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Effect of nmda antagonists on the activity ofglutaminase and aspartate aminotransferase in thedeveloping rat cerebellum
Author(s) -
Moran Julio,
Alavez Silvestre,
Riveragaxiola Maritza,
Valencia Antonio,
Hurtado Sandra
Publication year - 1999
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/s0736-5748(98)00063-x
Subject(s) - nmda receptor , cerebellum , glutaminase , glutamatergic , dizocilpine , glutamate receptor , endocrinology , medicine , biology , antagonist , neurotransmitter , agonist , receptor , enzyme , chemistry , central nervous system , biochemistry
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 theactivity of some enzymes involved in neurotransmitter synthesis. Two of these drugs ((5 R ,10 S )‐ (+)‐5‐methyl‐10,11‐dihydro‐5H‐dibenzo (a,d)cyclohepten‐5,10‐iminehydrogen 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 inthe cerebellum. These changes were observed only at a very precise time of development (i.e. 10to 19 postnatal day). The competitive antagonist, amino phosphonovaleric acid (APV), did notaffect any of the enzymes studied at all tested ages. When animals were treated with NMDA onlya slight, but significant, increase in the activity of glutaminase was observed at 9–11 postnatal dayonly. Any of the agonists or antagonists tested significantly affected the activity of lactatedehydrogenase as compared to control animals. Histologic observations of cerebella treated withthe indicated drugs showed that only MK‐801, and CPP to a lesser extent, induced a smallreduction in the width of the internal granule layer. The body weight of animals treated withMK‐801 was clearly reduced, but only in more mature rats (>16 postnatal day), when animals didnot show any alteration in the enzymes tested. These results support the suggestion thatpresynaptic influences, particularly from glutamatergic neurons, are critical to promote cerebellargranule neurons differentiation during critical periods of the cerebellar development.