogenesis suppression. Mechanistically, this study unveiled that the signal transducer and activator of transcription-3 (STAT3) / suppressor of cytokine signaling-3 (SOCS3) pathway is a critical signaling pathway through which WFA combined with LEP treatment promotes intrinsic neurogenesis after ICH. Collectively, the results of this study elucidate the neuroprotective effects of WFA and LEP in ICH, and highlight a potential approach for ICH cell therapy.

Keywords

Intracerebral hemorrhage; Leptin; Neurogenesis; Neuroprotection; Signal transducer and activator of transcription-3; Withaferin A.

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