Anxiety disorders are some of the most common psychiatric disorders today and occur
especially during adolescence when brain regions key for emotional regulation are still
maturing and thus vulnerable. Exposure to negative environmental factors during this period,
such as psychological stress, has been shown to affect this maturation by damaging the local
neuronal network. These damages could lead to the emergence of anxiety disorders along
with other psychiatric disorders. More specifically, stress induces neuroinflammation (NI) and
oxidative stress (OxS) which alter the maturation of parvalbumin-expressing interneurons
(PVI) and their protective perineuronal nets (PNN), known to be involved in neuronal
synchronizations and the preservation of the excitatory/inhibitory balance.
This project aims to investigate the mechanisms underlying the interaction between NI
and OxS that leads to brain alterations linked with anxiety during adolescence. More precisely
we explore a specific molecular pathway, the MMP9/RAGE pathway, which has been found
to mediate this interaction in an animal model for schizophrenia.
We used a translational approach with data coming from a clinical study on anxious
adolescence (the Mindfulteen study) and from an animal model of altered glucocorticoid
reactivity to stress, an alteration associated with anxiety traits. In humans, we explored the
MMP9/RAGE pathway in peripheral blood mononuclear cells (PBMC) stimulated with pro-
inflammatory and pro-oxidant challenges. In parallel, we used the animal model to further
analyse the pathway through immunohistochemistry, along with the presence of OxS and the
integrity of PVI/PNN in the brain.
Our human results did not show any significant differences in the MMP9/RAGE pathway
when comparing adolescents with low versus high anxiety. However, some tendencies of NI
and OxS inducing MMP9 were shown, especially in the less anxious subjects. As for the animal
model, we did not highlight significant differences in the PVI/PNN integrity, amount of OxS
and RAGE between animals of various glucocorticoid reactivity to stress.
As limitations in our human and animal exploration might have undermined our results,
it is important to keep investigating using our work as a step towards a better understanding
of anxiety and most importantly new perspectives of treatment for psychiatric patients.