Changes in neuronal protein 22 expression and cytoskeletal association in the alcohol-dependent and withdrawn rat brain.
The action of alcohol on neuronal pathways has been an issue of increasing research focus, with numerous findings contradicting the previously accepted idea that its effect is nonspecific. The human NP22 (hNP22) gene was revealed by its elevated expression in the frontal cortex of the human alcoholic. The sequences of hNP22 and the rat orthologue rNP22 contain a number of domains consistent with those of cytoskeletal-interacting proteins. Localization of rNP22 is restricted to the cytoplasm and processes of neurons and it colocalizes with elements of the microfilament and microtubule matrices including filamentous actin (F-actin), alpha-tubulin, tau, and microtubule-associated protein 2 (MAP2). Withdrawal of Wistar rats after alcohol dependence induced by alcohol vapor produced elevated levels of rNP22 mRNA and protein in the cortex, CA2, and dentate gyrus regions of the hippocampus. In contrast, there was decreased rNP22 expression in the striatum after chronic ethanol exposure. Chronic ethanol exposure did not markedly alter rNP22 colocalization with F-actin, alpha-tubulin, or MAP2, although colocalization at the periphery of the neuronal soma with F-actin was observed only after chronic ethanol exposure and withdrawal. Rat NP22 colocalization with MAP2 was reduced during withdrawal, whereas association with alpha-tubulin and actin was maintained. These findings suggest that the effect of chronic ethanol exposure and withdrawal on rNP22 expression is region selective. Rat NP22 may affect microtubule or microfilament function, thereby regulating the neuroplastic changes associated with the development of alcohol dependence and physical withdrawal.
Depaz
Iris M
IM
Alcohol Research Unit, Department of Biochemistry and Molecular Biosciences, School of Molecular and Microbial Sciences, University of Queensland, Australia.
de Las Heras
Rachel
R
Kroon
Paulus A
PA
Wilce
Peter A
PA
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000428:Alcohol Drinking / Q000378:metabolism; D000437:Alcoholism / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome / Q000378:metabolism; D014018:Tissue Distribution
D002492:Central Nervous System Depressants; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C486029:Tagln3 protein, rat; D000431:Ethanol