Resumo

The development of sensory systems occurs during a critical period when extensive axonal elimination and plasticity are involved in the fine organization of topographical maps. Essential fatty acids (EFAs) appear as precursors of signaling molecules including retrograde messengers which are involved in modulation of gene expression and regulation of neurotransmitter synthesis and release. α-Linolenic (ω-3) are considered EFAs, since the dietary intake is the only source available. These acids are precursors of long chain polyunsaturated fatty acids (LCPUFA) like docosahexaenoic acid (DHA), which are highly accumulated during fetal period and neonatal development in the brain and retina. In the present study, we tested the effect of DHA nutritional restriction in the structure of retinal terminal fields in the rodent superior colliculus (SC). We also tested DHA deprivation on the expression of AMPA receptor subunits GluR1 and GluR2 and in phosphorylated form of GAP-43 protein (pGAP43). Female Lister Hooded rats were fed (30g/day/animal) during 5 weeks before mating with either control (soy oil) or restricted (coconut oil) diets. After birth, litters were fed until postnatal day 13 (PND13), PND28 or PND 42 when they received an intraocular injection of anterograde neuronal tracer (HRP). Another group received a single retinal lesion at the temporal periphery at PND 21. Western blot tests were used to determine the protein content of GLUR1, GLUR2 and pGAP43 in the visual layers of the SC. DHA restriction produced a significant increase in the optical density in the superficial layers of the superior colliculus, as a result of axonal sprouting outside the main terminal zones. Increased optical density was observed in the intermediate and ventral aspects of the stratum griseum superficiale (SGS) at PND13. The same results were seen outside critical period (PND28 and PND42), suggesting a permanent disturbance in axonal connectivity. After a contralateral retinal lesion at PND21, the DHA restricted group displayed increased sprouting of intact axons at the lesion site as well as at loci uncorrelated to the denervation territories as compared to the control group. Moreover, DHA restriction decreased pGAP-43 expression and increased GluR1 and GluR2 subunits expression of the glutamate AMPA receptor. The data indicate that nutritional restriction of DHA during development induces a disruption in the topographical map organization and abnormal plasticity of retinotectal axons after the closure of the critical period. This effect was correlated to increased turnover/expression in AMPA receptors and decreased pGAP43 protein and is consistent with a role for EFAs as precursors of stabilizing synaptic agents in the developing and adult visual system.