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Article

Exo70 Protects Against Memory and Synaptic Impairments Following Mild Traumatic Brain Injury

1
Laboratorio de Función y Patología Neuronal, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8331150, Chile
2
Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Universidad de Magallanes, Punta Arenas 6210005, Chile
3
Departamento Biomédico, Universidad de Antofagasta, Antofagasta 1271155, Chile
4
Instituto Antofagasta, Universidad de Antofagasta, Antofagasta 1271155, Chile
*
Author to whom correspondence should be addressed.
Antioxidants 2025, 14(6), 640; https://doi.org/10.3390/antiox14060640 (registering DOI)
Submission received: 26 March 2025 / Revised: 17 May 2025 / Accepted: 22 May 2025 / Published: 26 May 2025
(This article belongs to the Special Issue Oxidative Stress in Brain Function—2nd Edition)

Abstract

Mild traumatic brain injury (mTBI), a leading cause of disability in young adults, often results from external forces that damage the brain. Cellularly, mTBI induces oxidative stress, characterized by excessive reactive oxygen species (ROS) and diminished antioxidant capacity. This redox imbalance disrupts hippocampal glutamatergic transmission and synaptic plasticity, where NMDA receptors (NMDARs) are crucial. The exocyst, a vesicle tethering complex, is implicated in glutamate receptor trafficking. We previously showed that Exo70, a key exocyst subunit, redistributes within synapses and increases its interaction with the NMDAR subunit GluN2B following mTBI, suggesting a role in GluN2B distribution from synaptic to extrasynaptic sites. This study investigated whether Exo70 could mitigate mTBI pathology by modulating NMDAR trafficking under elevated oxidative stress. Using a modified Maryland mTBI mouse model, we overexpressed Exo70 in CA1 pyramidal neurons via lentiviral transduction. Exo70 overexpression prevented mTBI-induced cognitive impairment, assessed by the Morris water maze. Moreover, these mice exhibited basal and NMDAR-dependent hippocampal synaptic transmission comparable to sham animals, preventing mTBI-induced deterioration. Preserved long-term potentiation, abundant synaptic GluN2B-containing NMDARs, and downstream signaling indicated that Exo70 overexpression prevented mTBI-related alterations. Our findings highlight Exo70’s crucial role in NMDAR trafficking, potentially counteracting oxidative stress effects. The exocyst complex may be a critical component of the machinery regulating NMDAR distribution in health and disease, particularly in pathologies featuring oxidative stress and NMDAR dysfunction, like mTBI.
Keywords: traumatic brain injury; exocyst; Exo70; NMDAR; LTP; memory traumatic brain injury; exocyst; Exo70; NMDAR; LTP; memory

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MDPI and ACS Style

Lira, M.; Abarca, J.; Mira, R.G.; Zamorano, P.; Cerpa, W. Exo70 Protects Against Memory and Synaptic Impairments Following Mild Traumatic Brain Injury. Antioxidants 2025, 14, 640. https://doi.org/10.3390/antiox14060640

AMA Style

Lira M, Abarca J, Mira RG, Zamorano P, Cerpa W. Exo70 Protects Against Memory and Synaptic Impairments Following Mild Traumatic Brain Injury. Antioxidants. 2025; 14(6):640. https://doi.org/10.3390/antiox14060640

Chicago/Turabian Style

Lira, Matías, Jorge Abarca, Rodrigo G. Mira, Pedro Zamorano, and Waldo Cerpa. 2025. "Exo70 Protects Against Memory and Synaptic Impairments Following Mild Traumatic Brain Injury" Antioxidants 14, no. 6: 640. https://doi.org/10.3390/antiox14060640

APA Style

Lira, M., Abarca, J., Mira, R. G., Zamorano, P., & Cerpa, W. (2025). Exo70 Protects Against Memory and Synaptic Impairments Following Mild Traumatic Brain Injury. Antioxidants, 14(6), 640. https://doi.org/10.3390/antiox14060640

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