Neuron-derived vesicles as therapeutic vectors: modulation of M6a content in EVs and their administration in a chronic stress model
Agustina Chmiel1,2, Ma. Victoria Bühler1,2, Maximiliano Cosenza1,2, Marcela A. Brocco1,2, Melisa Monteleone1,2
Instituto de Investigaciones Biotecnológicas (IIB-CONICET)
Escuela de Bio y Nanotecnología (EByN-UNSAM), San Martín, Buenos Aires. Argentina
Presenting Author: Marcela Brocco
mbrocco@iib.unsam.edu.ar
Chronic stress contributes to the development of mood disorders such as depression. Current treatments are often limited in efficacy and show adverse effects. We propose an alternative therapeutic strategy based on extracellular vesicles (EVs). Due to their small size and high biocompatibility EVs can facilitate biomolecule delivery to the brain. As a potential biomolecule of interest, we propose the neuronal protein M6a, which is involved in neuronal connectivity and whose levels are altered by chronic stress.
EVs were obtained from the neural cell line HT22 through differential centrifugation and characterized by TEM and nanoparticle analysis (NTA). EVs were loaded with M6a-GFP or GFP (control) plasmids. The loading was confirmed by plasmid DNA extraction.
In a murine model of chronic stress, treatment with loaded EVs partially reversed weight loss and restored hippocampal M6a levels, although no significant behavioral changes were observed. These effects were independent of the loaded plasmid, suggesting a possible neuroprotective role of endogenous factors present in HT22-derived EVs.
Current work focuses on obtaining EVs carrying M6a-GFP through plasmid overexpression in HT22 cells. Once such EVs are isolated, their function will be evaluated through the transference of M6a to recipient cells in HT22-3D spheroids and in differentiated HT22 cells.
We hope to obtain HT22-derived EVs with an increased proportion of M6a to test their neuroprotective effect in vivo.