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Expression of Phosphorylated cAMP Response Element Binding Protein (p-CREB) in Bladder Afferent Pathways in VIP−/− Mice with Cyclophosphamide (CYP)-Induced Cystitis

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Abstract

The expression of phosphorylated cAMP response element binding protein (p-CREB) in dorsal root ganglia (DRG) with and without cyclophosphamide (CYP)-induced cystitis (150 mg/kg, i.p; 48 h) was determined in VIP−/− and wild-type (WT) mice. p-CREB immunoreactivity (IR) was determined in bladder (Fast blue) afferent cells. Nerve growth factor (NGF) bladder content was determined by enzyme-linked immunosorbent assays. Basal expression of p-CREB-IR in DRG of VIP−/− mice was (p ≤ 0.01) greater in L1, L2, L5-S1 DRG compared to WT mice. CYP treatment in WT mice increased (p ≤ 0.05) p-CREB-IR in L1, L2, L5-S1 DRG. CYP treatment in VIP−/− mice (p ≤ 0.01) increased (p ≤ 0.01) p-CREB-IR in L6-S1 DRG compared to WT with CYP. In WT mice, bladder afferent cells (20–38%) in DRG expressed p-CREB-IR under basal conditions. With CYP, p-CREB-IR increased in bladder afferent cells (60–65%; L6-S1 DRG) in WT mice. In VIP−/− mice, bladder afferent cells (12–58%) expressed p-CREB-IR under basal conditions, and CYP increased p-CREB expression (78–84%) in L6-S1 DRG. Urinary bladder NGF expression in VIP−/− mice under basal conditions or after cystitis was significantly greater than WT. Detrusor smooth muscle thickness was significantly increased in VIP−/− mice. Bladder NGF expression may contribute to differences in p-CREB expression.

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Acknowledgments

The authors acknowledge the technical support of Susan E. Malley. This work was funded by NIH grants DK051369, DK060481, and DK065989. D.G. Jensen was supported by Drug Research Academy at Copenhagen University and Ferring Pharmaceutical, Copenhagen.

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Jensen, D.G., Studeny, S., May, V. et al. Expression of Phosphorylated cAMP Response Element Binding Protein (p-CREB) in Bladder Afferent Pathways in VIP−/− Mice with Cyclophosphamide (CYP)-Induced Cystitis. J Mol Neurosci 36, 299–309 (2008). https://doi.org/10.1007/s12031-008-9045-y

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