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Updated: Jun 3, 2025
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Modeling Neural Immune Signaling of Episodic and Chronic Migraine Using Spreading Depression In Vitro
Published on: June 13, 2011
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Progesterone receptors regulate susceptibility to spreading depression.
Suchitra Joshi1, John Williamson1, Serapio M Baca2
1Department of Neurology, University of Virginia, Charlottesville, VA 22908, USA.
Experimental Neurology
|January 8, 2025
Summary
Progesterone receptor signaling critically regulates cortical spreading depression (CSD), the mechanism behind migraine auras. Activating progesterone receptors increases CSD, while blocking them or genetic deletion suppresses it.
Area of Science:
- Neuroscience
- Endocrinology
- Migraine Pathophysiology
Background:
- Migraine with aura is linked to cortical spreading depression (CSD).
- Progesterone receptor (PR) signaling influences migraine susceptibility.
- The role of PR in regulating CSD remains unclear.
Purpose of the Study:
- To investigate whether progesterone receptor (PR) signaling regulates susceptibility to cortical spreading depression (CSD).
Main Methods:
- Utilized female mice (gonadally-intact and ovariectomized, estrogen-primed) with varying PR expression.
- Induced CSD via KCl application and recorded cortical activity.
- Modulated PR with segesterone (agonist) and RU-486 (antagonist).
- Assessed PR expression in somatosensory cortex using AAV9-flex-GFP.
- Evaluated CSD susceptibility after chemogenetic silencing of PR-expressing neurons.
Main Results:
- PRs are expressed in excitatory somatosensory cortical neurons, predominantly in layers 4-6.
- PR activation by segesterone increased CSD frequency and propagation speed.
- PR antagonism with RU-486 or genetic deletion of PRs suppressed CSD.
- Chemogenetic silencing of PR-expressing neurons reduced CSD frequency.
Conclusions:
- Progesterone-PR signaling critically regulates CSD susceptibility.
- This highlights a key mechanism in female hormonal regulation of migraine.
- Findings advance understanding of migraine pathophysiology.
Keywords:
Cortical spreading depression (CSD)MigraineProgesterone receptorsRU-486Somatosensory cortexhM4DiMore Related Videos
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