Blebbistatin, a Myosin II Inhibitor, Exerts Antidepressant-Like Activity and Suppresses Detrusor Overactivity in an Animal Model of Depression Coexisting with Overactive Bladder

Abstract

Overactive bladder (OAB) coexists with depression in women. Here, we assessed the effects of a 1-week treatment with blebbistatin, a myosin II inhibitor, on changes in behavior and detrusor overactivity (DO) symptoms induced by a 6-week administration of 13-cis-retinoic acid (13-cis-RA), with the aid of the forced swim test (FST), spontaneous locomotor activity test, and in vivo cystometric investigations in female Wistar rats. 13-cis-RA-induced depressive-like behavior and DO symptoms were associated with increased corticotropin-releasing factor (CRF) level in the plasma, prefrontal cortex (PFC), hippocampus (Hp), Barrington's nucleus (BN), and urinary bladder. Moreover, 13-cis-RA decreased brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) levels in plasma, PFC, Hp, and BN, while it increased BDNF and NGF levels in urinary bladder. Blebbistatin exerted antidepressant-like effect and attenuated changes in the cystometric parameters as well as the central and peripheral levels of CRF, BDNF, and NGF that were induced by 13-cis-RA, while it did not affect urine production, mean, systolic or diastolic blood pressure, or heart rate. The results point to blebbistatin as a potential treatment option for OAB coexisting with depression.

Intravesical administration of blebbistatin prevents cyclophosphamide‐induced toxicity of the urinary bladder in female Wistar rats

“…***P < 0.001 vs CON, **P < 0.01, *P < 0.05 vs CON,^^P < 0.001,^^P < 0.01,^P < 0.05 vs CYP (Tukey's post hoc test). One-way ANOVA: (1) for IL-1β: F(3,56) = 26.74, P < 0.0001; (2) for IL-6: F(3,56) = 8.002, P = 0.0002; (3) for IL-10: F(3,56) = 7.322, P = 0.0003; (4) for TNF-α: F(3,56) = 18.83; P < 0.0001; (5) for NGF: F(3,56) = 67.86, P < 0.0001; (6) for BDNF: F(3,56) = 14.35, P < 0.0001; (7) for IGFBP-3: F(3,56) = 6.806, P = 0.0005; (8) for HB-EGF: F(3,56) = 10.48, P < 0.0001; (9) for CXCL10: F(3,56) = 35.40, P < 0.0001; (10) for ORM1: F(3,56) = 25.94, P < 0.0001; (11) for T-H protein: F(3,56) = 36.85, P < 0.0001; (12) for HPX: F(3,56) = 7.297, P = 0.0003; and (13) for occludin: F(3,56) = 15.52, P < 0.0001. CON, control; CYP, cyclophosphamide the CYP-induced inflammation of the bladder and it is important for Il-6 and Il-10.…”

“…The control animals received a volume‐matched injection/infusions of the vehicle. The doses and pretreatment schedules were selected on the basis of the literature data and the results of our previous experiments . Cystometric studies and measurements of bladder edema and urothelium thickness were performed 24 hours after the last infusion of blebbistatin.…”

“…The animals were kept in environmentally controlled rooms with free access to food and water. Rats were randomly assigned to one of the following treatment groups: [5][6][7] Cystometric studies and measurements of bladder edema and urothelium thickness were performed 24 hours after the last infusion of blebbistatin. Due to the known light sensitivity, blebbistatin was always stored in the dark in the refrigerator just before usage.…”

Depression, isotretinoin, and folic acid: A practical review

“…FA significantly improved depression‐like behaviors in stress‐induced rats (Wróbel et al, ). FA supplementation for more than 6 months during pregnancy was associated with a decreased risk of p ostpartum depression 6–12 weeks after delivery in Chinese women (Yan et al, ).…”

“…BDNF was found to be decreased in plasma of depressed patients. ISO decreases BDNF level in the plasma in an animal model of depression coexisting with overactive bladder (Wróbel et al, ). Experimentally, FA significantly improved depression‐like behaviors in rats, and its antidepressant effects might be related to the increase of BDNF, among others, and repair of synaptic organization in the brain (Gao et al, ).…”