c9, t11-Conjugated Linoleic Acid Supplementation Improves Cognitive Memory in ω-3 Polyunsaturated Fatty Acid-Deficient Mice

Abstract

Long-chain polyunsaturated fatty acids (LC-PUFAs) are vital for brain health, with cis9, tran11-conjugated linoleic acid (c9, t11-CLA) showing neuroprotective effects. This study investigated the impact of gut microbiota-converted c9, t11-CLA on offspring cognitive development in an ω-3 PUFA deficiency model. c9, t11-CLA supplementation during gestation and lactation increased offspring body weight by 8% and improved cognitive functions, as evidenced by a 63% increase in novel object recognition time and reduced Morris water maze latency. c9, t11-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). Additionally, it enhances synaptic plasticity by activating the PTEN/AKT signaling pathway and regulating dendritic spine remodeling, as well as the transport of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) through proteins such as PAK3, Rab11FIP2 and CPT1C. Elevated levels of GluA4 in the hippocampus further facilitated long-term potentiation (LTP). These findings highlight c9, t11-CLA’s potential as a nutritional intervention for neurodevelopment.