Exo70 protects against memory and synaptic impairments following mild traumatic brain injury

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dc.catalogadorjwg
dc.contributor.authorLira, Matias
dc.contributor.authorAbarca, Jorge
dc.contributor.authorMira, Rodrigo G.
dc.contributor.authorZamorano, Pedro
dc.contributor.authorCerpa Nebott, Waldo Francisco
dc.date.accessioned2024-01-26T13:11:08Z
dc.date.available2024-01-26T13:11:08Z
dc.date.issued2023
dc.description.abstractMild traumatic brain injury (mTBI) is damage to the brain due to external forces. It is the most frequent form of brain trauma and a leading cause of disability in young adults. Hippocampal glutamatergic transmission and synaptic plasticity are impaired after mTBI, and NMDA receptors play critical in these functions. The Exocyst is a vesicle tethering complex implicated in the trafficking of glutamate receptors. We have previously shown that Exo70, a critical exocyst's subunit, redistributes in the synapse and increases its interaction with GluN2B in response to mTBI, suggesting a role in the distribution of the GluN2B subunit of NMDARs from synaptic to extrasynaptic membranes. We tested whether Exo70 could prevent NMDAR depletion from the synapse and limit mTBI pathology. To this end, we used a modified Maryland's model of mTBI in mice overexpressing Exo70 in CA1 pyramidal neurons through a lentiviral vector transduction. We showed that after mTBI, the overexpression of Exo70 prevented the cognitive impairment observed in mice infected with a control vector using the Morris' water maze paradigm. Following these findings, mice overexpressing Exo70 showed basal and NMDAR-dependent hippocampal synaptic transmission comparable to sham animals, preventing the deterioration induced by mTBI. Long-term potentiation, abundant synaptic GluN2B-containing NMDARs, and downstream signaling effectors showed that Exo70 overexpression prevented the mTBI-induced alterations. Our findings revealed a crucial role of Exo70 in NMDAR trafficking to the synapse and suggested that the Exocyst complex may be a critical component of the basal machinery that regulates NMDAR distribution in health and disease.
dc.fuente.origenORCID
dc.identifier.doi10.21203/rs.3.rs-3437728/v1
dc.identifier.urihttps://doi.org/10.21203/rs.3.rs-3437728/v1
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/80971
dc.information.autorucFacultad de Ciencias Biológicas; Cerpa Nebott, Waldo Francisco; 0000-0001-7344-0144; 16584
dc.language.isoen
dc.nota.accesoContenido completo
dc.rightsacceso abierto
dc.subjectTraumatic brain injury
dc.subjectExocyst
dc.subjectExo70
dc.subjectNMDAR
dc.subjectLTP
dc.subjectMemory
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.titleExo70 protects against memory and synaptic impairments following mild traumatic brain injury
dc.typepreprint
sipa.codpersvinculados16584
sipa.trazabilidadORCID;2024-01-15
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