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Up‐regulation of phosphorylated CREB but not c‐Jun in bladder afferent neurons in dorsal root ganglia after cystitis
Author(s) -
Qiao LiYa,
Vizzard Margaret A.
Publication year - 2003
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.11009
Subject(s) - creb , resiniferatoxin , medicine , endocrinology , stimulation , biology , receptor , transcription factor , gene , biochemistry , transient receptor potential channel , trpv1
We examined the changes of two transcription factors, CREB and c‐Jun, in dorsal root ganglia (DRG) after acute (8 or 48 hours) or chronic (10 days) cyclophosphamide (CYP)‐induced cystitis. Results showed an increase in the number of p‐CREB‐immunoreactive (‐IR) cells in the L1 and L2 DRG (5–7‐fold; P ≤ 0.05) as well as L6 and S1 DRG (2–4‐fold; P ≤ 0.05) after acute and chronic cystitis. The number of p‐CREB‐IR cells in the L4–L5 DRG was not altered with cystitis. The number of c‐Jun‐IR cells increased in the L1–L2 DRG (L1: 10‐fold; L2: 8‐fold; P ≤ 0.05) only with chronic cystitis, although it increased in the L6–S1 DRG with CYP‐induced cystitis of acute (2–3‐fold; P ≤ 0.05) and chronic (6–10‐fold; P ≤ 0.05) duration. After CYP treatment, the percentage of bladder afferent cells expressing p‐CREB immunoreactivity (3–7‐fold; P ≤ 0.05) increased in L1, L2, L6, and S1 DRG. The increase occurred 8 hours post‐CYP injection and was maintained with chronic cystitis. There were few c‐Jun‐IR cells in the bladder afferent population. These results demonstrate that CYP induces p‐CREB and c‐Jun expression in DRG in a time‐dependent manner. However, c‐Jun expression is not associated with bladder afferent neurons. Resiniferatoxin reduced CYP‐induced up‐regulation of p‐CREB in DRG, suggesting that cystitis can reveal an altered CREB phosphorylation that may be mediated by capsaicin‐sensitive bladder afferents. Colocalization of p‐CREB and Trk receptor(s) showed that a subpopulation of p‐CREB‐IR cells expressed p‐Trk with cystitis. These results suggest that up‐regulation of p‐CREB may be mediated by a neurotrophin/Trk signaling pathway. J. Comp. Neurol. 469:262–274, 2004. © 2003 Wiley‐Liss, Inc.