Excitotoxic neonatal damage induced by monosodium glutamate reduces several GABAergic markers in the cerebral cortex and hippocampus in adulthood.
Monosodium glutamate (MSG) administered to neonatal rats during the first week of life induces a neurodegenerative process, which is represented by several neurochemical alterations of surviving neurons in the brain, where signalling mediated by GABA is essential for excitation threshold maintenance. GABA-positive cells, [(3)H]-GABA uptake, expression of mRNA for GABA transporters GAT-1 and GAT-3, and expression of mRNA and protein for two main GABA synthesizing enzymes, GAD(65) and GAD(67), were measured at postnatal day 60, after MSG neonatal treatment in two critical cerebral regions, cerebral cortex and hippocampus. GABA-positive cells, [(3)H]-GABA uptake, and mRNA for GAT-1, were significantly diminished in both cerebral regions. In the cerebral cortex, MSG neonatal treatment also decreased the mRNA for GAD(67) and protein for GAD(65) without significant changes in its corresponding protein and mRNA, respectively. Moreover in the hippocampus, mRNA and protein for GAD(65) were increased, whilst GAD(67) protein was elevated without significant changes in its mRNA. Clearly these results confirm the GABA cells loss after MSG neonatal treatment in both cerebral regions. As most of the GABAergic markers measured were reduced in the cerebral cortex, this region seems to be more sensitive than hippocampus, where interesting compensatory changes over GAD(65) and GAD(67) proteins were observed. However, it is possible that others neurotransmission systems are also compensating the GABA-positive cells loss in the cerebral cortex, and that elevations in two main forms of GAD in the hippocampus are not sufficient to maintain the neural excitation threshold for this region.
Ureña-Guerrero
Mónica E
ME
Departamento de Biología Celular y Molecular, CUCBA, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico.
Orozco-Suárez
Sandra
S
López-Pérez
Silvia J
SJ
Flores-Soto
Mario E
ME
Beas-Zárate
Carlos
C
D000818:Animals; D000831:Animals, Newborn; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology; D012970:Sodium Glutamate / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000737:chemistry / Q000378:metabolism*
D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2; D012970:Sodium Glutamate