Effect of NMDA antagonists on the activity of glutaminase and aspartate aminotransferase in the developing rat cerebellum
Por:
Moran J., Alavez S., Rivera-Gaxiola M., Valencia A., Hurtado S.
Publicada:
1 ene 1999
Resumen:
Chronic treatment of rats from postnatal day 6 to 25 with drugs that interact with the N-methyl-D-aspartate (NMDA) receptor induced a differential effect on the activity of some enzymes involved in neurotransmitter synthesis. Two of these drugs ((5R, 10S)-(+)-5-methyl-10,11-dihydro-5H- dibenzo(a,d)cyclohepten-5,10-imine hydrogen maleate (MK-801) and 3-(2- carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP)) caused a marked reduction (20-40%) of glutaminase and aspartate aminotransferase activity in the cerebellum. These changes were observed only at a very precise time of development (i.e. 10 to 19 postnatal day). The competitive antagonist, amino phosphonovaleric acid (APV), did not affect any of the enzymes studied at all tested ages. When animals were treated with NMDA only a slight, but significant, increase in the activity of glutaminase was observed at 9-11 postnatal day only. Any of the agonists or antagonists tested significantly affected the activity of lactate dehydrogenase as compared to control animals. Histologic observations of cerebella treated with the indicated drugs showed that only MK-801, and CPP to a lesser extent, induced a small reduction in the width of the internal granule layer. The body weight of animals treated with MK-801 was clearly reduced, but only in more mature rats (> 16 postnatal day), when animals did not show any alteration in the enzymes tested. These results support the suggestion that presynaptic influences, particularly from glutamatergic neurons, are critical to promote cerebellar granule neurons differentiation during critical periods of the cerebellar development.
Filiaciones:
Moran J.:
Institute of Cell Physiology, National University of Mexico, Apartado Postal 70-253, 04510 Mexico DF, Mexico
Alavez S.:
Institute of Cell Physiology, National University of Mexico, Apartado Postal 70-253, 04510 Mexico DF, Mexico
Rivera-Gaxiola M.:
Institute of Cell Physiology, National University of Mexico, Apartado Postal 70-253, 04510 Mexico DF, Mexico
Valencia A.:
Institute of Cell Physiology, National University of Mexico, Apartado Postal 70-253, 04510 Mexico DF, Mexico
Hurtado S.:
Institute of Cell Physiology, National University of Mexico, Apartado Postal 70-253, 04510 Mexico DF, Mexico
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