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Updated: Aug 19, 2026
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Indomethacin reverses the microglial response to amyloid beta-protein
E E Netland1, J L Newton, R E Majocha
1Department of Medicine, The Miriam Hospital and Brown University School of Medicine, Providence, RI 02906, USA.
Abstract:
Alzheimer's disease (AD) brains display intense microglial immunoreactivity in the area of senile plaques, suggesting that amyloid beta-protein may stimulate microglial infiltration. The activated microglia may modulate an immune response in the brain. Non-steroidal anti-inflammatory drugs (NSAIDs) are candidate therapeutics for AD because their effects on immune system components may influence the course of the disease. The present study examined the effects of an NSAID (indomethacin) on amyloid beta-protein-induced microglial infiltration. Amyloid beta-protein was chronically infused into rat lateral ventricles for 2 weeks. Extracellular amyloid beta-protein deposited along the lining and diffused into the tissue surrounding the lateral ventricle. Immunocytochemical staining showed that animals receiving amyloid beta-protein exhibited dramatic microglial response when compared to vehicle-infused rats. Activated microglia surrounded immunopositive amyloid beta-protein deposits, but this response was significantly attenuated in animals receiving either concurrent i.c.v. or subcutaneous (s.c.) treatment with indomethacin. These results suggest that chronic amyloid beta-protein infusion induces the proliferation of activated microglia and that indomethacin may be an effective treatment for inhibiting microglial proliferation.
Insights
Non-steroidal anti-inflammatory drugs (NSAIDs) like indomethacin may reduce microglial activation in Alzheimer's disease (AD). This study shows indomethacin can inhibit amyloid beta-protein-induced microglial infiltration in the brain.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Alzheimer's disease (AD) is characterized by microglial activation around amyloid plaques.
- Microglia play a role in the brain's immune response, potentially influencing AD progression.
- Non-steroidal anti-inflammatory drugs (NSAIDs) are being investigated as potential AD therapeutics due to their immunomodulatory effects.
Purpose of the Study:
- To investigate the effect of indomethacin, a non-steroidal anti-inflammatory drug (NSAID), on amyloid beta-protein-induced microglial infiltration.
- To determine if indomethacin can attenuate the microglial response triggered by amyloid beta-protein deposition in the brain.
Main Methods:
- Chronic infusion of amyloid beta-protein into the lateral ventricles of rats for two weeks.
- Administration of indomethacin via intracerebroventricular (i.c.v.) or subcutaneous (s.c.) routes concurrently with amyloid beta-protein infusion.
- Immunocytochemical staining to assess microglial response and amyloid beta-protein deposition.
Main Results:
- Amyloid beta-protein infusion led to significant microglial infiltration and activation surrounding deposited plaques.
- Concurrent treatment with indomethacin (both i.c.v. and s.c.) significantly attenuated the amyloid beta-protein-induced microglial response.
- Indomethacin treatment reduced the proliferation of activated microglia in response to amyloid beta-protein.
Conclusions:
- Chronic amyloid beta-protein infusion stimulates microglial proliferation and activation in the brain.
- Indomethacin demonstrates efficacy in inhibiting amyloid beta-protein-induced microglial infiltration.
- These findings suggest indomethacin as a potential therapeutic agent for managing neuroinflammation in Alzheimer's disease.
