Microglia under psychosocial stressors along the aging trajectory: Consequences on neuronal circuits, behavior, and
Li Tian1, Chin Wai Hui2, Kanchan Bisht2
1Neuroscience Center, University of Helsinki, Viikinkaari 4, Helsinki FIN-00014, Finland; Psychiatry Research Center, Beijing Huilongguan Hospital, Peking University, Beijing, China.
Abstract:
Mounting evidence indicates the importance of microglia for proper brain development and function, as well as in complex stress-related neuropsychiatric disorders and cognitive decline along the aging trajectory. Considering that microglia are resident immune cells of the brain, a homeostatic maintenance of their effector functions that impact neuronal circuitry, such as phagocytosis and secretion of inflammatory factors, is critical to prevent the onset and progression of these pathological conditions. However, the molecular mechanisms by which microglial functions can be properly regulated under healthy and pathological conditions are still largely unknown. We aim to summarize recent progress regarding the effects of psychosocial stress and oxidative stress on microglial phenotypes, leading to neuroinflammation and impaired microglia-synapse interactions, notably through our own studies of inbred mouse strains, and most importantly, to discuss about promising therapeutic strategies that take advantage of microglial functions to tackle such brain disorders in the context of adult psychosocial stress or aging-induced oxidative stress.
Insights
Microglia, the brain's immune cells, are crucial for brain health. Understanding how stress and aging affect microglia is key to developing new therapies for neuropsychiatric disorders and cognitive decline.
Area of Science:
- Neuroscience
- Immunology
- Neurobiology
Background:
- Microglia are vital for brain development, function, and aging.
- Their dysregulation contributes to neuropsychiatric disorders and cognitive decline.
- Maintaining microglial homeostasis is critical for preventing brain pathology.
Purpose of the Study:
- To review the impact of psychosocial and oxidative stress on microglial phenotypes.
- To explore how these stresses affect neuroinflammation and microglia-synapse interactions.
- To discuss therapeutic strategies targeting microglial function in stress and aging.
Main Methods:
- Analysis of inbred mouse strains under stress and aging conditions.
- Review of current literature on microglial function and neuroinflammation.
- Investigation of microglia-synapse interactions.
Main Results:
- Psychosocial and oxidative stress alter microglial phenotypes, promoting neuroinflammation.
- Impaired microglia-synapse interactions are linked to stress and aging.
- Specific molecular mechanisms regulating microglial function remain largely unknown.
Conclusions:
- Microglial dysfunction is implicated in stress-related and aging-related brain disorders.
- Targeting microglial pathways offers potential therapeutic avenues.
- Further research is needed to elucidate regulatory mechanisms for therapeutic development.
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