Electrophysiology and immunohistochemistry in the hippocampal ca1 and the dentate gyrus of rats chronically exposed to 1-bromopropane, a substitute for specific chlorofluorocarbons.
1-Bromopropane is a newly introduced substitute for specific chlorofluorocarbons whose production was prohibited because of depletion of ozone layers. In this study, we analyzed disinhibitory effects induced by repetitive inhalation of 1-bromopropane for 12 weeks in the hippocampal CA1 and the dentate gyrus. In addition, reversal of the disinhibitory effects was examined 4 weeks after 1-bromopropane inhalation ceased. Exposure rats were placed in a stainless steel inhalation chamber at a concentration of 700 ppm, while the control group was provided only room air in the same type of chamber. Paired-pulse inhibition of population spike was considerably decreased (P<0.05) at 5 ms interpulse intervals in the CA1, and at 10 and 20 ms (P<0.05) interpulse intervals in the dentate gyrus in slices obtained from exposed rats following 4-, 8- and 12-week inhalation periods. The paired-pulse inhibition was decreased at 5 ms interpulse intervals in the dentate gyrus after 12 weeks of inhalation. These changes were not associated with the paired-pulse ratio of field excitatory postsynaptic potentials, suggesting a reduction of recurrent inhibition. The disinhibition was counteracted with the N-methyl-d-aspartate receptor antagonist dl-2-amino-5-phosphonopentameric acid in the dentate gyrus, whereas it was unchanged in the CA1. Tiagabine, a selective inhibitor of GABA transporter GAT1, increased the paired-pulse inhibition in the dentate gyrus, and the increase was less in the exposed rats compared with control rats (P<0.0003). The changes in both areas recovered to control levels 4 weeks after cessation of inhalation. Our electrophysiological studies suggest differential and reversible disinhibitory effects in the dentate gyrus and the CA1. 1-Bromopropane-induced disinhibition was further analyzed by immunohistochemical methods. There were no apparent morphological defects in either excitatory or inhibitory neuronal components, supporting the reversibility of physiological changes. In conclusion, chronic inhalation of 1-bromopropane induces a disinhibition in the CA1 and dentate gyrus that is reversible following cessation of exposure.
The First Department of Medical Technology, School of Health Sciences, University of Occupational and Environmental Health, Iseigaoka 1-1, Yahatanishi-ku, Kitakyushu 807-8555, Japan. yukiko@med.uoeh-u.ac.jp
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Fueta
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Fukuda
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Ishidao
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Hori
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D015415:Biomarkers; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D017402:Chlorofluorocarbons / Q000633:toxicity; D018891:Dentate Gyrus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D050485:GABA Plasma Membrane Transport Proteins; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D006842:Hydrocarbons, Brominated / Q000633:toxicity*; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity; D027361:Organic Anion Transporters; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D015415:Biomarkers; D002352:Carrier Proteins; D017402:Chlorofluorocarbons; D018691:Excitatory Amino Acid Antagonists; D050485:GABA Plasma Membrane Transport Proteins; D006842:Hydrocarbons, Brominated; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D027361:Organic Anion Transporters; C493415:Slc6a1 protein, rat; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C118559:1-bromopropane