平成14年度 本態性多種化学物質過敏状態の調査研究 研究報告書

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1 226

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3 µ 228

4 Ω 229

5 230

6 0 ppb 2000ppb DG subthreshold (µa) 91 ± ± 68 max stim. (µa) 755 ± 287 n= ± 300 max PS (mv) 8.7 ± ± 4.3 n=61 CA1 subthreshold (µa) 36 ± ± 13 max stim. (µa) 225 ± 123 n= ± 71 n=18 max PS (mv) 14.8 ± ±

7 2 FA FA exposed; 2000ppb LTPEPSP 232

8 3 FA pepsp 4 FA LTP TBS EPSP 10 V 233

9 5 LTP 0 TBS TBS 10 pepsp pepsp 234

10 6 FA LTP t-testtbs 10 pepsp pepsp 235

11 7 080, ppb FA LTP 8 FA LTP 236

12 9 LTP 237

13 10 EPSP 11 LTP 238

14 239

15 CHANGES IN AMOUNT OF ACTIVE KINASES (%) CaM KIIα * Cx CA1 CA3 DG CaM KIIβ PKCα * Control Formaldehyde p42mapk ** Cx CA1 CA3 DG Cx CA1 CA3 DG Cx CA1 CA3 DG

16 250 Control CHANGES IN AMOUNT OF PROTEINS (%) ** Synapsin I * ** Folmaldehyde GluR1 0 Cortex CA1 CA3 DG Cortex CA1 CA3 DG

17 150 CHANGES IN CRH LEVELS (%) * Control Folmaldehyde 0 Cortex Hippocampus

18 15 243

19 16 244

20 17 245

21 18 246

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24 249

25 Abstract Electrophysiological, neurochemical and behavioral analysis on disturbance of neuronal information processing in mice chronically exposed to a low concentration of formaldehyde Yukiko FUETA 1, Kiyohisa NATSUME 2, Kohji FUKUNAGA 3, Shuji AOU 2 (The authors were in equal contribution.) 1 Department of Medical Technology I, School of Health Sciences, University of Occupational and Environmental Health 2 Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology 3 Department of Pharmacology, Tohoku University, Graduate School of Pharmacology Sciences To investigate effects of long-term inhalation (12w) of a low concentration of formaldehyde (FA) on neuronal information processing in the hippocampal formation, we analyzed paired-pulse responses of population spike (PS) and field excitatory postsynaptic potential (fepsp), and long-term potentiation (LTP) using slices, and then combined the 250

26 electrophysiological results with neurochemical study of intracellular signaling. LTP induced by a-burst stimulation applied to Schaffer collaterals in the CA1 was significantly suppressed in the mice exposed to 80, 400 and 2000 ppb FA. In mice exposed to 2000ppb FA, granule cell disinhibition in the dentate gyrus and a decrease in paired-pulse inhibition of fepsps in the CA1 were confirmed. The electrophysiological results suggest that inhibitory system and memory processing can be impaired in the mice exposed to FA. Since the suppression of LTP induction was observed following exposure to FA, we next investigated amount of the active forms of CA 2+ /calmodulin-dependent protein kinase II (CaMKII), protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) which are involved in the hippocampal LTP induction. We also assessed amount of the synaptic components such as synapsin I and an AMPA type glutamate receptor (GluR1 subunit). The amount of active CaMKII and CaMKII significantly increased in the CA1 without changes in the active PKC. Significant increases in amount of synapsin I in the CA1 region and the DG were also evident in the FA-exposed mice. An open field test disclosed an increase in searching behavior, rearing, while there was no change in the fear behavior of the FA-exposed mice in the elevated maze test. The abnormalities in the expression of the signaling molecules and synaptic components may be associated with the suppression of LTP induction and disturbance of the neural functions by exposure to FA. 251

1 Department of Legal Medicine, Toyama University School of Medicine 2 3 4 5 6 7 8 Department of Ophthalmology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama VEGF Key words

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