Cognitive deficits and changes in gene expression of NMDA receptors after prenatal methylmercury exposure.
Previous studies showed learning and memory deficit in adult rats that were prenatally exposed to methylmercury chloride (MMC) in an advanced stage of pregnancy (15 days). Under these conditions, the cognitive deficits found at 60 days of age paralleled particularly changes in the N-methyl-D-aspartate (NMDA) receptor characteristics. In the present study, we report the behavioral effects of a single oral dose of MMC (8 mg/kg) administered earlier at gestational day 8. The use of different learning and memory tests (passive avoidance, object recognition, water maze) showed a general cognitive impairment in the in utero-exposed rats tested at 60 days of age compared with matched controls. Considering the importance of the glutamatergic receptor system and its endogenous ligands in learning and memory process regulation, we surmised that MMC could affect the gene expression of NMDA receptor subtypes. The use of a sensitive RNase protection assay allowed the evaluation of gene expression of two families of NMDA receptors (NR-1 and NR-2 subtypes). The result obtained in 60-day-old rats prenatally exposed to MMC, showed increased mRNA levels of the NR-2B subunit in the hippocampus but not in the frontal cortex. The data suggest that the behavioral abnormalities of MMC-exposed rats might be ascribed to a neurotoxic effect of the metal that alters the gene expression of a specific NMDA receptor subunit in the hippocampus.
Baraldi
Mario
M
Department of Pharmaceutical Sciences, University of Modena and Reggio Emilia, Via Campi 183, 41100 Modena, Italy. baraldi.mario@unimo.it
Zanoli
Paola
P
Tascedda
Fabio
F
Blom
Joan M C
JM
Brunello
Nicoletta
N
D000818:Animals; D001522:Behavior, Animal; D003072:Cognition Disorders / Q000139:chemically induced*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D006624:Hippocampus / Q000502:physiology; D007858:Learning; D008568:Memory; D008767:Methylmercury Compounds / Q000009:adverse effects* / Q000493:pharmacokinetics; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis / Q000187:drug effects* / Q000502:physiology
D008767:Methylmercury Compounds; D016194:Receptors, N-Methyl-D-Aspartate