Changes in NMDA-receptor gene expression are associated with neurotoxicity induced neonatally by glutamate in the rat brain.
The N-methyl-D-aspartate receptor (NMDA-R) is fully functional in the rat early in embryogenesis, and diverse neuronal plasticity events are regulated through its activation later in postnatal development. On the other hand, systemic administration of glutamate (Glu) to rats at birth induces neuronal degeneration in glutamatergic central nervous system regions via Glu receptor activation. However, it is not known whether an increase in neonatal Glu levels modifies the gene expression of NMDA-R subunits, or if these putative changes are related to gamma-aminobutyric acid-mediated (GABAergic) neurotransmission. We measured, by means of semi-quantitative reverse transcriptase polymerase chain reaction, changes in gene expression of the NMDA-R subunits: NMDA-R1, NMDA-R 2A and NMDA-R 2B in cerebral cortex (CC), striatum (ST) and hippocampus (HP) in the brains of rats treated neonatally with monosodium L-glutamate (MSG). These studies were supported by histological and quantitative analysis of the glia. Our results showed histological evidence of neuronal damage, and increased glial cell number and activity were detected. This was seen mainly in the ST and HP of MSG-treated animals. Significant increases in NMDA-R1, 2A and 2B subunits gene expression was also observed in ST and HP but not in CC, where only NMDA-R 2B was increased in MSG-treated rats. Our data suggest that increases in Glu levels and activation of Glu-receptors after neonatal administration of MSG induce an increase in glial cell reactivity and important changes in NMDA-R molecular composition, with signs of neuronal damage.
Beas-Zárate
C
C
Lab. de Neuroquimica, Div. Neurociencias, C.I.B.O., IMSS, Depto. de Biol. Cel. y Molec. C.U.C.B.A., U. de G., APDO, Postal No. 4-160, 44421, Jalisco, Guadalajara, Mexico. cbeasruve@infosel.net.mx
Rivera-Huizar
S V
SV
Martinez-Contreras
A
A
Feria-Velasco
A
A
Armendariz-Borunda
J
J
D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D017931:DNA Primers; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018698:Glutamic Acid / Q000633:toxicity*; D007150:Immunohistochemistry; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D005904:Glial Fibrillary Acidic Protein; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid