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Adult zymosan re-exposure exacerbates the molecular alterations in the brainstem rostral ventromedial medulla of rats with early life zymosan-induced cystitis. Neurobiol Pain 2024;16:100160

Date

09/10/2024

Pubmed ID

39252992

Pubmed Central ID

PMC11381896

DOI

10.1016/j.ynpai.2024.100160

Scopus ID

2-s2.0-85201495440 (requires institutional sign-in at Scopus site)

Abstract

Recent evidence suggests that the descending modulatory pathways from the brainstem rostral ventromedial medulla (RVM) are important for bladder inflammatory pain. This study aimed to identify the long-term molecular changes in RVM neurons due to early life cystitis during neuronal development and the effect of reexposure later in adulthood. RVM tissues from two treatment protocols were used: (1) neonatal zymosan exposures with acute adult rechallenge (RC) and (2) only neonatal zymosan exposures (NRC). RNAseq analysis showed upregulation of several genes associated with synaptic plasticity (Grin1, Grip2, Notch1, Arc, and Scn2b) in the cystitis groups compared to controls in both protocols. The RC protocol exhibited a stronger treatment effect with significantly higher fold differences between the groups compared to the NRC protocol (p < 0.001, fold differences RC vs NRC). In microarrays, miR-34a-5p showed cystitis-induced downregulation in both protocols. Bioinformatics analysis identified multiple 3'UTRs complementary binding sites for miR-34a-5p on Grin2b, Notch1, Grip2, Scn2b, and Arc genes. The enhanced response in the RC protocol indicates a possible priming effect of early life cystitis on rechallenge in adulthood. These long-term molecular alterations may play a critical role in the development of chronic bladder pain conditions as seen in patients with Interstitial Cystitis/Bladder pain syndrome.

Author List

Talluri B, Addya S, Terashvili M, Medda BK, Banerjee A, Shaker R, Sengupta JN, Banerjee B

Authors

Anjishnu Banerjee PhD Associate Professor in the Data Science Institute department at Medical College of Wisconsin
Bidyut K. Medda PhD Associate Professor in the Medicine department at Medical College of Wisconsin