Neuromodulation and inflammation in stress-related mental disorders

PI: Dimitri De Bundel

 

C4N researchers:

Wissal Allaoui (PhD student)

Anouk Pierre (PhD student)

Andries Van Schuerbeek (PhD student)

Blazej Pedzich (PhD student)

An De Prins (PhD student)

 

Acute stress promotes adaptation to mental or physical challenges but excessive and chronic stress can lead to maladaptive changes in the brain that culminate in disrupted reward and fear processing as observed in major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). These stress-related mental disorders are a major source of disability worldwide and presently available treatments are ineffective in up to one third of patients. Identification of the biological processes that contribute to treatment resistance is needed for the discovery of novel targets and further therapeutic translation. Inflammation is associated with symptom severity and treatment resistance and may be a key obstacle in successful treatment of patients with MDD or PTSD. We study the interaction between stress and inflammation to determine the potential effects of innovative experimental approaches in rodent models for stress-related mental disorders.

In a first line of research we investigate how gut-brain peptide systems such as ghrelin and neuromedin u directly affect stress and fear processing through modulation of specific brain circuits and indirectly by their effects on inflammation. In a second line of research we similarly investigate how serotoninergic hallucinogens affect fear processing directly by altering neuronal activity and indirectly by supressing inflammation. In a third line of research, we examine the effect of transcranial direct current stimulation on fear processing. This non-invasive brain modulation technique is based on the delivery of a constant direct current to the surface of the scalp and has been proposed as an adjuvant therapy for stress-related mental disorders but the putative mechanism of action remains unknown. We will evaluate the potential involvement of neurotrophic factors and inflammatory cytokines.