Effect of D-cycloserine on spatial learning performance and memory function-related gene expression in mice following toluene exposure.
D-cycloserine (DCS), a partial N-methyl-D-aspartate (NMDA) receptor agonist, is a well-known cognitive enhancer. To investigate the effect of DCS in cognitive function following toluene exposure, eight-week-old male C3H/HeN mice were exposed to filtered air (0 ppm) or 50 ppm toluene for 6 h a day on 5 consecutive days a week for 6 weeks. The day after the day of final exposure, a spatial learning task was performed using a Morris water maze apparatus. During the learning task, some mice were treated with DCS intraperitoneally (20 mg/kg) 30 min before the first trial of the acquisition phase and probe trial. After completion of the spatial learning task, the hippocampus was collected from each mouse to examine memory function-related gene expression using the real-time RT-PCR method. During the acquisition phase, on day 3 and 4, toluene-exposed mice with DCS treatment showed significantly better learning performance than corresponding saline treated groups. Moreover, the toluene-exposed mice with DCS treatment also showed significantly improved memory retention during the probe trial and up-regulation of hippocampal NMDA receptor subunit 2B mRNA expression compared with the saline treated groups. Our findings indicate that a subunit-specific modulation of hippocampal NMDA receptor mRNA expression by DCS contributes to improvement of spatial learning performance in mice following toluene exposure.
Win-Shwe
Tin-Tin
TT
Research Center for Environmental Risk, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8506, Japan.
Kageyama
Shiho
S
Tsukahara
Shinji
S
Nakajima
Daisuke
D
Fujimaki
Hidekazu
H
D000818:Animals; D003523:Cycloserine / Q000008:administration & dosage / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D006624:Hippocampus / Q000378:metabolism; D007858:Learning / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D012333:RNA, Messenger / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists* / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012997:Solvents / Q000009:adverse effects*; D013037:Spatial Behavior / Q000187:drug effects* / Q000502:physiology*; D013268:Stimulation, Chemical; D014050:Toluene / Q000009:adverse effects*
D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D012997:Solvents; D014050:Toluene; D003523:Cycloserine