Cette découverte pourrait avoir des conséquences considérables pour le traitement des maladies du cerveau causées par des anomalies dans le traitement et l’échange d’informations synaptiques.
Les biochimistes utilisent des enzymes pour modifier la façon dont les cellules du cerveau interagissent entre elles.
Pendant que vous lisez cette phrase, les neurones de votre cerveau communiquent entre eux en émettant des signaux électriques rapides. Ils communiquent entre eux par l’intermédiaire de synapses, qui sont de minuscules jonctions spécialisées.
Il existe de nombreux types de synapses qui se développent entre les neurones, y compris les synapses “excitatrices” et “inhibitrices”, et les scientifiques ne sont toujours pas certains des méthodes spécifiques par lesquelles ces structures sont formées. Une équipe de biochimistes a apporté un éclairage important sur ce sujet en démontrant que les types de substances chimiques produites par les synapses déterminent en définitive les types de synapses qui se forment entre les neurones.
De gauche à droite : Nicole Wong et Matthew Xu-Friedman de l’Université de Buffalo, et Soham Chanda, professeur adjoint au département de biochimie et de biologie moléculaire du CSU. Crédit : Douglas Levere/Université de Buffalo
Une équipe de chercheurs de l’Université d’État du Colorado, de l’Université de Buffalo, de l’Université de Stanford et de l’Université d’État de Californie à Fullerton a mené ces recherches.
Soham Chanda, professeur adjoint au département de biochimie et de biologie moléculaire de l’université d’État du Colorado, a dirigé l’étude publiée dans le magazine “The American”. Nature Communications that demonstrates the possibility of changing the identity of synapses between neurons, both in vitro and in vivo, through enzymatic means. The other senior scientists who contributed to the project were Thomas Südhof of Stanford University and Matthew Xu-Friedman of the 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
