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Bulk RNA-Seq of male and female lumbosacral dorsal root ganglia after VEGFA-instillation

ABSTRACT: This study examined transcriptomics in lumbosacral dorsal root ganglia that carries bladder afferent signals in a bladder-origin visceral pain animal model. C57BL6/J male and female mice underwent intravesical instillations of VEGF165, a mouse recombinant of VEGFA to induce visceral hypersensitivity. Saline-instilled male and female mice were used as controls. Across the four experimental groups, we found significant sex differences in the transcriptome profile in both saline-instilled animals and VEGF-induced signaling pathway changes in the lumbosacral sensory ganglia. These findings provide insight into potential molecular targets for alleviating visceral pain symptoms when considering sex as a biological variable.

ORGANISM(S): Mus musculus

PROVIDER: GSE294967 | GEO | 2025/12/30

REPOSITORIES: GEO

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Project description:Vagal afferent neurons are thought to convey primarily physiological information, whereas spinal afferents transmit noxious signals from the viscera to the central nervous system. In order to elucidate molecular identities for these different properties, we compared gene expression profiles of neurons located in nodose ganglia (NG) and dorsal root ganglia (DRG) in mice. Intraperitoneal administration of Alexa Fluor-488 conjugated Cholera toxin B allowed identification of neurons projecting to the viscera. Fluorescent neurons in DRG (from T10 to T13) and NG were isolated using laser capture microdissection. Gene expression profiles of visceral afferent neurons, obtained by microarray hybridization, were analysed using multivariate spectral map analysis, SAM algorithm (Significance Analysis of Microarray data) and fold-difference filtering. A total of 1996 genes were found to be differentially expressed in DRG versus NG, including 41 G-protein coupled receptors and 60 ion channels. Expression profiles obtained on laser-captured neurons were contrasted to those obtained on whole ganglia demonstrating striking differences and the need for microdissection when studying visceral sensory neurons because of dilution of the signal by somatic sensory neurons. Furthermore, a detailed catalogue of all adrenergic and cholinergic, GABA, glutamate, serotonin and dopamine receptors, voltage-gated potassium, sodium and calcium channels and transient receptor potential cation channels present in visceral afferents is provided. Our genome-wide expression profiling data provide novel insight into molecular signatures that underlie both functional differences and similarities between NG and DRG visceral sensory neurons. Moreover, these findings will offer novel insight into mode of action of pharmacologic agents modulating visceral sensation. Experiment Overall Design: Three separate experiments were performed. First, 5 whole dorsal root ganglia were compared to 7 whole nodose ganglia. Second, Laser captured visceral neurons derived from 5 dorsal root ganglia and 5 nodose ganglia were compared on MG-U74Av2. Third, Laser captured visceral neurons derived from 9 dorsal root ganglia and 11 nodose ganglia were compared on Mouse430_2.

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Bulk RNA-Seq of male and female lumbosacral dorsal root ganglia after VEGFA-instillation

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