Selective oestrogen receptor modulators decrease the inflammatory response of glial cells

Area of Science:

• Neuroscience
• Pharmacology

Background:

• Neuroinflammation, characterized by glial cell activation and pro-inflammatory cytokine release, is implicated in neurological disorders.
• While glial activation is protective, chronic inflammation can cause neurotoxicity.
• Oestradiol and selective estrogen receptor modulators (SERMs) can mitigate neuroinflammation.

Purpose of the Study:

• To investigate the neuroprotective effects of SERMs on glial inflammatory responses.
• To evaluate the efficacy of tamoxifen, raloxifene, ospemifene, and bazedoxifene in reducing neuroinflammation.

Main Methods:

• In vitro studies using microglia and astrocyte cell cultures exposed to lipopolysaccharide (LPS).
• In vivo studies in rats assessing microglia activation and reactive astrocyte numbers after LPS administration or injury.
• Analysis of cytokine and chemokine expression and release.

Main Results:

• Tamoxifen and raloxifene reduced inflammatory responses in microglia and astrocytes in vitro and in vivo.
• These SERMs decreased microglia activation and the number of reactive astrocytes after injury.
• Ospemifene and bazedoxifene inhibited the expression and release of key inflammatory molecules in astrocytes.

Conclusions:

• Oestrogenic compounds, including SERMs, effectively counteract neuroinflammation by targeting glial inflammatory pathways.
• SERMs demonstrate potential as therapeutic agents for neurodegenerative conditions characterized by brain inflammation.