Elucidation of the pathology of mental disorders focusing on polyunsaturated fatty acids and FABPs

Abstract

Polyunsaturated fatty acids (PUFAs) are essential for brain development and function, and an imbalance of brain PUFAs is linked to mental disorders like autism and schizophrenia. However, the cellular and molecular mechanisms underlying the effects of PUFAs on the brain remain largely unknown. Since they are insoluble in water, specific transporters like fatty acid binding proteins (FABPs), are required for transport and function of PUFAs within cells. We focused on the relationship between FABP-mediated homeostasis of brain PUFAs and neural plasticity. We found that FABP3, with a high affinity for n-6 PUFAs, is predominantly expressed in the GABAergic inhibitory interneurons of the anterior cingulate cortex (ACC) in the adult mouse brain. FABP3 knockout (KO) mice show increased GABA synthesis and inhibitory synaptic transmission in the ACC. We also found that FABP7 controls lipid raft function in astrocytes, and astrocytes lacking FABP7 exhibit changes in response to external stimuli. Furthermore, in FABP7 KO mice, dendritic protrusion formation in pyramidal neurons becomes abnormal, and we have reported a decrease in spine density and excitatory synaptic transmission. Here, we introduced recent advances in the understanding of the functions of PUFAs and FABPs in the brain, focusing especially on FABP3 and FABP7, in relation to human mental disorders.