Adult zymosan re-exposure exacerbates the molecular alterations in the brainstem rostral ventromedial medulla of rats with early life zymosan-induced cystitis

•The study delineated the underlying long-term molecular changes in brainstem RVM neurons following neonatal cystitis in rats.•The findings suggests that adult rechallenge exacerbates the underlying molecular responses of neonatal cystitis due to priming effect of prior exposures during development....

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Published in:Neurobiology of pain 2024-07, Vol.16, p.100160, Article 100160
Main Authors: Talluri, Bhavana, Addya, Sankar, Terashvili, Maia, Medda, Bidyut K, Banerjee, Anjishnu, Shaker, Reza, Sengupta, Jyoti N, Banerjee, Banani
Format: Article
Language:English
Subjects:
Brainstem RVM
Cystitis
Glutamatergic neurons
microRNAs
Original
Synapse associated genes
Synaptoneurosomes
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Summary:•The study delineated the underlying long-term molecular changes in brainstem RVM neurons following neonatal cystitis in rats.•The findings suggests that adult rechallenge exacerbates the underlying molecular responses of neonatal cystitis due to priming effect of prior exposures during development.•Several miRNAs and target genes associated with glutamatergic neurotransmission were differentially expressed in RVM neurons following induction of cystitis.•Identification of differentially expressed miRNAs and their target genes in RVM may help in defining the molecular mechanism of cystitis associated bladder pain conditions.•The outcome will certainly facilitate the development of mechanism-based approaches for treating IC/BPS. 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 
ISSN:2452-073X
2452-073X
DOI:10.1016/j.ynpai.2024.100160