Impulsivity and Concussion in Juvenile Rats: Examining Molecular and Structural Aspects of the Frontostriatal Pathway
Impulsivity and Concussion in Juvenile Rats: Examining Molecular and Structural Aspects of the Frontostriatal Pathway
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DOI：
10.1371/journal.pone.0139842
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发表时间：
2015-10-08
期刊：
影响因子：
3.7
通讯作者：
Mychasiuk, Richelle
中科院分区：
文献类型：
--
作者：
Hehar, Harleen;Yeates, Keith;Mychasiuk, Richelle
冲动和不良的执行控制与许多发育和神经精神疾病的发病机制有关。同样，脑震荡/轻度创伤性脑损伤（mTBI）与神经精神障碍的风险增加、冲动和注意力不集中的发展有关。因此，研究人员和流行病学家考虑脑震荡是否会引起注意力缺陷/多动障碍（ADHD）的症状，或者仅仅是暴露了已经存在的冲动倾向。本研究的目的是确定青春期的一次脑震荡是否会诱发adhd样的冲动性和反应抑制受损，并随后确定儿童mTBI之前的固有冲动性是否会加剧脑震荡后的症状，特别强调冲动和注意力不集中行为。由于这些行为被认为与涉及伏隔核（NAc）和前额叶皮层（PFC）的额纹状体回路有关，因此我们检测了这两个区域的8个基因（Comt、Drd2、Drd3、Drd4、Maoa、Sert、Tph1和Tph2）的表达模式。此外，NAc中棘神经元的高尔基-考克斯染色提供了mtbi诱导的结构变化的神经解剖学检查。研究发现，早期的一次脑损伤可能导致冲动和反应抑制障碍，这在男性中更为明显。有趣的是，当具有内在冲动性的动物经历mTBI时，雌性动物的损伤相关缺陷会加剧。单次震荡增加了树突分支，但减少了NAc的突触密度，这些变化可能与冲动性的增加有关。最后，尽管行为表型非常相似，mtbi诱导的冲动性与与固有冲动性相关的基因表达模式显著不同的基因表达修饰有关。我们的研究结果表明，考虑到依赖于性别和行为表型病因学的额纹状体回路分子谱的显著差异，需要根据个体的病前特征定制mTBI的治疗策略。
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.