title: Neurotransmitter Systems in a Mild Blast Traumatic Brain Injury Model: Catecholamines and Serotonin.
abstract: Exposure to improvised explosive devices can result in a unique form of traumatic brain injury--blast-induced traumatic brain injury (bTBI). At the mild end of the spectrum (mild bTBI [mbTBI]), there are cognitive and mood disturbances. Similar symptoms have been observed in post-traumatic stress disorder caused by exposure to extreme psychological stress without physical injury. A role of the monoaminergic system in mood regulation and stress is well established but its involvement in mbTBI is not well understood. To address this gap, we used a rodent model of mbTBI and detected a decrease in immobility behavior in the forced swim test at 1 d post-exposure, coupled with an increase in climbing behavior, but not after 14 d or later, possibly indicating a transient increase in anxiety-like behavior. Using in situ hybridization, we found elevated messenger ribonucleic acid levels of both tyrosine hydroxylase and tryptophan hydroxylase 2 in the locus coeruleus and the dorsal raphe nucleus, respectively, as early as 2 h post-exposure. High-performance liquid chromatography analysis 1 d post-exposure primarily showed elevated noradrenaline levels in several forebrain regions. Taken together, we report that exposure to mild blast results in transient changes in both anxiety-like behavior and brain region-specific molecular changes, implicating the monoaminergic system in the pathobiology of mbTBI.
authors.affiliation: 1 Department of Neuroscience, Karolinska Institutet , Stockholm, Sweden .
authors.forename: Lizan
authors.initials: L
authors.lastname: Kawa
authors.affiliation: 1 Department of Neuroscience, Karolinska Institutet , Stockholm, Sweden .
authors.forename: Ulf P
authors.initials: UP
authors.lastname: Arborelius
authors.affiliation: 2 Department of Physiology and Pharmacology, Karolinska Institutet , Stockholm, Sweden .
authors.forename: Takashi
authors.initials: T
authors.lastname: Yoshitake
authors.affiliation: 2 Department of Physiology and Pharmacology, Karolinska Institutet , Stockholm, Sweden .
authors.forename: Jan
authors.initials: J
authors.lastname: Kehr
authors.affiliation: 1 Department of Neuroscience, Karolinska Institutet , Stockholm, Sweden .
authors.forename: Tomas
authors.initials: T
authors.lastname: Hökfelt
authors.affiliation: 1 Department of Neuroscience, Karolinska Institutet , Stockholm, Sweden .
authors.forename: Mårten
authors.initials: M
authors.lastname: Risling
authors.affiliation: 3 Department of Anatomy, Physiology and Genetics, the Uniformed Services University , Bethesda, Maryland.
authors.forename: Denes
authors.initials: D
authors.lastname: Agoston
mesh_terms: D000818:Animals; D001007:Anxiety / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D001522:Behavior, Animal / Q000502:physiology*; D001753:Blast Injuries / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D001930:Brain Injuries / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D002395:Catecholamines / Q000378:metabolism*; D004195:Disease Models, Animal; D065847:Dorsal Raphe Nucleus / Q000201:enzymology; D008125:Locus Coeruleus / Q000201:enzymology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D014365:Tryptophan Hydroxylase / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D002395:Catecholamines; D012701:Serotonin; D014446:Tyrosine 3-Monooxygenase; D014365:Tryptophan Hydroxylase; C504569:tph2 protein, rat
keywords: PTSD; anxiety; mood disorder; noradrenaline; stress