Extracellular vesicles (EVs) play an important role in intercellular communication as carriers of signalling molecules such as bioactive miRNAs, proteins and lipids. EVs are key players in the functioning of the central nervous system (CNS) by influencing synaptic events and modulating recipient neurons. However, the specific role of neuron‐to‐neuron communication via EVs is still not well understood. Here, we provide evidence that primary neurons uptake neuron‐derived EVs in the soma, dendrites, and even in the dendritic spines, and carry synaptic proteins. Neuron‐derived EVs increased spine density and promoted the phosphorylation of Akt and ribosomal protein S6 (RPS6), via TrkB‐signalling, without impairing the neuronal network activity. Strikingly, EVs exerted a trophic effect on challenged nutrient‐deprived neurons. Altogether, our results place EVs in the spotlight for synaptic plasticity modulation as well as a possible therapeutic tool to fight neurodegeneration.
17 February 2010 in International Journal of Neuropsychopharmacology
Major depression, affecting an estimated 350 million people worldwide, poses a serious social and economic threat to modern societies. There are currently two major problems calling for innovative research approaches, namely, the absence of biomarkers predicting antidepressant response and the lack of conceptually novel antidepressant compounds. Both, biomarker predictinga prioriwhether an individual patient will respond to the treatment of choice as well as an early distinction of responders and nonresponders during antidepressant therapy can have a significant impact on improving this situation. Biosignatures predicting antidepressant responsea priorior early in treatment would enable an evidence-based decision making on available treatment options. However, research to date does not identify any biologic or genetic predictors of sufficient clinical utility to inform the selection of specific antidepressant compound for an individual patient. In this review, we propose an optimized translational research strategy to overcome some of the major limitations in biomarker discovery. We are confident that early transfer and integration of data between both species, ideally leading to mutual supportive evidence from both preclinical and clinical studies, are most suitable to address some of the obstacles of current depression research.