A2: Modulation of synaptic plasticity after trauma

PI: T. Böckers

A severe trauma is often (about 33-58%) associated with acute or chronic alterations of the central nervous system leading to psychiatric disturbances ranging from posttraumatic stress disorders (PTSD) to depressive illnesses and severe anxiety disorders that are accompanied by the perturbation of social interactions. Over the last years it could be shown that the number, morphology and molecular composition of excitatory synapses are one of the key structures that are causative for neuropsychiatric as well as neurodegenerative disorders (“synaptopathies”). During the first funding period we found that thorax trauma (TXT) causes a dramatic reduction of synapses (50%) in the hippocampus. The loss of synapses that are causative for memory impairments are most likely caused by CRH release and BDNF reduction within the hippocampus. Therefore, we propose that a peripheral trauma is also causing a brain region specific “synaptopathy”. 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 and synapse number is only very slowly recovering after trauma. Synapses missing isoforms of the scaffolding molecule Shank3 show only a slight reduction of excitatory synapses and morphological signs of synaptic plasticity after TBI are missing. The establishment of an ELISA for the detection of Shank3 in mouse and man enables us to detect altering Shank3 levels tissue from humans and trauma animal models as well as in blood and CSF. Now, we plan to analyze whether the loss of hippocampal synapses after TXT is not restricted to thoracic injuries and to further elucidate the hitherto unknown signaling pathways. The TBI model provides the possibility to study synaptic plasticity. Therefore, TBI can be employed as a unique model to study how/if neuronal activity and protein function contributes to plasticity and the integrity of synaptic subcompartments within the CNS. Moreover, we plan to analyze serum Shank3 levels in response to inflammation and peripheral trauma in tissue, serum and CSF in mice and man.

Principle Investigator

  • 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
  • Homepage
Shank molecules are selectively located in postsynaptic densities of excitatory synapses (yellow dots)