Abstract
AimsThe patients with Parkinson’s disease (PD) present with lower urinary tract symptoms (LUTS), but the efficacy of subthalamic nucleus deep brain stimulation (STN-DBS) on LUTS is unknown. The medial prefrontal cortex (mPFC) is a known higher micturition center which are modulated by STN-DBS. We aim to clarify STN-DBS-related changes in the neuronal activity of the mPFC in terms of bladder contraction, using normal and PD rats.MethodsExperiments in normal and 6-hydroxydopamine hemi-lesioned PD rats were conducted under urethane anesthesia. STN-DBS was applied to the left STN, with simultaneous monitoring of bladder contractions. The mPFC’s local field potential (LFP) was recorded before, during, and after STN-DBS (n = 6: normal rats, n = 6: PD rats). Before, during and after STN-DBS (n = 5: normal rats, n = 6: PD rats), extracellular fluid was collected from mPFC.ResultsSTN-DBS significantly increased bladder inter-contraction interval. STN-DBS significantly decreased mPFC alpha power in normal rat and increased alpha power in PD rat. The mPFC levels of levodopa, dopamine, serotonin and their metabolites in PD rats decreased significantly during and after STN-DBS, whereas the serotonin and its metabolites and homovanillic acid (HVA) levels decreased significantly in normal rats following STN-DBS.ConclusionSTN-DBS increased intercontraction intervals for the bladder in both normal and PD rats, as assessed by alpha power and catecholamine levels in mPFC, probably due to changes in neural activity. The effect of STN-DBS on mPFC levels of catecholamine differentiated between the normal and PD rats.
Highlights
Subthalamic nucleus deep brain stimulation (STN-DBS) is known to dramatically alleviate motor complications of advanced-stage Parkinson’s disease (PD) (Okun, 2012)
The present study aims to clarify the changes in the medial prefrontal cortex (mPFC) neuronal activity induced by STN-DBS and their relation to bladder contraction/relaxation cycle in a rat model of PD
In PD rats the levels of LDOPA, DOPAC, and DA decreased significantly during and after STN-DBS (p < 0.01), while HVA levels decreased significantly only after STN-DBS (p < 0.01)
Summary
Subthalamic nucleus deep brain stimulation (STN-DBS) is known to dramatically alleviate motor complications of advanced-stage Parkinson’s disease (PD) (Okun, 2012). It is well known that several non-motor symptoms are prevalent and severe among patients with advanced-stage PD (Kalia and Lang, 2015), including lower urinary tract symptoms (LUTS), which may contribute significantly to the QOL deterioration (Sakakibara et al, 2016). We have previously reported that, in cats, some nuclei in the basal ganglia such as the striatum (Yamamoto et al, 2009), substantia nigra (Sakakibara et al, 2002), and STN (Sakakibara et al, 2003) are involved in bladder contraction, and most recorded neurons fire preferentially during the isovolumetric bladder relaxation phase, suggesting that they inhibit bladder contraction (Sakakibara et al, 2002, 2003; Yamamoto et al, 2009). We have reported that most recorded mPFC neurons fire preferentially during the isovolumetric bladder relaxation phase in normal cats (Yamamoto et al, 2010)
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