Impact of fatty acids on glutamate-related gene expression in the hippocampus: Focus on lauric acid

Excessive dietary fat consumption has been linked to impairments in synaptic plasticity in the hippocampus (HIP), a brain region crucial for learning and memory that relies on balanced glutamatergic neurotransmission. This study investigates the acute effects of three fatty acids (FAs)—lauric acid (LA), palmitic acid (PA), and oleic acid (OA)—on glutamate (GLU)-related gene expression in the HIP of male and female young mice. Hippocampal slices were treated with FAs, and mRNA levels of genes involved in GLU transport, GLU-glutamine (GLN) cycling, and GLU receptor subunit encoding were quantified using RT-PCR. FA treatment reduced mRNA levels of enzymes involved in the conversion of GLU to GLN (glutamine synthetase; GS), GABA (glutamate decarboxylase 1; GAD67), and α-ketoglutarate (glutamate pyruvate transaminase 2; AAT2). Additionally, the expression of glutamine transporters (SNAT1, SNAT2, SNAT3), the astrocytic GLU transporter GLT-1, and the NMDA receptor subunit NMDA2a was also reduced. These effects were most pronounced with LA. Notably, while the HIP showed similar sensitivity to fatty acids across sexes, overall gene expression levels were lower in females. These findings highlight the acute susceptibility of hippocampal GLU-related pathways to FA exposure, particularly LA, suggesting potential risks of high-LA diets on cognitive function. Further research is needed to explore the long-term consequences of dietary fat on hippocampal health and its sex-specific effects.