<i>c</i> 9, <i>t</i> 11-Conjugated linoleic acid supplementation improves cognitive memory in ω-3 polyunsaturated fatty acid-deficient mice

Long-chain polyunsaturated fatty acids (LC-PUFAs) are vital for brain health, with <i>cis</i>9, <i>trans</i>11-conjugated linoleic acid (<i>c</i>9, <i>t</i>11-CLA) showing neuroprotective effects. This study investigated the impact of <i>c</i>9, <i>t</i>11-CLA on offspring cognitive development in an ω-3 PUFA deficiency model. <i>c</i>9, <i>t</i>11-CLA supplementation during gestation and lactation improved episodic-like memory and learning ability, as evidenced by a 63% increase in novel object recognition time and reduced Morris water maze latency. <i>c</i>9, <i>t</i>11-CLA altered brain lipid profiles and promoted myelination in the prefrontal cortex of pubescent offspring mice by upregulating the protein levels of myelin-associated glycoprotein (MAG) and platelet-derived growth factor receptor alpha (PDGFRα). In addition, although proteomic KEGG analysis and western blotting verified that <i>c</i>9, <i>t</i>11-CLA supplementation appears to modulate the PTEN/AKT signaling pathway in the hippocampus, its relationship with synaptic plasticity remains speculative. Western blot validation further revealed that <i>c</i>9, <i>t</i>11-CLA supplementation enhanced α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) activation and trafficking through increased phosphorylation of Ca/calmodulin-dependent protein kinase II alpha (CaMKIIα) at Thr286, ultimately strengthening synaptic plasticity as evidenced by significant upregulation of postsynaptic density protein 95 (PSD95), p-CaMKIIα/CaMKIIα, and glutamate ionotropic receptor AMPA type subunit 1 (GluA1). These findings highlight the potential of <i>c</i>9, <i>t</i>11-CLA as a nutritional intervention for neurodevelopment and provide preliminary insights into the mechanisms by which <i>c</i>9, <i>t</i>11-CLA supplementation may regulate cognitive function.