TY - JOUR
T1 - Athymic nude mice are insensitive to low-level toluene-induced up-regulation of memory-related gene expressions in the hippocampus
AU - Win-Shwe, Tin Tin
AU - Tsukahara, Shinji
AU - Ahmed, Sohel
AU - Fukushima, Atsushi
AU - Yamamoto, Shoji
AU - Kakeyama, Masaki
AU - Nakajima, Daisuke
AU - Goto, Sumio
AU - Kobayashi, Takahiro
AU - Fujimaki, Hidekazu
N1 - Funding Information:
This research was partly supported by grants from the Ministry of the Environment, Japan and the Ministry of Education, Culture, Sports, Science and Technology, Japan. We thank Ms. Kaoru Ohnishi (National Institute for Environmental Studies) for her technical assistance during this study.
PY - 2007/9
Y1 - 2007/9
N2 - The function of the N-methyl-d-aspartate (NMDA) subtype of glutamatergic receptors is known to be antagonized by toluene, a well-characterized neurotoxic chemical known to impair memory functions. Recently, peripheral T cells have been clearly shown to play an important role in cognitive and behavioral functions. In the present study, we investigated the role of peripheral T cells in the hippocampal mRNA expression of memory-related genes induced by low levels of toluene exposure in mice. BALB/c wild-type (WT) and nude mice were exposed to 9 ppm of toluene or filtered air (0 ppm toluene; control groups) in a nose-only exposure chamber for 30 min on 3 consecutive days followed by weekly sessions for 4 weeks. Twenty-four hours after the last exposure, the hippocampi were collected and the inducibility of memory-related genes was examined using a real-time quantitative PCR method. NMDA NR2A, calcium/calmodulin-dependent protein kinase IV (CaMKIV), cyclic AMP-responsive element binding protein 1 (CREB1), and BDNF were significantly up-regulated in the hippocampi of WT mice exposed to 9 ppm of toluene, compared to the expressions observed in WT mice exposed to filtered air, but similar results were not observed in nude mice. To investigate the possible involvement of peripheral T cells in the toluene-induced up-regulation of memory-related genes in WT mice, we examined the mRNA expression of Thy-1 (a pan T cell-specific marker) and quantified the number of cells that were immunoreactive to a T cell antigen receptor, CD3 (CD3-ir). Both the expression of Thy-1 mRNA and the number of CD3-ir cells were significantly higher in the hippocampi of the WT mice exposed to 9 ppm of toluene, compared with that in WT mice exposed to filtered air; similar results were not observed in nude mice. We also examined the expression of chemokine genes like CCL2 and CCL3. The expression of CCL3 mRNA was significantly up-regulated only in the toluene-exposed WT mice. Although other differences unrelated to immune function may exist between WT and nude mice from the same background, the findings of the present study strongly suggest that the recruitment of peripheral T cells in the hippocampi of BALB/c WT mice exposed to low levels of toluene may be involved in the toluene-induced up-regulation of memory-related genes at the mRNA level.
AB - The function of the N-methyl-d-aspartate (NMDA) subtype of glutamatergic receptors is known to be antagonized by toluene, a well-characterized neurotoxic chemical known to impair memory functions. Recently, peripheral T cells have been clearly shown to play an important role in cognitive and behavioral functions. In the present study, we investigated the role of peripheral T cells in the hippocampal mRNA expression of memory-related genes induced by low levels of toluene exposure in mice. BALB/c wild-type (WT) and nude mice were exposed to 9 ppm of toluene or filtered air (0 ppm toluene; control groups) in a nose-only exposure chamber for 30 min on 3 consecutive days followed by weekly sessions for 4 weeks. Twenty-four hours after the last exposure, the hippocampi were collected and the inducibility of memory-related genes was examined using a real-time quantitative PCR method. NMDA NR2A, calcium/calmodulin-dependent protein kinase IV (CaMKIV), cyclic AMP-responsive element binding protein 1 (CREB1), and BDNF were significantly up-regulated in the hippocampi of WT mice exposed to 9 ppm of toluene, compared to the expressions observed in WT mice exposed to filtered air, but similar results were not observed in nude mice. To investigate the possible involvement of peripheral T cells in the toluene-induced up-regulation of memory-related genes in WT mice, we examined the mRNA expression of Thy-1 (a pan T cell-specific marker) and quantified the number of cells that were immunoreactive to a T cell antigen receptor, CD3 (CD3-ir). Both the expression of Thy-1 mRNA and the number of CD3-ir cells were significantly higher in the hippocampi of the WT mice exposed to 9 ppm of toluene, compared with that in WT mice exposed to filtered air; similar results were not observed in nude mice. We also examined the expression of chemokine genes like CCL2 and CCL3. The expression of CCL3 mRNA was significantly up-regulated only in the toluene-exposed WT mice. Although other differences unrelated to immune function may exist between WT and nude mice from the same background, the findings of the present study strongly suggest that the recruitment of peripheral T cells in the hippocampi of BALB/c WT mice exposed to low levels of toluene may be involved in the toluene-induced up-regulation of memory-related genes at the mRNA level.
KW - Hippocampus
KW - Memory
KW - NMDA receptor
KW - Nude mice
KW - T cells
KW - Toluene
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U2 - 10.1016/j.neuro.2007.08.002
DO - 10.1016/j.neuro.2007.08.002
M3 - Article
C2 - 17870172
AN - SCOPUS:34948884466
SN - 0161-813X
VL - 28
SP - 957
EP - 964
JO - NeuroToxicology
JF - NeuroToxicology
IS - 5 SPEC. ISS.
ER -