Potential use of the circulating neuronal glycoprotein M6a as a stress biomarker.

MELISA C MONTELEONE

Congreso; XXXV Reunión Anual SAN 2020; 2020

Depression affects hundreds of people. Despite its complex etiology, it is acceptedthat chronic stress is a key factor in its onset. Since stress main effects occur in thebrain, an inaccessible area, we focused in detecting stress molecules in peripheralfluids such as blood or saliva. We showed that the neural glycoprotein M6a can bedetected in serum. M6a contributes to neural plasticity promoting neurite andfilopodium growth and synaptogenesis (Alfonso 2004, Brocco 2010, Formoso2016). Next, we showed that M6a is carried in extracellular vesicles (EVs). EVs areliberated by cells in physiological and pathological conditions, can be isolated fromalmost all fluids and are used in the diagnosis of several diseases.Then, we showed that M6a-carrying EVs, but not EVs without M6a, induced aphenotypical change in COS-7 cells observed as filopodium formation. Thisindicates that M6a coupled to EVs might participate in cellular communication andcontribute to cellular plasticity maintenance.Since M6a has also been related to several neuropsychiatric disorders, we studiedserum M6a levels in chronically stressed animals. We found that stress alteredM6a levels in blood. Thus, we proposed M6a as a putative stress biomarker(Monteleone, 2017).Now using patient saliva samples, we showed that M6a levels positively correlatedwith the scores for the perceived stress scale in individuals diagnosed withdepression. This reinforces the idea of M6a as a stress-responsive protein whoselevels changes when the individual experiences stress. Furthermore, salivasamples of depressed patients treated with classic antidepressants differed in theirM6a levels with respect to untreated patients. This suggests a potential use of M6afor evaluation of antidepressant treatment efficacy (Monteleone 2020, submitted).These findings encourage us to continue the study of M6a as a putative stressbiomarker and also to determine if EVs can per se be messengers of the stresssignal.