title: High postnatal susceptibility of hippocampal cytoskeleton in response to ethanol exposure during pregnancy and lactation.
abstract: Ethanol exposure to offspring during pregnancy and lactation leads to developmental disorders, including central nervous system dysfunction. In the present work, we have studied the effect of chronic ethanol exposure during pregnancy and lactation on the phosphorylating system associated with the astrocytic and neuronal intermediate filament (IF) proteins: glial fibrillary acidic protein (GFAP), and neurofilament (NF) subunits of low, medium, and high molecular weight (NFL, NFM, and NFH, respectively) in 9- and 21-day-old pups. Female rats were fed with 20% ethanol in their drinking water during pregnancy and lactation. The homeostasis of the IF phosphorylation was not altered in the cerebral cortex, cerebellum, or hippocampus of 9-day-old pups. However, GFAP, NFL, and NFM were hyperphosphorylated in the hippocampus of 21-day-old pups. PKA had been activated in the hippocampus, and Ser55 in the N-terminal region of NFL was hyperphosphorylated. In addition, JNK/MAPK was activated and KSP repeats in the C-terminal region of NFM were hyperphosphorylated in the hippocampus of 21-day-old pups. Decreased NFH immunocontent but an unaltered total NFH/phosphoNFH ratio suggested altered stoichiometry of NFs in the hippocampus of ethanol-exposed 21-day-old pups. In contrast to the high susceptibility of hippocampal cytoskeleton in developing rats, the homeostasis of the cytoskeleton of ethanol-fed adult females was not altered. Disruption of the cytoskeletal homeostasis in neural cells supports the view that regions of the brain are differentially vulnerable to alcohol insult during pregnancy and lactation, suggesting that modulation of JNK/MAPK and PKA signaling cascades target the hippocampal cytoskeleton in a window of vulnerability in 21-day-old pups. Our findings are relevant, since disruption of the cytoskeleton in immature hippocampus could contribute to later hippocampal damage associated with ethanol toxicity.
authors: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brazil.
authors: Karina Pires
authors: KP
authors: Reis
authors: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brazil.
authors: Luana
authors: L
authors: Heimfarth
authors: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brazil.
authors: Paula
authors: P
authors: Pierozan
authors: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brazil.
authors: Fernanda
authors: F
authors: Ferreira
authors: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brazil.
authors: Samanta Oliveira
authors: SO
authors: Loureiro
authors: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brazil.
authors: Carolina Gonçalves
authors: CG
authors: Fernandes
authors: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brazil.
authors: Rônan Vivian
authors: RV
authors: Carvalho
authors: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brazil. Electronic address: rpureur@ufrgs.br.
authors: Regina
authors: R
authors: Pessoa-Pureur
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000633:toxicity*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects*; D002149:Energy Intake / Q000187:drug effects; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000196:embryology; D006706:Homeostasis; D007382:Intermediate Filaments / Q000187:drug effects; D007774:Lactation; D020935:MAP Kinase Signaling System / Q000187:drug effects; D016900:Neurofilament Proteins / Q000378:metabolism; D010766:Phosphorylation; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002492:Central Nervous System Depressants; D005904:Glial Fibrillary Acidic Protein; D016900:Neurofilament Proteins; D000431:Ethanol; D017868:Cyclic AMP-Dependent Protein Kinases
keywords: Alcoholism; Cytoskeleton; Development; Hippocampus; JNK/MAPK; PKA