2. Academic Validation
  3. Nervonic acid protects against oligodendrocytes injury following chronic cerebral hypoperfusion in mice

Nervonic acid protects against oligodendrocytes injury following chronic cerebral hypoperfusion in mice

  • Eur J Pharmacol. 2024 Nov 5:982:176932. doi: 10.1016/j.ejphar.2024.176932.
Wanqing Zheng 1,  Genghua Xu 1,  Zhengwei Lue 2,  Xinyu Zhou 1,  Ning Wang 2,  Yun Ma 2,  Wenyue Yuan 2,  Lushan Yu 3,  Danyan Zhu 4,  Xiangnan Zhang 5
Affiliations

Affiliations

  • 1 Institute of Pharmacology & Toxicology, State Key Laboratory of Advanced Drug Delivery and Release Systems, College of Pharmaceutical Sciences, Zhejiang University, 310058, Hangzhou, China.
  • 2 Jinhua Institute of Zhejiang University, 321299, Jinhua, China.
  • 3 Institute of Drug Metabolism and Pharmaceutical Analysis, State Key Laboratory of Advanced Drug Delivery and Release Systems, College of Pharmaceutical Sciences, Zhejiang University, 310058, Hangzhou, China; Jinhua Institute of Zhejiang University, 321299, Jinhua, China.
  • 4 Institute of Pharmacology & Toxicology, State Key Laboratory of Advanced Drug Delivery and Release Systems, College of Pharmaceutical Sciences, Zhejiang University, 310058, Hangzhou, China. Electronic address: zdyzxb@zju.edu.cn.
  • 5 Institute of Pharmacology & Toxicology, State Key Laboratory of Advanced Drug Delivery and Release Systems, College of Pharmaceutical Sciences, Zhejiang University, 310058, Hangzhou, China; Institute of Drug Metabolism and Pharmaceutical Analysis, State Key Laboratory of Advanced Drug Delivery and Release Systems, College of Pharmaceutical Sciences, Zhejiang University, 310058, Hangzhou, China. Electronic address: xiangnan_zhang@zju.edu.cn.
PMID: 39182543 DOI: 10.1016/j.ejphar.2024.176932
Abstract

Chronic cerebral hypoperfusion (CCH) has been acknowledged as a potential contributor to cognitive dysfunction and brain injury, causing progressive demyelination of white matter, oligodendrocytes Apoptosis and microglia activation. Nervonic acid (NA), a naturally occurring fatty acid with various pharmacological effects, has been found to alleviate neurodegeneration. Nonetheless, evidence is still lacking on whether NA can protect against neurological dysfunction resulting from CCH. To induce CCH in mice, we employed the right unilateral common carotid artery occlusion (rUCCAO) method, followed by oral administration of NA daily for 28 days after the onset of hypoperfusion. We found that NA ameliorated cognitive function, as evidenced by improved performance of NA-treated mice in both novel object recognition test and Morris water maze test. Moreover, NA mitigated demyelination and loss of oligodendrocytes in the corpus callosum and hippocampus of rUCCAO-treated mice, and prevented oligodendrocyte Apoptosis. Furthermore, NA protected primary cultured murine oligodendrocytes against oxygen-glucose deprivation (OGD)-induced cell death in a concentration-dependent manner. These findings indicated that NA promotes oligodendrocyte maturation both in vivo and in vitro. Our findings suggest that NA offers protective effects against cerebral hypoperfusion, highlighting its potential as a promising treatment for CCH and related neurological disorders.

Keywords

Apoptosis; Chronic cerebral hypoperfusion; Nervonic acid; Oligodendrocyte; White matter injury.

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