(A Study from Desmedt’s team in collaboration with PV Piazza & Lundbeck Lab.)
Comment

The paper shows (in collaboration with Lundbeck Laboratory) that acute administration of brexpiprazole, a new antipsychotic drug with pro-cognitive effects in rodents, (0.3 mg/kg) 7 days’ post-trauma persistently prevents the expression of PTSD-like memory in mice, while promoting normal fear memory. Specifically, It specifically blocks the emotional hypermnesia of PTSD while enhancing (with superior efficacy when compared to diazepam, prazosin and escitalopram) memory for the traumatic context, which is impaired in PTSD. Moreover, this treatment also normalizes most of the alterations in the hippocampal-amygdalar network activation associated with PTSD-like memory. These preclinical data indicate that brexpiprazole could represent a new pharmacological treatment of PTSD promoting the normalization of traumatic memory.
Reference

Ducourneau E.G., Guette C., Perrot D., Mondesir M., Mombereau C., Arnt J. Desmedt* A. and Piazza* P.V. Brexpiprazole blocks Posttraumatic stress disorder-like memory while promoting normal fear memory. Molecular Psychiatry. 2020 Aug 19.
*co-last authorship.

doi: 10.1038/s41380-020-0852-z
First author

Eva Ducourneau
Team Marighetto/Desmedt
(“Pathophysiology of declarative memory”)

Contact
Aline Desmedt
Team Marighetto/Desmedt
(“Pathophysiology of declarative memory”)

Meeting room: Amphi du Centre Broca

Dr. Marloes Henckens from Department of Cognitive Neuroscience, Donders Institute for Brain (Netherlands)'s lab will give a presentation entitled 'The neural signature of trauma susceptibility'

Invitant : Aline Desmedt, PhD , Maitre de Conférence au Neurocentre Magendie, Team Marighetto 'Pathophysiology of declarative memory'

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.

Aline Desmedt est intervenu dans l'émission de France 5 pour expliquer son modèle d'étude du PTSD. Retrouvez son intervention au bout de 20'30".
https://www.france.tv/france-5/enquete-de-sante/516655-attentats-agressions-surmonter-le-traumatisme.html

Zoom sur les travaux d'Aline Desmedt à l'occasion de la semaine du cerveau 2018.

Neurocentre Magendie de 9 à 12h30
Valérie Crepel (Inmed, Marseille)
Abnormal synaptic transmission in epilepsy: role of kainate receptors
Fadel Tissir (UCLouvain, Belgique)
Linking genes to brain development and disorders. A focus on corticogenesis
Pierre Trifilieff (NutriNeuro, Bordeaux)
Modulation of dopamine transmission by membrane lipid composition: from receptor signaling to reward processing
Claire Rampon (CRCA, Université Paul Sabatier, Toulouse)
New neurons for old brains : manipulating adult hippocampal neurogenesis in Alzheimer's disease
Olivier Nicole (IMN, Bordeaux)
Cortical switch in the composition of synaptic GluN2-containing NMDA receptors drives the formation of long-lasting associative memory
Aline Desmedt (Neurocentre Magendie, Bordeaux)
PTSD-like memory is associated with specific hippocampal and amygdala neuromorphological alterations



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