The development of lasting impairments: A mild pediatric brain injury alters gene expression, dendritic morphology, and synaptic connectivity in the prefrontal cortex of rats

R. Mychasiuk, H. Hehar, I. Ma, B. Kolb, M. J. Esser

Research output: Contribution to journalArticleResearchpeer-review

29 Citations (Scopus)

Abstract

Apart from therapeutic discovery, the study of mild traumatic brain injury (mTBI) has been focused on two challenges: why do a majority of individuals recover with little concern, while a considerable proportion suffer with persistent and often debilitating symptomology; and, how do mild injuries significantly increase risk for an early-onset neurodegeneration? Owing to a lack of observable damage following mTBI, this study was designed to determine if there were changes in neuronal morphology, synaptic connectivity, and epigenetic patterning that could contribute to the manifestation of persistent neurological dysfunction. Prefrontal cortex tissue from male and female rats was used for Golgi-Cox analysis along with the profiling of changes in gene expression (BDNF, DNMT1, FGF2, IGF1, Nogo-A, OXYR, and TERT) and telomere length (TL), following a single mTBI or sham injury in the juvenile period. Golgi-Cox analysis of dendritic branch order, dendritic length, and spine density demonstrate that an early mTBI increases complexity of pyramidal neurons in the mPFC. Furthermore, there are also substantial changes in the expression levels of the seven genes of interest and TL following a single mild injury in this brain region. The results from the neuroanatomical measures and changes in gene expression indicate that the mTBI disrupts normal pruning processes that are typically underway at this point in development. In addition, there are significant interactions between the social environment and epigenetic processes that work in concert to perpetuate neurological dysfunction.

Original languageEnglish
Pages (from-to)145-155
Number of pages11
JournalNeuroscience
Volume288
DOIs
Publication statusPublished - 2 Mar 2015
Externally publishedYes

Keywords

  • Epigenetics
  • Golgi-Cox
  • Neurodegeneration
  • Pruning
  • QRT-PCR
  • Telomere

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