The effect of aged microglia on synaptic impairment and its relevance in neurodegenerative diseases

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dc.contributor.authorJose Trivino, Juan
dc.contributor.authorvon Bernhardi, Rommy
dc.date.accessioned2025-01-20T23:51:28Z
dc.date.available2025-01-20T23:51:28Z
dc.date.issued2021
dc.description.abstractMicroglia serve key functions in the central nervous system (CNS), participating in the establishment and regulation of synapses and the neuronal network, and regulating activity-dependent plastic changes. As the neuroimmune system, they respond to endogenous and exogenous signals to protect the CNS. In aging, one of the main changes is the establishment of inflamm-aging, a mild chronic inflammation that reduces microglial response to stressors. Neuroinflammation depends mainly on the increased activation of microglia. Microglia over-activation may result in a reduced capacity for performing normal functions related to migration, clearance, and the adoption of an anti-inflammatory state, contributing to an increased susceptibility for neurodegeneration. Oxidative stress contributes both to aging and to the progression of neurodegenerative diseases. Increased production of reactive oxygen species (ROS) and neuroinflammation associated with age-and disease dependent mechanisms affect synaptic activity and neurotransmission, leading to cognitive dysfunction. Astrocytes prevent microglial cell cytotoxicity by mechanisms mediated by transforming growth factor 131 (TGF131). However, TGF131-Smad3 pathway is impaired in aging, and the age-related impairment of TGF13 signaling can reduce protective activation while facilitating cytotoxic activation of microglia. A critical analysis on the effect of aging microglia on neuronal function is relevant for the understanding of age-related changes on neuronal function. Here, we present evidence in the context of the ?microglial dysregulation hypothesis?, which leads to the reduction of the protective functions and increased cytotoxicity of microglia, to discuss the mechanisms involved in neurodegenerative changes and Alzheimer?s disease.
dc.fuente.origenWOS
dc.identifier.doi10.1016/j.neuint.2021.104982
dc.identifier.eissn1872-9754
dc.identifier.issn0197-0186
dc.identifier.urihttps://doi.org/10.1016/j.neuint.2021.104982
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/94820
dc.identifier.wosidWOS:000636077900005
dc.language.isoen
dc.revistaNeurochemistry international
dc.rightsacceso restringido
dc.subjectAging
dc.subjectAlzheimer?s disease
dc.subjectGlial cells
dc.subjectNeurodegeneration
dc.subjectNeuroinflammation
dc.subjectNeuronal function
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleThe effect of aged microglia on synaptic impairment and its relevance in neurodegenerative diseases
dc.typeartículo
dc.volumen144
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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