Omega-3 Supplementation Improves Cortico-Limbic Neuroplasticity and Reduces Amyloid-Related Pathology

Omega-3 polyunsaturated fatty acids (n-3 PUFA) are crucial for brain health and neuroplasticity. n-3 PUFA deficiency is associated with deficits in mood regulation and memory. This study evaluated the effects of chronic n-3 PUFA supplementation on the prefrontal cortex (PFC) and hippocampus (HIPP) in female rats exposed to a lifelong n-3 PUFA–deficient diet.

Female Wistar rats were exposed to either an n-3 PUFA–poor diet (rich in omega-6) or an n-3 PUFA–enriched diet (rich in α-linolenic acid) from conception until 8 weeks. After 9 weeks, n-3 PUFA supplementation was introduced until 16 weeks. At 16 weeks, neurochemical analyses were conducted in the PFC and HIPP, measuring neurotransmitters (5-HT, DA, NA), neurotrophic factors (BDNF, NGF), synaptic markers (SYN, CAMKII), and amyloid-related markers (amyloid oligomers, APP) using HPLC and Western blotting.

Our results showed that n-3 PUFA supplementation reversed most neurochemical alterations induced by the n-3 PUFA–poor diet in both the PFC and HIPP. Reduced levels of 5-HT and DA in both brain regions under the n-3 PUFA–poor diet were restored to control values following supplementation, while increased NA levels were normalized. SYN expression was reduced in both regions under the n-3 PUFA–poor diet and was restored after supplementation. CAMKII expression was also restored in the PFC, whereas no significant changes were observed in the HIPP. BDNF levels were reduced in both the PFC and HIPP under the n-3 PUFA–poor diet and were fully restored following supplementation. NGF levels were similarly restored in the HIPP, and no significant changes were detected in PFC. Amyloid-related markers showed limited recovery and remained elevated compared to control levels.

We concluded that n-3 PUFA supplementation restores neurotransmitter balance, synaptic function, and neurotrophic support, suggesting its therapeutic potential in neurodegenerative disorders. However, the partial reversal of amyloid-related markers indicates that early-life nutritional deficiency may lead to persistent neurodegenerative vulnerability.