title: Differential expression of astrocytic connexins in a mouse model of prenatal alcohol exposure.
abstract: Maternal alcohol consumption during gestation can cause serious injury to the fetus, and may result in a range of physiological and behavioral impairments, including increased seizure susceptibility, that are collectively termed fetal alcohol spectrum disorder (FASD). The cellular mechanisms underlying increased seizure susceptibility in FASD are not well understood, but could involve altered excitatory coupling of neuronal populations mediated by gap junction proteins. We utilized a mouse model of the prenatal alcohol exposure (PAE) to study the expression pattern of connexin (Cx) major components of gap junctions, and pannexin proteins, which form membrane channels, in the brain of 2-3weeks old PAE and control postnatal offspring. PAE during the first trimester-equivalent period of pregnancy in mice resulted in significant up-regulation of Cx30 mRNA and Cx30 total protein in the hippocampus of PAE animals compared to age-matched controls. Surface level expression of both dimeric and monomeric Cx30 were also found to be significantly up-regulated in both hippocampus and cerebral cortex of PAE animals compared to age-matched controls. On the membrane surface, the fast migrating form of Cx43 was found to be up-regulated in the hippocampus of PAE mice. However, we did not see any up-regulation of the phosphorylated forms of Cx43 on the membrane surface. These results indicate that the expression and processing of astrocytic connexins (Cx30, Cx43) are up-regulated in the brain of PAE offspring, and these changes could play a role in the cerebral hyperexcitability observed in these animals.
authors.affiliation: Division of Fundamental Neurobiology, Toronto Western Research Institute, UHN, Toronto, ON, Canada.
authors.forename: Meera
authors.initials: M
authors.lastname: Ramani
authors.affiliation: Division of Fundamental Neurobiology, Toronto Western Research Institute, UHN, Toronto, ON, Canada.
authors.forename: Shanthini
authors.initials: S
authors.lastname: Mylvaganam
authors.affiliation: Division of Fundamental Neurobiology, Toronto Western Research Institute, UHN, Toronto, ON, Canada.
authors.forename: Michal
authors.initials: M
authors.lastname: Krawczyk
authors.affiliation: Division of Fundamental Neurobiology, Toronto Western Research Institute, UHN, Toronto, ON, Canada.
authors.forename: Lihua
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Psychology, York University, Toronto, ON, Canada.
authors.forename: Christiane
authors.initials: C
authors.lastname: Zoidl
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
authors.forename: James
authors.initials: J
authors.lastname: Brien
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
authors.forename: James N
authors.initials: JN
authors.lastname: Reynolds
authors.affiliation: Division of Clinical Pharmacology & Toxicology, The Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Bhushan
authors.initials: B
authors.lastname: Kapur
authors.affiliation: Robarts Research Institute, Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada.
authors.forename: Michael O
authors.initials: MO
authors.lastname: Poulter
authors.affiliation: Department of Psychology, York University, Toronto, ON, Canada.
authors.forename: Georg
authors.initials: G
authors.lastname: Zoidl
authors.affiliation: Division of Fundamental Neurobiology, Toronto Western Research Institute, UHN, Toronto, ON, Canada; Departments of Medicine (Neurology) and Physiology, University of Toronto, Toronto, ON, Canada. Electronic address: carlen@uhnresearch.ca.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Carlen
mesh_terms: D000438:Alcohols / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D000075302:Connexin 30 / Q000235:genetics / Q000378:metabolism; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*
chemical_list: D000438:Alcohols; D000075302:Connexin 30; D018031:Connexin 43
keywords: Astrocytes; Astrocytic connexins; Connexins; FASD; Gap junctions; Hyperexcitability; Prenatal alcohol exposure