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Published on: October 24, 2018
Chronic stress induced disturbances in Laminin: A significant contributor to modulating microglial pro-inflammatory
Giovanni Pietrogrande1, Nishani Mabotuwana2, Zidan Zhao1
1School of Biomedical Sciences and Pharmacy and the Priority Research Centre for Stroke and Brain Injury, University of Newcastle, Callaghan 2308, NSW, Australia; Hunter Medical Research Institute, Newcastle 2305, NSW, Australia.
Abstract:
Over the last decade, evidence supporting a link between microglia enhanced neuro-inflammatory signalling and mood disturbance has continued to build. One issue that has not been well addressed yet are the factors that drive microglia to enter into a higher pro-inflammatory state. The current study addressed the potential role of the extracellular matrix protein Laminin. C57BL6 adult mice were either exposed to chronic stress or handled for 6 consecutive weeks. Changes in Laminin, microglial morphology and pro-inflammatory cytokine expression were examined in tissue obtained from mice exposed to a chronic restraint stress procedure. These in vivo investigations were complemented by an extensive set of in vitro experiments utilising both a primary microglia and BV2 cell line to examine how Laminin influenced microglial pro-inflammatory tone. Chronic stress enhanced the expression of Laminin, microglial de-ramification and pro-inflammatory cytokine signalling. We further identified that microglia when cultured in the presence of Laminin produced and released significantly greater levels of pro-inflammatory cytokines; took longer to return to baseline following stimulation and exhibited enhanced phagocytic activity. These results suggest that chronic restraint stress is capable of modulating Laminin within the CNS, an effect that has implications for understanding environmental mediated disturbances of microglial function.
Insights
Chronic stress increases Laminin, a protein that drives microglia, immune cells in the brain, toward a pro-inflammatory state, potentially linking stress to mood disturbances.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Growing evidence links microglia-driven neuroinflammation to mood disorders.
- Factors initiating microglial pro-inflammatory states remain unclear.
- The role of extracellular matrix proteins in this process is under-investigated.
Purpose of the Study:
- To investigate the role of Laminin, an extracellular matrix protein, in mediating microglial pro-inflammatory responses.
- To determine if chronic stress influences Laminin expression and microglial activation in the central nervous system (CNS).
Main Methods:
- In vivo studies using C57BL6 mice exposed to chronic restraint stress or handling.
- In vitro experiments with primary microglia and BV2 cell lines.
- Analysis of Laminin expression, microglial morphology, and pro-inflammatory cytokine levels.
- Assessment of microglial phagocytic activity and response kinetics.
Main Results:
- Chronic stress elevated Laminin expression, induced microglial de-ramification, and enhanced pro-inflammatory cytokine signaling.
- Laminin exposure in vitro increased pro-inflammatory cytokine release from microglia.
- Laminin-treated microglia showed delayed return to baseline and enhanced phagocytosis.
- Laminin modulates microglial pro-inflammatory tone and function.
Conclusions:
- Chronic stress alters CNS Laminin expression, impacting microglial function.
- Laminin is a key factor driving microglia into a pro-inflammatory state.
- These findings suggest a mechanism for environmental influences on stress-related mood disturbances via microglial modulation.
