Diminished levels of docosahexaenoic acid (DHA, 22:6n-3), the major polyunsaturated fatty acid (FA) synthesized from alpha linolenic acid (ALA, 18:3n-3), have been implicated in changes in neurotransmitter production, ion channels disruption and impairments of a variety of cognitive, behavioural and motor functions in the developing and the adult mammal. We studied neuronal migration in the cortex and hippocampus of newborn and postnatal rats after ALA-deficiency, beginning on the 2nd day after conception and continuing for three weeks after birth. A marked decrease in the migration of bromodeoxyuridine(+)/NeuN(+)/Neurofilament(+) and glia fibrilary acidic protein(-) neuronal cells to the dense cortical plate was accompanied by a corresponding abundance of non-migrating cells in several regions such as cortical layers IV-VI, corpus callosum and the sub-ventricular zone of ALA-deficient newborn. Similarly, a delayed migration of cells to CA1 and dentate gyrus areas was noticed while most cells were retained in the subicular area adjacent to the hippocampus. The delay in migration was transient most likely due to a temporary reelin disorganization.
In addition to these changes a drastic reduction in tyrosine hydroxylase (TH) and vesicular monoamine transporter-2 (VMAT-2) levels, both of which are prerequisites for appropriate synthesis and transport of DA were noticed by RNA subtractive hybridization and proteomic techniques. Concomitantly, a large increase in DA receptors DAR1 and DAR2 were noticed. The transient impairment induced by ALA deprivation may compromise the organization of neuronal assemblies and result in aberrant neuronal connectivity (lateral connections) to enhance the risk of neurodevelopmental disorders including cerebral palsy.
