Institute of Pharmacology & Toxicology, 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.
Eur J Pharmacol. 2024 Nov 5;982:176932. doi: 10.1016/j.ejphar.2024.176932. Epub 2024 Aug 23.
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.
慢性脑灌注不足（CCH）被认为是认知功能障碍和脑损伤的潜在原因，可导致白质脱髓鞘、少突胶质细胞凋亡和小胶质细胞激活。神经酸（NA）是一种具有多种药理作用的天然脂肪酸，已被发现可减轻神经退行性变。然而，关于 NA 是否能预防 CCH 引起的神经功能障碍，目前仍缺乏证据。为了在小鼠中诱导 CCH，我们采用了右侧颈总动脉单侧闭塞（rUCCAO）方法，在低灌注发生后每天给予 NA 口服治疗 28 天。我们发现 NA 改善了认知功能，NA 治疗组小鼠在新物体识别试验和 Morris 水迷宫试验中的表现均有所改善。此外，NA 减轻了 rUCCAO 治疗组小鼠胼胝体和海马中的脱髓鞘和少突胶质细胞丢失，并预防了少突胶质细胞凋亡。此外，NA 以浓度依赖的方式保护原代培养的小鼠少突胶质细胞免受氧葡萄糖剥夺（OGD）诱导的细胞死亡。这些发现表明，NA 促进了体内和体外少突胶质细胞的成熟。我们的研究结果表明，NA 对脑灌注不足具有保护作用，突出了其作为治疗 CCH 和相关神经疾病的有前途的治疗方法的潜力。
