title: Neonatal toluene exposure alters glutamate-induced calcium signaling in developing cerebellar granule neurons.
abstract: 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.
authors.affiliation: Institute of Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan.
authors.forename: Hwei-Hsien
authors.initials: HH
authors.lastname: Chen
authors.forename: Chao-Ting
authors.initials: CT
authors.lastname: Wei
authors.forename: Ming-Huan
authors.initials: MH
authors.lastname: Chan
mesh_terms: 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*
chemical_list: D014050:Toluene; D018698:Glutamic Acid