title: Cholinergic alterations following alcohol exposure in the frontal cortex of Aldh2-deficient mice models.
abstract: We investigated the effects of alcohol (EtOH) and acetaldehyde (ACe) on choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in the frontal cortex of Aldh2-/- (KO) mice. KO mice were used as models of Aldh2-deficient humans to examine ACe effects. Brain samples were analyzed at 40 and 120 min after 2- and 4-g/kg intraperitoneal EtOH administration by RT-PCR and Western blot. Wild-type (WT) mice exhibited a remarkable decrease in ChAT and AChE mRNA expression at both time points only after 4-g/kg EtOH treatment compared with the naive control, whereas KO mice showed a considerable reduction in cholinergic markers after 2- and 4-g/kg EtOH treatment. The 4-g/kg EtOH-induced decrease in ChAT and AChE RNA expression at both time points was significantly greater than that in obtained with the administration of 2-g/kg at 40 min in WT mice. KO mice showed a significant difference in ChAT mRNA at 40 min between the EtOH groups. The findings regarding the ChAT mRNA levels are consistent with the results of Western blot in both types of mice, with some exceptions. EtOH-induced ChAT and AChE expression in KO mice was significantly lower than that in WT mice. This genotype effect occurred mostly at 40 min after EtOH dosing. Only ACe was quantified in the brains of KO mice, whereas EtOH was detected in both types of mice in vivo. These results suggest that EtOH and ACe combined or high EtOH alone alters cholinergic markers expression via changes in presynaptic and postsynaptic processes in the mice frontal cortex, thus indicating that central cholinergic neurons may be sensitive to EtOH and ACe.
authors: Department of Forensic Medicine, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Miki, Kita, Kagawa 761-0793, Japan. jamaldr68@yahoo.com
authors: Mostofa
authors: M
authors: Jamal
authors: Kiyoshi
authors: K
authors: Ameno
authors: Takanori
authors: T
authors: Miki
authors: Weihuan
authors: W
authors: Wang
authors: Mitsuru
authors: M
authors: Kumihashi
authors: Toyohi
authors: T
authors: Isse
authors: Toshihiro
authors: T
authors: Kawamoto
authors: Kyoko
authors: K
authors: Kitagawa
authors: Keiichi
authors: K
authors: Nakayama
authors: Iwao
authors: I
authors: Ijiri
authors: Hiroshi
authors: H
authors: Kinoshita
mesh_terms: D000079:Acetaldehyde / Q000032:analysis; D000110:Acetylcholinesterase / Q000378:metabolism*; D000444:Aldehyde Dehydrogenase / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D002849:Chromatography, Gas; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage* / Q000032:analysis; D005625:Frontal Lobe / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D005838:Genotype; D051379:Mice; D018345:Mice, Knockout; D017551:Microdialysis; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D012333:RNA, Messenger; D000431:Ethanol; D000444:Aldehyde Dehydrogenase; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D000079:Acetaldehyde