Key Points
Neurological disorders, including memory loss, cognitive impairment, late-life depression, and dementia, have been attributed to aging. The inflammation provoked by D-galactose (D-gal)-induced oxidation is regarded to play a central role in the brain host defenses involved in neuronal loss and behavioral deficits (i.e., anxiety, depression, and memory defects). Evidence has shown the ameliorative effects of n-3 PUFAs on memory defects and cognitive impairment and the neuroprotective activities of n-3 PUFAs against neurodegenerative disorders. Both a high glucose level and tissue-accumulated D-gal react with the amino groups in proteins to form advanced glycation end-products (AGEs). The binding of AGEs to the receptor for AGEs (RAGE) is linked to aging, neuroinflammation, and neurodegenerative diseases, such as cognitive impairment. In this study, the effects of high dietary intake of n-3 PUFAs on cognition and depressive-like behavior in an accelerated senescence rat model with prediabetes was assessed. The potential mechanism underlying D-gal-induced oxidative stress in animal models to mimic natural aging was studied. The MWM test is one of the primary methods used to evaluate D-gal-induced cognitive impairment in test animals. D-Gal-treated murine animals had poor cognitive ability, and D-gal-treated rats developed pre-DM status. In this study, the time of escape latency was significantly shorter in the n-3 PUFA-treated groups, especially in the flaxseed oil group. In the present study, the results of the MWM behavior test and levels of TNF-α indicated that high dietary intake of n-3 PUFAs exerted two effects, reducing the levels of brain RAGE and plasma TNF-α and attenuating the abnormal metabolic characteristics in the D-gal-treated aging rats. The data suggest that fish and flaxseed oils exerted a protective effect on cognitive impairment and reduced incidence of depressive-like behavior in D-gal- and sucrose-induced prediabetic aging rats. n-3 PUFA-rich oil diets, especially a fish-oil rich diet, reduced the plasma levels of NEFAs, TNF-α, and brain dopamine and RAGE expression but not glycemic status, improving the time of escape latency and time spent in the target quadrant in the MWM test. The increased intake of n-3 PUFAs, particularly ALA and EPA, may contribute to the production of eicosanoids with lower inflammatory potential than that of AA analogs. The reduced n-6/n-3 fatty acid ratio in the brain may affect the chronic inflammatory status (i.e. TNF-α) of the neurodegeneration process.
ABSTRACT
Nutritional deficit of n-3 polyunsaturated fatty acids (PUFAs) is closely related to cognitive impairment and depression in later life. Cognitive impairment and depression lead to comorbidities, such as metabolic syndrome, in elderly people. The aim of this study is to evaluate the effects of dietary n-3 PUFAs on cognition and depressive-like behavior in an accelerated senescence rat model with prediabetic status. Rats were cotreated with d-gal and sucrose solution for 7 months and then fed fish-oil- or flaxseed-oil-rich diets for 3 months. Cognitive impairment analysis and depressive-like behavioral testing were conducted using the Morris water maze (MWM) test and forced swimming test (FST), respectively. The MWM test results revealed that the d-gal + sucrose + flaxseed oil (DSFS) group had a significantly shorter mean latency time in the short-term spatial memory trial on day 2 than did the d-gal + sucrose + fish oil (DSFO) group. The FST results demonstrated that the DSFO group exhibited a significantly shorter immobility time and longer climbing time than did the control group. Western blot analysis of the receptor for advanced glycation end-product (RAGE) level identified a significant difference in the DSFO group compared with the control group. Significantly lower n-6/n-3 PUFA ratios were observed in the frontal cortices of the DSFO and DSFS groups. In conclusion, fish and flaxseed oils exerted a protective effect on cognitive impairment and decreased the incidence of depressive-like behavior in d-gal- and sucrose-fed prediabetic aging rats. n-3 PUFA-rich oil diets, particularly the fish oil diet, reduced the plasma levels of nonesterified fatty acids, tumor necrosis factor-α, and brain dopamine and RAGE expression but not glycemic status, resulting in an improvement in the time of escape latency and the time spent in the target quadrant in the MWM test.
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