Activation of nucleotide-binding oligomerization domain-containing protein 1 by diaminopimelic acid contributes to cerebral ischemia-induced cognitive impairment

• Published in: Neuroscience letters Vol. 743; p. 135547
• Main Authors: Liu, Yang, Guo, Ying
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 19.01.2021
• Subjects: Animals; Autophagy; Brain Ischemia - chemically induced; Brain Ischemia - metabolism; Brain Ischemia - pathology; Cerebral ischemia-reperfusion; Cognitive Dysfunction - chemically induced; Cognitive Dysfunction - metabolism; Cognitive Dysfunction - pathology; DAP; Diaminopimelic Acid - toxicity; Infarction, Middle Cerebral Artery - metabolism; Infarction, Middle Cerebral Artery - pathology; Inflammation; Maze Learning - drug effects; Maze Learning - physiology; Mice; Mice, Inbred C57BL; NOD1; Nod1 Signaling Adaptor Protein - metabolism; Random Allocation; DAP; NOD1; Inflammation; Autophagy; Cerebral ischemia-reperfusion
• ISSN: 0304-3940; 1872-7972; 1872-7972
• DOI: 10.1016/j.neulet.2020.135547

•NOD1 was substantially upregulated in the hippocampus of MCAO mice.•NOD1 is involved in cerebral I/R injury suggesting that NOD1.•The NOD1 receptor, treatment resulted in significantly enhanced proinflammatory cytokine production. Cerebral ischemia-reperfusion (I/R)-induced brain tissue injury is a major obstacle for acute stroke management. Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) is reported to play a critical role in the regulation of myocardial or hepatic I/R injury. However, its role in cerebral I/R remains elusive. The mouse model of middle cerebral artery occlusion (MCAO) was applied in the study. The cerebral I/R mice were received either PBS or diaminopimelic acid (DAP)-pretreatment. All sham, MCAO, and MCAO + DAP mice were subject to the neurological behavior tests. The proinflammatory cytokines and autophagy-related proteins were determined by ELISA, RT-qPCR, and Western blot analysis, respectively. We found that NOD1 was substantially upregulated in the hippocampus of MCAO mice. DAP treatment significantly enhanced proinflammatory cytokine production and autophagy-related protein expression, leading to enlarged cerebral infarction size and poor neurological performance in MCAO + DAP mice compared to MCAO mice. We concluded that activation of NOD1 promotes cerebral I/R injury suggesting that NOD1 may serve as a promising target for alleviating the adverse effects of cerebral I/R.