Shrimp Oil Enhances Cognition by Suppressing Neuroinflammation in a Chronic Cerebral Hypoperfusion Rat Model

Vascular dementia (VaD) is the second most common age-related condition worldwide in aging populations. Neuroinflammation is a key contributor to the pathological process of VaD. Shrimp oil is a by-product of shrimp processing that is rich in astaxanthin and lipids. This study aimed to investigate the effect of shrimp oil on neuroinflammation and its underlying mechanisms in chronic cerebral hypoperfusion (CCH) rats. Male Wistar rats subjected to bilateral common carotid artery occlusion received oral shrimp oil or piracetam once daily for 5 weeks. Shrimp oil significantly improved muscle coordination and enhanced reference spatial memory. Proteomic profiling showed that shrimp oil mitigated the CCH-induced proteomic signature, specifically reprogramming protein clusters related to neuroinflammation and AMPK-SIRT1 signaling. Western blot analysis indicated that shrimp oil reduced the expression of neuroinflammation-associated proteins, including TLR4 and NF-κB, and suppressed M1 microglial activation, NLRP3 inflammasome activation, and pyroptosis. These effects were accompanied by increased expression of myelination-related proteins, including oligodendrocyte transcription factor 1 (OLIG1) and myelin basic protein (MBP). Inflammation was more likely suppressed by upregulated AMPK and sirtuin-1 (SIRT1) pathway, but not related to PPARγ signaling. These findings suggest that shrimp oil is a promising candidate for the treatment of VaD.