High postnatal susceptibility of hippocampal cytoskeleton in response to ethanol exposure during pregnancy and lactation
| Autor: | Karina Pires Reis, Carolina Gonçalves Fernandes, Fernanda Silva Ferreira, Samanta Oliveira Loureiro, Rônan Vivian Carvalho, Regina Pessoa-Pureur, Luana Heimfarth, Paula Pierozan |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_specialty
Cerebellum Health (social science) Neurofilament MAP Kinase Signaling System Central nervous system Intermediate Filaments Hippocampus Hippocampal formation Toxicology Biochemistry Behavioral Neuroscience Neurofilament Proteins Pregnancy Lactation Internal medicine Glial Fibrillary Acidic Protein medicine Animals Homeostasis Phosphorylation Rats Wistar Cytoskeleton Ethanol Glial fibrillary acidic protein biology Body Weight Central Nervous System Depressants General Medicine Cyclic AMP-Dependent Protein Kinases Rats medicine.anatomical_structure Endocrinology Animals Newborn Neurology Cerebral cortex biology.protein Female Energy Intake |
| Zdroj: | Alcohol. 49:665-674 |
| ISSN: | 0741-8329 |
| DOI: | 10.1016/j.alcohol.2015.06.005 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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