Dataset Information

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.

SUBMITTER: Hehar H

PROVIDER: S-EPMC4598031 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Impulsivity and Concussion in Juvenile Rats: Examining Molecular and Structural Aspects of the Frontostriatal Pathway.

Hehar Harleen H Yeates Keith K Kolb Bryan B Esser Michael J MJ Mychasiuk Richelle R

PloS one 20151008 10

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 te ...[more]

PMID: 26448536

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Project description:BackgroundVaccine pharmacovigilance relates to the detection of adverse events, their assessment, understanding, and prevention, and communication of their risk to the public. These activities can be tedious and long lasting for regulatory authority scientists and may be affected by community practices and public health policies. To better understand underlying challenges, we examined vaccine adverse event reports, assessed whether data-driven techniques can provide additional insight in safety characterization, and wondered on the impact of socioeconomic parameters.MethodsFirst, we integrated VAERS content with additional sources of drug and molecular data and examined reaction and outcome occurrence by using disproportionality metrics and enrichment analysis. Second, we reviewed social and behavioral determinants that may affect vaccine pharmacovigilance aspects.ResultsWe describe our experience in processing more than 607000 vaccine adverse event reports and report on the challenges to integrate more than 95500 VAERS medication narratives with structured information about drugs and other therapeutics or supplements. We found that only 12.6% of events were serious, while 8.97% referred to polypharmacy cases. Exacerbation of serious clinical patient outcomes was observed in 8.88% VAERS cases in which drugs may interact with vaccinations or with each other, regardless of vaccine activity interference. Furthermore, we characterized the symptoms reported in those cases and summarized reaction occurrence among vaccine-types. Last, we examine socioeconomic parameters and cost-management features, explore adverse event reporting trends, and highlight perspectives relating to the use and development of digital services, especially in the context of personalized and collaborative health-care.ConclusionsThis work provides an informative review of VAERS, identifies challenges and limitations in the processing of vaccine adverse event data, and calls for the better understanding of the socioeconomic landscape pertaining vaccine safety concerns. We expect that adoption of computational techniques for integrated safety assessment and interpretation is key not only to pharmacovigilance practice but also to stakeholders from the entire healthcare system.

Dataset Information

Impulsivity and Concussion in Juvenile Rats: Examining Molecular and Structural Aspects of the Frontostriatal Pathway.

Publications

Impulsivity and Concussion in Juvenile Rats: Examining Molecular and Structural Aspects of the Frontostriatal Pathway.

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