Increased hippocampal mRNA expression of neuronal synaptic plasticity related genes in mice chronically exposed to toluene at a low-level human occupational-exposure.
Although neurological symptoms in individuals exposed to toluene both inside and outside the homes have been reported well, the chronic effects of low-level toluene-exposure on the hippocampal expression of neuronal synaptic plasticity related genes have not been studied in vivo. In the present study, to understand the possible adult hippocampal neurobiological responses of mice chronic exposure to toluene at a low-level human occupational-exposure, we exposed 10-week-old C3H/HeN female mice to 50 ppm toluene or filtered air for 6 h a day, on 5-consecutive days of a week for 6 and 12 weeks, in a whole-body exposure chamber. Then, by a quantitative real-time PCR method, we investigated the hippocampal mRNA-expression of several genes, functions of which are necessary to maintain the homeostasis of neuronal synaptic plasticity. We observed that chronic exposure of mice to 50 ppm toluene for a longer period (12 weeks) caused a significant up-regulation of NMDA receptor subunit 2B (NMDA NR2B) expression associated with a simultaneous induction of CaMKIV, CREB-1, and FosB/DeltaFosB in the same hippocampal tissues. Our data indicate that the in vivo transcriptional up-regulation of these genes in the adult hippocampus of our experimental mouse model following the chronic exposure to toluene may be an NMDA-receptor related neuroprotective mechanism of gene expression.
Ahmed
Sohel
S
Environmental Health Sciences Division, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba 305-8506, Ibaraki, Japan. ahmed.sohel@nies.go.jp
Tin-Tin-Win-Shwe
Yamamoto
Shoji
S
Tsukahara
Shinji
S
Kunugita
Naoki
N
Arashidani
Keiichi
K
Fujimaki
Hidekazu
H
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000096:biosynthesis; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000235:genetics*; D016273:Occupational Exposure / Q000009:adverse effects*; D011247:Pregnancy; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012997:Solvents; D014050:Toluene / Q000633:toxicity*; D015854:Up-Regulation / Q000187:drug effects
D017362:Cyclic AMP Response Element-Binding Protein; D018076:DNA, Complementary; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D012997:Solvents; D014050:Toluene; D017871:Calcium-Calmodulin-Dependent Protein Kinases