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Séminaire - Marloes HenckensThe neural signature of trauma susceptibility

Abstract :

Posttraumatic stress disorder (PTSD) is a psychiatric disorder which can develop after exposure to a traumatic event. Flashbacks, spontaneous recollection and recurrent nightmares of the trauma are amongst the most devastating symptoms of PTSD, through which patients continuously relive their trauma. Interestingly, only a small fraction (8-10%) of all trauma-exposed individuals eventually develops PTSD, whereas the rest is resilient and remains healthy. But how is the vulnerable brain different from the resilient one and when do these differences arise? Understanding the mechanisms behind these inter-individual differences could contribute to new clinical intervention strategies.

The use of a mouse model for PTSD allows us to study the mechanisms underlying relative resilience or susceptibility to PTSD in a longitudinal fashion, under controlled settings, while allowing for more invasive brain measurements. In this model, mice are first exposed to a traumatic event (i.e., severe unpredictable foot shock), followed by a trigger (i.e., mild predictable foot shock) in a different context one day later. Following a week of recovery, eventual development of PTSD-like symptomatology is assessed using a battery of behavioural tests to identify mice resilient and vulnerable to the trauma.

Combining this model with functional MRI obtained both before and after trauma exposure, allowed us to study the development of a potential imbalance in neural network function as a consequence of trauma in the PTSD-vulnerable vs resilient brain, as well as the potential presence of neural abnormalities prior to trauma exposure in these animals. To study brain responses to the trauma itself, we used the so-called targeted recombination in active populations (TRAP) mice, in which the injection of tamoxifen opens up a temporal window in which all neurons expressing certain immediate early genes (reflecting neuronal activity), are permanently fluorescently labelled. We injected these animals with tamoxifen just prior to trauma exposure, and again assessed PTSD-symptoms later on. By re-exposing them to the traumatic context just before sacrifice and analysing trauma retrieval-induced neuronal activity by immunohistochemistry, we were moreover able to analyse the storage of the trauma memory into long-term memory.
This allowed us to assess whether aberrant storage of the trauma memory could explain the emotional hypermnesia and contextual hypomnesia of the trauma that seem to characterize PTSD patients.

Selected publications

Modulation of the Hypothalamic-Pituitary-Adrenal Axis by Early Life Stress Exposure.van Bodegom M, Homberg JR, Henckens MJAG.Front Cell Neurosci. 2017 Apr 19;11:87. doi: 10.3389/fncel.2017.00087. eCollection 2017. Review.

Epigenetic programming of the neuroendocrine stress response by adult life stress.Dirven BCJ, Homberg JR, Kozicz T, Henckens MJAG. J Mol Endocrinol. 2017 Jul;59(1):R11-R31. doi: 10.1530/JME-17-0019. Epub 2017 Apr 11. Review

Region-specific roles of the corticotropin-releasing factor-urocortin system in stress. Henckens MJ, Deussing JM, Chen A. Nat Rev Neurosci. 2016 Oct;17(10):636-51. doi: 10.1038/nrn.2016.94. Epub 2016 Sep 2. Review.
PMID:27586075