Post-weaning DHA or EPA supplementation attenuates depressive-like behavior and myelination deficits induced by maternal high-fat diet in rat offspring

Depression affects younger populations, while imbalanced diet may contribute to disease development, with myelin abnormalities representing one possible underlying mechanism. We previously showed that maternal high-fat diet (HFD; 60% energy from fat) during pregnancy and lactation induces depressive-like behavior and myelin-related alterations in the prefrontal cortex (PFC) of rat offspring. We investigated whether post-weaning docosahexaenoic acid (DHA)- or eicosapentaenoic acid (EPA)-enriched diets until adulthood could reverse these abnormalities.

Depressive-like behavior was assessed in the forced swimming test (FST), while myelin-related changes were analyzed using RT-qPCR, ELISA, and immunofluorescence staining. Both DHA and EPA-enriched diets normalized increased immobility time in adult offspring. In male offspring, both diets normalized the mRNA levels of genes encoding myelin-oligodendrocyte glycoprotein (MOG), 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase), and transferrin, whereas only additionally restored the mRNA levels of genes encoding myelin and lymphocyte protein (MAL) and kallikrein 6 (KLK6).

At the protein level, DHA normalized only MOG, while restored MOG, MAL, and CNPase levels. In females, both DHA and increased Mog mRNA levels, whereas DHA additionally increased Klk6 mRNA expression compared to offspring exposed to maternal HFD and post-weaning SD. At the cellular level, DHA and produced sex-specific effects, with broader restoration of oligodendrocytes and myelin intensity in males.

Maternal HFD also decreased brain-derived neurotrophic factor (BDNF) levels in male offspring (mRNA and protein level), while post-weaning DHA and supplementation restored Bdnf mRNA expression. Overall, post-weaning DHA and alleviated maternal HFD-induced FST-assessed depressive-like behavior and partially restored myelin-related abnormalities in the PFC, with exerting broader molecular and cellular effects than DHA. We thank Renata Pieniążek for her technical assistance.

The research was carried out with the use of the CEPHARES IP PAS infrastructure, co-financed by the European Union—the European Regional Development Fund under Measure 4.2 of the Smart Growth Operational Programme 2014-2020. This study was supported by the research grant UMO-2020/39/D/NZ5/02581 (SONATA 16) from the National Science Center, Kraków, Poland (to I. Department of Drug Addiction Pharmacology, Maj Institute of Pharmacology Polish Academy of Sciences, 12 Smętna Street, 31-343, Kraków, Poland Maya Śliwa, Małgorzata Frankowska, Joanna Jastrzębska, Małgorzata Filip & Irena Smaga Laboratory of Microscopic Imaging, CEPHARES, Maj Institute of Pharmacology Polish Academy of Sciences, 12 Smętna Street, 31-343, Kraków, Poland The authors declare no competing interests.

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