title: Impulsivity and Concussion in Juvenile Rats: Examining Molecular and Structural Aspects of the Frontostriatal Pathway.
abstract: Impulsivity and poor executive control have been implicated in the pathogenesis of many developmental and neuropsychiatric disorders. Similarly, concussions/mild traumatic brain injuries (mTBI) have been associated with increased risk for neuropsychiatric disorders and the development of impulsivity and inattention. Researchers and epidemiologists have therefore considered whether or not concussions induce symptoms of attention-deficit/hyperactivity disorder (ADHD), or merely unmask impulsive tendencies that were already present. The purpose of this study was to determine if a single concussion in adolescence could induce ADHD-like impulsivity and impaired response inhibition, and subsequently determine if inherent impulsivity prior to a pediatric mTBI would exacerbate post-concussion symptomology with a specific emphasis on impulsive and inattentive behaviours. As these behaviours are believed to be associated with the frontostriatal circuit involving the nucleus accumbens (NAc) and the prefrontal cortex (PFC), the expression patterns of 8 genes (Comt, Drd2, Drd3, Drd4, Maoa, Sert, Tph1, and Tph2) from these two regions were examined. In addition, Golgi-Cox staining of medium spiny neurons in the NAc provided a neuroanatomical examination of mTBI-induced structural changes. The study found that a single early brain injury could induce impulsivity and impairments in response inhibition that were more pronounced in males. Interestingly, when animals with inherent impulsivity experienced mTBI, injury-related deficits were exacerbated in female animals. The single concussion increased dendritic branching, but reduced synaptic density in the NAc, and these changes were likely associated with the increase in impulsivity. Finally, mTBI-induced impulsivity was associated with modifications to gene expression that differed dramatically from the gene expression pattern associated with inherent impulsivity, despite very similar behavioural phenotypes. Our findings suggest the need to tailor treatment strategies for mTBI in light of an individual's premorbid characteristics, given significant differences in molecular profiles of the frontostriatal circuits that depend upon sex and the etiology of the behavioural phenotype.
authors.affiliation: Alberta Children's Hospital Research Institute, University of Calgary, Faculty of Medicine, Calgary, Canada.
authors.forename: Harleen
authors.initials: H
authors.lastname: Hehar
authors.affiliation: Alberta Children's Hospital Research Institute, University of Calgary, Department of Psychology, Calgary, Canada.
authors.forename: Keith
authors.initials: K
authors.lastname: Yeates
authors.affiliation: Canadian Centre for Behavioural Neuroscience, University of Lethbridge, Lethbridge, Canada.
authors.forename: Bryan
authors.initials: B
authors.lastname: Kolb
authors.affiliation: Alberta Children's Hospital Research Institute, University of Calgary, Faculty of Medicine, Calgary, Canada.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Esser
authors.affiliation: Alberta Children's Hospital Research Institute, University of Calgary, Faculty of Medicine, Calgary, Canada.
authors.forename: Richelle
authors.initials: R
authors.lastname: Mychasiuk
mesh_terms: D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000378:metabolism / Q000473:pathology; D001924:Brain Concussion / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D007175:Impulsive Behavior / Q000502:physiology*; D008297:Male; D009714:Nucleus Accumbens / Q000378:metabolism*; D010641:Phenotype; D017397:Prefrontal Cortex / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D059467:Transcriptome