Neonatal toluene exposure alters glutamate-induced calcium signaling in developing cerebellar granule neurons.
Glutamatergic neurotransmission is critical both for neurogenesis and mature functioning of the central nervous system (CNS), and is thought to be one target for toluene-induced damage. It has been reported that toluene antagonizes the function of N-methyl-D-aspartate (NMDA) receptor. In this study, we examined the effect that neonatal toluene exposure has on NMDA receptor in cerebellar granule neurons. Sprague-Dawley rats were treated with 0, 200, 500, and 1000 mg/kg of toluene by intraperitoneal injection from postnatal day (PN) 4 to 7. After culture under toluene-free condition, Ca2+ signaling in response to glutamate and NMDA was measured using fura-2 Ca2+ imaging for up to 14 days. Toluene exposure dose-dependently reduced glutamate/glycine and NMDA/glycine induced Ca2+ signaling in culture cerebellar granule neurons at DIV5 (day in vitro), and the effects were gradually recovered. The effects of toluene exposure on NMDA-stimulated Ca2+ signals in response to NMDA receptor inhibitors were also compared. The results indicated that neonatal toluene exposure can induce long-term but reversible changes in NMDA-induced Ca2+ signaling pathway. Such changes could be involved in the impairment of CNS function and development observed in fetal solvent syndrome.
Chen
Hwei-Hsien
HH
Institute of Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan.
Wei
Chao-Ting
CT
Chan
Ming-Huan
MH
D000818:Animals; D000831:Animals, Newborn; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects* / Q000254:growth & development; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014050:Toluene / Q000008:administration & dosage*
D014050:Toluene; D018698:Glutamic Acid