Activated microglia-induced deficits in excitatory synapses through IL-1β: implications for cognitive impairment in sepsis
Abstract
Recent clinical studies have shown that sepsis survivors may develop long-term cognitive impairments. The cellular and molecular mechanisms involved in these events are not well understood. This study investigated synaptic deficits in sepsis and the involvement of glial cells in this process. Septic animals showed memory impairment and reduced numbers of hippocampal and cortical excitatory synapses, identified by synaptophysin/PSD-95 co-localization, 9 days after disease onset. The behavioral deficits and synaptophysin/PSD-95 co-localization were rescued to normal levels within 30 days post-sepsis. Septic mice presented activation of microglia and reactive astrogliosis, which are hallmarks of brain injury and could be involved in the associated synaptic deficits. We treated neuronal cultures with conditioned medium derived from cultured astrocytes (ACM) and microglia (MCM) that were either non-stimulated or stimulated with lipopolysaccharide (LPS) to investigate the molecular mechanisms underlying synaptic deficits in sepsis. ACM and MCM increased the number of synapses between cortical neurons in vitro, and these effects were antagonized by LPS stimulation. LPS-MCM reduced the number of synapses by 50%, but LPS-ACM increased the number of synapses by 500%. Analysis of the composition of these conditioned media revealed increased levels of IL-1β in LPS-MCM. Furthermore, inhibition of IL-1β signaling through the addition of a soluble IL-1β receptor antagonist (IL-1 Ra) fully p…
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Activated microglial cells in septic animals exhibit heightened secretion of pro-inflammatory factors that result in synaptic impairment, forming cellular basis of memory and cognitive decline.
“It has been previously reported that activated microglial cells in septic animals exhibit heightened secretion of pro-inflammatory factors that result in synaptic impairment, which forms the cellular basis of memory and cognitive decline (Moraes et al., 2015).”
From miR-142-3p Regulates BDNF Expression in Activated Rodent Microglia Through Its Target CAMK2A (2020) · cites this paper as Moraes et al., 2015
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Brain Barrier Breakdown as a Cause and Consequence of Neuroinflammation in Sepsis
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miR-142-3p Regulates BDNF Expression in Activated Rodent Microglia Through Its Target CAMK2A
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- Authors
- Moraes, C. A., Santos, G., Spohr, T. C. L. D. S. E., D’Avila, J. C., Lima, F. R. S., Benjamim, C. F., Bozza, F. A., & Gomes, F. C. A.
- Venue
- Molecular Neurobiology
- Published
- 2014-09-27
- Volume
- 52
- Issue
- 1
- Pages
- 653-663
- ISSN
- 0893-7648
- 1559-1182
- Cited by
- 142
- References
- 6
- Language
- en
- Licence
- www.springer.com/tdm (tdm)
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