RESUMO
Retinocollicular connections form precise topographical maps that are normally completed through the selective elimination of misplaced axons and the stabilization of topographically ordered axon terminals during early development. Omega-3 fatty acids, acquired exclusively through the diet, and its main metabolite, docosahexaenoic acid (DHA), are involved in brain development and synaptic maturation. We have previously shown that the nutritional restriction of omega-3/DHA results in abnormal retinocollicular topographical fine-tuning. Therefore, we studied the role of omega-3 fatty acids nutritional supplementation and the developmental time windows during which this postnatal supplementation would restore normal topographical maps in the visual system. Female rats and their litters were chronically fed with either control (soy oil) or restricted omega-3 (coconut oil) diets. Fish oil supplementation was introduced between either postnatal day (PND) 7-13, PND7-28 or PND21-42. At PND13, PND28 or PND42, animals received an anterograde eye injection of a neuronal tracer to visualize retinocollicular axons. Confirming previous observations we found that an omega-3/DHA deficiency resulted in an abnormally high innervation density of retinal axons at the visual layers of the superior colliculus (SC). Although a short-term fish oil supplementation between PND7-13 could not restore normal retinocollicular topography, an extended treatment between PND7-28 completely recovered normal innervation densities of retinotectal axons. However, a late onset supplementation protocol, between PND28-42, was no longer effective in the restoration of the abnormal topographical pattern induced by an early omega-3 nutritional malnutrition. The results suggest a critical period for omega3/DHA dietary intake for the proper development of visual topographical maps.
Assuntos
Ácidos Graxos Ômega-3/administração & dosagem , Retina/crescimento & desenvolvimento , Colículos Superiores/crescimento & desenvolvimento , Vias Visuais/crescimento & desenvolvimento , Animais , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/administração & dosagem , Feminino , Ratos , Retina/citologia , Colículos Superiores/citologia , Fatores de TempoRESUMO
Adenosine is a neuromodulator implicated in nervous system development and plasticity and its effects are mediated by inhibitory (A(1), A(3)) and excitatory (A(2a), A(2b)) receptors. The role of adenosine in the synaptic activity depends mainly on a balanced activation of A(1) and A(2a) receptors which are activated by various ranges of adenosine concentrations. Herein, we investigated the expression of A(1) and A(2a) receptors and also the accumulation of cAMP in the superior colliculus at different stages of development. Furthermore, we examined the effects of an acute in vivo blockade of adenosine deaminase during the critical period when the elimination of misplaced axons/terminals takes place with a simultaneous fine tuning of terminal arbors into appropriate terminal zones. Lister Hooded rats ranging from postnatal days (PND) 0-70 were used for ontogeny studies. Our results indicate that A(1) expression in the visual layers of the superior colliculus is higher until PND 28, while A(2a) expression increases after PND 28 in a complementary developmental pattern. Accordingly, the incubation of collicular slices with 5'-N-ethylcarboxamido-adenosine, a non-specific adenosine receptor agonist, showed a significant reduction in cAMP accumulation at PND 14 and an increase in adults. For the anatomical studies, the uncrossed retinotectal projections were traced after the intraocular injection of horseradish peroxidase. One group received daily injections of an adenosine deaminase inhibitor (erythro-9(2-hydroxy-3-nonyl adenine), 10 mg/kg i.p.) between PND 10 and 13, while control groups were treated with vehicle injections (NaCl 0.9%, i.p.). We found that a short-term blockade of adenosine deaminase during the second postnatal week induced an expansion of retinotectal terminal fields in the rostrocaudal axis of the tectum. Taken together, the results suggest that a balance of purinergic A(1) and A(2a) receptors through cAMP signaling plays a pivotal role during the development of topographic order in the retinotectal pathway.