Zusammenstellung von Bildern aus dem Sonderforschungsbereich

A02: Modulation of synaptic plasticity after trauma

PI: T. Böckers

During the second funding period we have been analyzing synaptic dynamics and plasticity after traumatic injuries: (I) A peripheral trauma causes a dramatic reduction of synapses (50%) in the hippocampus that could be responsible for a delirium-like state. The loss of synapses is caused by local CRH release and BDNF reduction within the hippocampus. In addition, upon CRH action, mitochondria of hippocampal neurons are structurally altered and also recover after time. The intracellular molecular pathways downstream from CRH receptor 1 leading to these structural alterations (synapses, mitochondria) are different. (II) A traumatic brain injury (TBI) causes the loss of hippocampal synapses at the injury site as well as at the contralateral site within a week after injury. Interestingly, synapses missing isoforms of the scaffolding molecule Shank3 show only a slight reduction of excitatory synapses and no morphological signs of synaptic plasticity after TBI. (III) The establishment of an ELISA for the detection of Shank3 in mouse is helping to determine exact Shank3 concentrations in selected brain regions of WT and (Shank3) KO animals. Based on these results, we plan to work on the following hypotheses in the next funding period: H1 The loss of synapses and the alterations of mitochondria after CRH application (release) are mediated by CRH receptor 1 dependent, complex intracellular signaling cascades in hippocampal neurons. H2 The TBI model provides the possibility to study the early molecular mechanisms of a plastic vs. a “non-plastic” Shank3 KO brain. H3 iPSC derived cortical/ hippocampal neurons and brain organoids can serve as a human in vitro model for brain affection after trauma.

Projektleiter

Prof. Dr. med Tobias M. Böckers
Universität Ulm
Institut für Anatomie und Zellbiologie
Albert-Einstein-Allee 14
89081 Ulm
Tel.: +49 731 500 23220/23221
Fax: +49 731 500 23217
tobias.boeckers(at)uni-ulm.de
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