Changes in the function of the inhibitory neurotransmitter system in the rat brain following subchronic inhalation exposure to 1-bromopropane.
1-Bromopropane (1-BP) has been widely used as a cleaning agent and a solvent in industries, but the central neurotoxicity of 1-BP remains to be clarified. In the present study, we investigated the effects of subchronic inhalation exposure to 1-BP vapor on the function of the inhibitory neurotransmitter system mediated by gamma-aminobutyric acid (GABA) in the rat brain. Male Wistar rats were exposed to 1-BP vapor for 12 weeks (6h/day, 5 days/week) at a concentration of 400 ppm, and, in order to investigate the expression and function of brain GABA type A (GABAA) receptors, total/messenger RNA was prepared from the neocortex, hippocampus, and cerebellum of the control and 1-BP-exposed rats. Moreover, hippocampal slices were prepared, and the population spike (PS) amplitude and the slope of the field excitatory postsynaptic potential (fEPSP) were investigated in the paired-pulse configuration of the extracellular recording technique. Using the Xenopus oocyte expression system, we compared GABA concentration-response curves obtained from oocytes injected with brain subregional mRNAs of control and 1-BP exposed rats, and observed no significant differences in apparent GABA affinity. On the other hand, paired-pulse inhibition of PS amplitude was significantly decreased in the hippocampal dentate gyrus (DG) by exposure to 1-BP, without any effect on the paired-pulse ratio of the fEPSP slopes, suggesting neuronal disinhibition in the DG. Moreover, RT-PCR analysis indicated decreased levels of GABAA receptor beta3 and delta subunit mRNAs in the hippocampus of 1-BP-exposed rats. These results demonstrate that subchronic inhalation exposure to 1-BP vapor reduces the function of the hippocampal GABAergic system, which could be due to changes in the expression and function of GABAA receptors, especially the delta subunit-containing GABAA receptors.
Ueno
Susumu
S
Department of Pharmacology, School of Medicine, University of Occupational and Environmental Health, Japan. susumu@med.uoeh-u.ac.jp
Yoshida
Yasuhiro
Y
Fueta
Yukiko
Y
Ishidao
Toru
T
Liu
Jiqin
J
Kunugita
Naoki
N
Yanagihara
Nobuyuki
N
Hori
Hajime
H
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006842:Hydrocarbons, Brominated / Q000737:chemistry / Q000633:toxicity; D019570:Inhalation Exposure; D008297:Male; D008845:Microinjections; D019579:Neocortex / Q000187:drug effects / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects*; D018377:Neurotransmitter Agents / Q000378:metabolism* / Q000494:pharmacology; D009865:Oocytes; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012997:Solvents / Q000737:chemistry / Q000633:toxicity*; D014835:Volatilization; D014982:Xenopus laevis; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000494:pharmacology
C546276:Gabrb3 protein, rat; D006842:Hydrocarbons, Brominated; D018377:Neurotransmitter Agents; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D012997:Solvents; D005680:gamma-Aminobutyric Acid; C118559:1-bromopropane