Project Details
Description
The Parties will perform experiments designed to determine whether high levels of andr sulphates in the colon lumen produce sensitization of colon projecting DRG neurons am whether androgen sulphates activate and/or sensitize these neurons via activation of the receptor. All work will be performed in male and female mice. Colonic DHEAS will be increased by giving mice a daily dose of DHEAS for seven days in healthy mice, mice s to chronic stress and mice in the post-inflammatory phase of DSS induced colitis. Effec colonic sensitivity will be assessed by measuring sensitivity to mechanical colon distent by conditioned place preference. DRG sensitization will be measured in calcium imagin patch clamp experiments. Gene expression in DRG neurons will be measured by RT-PC RNA obtained from DRG neurons isolated by laser capture microdissection. We will pe pharmacological and DRG neuron specific gene knockout experiments to assess the roh NMDA receptor expressed on DRG neurons in DHEAS induced visceral pain. We will investigate the role of colon DRG neuron activity in promoting DHEAS induced viscera modulating the activity ofDRG neurons using a chemo-genetic strategy. Additional exp will investigate the contributions of central sensitization and descending pain modulatm pathways to DHEAS induced visceral pain.
No materials will be shared between BCM and UTMB. This work represents a new collaboration to investigate a mechanistic component of a larger project initiated previo1 BCM to elucidate the pathogenic actions of DHEAS in patients and animal models. BC performed extensive studies to characterize the molecular targets on which DHEAS act humans and animal models, and plans to submit an NIH grant application on this subjec near future. Dr. Winston will conduct some specific experiments to validate BCM resul1 showing that DHEAS induces pain via actions on nociceptive neurons that populate the intestines. It is anticipated that Dr. Winston will be a co-investigator on the BCXM grai application.
Status | Active |
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Effective start/end date | 4/15/24 → 4/30/25 |
Funding
- Baylor College of Medicine ( Award # ): $26,800.00
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