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Los bioquímicos de Stanford lograron cambiar la forma en que el cerebro se comunica consigo mismo

Este hallazgo podría tener implicaciones de gran alcance para el tratamiento de enfermedades cerebrales causadas por anormalidades en el procesamiento e intercambio de información sináptica.

Los bioquímicos utilizan enzimas para cambiar la forma en que las células cerebrales interactúan entre sí.

Mientras lees esta oración, las neuronas de tu cerebro se comunican entre sí emitiendo señales eléctricas rápidas. Se comunican entre sí a través de sinapsis, que son pequeñas uniones especializadas.

Hay muchos tipos de sinapsis que se desarrollan entre las neuronas, incluidos «excitadores» e «inhibidores», y los científicos aún no están seguros de los métodos específicos mediante los cuales se forman estas estructuras. Un equipo de bioquímica ha proporcionado información importante sobre este tema al demostrar que los tipos de sustancias químicas producidas por las sinapsis determinan en última instancia qué tipos de sinapsis se producen entre las neuronas.

Nicole Wong, Matthew Xu Friedman y Soham Chanda

De izquierda a derecha: Nicole Wong y Matthew Xu-Friedman de la Universidad de Buffalo, y Soham Chanda, profesor asistente en el Departamento de Bioquímica y Biología Molecular de la CSU. Crédito: Douglas Levere/Universidad de Buffalo

Un equipo de investigadores de universidad estatal de colorado, universidad de búfalo, Universidad Stanfordy la Universidad Estatal de California, Fullerton realizaron la investigación.

Soham Chanda, profesor asistente en el Departamento de Bioquímica y Biología Molecular de la Universidad Estatal de Colorado, dirigió el estudio publicado en University at Buffalo.

In the lab, Chanda and colleagues were able to make synapse changes between excitatory and inhibitory types, using only enzymes, by making the neurons express just a few genes that induced a cascade of changes in the synapses’ machinery. Such a breakthrough could have major implications for treating brain diseases that are caused by malfunctions in synaptic information processing and exchange.

“We know very little about how the human brain functions, and at the center of it, we need to understand how neurons communicate with each other,” Chanda said. “Understanding the fundamental mechanisms of synapse formation and maintenance has tremendous implications in understanding brain disorders.”

Their results show that the cell-adhesion proteins expressed in the synaptic junction area are not the only purveyors of the synapses’ function, as some have thought; rather, chemicals called neurotransmitters that are released from the presynaptic site (where the information is coming from) also seem to play a major role in controlling which types of synapses form, and where.

The CSU team used stem cell-derived human neurons to demonstrate their ability to produce certain types of synaptic connections by the controlled release of specific neurotransmitters. Collaborators at the University at Buffalo showed the same phenomenon in live mouse brains.

“Synapses need lots of other machinery; the neurons took care of all that and turned excitatory synapses into inhibitory ones – a fundamental change in their identity,” Xu-Friedman said.

Chanda is fascinated by neurons, “because no other cell type in the human body has the same level of functional complexity that is tied so closely to their shape and structure.”

University at Buffalo biological sciences researchers Matthew A. Xu-Friedman and Nicole F. Wong also made significant contributions, with Xu-Friedman serving as a senior author alongside Stanford University’s Chanda and Thomas C. Südhof, and Wong serving as a first author alongside Colorado State University’s Scott R. Burlingham and Lindsay Peterkin. Chanda earned his Ph.D. in Xu-lab Friedman’s at the University at Buffalo over a decade ago and finished his postdoctoral studies in Südhof’s group at Stanford in 2018.

The study was funded by Colorado State University and the National Institutes of Health.

Reference: “Induction of synapse formation by de novo neurotransmitter synthesis” by Scott R. Burlingham, Nicole F. Wong, Lindsay Peterkin, Lily Lubow, Carolina Dos Santos Passos, Orion Benner, Michael Ghebrial, Thomas P. Cast, Matthew A. Xu-Friedman, Thomas C. Südhof, and Soham Chanda, 1 June 2022, Nature Communications.
DOI: 10.1038/s41467-022-30756-z

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