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One generation of n-3 polyunsaturated fatty acid deprivation increases depression and aggression test scores in rats
James C DeMar1, Kiazong Ma, Jane M Bell
1Brain Physiology and Metabolism Section, National Institute on Aging, and Child Psychiatry Branch, National Institutes of Health Bethesda, MD, 20892, USA.
Insights
A diet lacking omega-3 fatty acids (n-3 PUFAs) in male rats altered brain lipid composition, increasing depression and aggression. This highlights the role of n-3 PUFAs in brain health and behavior.
Area of Science:
- Neuroscience
- Nutritional Science
- Biochemistry
Background:
- Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are crucial for brain function.
- Disruptions in n-3 PUFA metabolism are implicated in various neurological and psychiatric disorders.
Purpose of the Study:
- To investigate the effects of n-3 PUFA deficiency on brain lipid composition and behavior in a rat model.
- To establish a single-generational n-3 PUFA-deprived rat model for studying brain PUFA metabolism.
Main Methods:
- Male rat pups were fed diets deficient or adequate in n-3 PUFAs for 15 weeks.
- Behavioral tests assessed locomotor activity, depression, and aggression.
- Brain lipid composition was analyzed post-behavioral testing.
Main Results:
- N-3 PUFA-deprived rats showed reduced docosahexaenoic acid (22:6n-3) and increased docosapentaenoic acid (22:5n-6) in brain phospholipids.
- Depression scores (forced-swim test) and aggression scores (resident-intruder test) were significantly higher in n-3 PUFA-deprived rats.
- Locomotor activity (open-field test) did not differ significantly between groups.
Conclusions:
- Single-generational n-3 PUFA deprivation significantly alters brain lipid composition and induces depression-like and aggression-like behaviors in rats.
- This rat model may be valuable for understanding the contribution of disturbed brain PUFA metabolism to human mood and behavioral disorders.
- Findings underscore the importance of adequate n-3 PUFA intake for maintaining brain health and normal behavior.
Abstract:
Male rat pups at weaning (21 days of age) were subjected to a diet deficient or adequate in n-3 polyunsaturated fatty acids (n-3 PUFAs) for 15 weeks. Performance on tests of locomotor activity, depression, and aggression was measured in that order during the ensuing 3 weeks, after which brain lipid composition was determined. In the n-3 PUFA-deprived rats, compared with n-3 PUFA-adequate rats, docosahexaenoic acid (22:6n-3) in brain phospholipid was reduced by 36% and docosapentaenoic acid (22:5n-6) was elevated by 90%, whereas brain phospholipid concentrations were unchanged. N-3 PUFA-deprived rats had a significantly increased (P = 0.03) score on the Porsolt forced-swim test for depression, and increased blocking time (P = 0.03) and blocking number (P = 0.04) scores (uncorrected for multiple comparisons) on the isolation-induced resident-intruder test for aggression. Large effect sizes (d > 0.8) were found on the depression score and on the blocking time score of the aggression test. Scores on the open-field test for locomotor activity did not differ significantly between groups, and had only small to medium effect sizes. This single-generational n-3 PUFA-deprived rat model, which demonstrated significant changes in brain lipid composition and in test scores for depression and aggression, may be useful for elucidating the contribution of disturbed brain PUFA metabolism to human depression, aggression, and bipolar disorder.
