Perinatal exposure to alcohol reduces the expression of complexins I and II.
Perinatal exposure to alcohol (PEA) induces general developmental and specific neuropsychiatric disturbances. Ethanol affects amino acid neurotransmission and synaptic plasticity. We were interested in the transcriptional effects of ethanol on the expression of complexins I and II, two synaptic vesicle proteins (SVP) with relevance for cognition and memory. We exposed pregnant Wistar inbred rats (N=4) and their pups until postnatal day 8 (P8) in vapor chambers and performed in situ-hybridizations regarding complexins I and II at P8 as well as neurobehavioral testing in adult animals of the same litters. At P8, serum ethanol levels of 281+/-58 mg/dl were achieved. PEA animals presented a pronounced retardation of postnatal growth. Significantly lower expression levels of complexin I was observed in CA1, together with trends of reductions in other hippocampal and cortical regions. Complexin II was found reduced in anterior cingulate, prefrontal and fronto-parietal cortex. Adult rats of exposed litters showed worse performance in hippocampus-dependent learning (Morris water maze). The observed suppression of complexins I and II reveals disturbed synaptic plasticity and corresponds with long lasting, ethanol-induced deficits of learning and memory. Further investigations should focus on other synaptic vesicle protein genes in order to unravel the molecular basis of ethanol-induced neurocognitive disabilities.
Zink
Mathias
M
Central Institute of Mental Health, Department of Psychiatry and Psychotherapy, University of Heidelberg, Mannheim, Germany. mathias.zink@zi-mannheim.de
Araç
Gülsemin
G
Frank
Stefanie Th
ST
Gass
Peter
P
Gebicke-Härter
Peter J
PJ
Spanagel
Rainer
R
D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism*; D000280:Administration, Inhalation; D019973:Alcohol-Related Disorders / Q000097:blood / Q000235:genetics* / Q000523:psychology; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D008297:Male; D018811:Maternal Exposure; D018782:Maze Learning / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics* / Q000523:psychology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D033942:Adaptor Proteins, Vesicular Transport; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C095992:complexin I; C095993:complexin II; D000431:Ethanol