Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Klaus,B.
Investigation of the role of micro-RNA 451 in traumatic brain injury-induced neurogenesis
An experimental study in controlled cortical impact model of mice
Humanmedizin; [ Diplomarbeit/Master Thesis (UNI) ] Medical University of Graz; 2019. pp.76.
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Schäfer Ute
- Ücal Muammer
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- Abstract:
- Aim: The aim of this study is to evaluate the potential role of miR451 in injury-induced neurogenesis by comparing behavioural and histological differences in miR451-/- and wild-type mice in an in-vivo trauma model. Introduction: The role of micro-RNAs, which are endogenous, non-coding, small RNA molecules, in the posttranscriptional regulation of gene expression has more and more come into focus. One of these micro-RNAs is the miR451, whose impact on oncogenesis, especially in the glioblastoma multiforme has been described and which might also influence the endogenous response to injury-induced loss of neuronal tissue. MiR451 is increased in the cerebrospinal fluid of patients with traumatic brain injury compared to non-injured controls and the influence of miR451 in neurogenic maturation processes has been shown in vitro. Methods: Wild-type mice and miR451-/- mice were craniectomized, and received a moderate brain trauma with controlled cortical impact (CCI). Newly proliferating cells were labelled with BrdU injections after CCI (at days 2-8). Potential differences in memory formation and spatial learning were monitored with a behavioural testing setup in an IntelliCage. Post-CCI neurogenesis was assessed with BrdU/NeuN co-immunostaining. Results: Increase in neurogenesis at the hippocampal dentate gyri detected 45 days after CCI was more prominent in the miR451-/- animals, both at the ipsi- and the contralateral sides. Newly produced neurons were detected in the hilus after brain injury in both animal groups, but the increase was particularly pronounced in the miR451-/- animals. A CCI-induced disturbance in short-term memory was detected in the IntelliCage, but the effect was independent of miR451 expression. CCI-induced deficits in the learning performance in IntelliCage were not detected in wild-type or miR451-/- mice. Discussion: Histological findings suggest that miR451-/- could play an important role in post-TBI neurogenesis. However, the higher neurogenesis in the dentate gyrus at day 45 did not show any detectable correlation in functional behavioural tests at 16-20 days post-TBI. Increased number of newly produced neurons aberrantly migrated from SGZ to hilus suggests that miR451-/- animals could be more susceptible to TBI-induced epileptogenesis. Whether this aberrant migration is caused purely by higher proliferation or whether miR451 has a regulatory role in neuronal migration remain to be further elucidated.