Nutritional tryptophan restriction impairs plasticity of retinotectal axons during the critical period.
The use-dependent specification of neural circuits occurs during post-natal development with a conspicuous influence of environmental factors, such as malnutrition that interferes with the major steps of brain maturation. Serotonin (5-HT), derived exclusively from the essential aminoacid tryptophan, is involved in mechanisms of development and use-dependent plasticity of the central nervous system. We studied the effects of the nutritional restriction of tryptophan in the plasticity of uncrossed retinotectal axons following a retinal lesion to the contralateral retina during the critical period in pigmented rats. Litters were fed through their mothers with a low tryptophan content diet, based on corn and gelatin, a complemented diet with standard tryptophan requirements for rodents or standard laboratory diet. The results suggest a marked reduction in the plasticity of intact axons into denervated territories in the tryptophan restricted group in comparison to control groups. Tryptophan complementation between PND10-21 completely restored retinotectal plasticity. However, the re-introduction of tryptophan after the end of the critical period (between PND28-P41) did not restore the sprouting ability of uncrossed axons suggesting a time-dependent effect to the reversion of plasticity deficits. Tryptophan-restricted animals showed a reduced activity of matrix metalloproteinase-9 and altered expressions of phosphorylated forms of ERK1/2 and AKT. Our results demonstrate the influence of this essential aminoacid as a modulator of neural plasticity during the critical period through the reduction of serotonin content which alters plasticity-related signaling pathways and matrix degradation.
Penedo
Letícia Abel
LA
Neuroscience Program, Biology Institute, Federal Fluminense University, Brazil, Niterói, RJ, Brazil.
Oliveira-Silva
Priscilla
P
Gonzalez
Ericka M C
EM
Maciel
Rafaela
R
Jurgilas
Patricia B
PB
Melibeu
Adriana da Cunha Faria
Ada C
Campello-Costa
Paula
P
Serfaty
Claudio Alberto
CA
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D006735:Horseradish Peroxidase / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009415:Nerve Net / Q000254:growth & development / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D051058:Oncogene Protein v-akt / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D012160:Retina / Q000187:drug effects / Q000254:growth & development* / Q000293:injuries / Q000378:metabolism; D014364:Tryptophan / Q000008:administration & dosage / Q000172:deficiency*; D014795:Visual Pathways / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism
D014364:Tryptophan; D006735:Horseradish Peroxidase; D051058:Oncogene Protein v-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D020780:Matrix Metalloproteinase 9