Developmental regulation of BDNF and NT-3 expression by quinolinic acid in the striatum and its main connections.

:Interactions between neurotrophic factors and neurotransmitters participate in the formation and maintenance of appropriate connections, as well as in neurodegenerative processes. Here we have measured changes in the developmental expression pattern of BDNF and NT-3 in the striatum, cortex, and substantia nigra induced by intrastriatal injection of the N-methyl-d-aspartate glutamate receptor agonist quinolinic acid (QUIN). Animals were injected at different postnatal ages, and BDNF and NT-3 mRNA levels were determined 6 h after lesion using a ribonuclease protection assay. Our results show a biphasic increase in BDNF mRNA levels in striatum and in the ipsilateral cortex at postnatal day (P)5 and P21. In contrast, although NT-3 expression did not change in the striatum, it was down-regulated in the ipsilateral cortex at P5 and P30. Intrastriatal QUIN injection did not induce changes in either BDNF or NT-3 expression in the ipsilateral substantia nigra. These findings show that neurotrophin expression is developmentally regulated after excitotoxic injury, which suggests that this endogenous response may be involved in different neuronal maturation and vulnerability during development.

Checa N ，Canals JM ，Alberch J 《EXPERIMENTAL NEUROLOGY》

TrkB and TrkC are differentially regulated by excitotoxicity during development of the basal ganglia.

During development neurons are protected against various insults by intrinsic properties. Here we evaluate trkB (both full-length and truncated forms) and trkC expression in the striatum, cortex, and substantia nigra after intrastriatal injection of quinolinic acid (QUIN) at different stages of postnatal (P) development, by RNase protection assay and in situ hybridization. During normal development, a region-specific regulation of trkB and trkC was observed, showing the maximal mRNA levels at P5. Excitotoxic lesion did not modify striatal trkB mRNA levels at any age examined. However, trkC decreased after QUIN injection at P5 in the striatum (52 +/- 2% of control levels). On the other hand, regulation of trkB and trkC expression was observed in cortex and substantia nigra after striatal excitotoxic lesion. Both full-length and truncated receptor isoforms of trkB were enhanced in the cortex when striatal injury was produced at P21 (268 +/- 38 and 206 +/- 35%) or P30 (174 +/- 35 and 157 +/- 13%). In situ hybridization studies localized this increase in trkB expression in layers II/III and V along the cerebral cortex. Within the substantia nigra, striatal excitotoxicity at P5 selectively decreased the truncated form of trkB (70 +/- 7%), whereas the full-length form was up-regulated at P30 (130 +/- 2%). A biphasic increase in trkC mRNA levels was observed at P5 (151 +/- 3%) and P21 (168 +/- 4%). These changes were localized in the substantia nigra pars compacta. Triple-labeling studies disclosed that all these changes were mainly located in neurons. These results demonstrate that the endogenous response to excitotoxicity includes transneuronal regulation of neurotrophin receptors, which is specific for each nucleus and depends on the developmental stage.

Checa N ，Canals JM ，Gratacòs E ，Alberch J ... -  《-》

Divergent regulatory mechanisms governing BDNF mRNA expression in cerebral cortex and substantia nigra in response to striatal target ablation.

Rite I ，Machado A ，Cano J ，Venero JL ... -  《EXPERIMENTAL NEUROLOGY》

Mice heterozygous for neurotrophin-3 display enhanced vulnerability to excitotoxicity in the striatum through increased expression of N-methyl-D-aspartate receptors.

Torres-Peraza J ，Pezzi S ，Canals JM ，Gavaldà N ，García-Martínez JM ，Pérez-Navarro E ，Alberch J ... -  《NEUROSCIENCE》

Differential regulation of the expression of nerve growth factor, brain-derived neurotrophic factor, and neurotrophin-3 after excitotoxicity in a rat model of Huntington's disease.

Canals JM ，Marco S ，Checa N ，Michels A ，Pérez-Navarro E ，Arenas E ，Alberch J ... -  《-》