A2: Modulation of synaptic plasticity after trauma
PI: T. Böckers
A severe trauma is oftentimes (about 33-58%) associated with acute or chronic alterations of the central nervous system leading to psychiatric disturbances. Over the last years it could be shown that the number, morphology and molecular composition of excitatory as well as inhibitory synapses are one of the key structures that are causative for neuropsychiatric as well as neurodegenerative disorders (“synaptopathies”). Therefore, synaptic contacts seem to play an essential role for acute as well as chronic diseases of the central nervous system (CNS). In excitatory synapses glutamate receptors, cell adhesion molecules as well as scaffolding proteins of the postsynaptic density (PSD) like MaGuks/ProSAP/Shanks and local signaling pathways are of special interest since they organise and fine-tune synaptic function. Moreover, the relationship of inhibition vs. excitation in brain region specific microcircuits needs to be analysed since it is known to modulate brain function.
This study aims to analyse the role of synaptic contacts/synaptic molecules according to traumatic injuries focusing on three major questions:
(1) Can we detect specific synaptic proteins after traumatic events in the serum of patients and is the appearance and/or the amount of protein related to the severity of the trauma?
(2) What is the time-course of de- and regeneration of synaptic contacts after head trauma, what brain regions are mainly involved and is the program of synaptogenesis comparable to early brain development? What is the role of major plasticity genes of the ProSAP/Shank family?
(3) How does the brain react to a severe trauma of the periphery and how does this relate to the observations that have been seen after a direct head/brain trauma?