title: Effects of ethanol and NAP on cerebellar expression of the neural cell adhesion molecule L1.
abstract: The neural cell adhesion molecule L1 is critical for brain development and plays a role in learning and memory in the adult. Ethanol inhibits L1-mediated cell adhesion and neurite outgrowth in cerebellar granule neurons (CGNs), and these actions might underlie the cerebellar dysmorphology of fetal alcohol spectrum disorders. The peptide NAP potently blocks ethanol inhibition of L1 adhesion and prevents ethanol teratogenesis. We used quantitative RT-PCR and Western blotting of extracts of cerebellar slices, CGNs, and astrocytes from postnatal day 7 (PD7) rats to investigate whether ethanol and NAP act in part by regulating the expression of L1. Treatment of cerebellar slices with 20 mM ethanol, 10(-12) M NAP, or both for 4 hours, 24 hours, and 10 days did not significantly affect L1 mRNA and protein levels. Similar treatment for 4 or 24 hours did not regulate L1 expression in primary cultures of CGNs and astrocytes, the predominant cerebellar cell types. Because ethanol also damages the adult cerebellum, we studied the effects of chronic ethanol exposure in adult rats. One year of binge drinking did not alter L1 gene and protein expression in extracts from whole cerebellum. Thus, ethanol does not alter L1 expression in the developing or adult cerebellum; more likely, ethanol disrupts L1 function by modifying its conformation and signaling. Likewise, NAP antagonizes the actions of ethanol without altering L1 expression.
authors.affiliation: Veterans Affairs Boston Healthcare System, Boston, Massachusetts, United States of America.
authors.forename: Devon M
authors.initials: DM
authors.lastname: Fitzgerald
authors.forename: Michael E
authors.initials: ME
authors.lastname: Charness
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Leite-Morris
authors.forename: Suzhen
authors.initials: S
authors.lastname: Chen
mesh_terms: D000375:Aging / Q000187:drug effects / Q000378:metabolism; D000437:Alcoholism / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001681:Biological Assay; D002531:Cerebellum / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D039842:Neural Cell Adhesion Molecule L1 / Q000235:genetics* / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology*; D011786:Quality Control; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results
chemical_list: D039842:Neural Cell Adhesion Molecule L1; D009842:Oligopeptides; D012333:RNA, Messenger; D000431:Ethanol; C425904:davunetide