Central nervous system control of micturition in rodents through neuroprotection and endocannabinoids -- Dopaminergic and cannabinoid contribution

Micturition consists of reflexes involving the central and peripheral nervous system controlling the bladder and urethra. A better understanding of the underlying contribution of the dopaminergic and cannabinoid systems to the control of micturition could help direct therapeutic modalities for related voiding dysfunction.;Disruption of the central control of the voiding reflex, and bladder dysfunction, commonly occur with neurodegenerative disorders such as Parkinson's disease (PD), possibly due to an imbalance in the dopaminergic system. Chronological development of bladder dysfunction has been shown after producing a unilateral lesion in the medial forebrain bundle with 6-OHDA. Rat bone marrow-derived mesenchymal stem cells (rBMSC) or cells protected by microencapsulation (ErBMSC) were transplanted into the substantia nigra pars compacta (SNpc). Urodynamic effects of the 6-OHDA lesion persisted up to 42 days after vehicle injection. Transplantation of rBMSC alone improved the urodynamic pressures at 42 days after treatment more markedly than ErBMSC. This was associated with a higher number of TH-positive neurons in the treated SNpc of rBMSC animals, suggesting that functional improvements require a juxtacrine effect.;Systemic administration of cannabinoid (CB) receptor agonists affects bladder function, but the main site of action (peripheral tissues versus central nervous system) or the contribution of individual CB receptors (type 1 [CB 1R] and type 2 [CB2R]) to normal micturition has not been clearly defined. Central application of CB receptor agonist localized to the spinal cord with intrathecal administration was found to increase bladder capacity (BC) during conscious cystometry, possibly mediated by the activation of spinal TRPV1 channels, and likely through an afferent pathway. The overall involvement of CB1R and CB2R in micturition was examined individually by characterizing the in vivo and in vitro bladder function in their respective KO mouse. The absence of CB1R was associated with a smaller BC and more spontaneous activity during cystometry and a lower response to electrical stimulation of nerves. On the other hand, lack of CB2R was linked with lower BC and higher bladder compliance than when CB2R is present.;In conclusion, these studies have determined that the dopaminergic and CB system play a significant role in the CNS control of micturition.