Browsing by Author "Lira, Matias"

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    Effect of Alcohol on Hippocampal-Dependent Plasticity and Behavior: Role of Glutamatergic Synaptic Transmission
    (Frontiers Media S.A., 2020) Mira, Rodrigo G.; Lira, Matias; Cerpa Nebott Waldo Francisco; Tapia-Rojas, Cheril; Rebolledo, Daniela; Quintanilla, Rodrigo A.
    © Copyright © 2020 Mira, Lira, Tapia-Rojas, Rebolledo, Quintanilla and Cerpa. Problematic alcohol drinking and alcohol dependence are an increasing health problem worldwide. Alcohol abuse is responsible for approximately 5% of the total deaths in the world, but addictive consumption of it has a substantial impact on neurological and memory disabilities throughout the population. One of the better-studied brain areas involved in cognitive functions is the hippocampus, which is also an essential brain region targeted by ethanol. Accumulated evidence in several rodent models has shown that ethanol treatment produces cognitive impairment in hippocampal-dependent tasks. These adverse effects may be related to the fact that ethanol impairs the cellular and synaptic plasticity mechanisms, including adverse changes in neuronal morphology, spine architecture, neuronal communication, and finally an increase in neuronal death. There is evidence that the damage that occurs in the different brain structures is varied according to the stage of development during which the subjects are exposed to ethanol, and even much earlier exposure to it would cause damage in the adult stage. Studies on the cellular and cognitive deficiencies produced by alcohol in the brain are needed in order to search for new strategies to reduce alcohol neuronal toxicity and to understand its consequences on memory and cognitive performance with emphasis on the crucial stages of development, including prenatal events to adulthood.
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    Exo70 protects against memory and synaptic impairments following mild traumatic brain injury
    (2023) Lira, Matias; Abarca, Jorge; Mira, Rodrigo G.; Zamorano, Pedro; Cerpa Nebott, Waldo Francisco
    Mild 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.