Region-specific disruption of synapsin phosphorylation following ethanol administration in brain-injured mice

Introduction: Civilians and military personnel develop a range of physical and psychosocial impairments following traumatic brain injury (TBI), including alcohol abuse. As a consequence, increased rates of alcohol misuse magnify TBI-induced pathologies and impede rehabilitation efforts. Therefore, a...

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Main Authors: James P Caruso, Laura L Susick, Jennifer L Charlton, Emily L Henson, Alana C Conti
Format: Article
Language:English
Published: Wolters Kluwer Medknow Publications 2016-01-01
Series:Brain Circulation
Subjects:
Online Access:http://www.braincirculation.org/article.asp?issn=2394-8108;year=2016;volume=2;issue=4;spage=183;epage=188;aulast=Caruso
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author James P Caruso
Laura L Susick
Jennifer L Charlton
Emily L Henson
Alana C Conti
author_facet James P Caruso
Laura L Susick
Jennifer L Charlton
Emily L Henson
Alana C Conti
author_sort James P Caruso
collection DOAJ
description Introduction: Civilians and military personnel develop a range of physical and psychosocial impairments following traumatic brain injury (TBI), including alcohol abuse. As a consequence, increased rates of alcohol misuse magnify TBI-induced pathologies and impede rehabilitation efforts. Therefore, a developed understanding of the mechanisms that foster susceptibility of the injured brain to alcohol sensitivity and the response of the injured brain to alcohol is imperative for the treatment of TBI patients. Alcohol sensitivity has been demonstrated to be increased following experimental TBI and, in additional studies, regulated by presynaptic vesicle release mechanisms, including synapsin phosphorylation. Materials and Methods: Mice were exposed to controlled midline impact of the intact skull and assessed for cortical, hippocampal, and striatal expression of phosphorylated synapsin I and II in response to high-dose ethanol exposure administered 14 days following injury, a time point at which injured mice demonstrate increased sedation after ethanol exposure. Results and Discussion: Immunoblot quantitation revealed that TBI alone, compared to sham controls, significantly increased phosphorylated synapsin I and II protein expression in the striatum. In sham controls, ethanol administration significantly increased phosphorylated synapsin I and II protein expression compared to saline-treated sham controls; however, no significant increase in ethanol-induced phosphorylated synapsin I and II protein expression was observed in the striatum of injured mice compared to saline-treated TBI controls. A similar expression pattern was observed in the cortex although restricted to increases in phosphorylated synapsin II. Conclusion: These data show that increased phosphorylated synapsin expression in the injured striatum may reflect a compensatory neuroplastic response to TBI which is proposed to occur as a result of a compromised presynaptic response of the injured brain to high-dose ethanol. These results offer a mechanistic basis for the altered ethanol sensitivity observed following experimental TBI and contribute to our understanding of alcohol action in the injured brain.
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spelling doaj.art-2974933ce11f458e8ea070cb3439bcdf2022-12-22T03:18:08ZengWolters Kluwer Medknow PublicationsBrain Circulation2455-46262016-01-012418318810.4103/2394-8108.195284Region-specific disruption of synapsin phosphorylation following ethanol administration in brain-injured miceJames P CarusoLaura L SusickJennifer L CharltonEmily L HensonAlana C ContiIntroduction: Civilians and military personnel develop a range of physical and psychosocial impairments following traumatic brain injury (TBI), including alcohol abuse. As a consequence, increased rates of alcohol misuse magnify TBI-induced pathologies and impede rehabilitation efforts. Therefore, a developed understanding of the mechanisms that foster susceptibility of the injured brain to alcohol sensitivity and the response of the injured brain to alcohol is imperative for the treatment of TBI patients. Alcohol sensitivity has been demonstrated to be increased following experimental TBI and, in additional studies, regulated by presynaptic vesicle release mechanisms, including synapsin phosphorylation. Materials and Methods: Mice were exposed to controlled midline impact of the intact skull and assessed for cortical, hippocampal, and striatal expression of phosphorylated synapsin I and II in response to high-dose ethanol exposure administered 14 days following injury, a time point at which injured mice demonstrate increased sedation after ethanol exposure. Results and Discussion: Immunoblot quantitation revealed that TBI alone, compared to sham controls, significantly increased phosphorylated synapsin I and II protein expression in the striatum. In sham controls, ethanol administration significantly increased phosphorylated synapsin I and II protein expression compared to saline-treated sham controls; however, no significant increase in ethanol-induced phosphorylated synapsin I and II protein expression was observed in the striatum of injured mice compared to saline-treated TBI controls. A similar expression pattern was observed in the cortex although restricted to increases in phosphorylated synapsin II. Conclusion: These data show that increased phosphorylated synapsin expression in the injured striatum may reflect a compensatory neuroplastic response to TBI which is proposed to occur as a result of a compromised presynaptic response of the injured brain to high-dose ethanol. These results offer a mechanistic basis for the altered ethanol sensitivity observed following experimental TBI and contribute to our understanding of alcohol action in the injured brain.http://www.braincirculation.org/article.asp?issn=2394-8108;year=2016;volume=2;issue=4;spage=183;epage=188;aulast=CarusoAlcoholdiffuse brain injuryphosphorylated synapsinpresynapticstriatum
spellingShingle James P Caruso
Laura L Susick
Jennifer L Charlton
Emily L Henson
Alana C Conti
Region-specific disruption of synapsin phosphorylation following ethanol administration in brain-injured mice
Brain Circulation
Alcohol
diffuse brain injury
phosphorylated synapsin
presynaptic
striatum
title Region-specific disruption of synapsin phosphorylation following ethanol administration in brain-injured mice
title_full Region-specific disruption of synapsin phosphorylation following ethanol administration in brain-injured mice
title_fullStr Region-specific disruption of synapsin phosphorylation following ethanol administration in brain-injured mice
title_full_unstemmed Region-specific disruption of synapsin phosphorylation following ethanol administration in brain-injured mice
title_short Region-specific disruption of synapsin phosphorylation following ethanol administration in brain-injured mice
title_sort region specific disruption of synapsin phosphorylation following ethanol administration in brain injured mice
topic Alcohol
diffuse brain injury
phosphorylated synapsin
presynaptic
striatum
url http://www.braincirculation.org/article.asp?issn=2394-8108;year=2016;volume=2;issue=4;spage=183;epage=188;aulast=Caruso
work_keys_str_mv AT jamespcaruso regionspecificdisruptionofsynapsinphosphorylationfollowingethanoladministrationinbraininjuredmice
AT lauralsusick regionspecificdisruptionofsynapsinphosphorylationfollowingethanoladministrationinbraininjuredmice
AT jenniferlcharlton regionspecificdisruptionofsynapsinphosphorylationfollowingethanoladministrationinbraininjuredmice
AT emilylhenson regionspecificdisruptionofsynapsinphosphorylationfollowingethanoladministrationinbraininjuredmice
AT alanacconti regionspecificdisruptionofsynapsinphosphorylationfollowingethanoladministrationinbraininjuredmice