The subthalamic stimulation inhibit bladder contraction by modulating local field potential and catecholamine in the medial prefrontal cortex.

Yamamoto T1, Sakakibara R2, Uchiyama T3, Kitajo K1, Kuwabara S3, Yamaguchi A1

Research Type

Basic Science / Translational

Abstract Category

Neurourology

Abstract 513
Open Discussion ePosters
Scientific Open Discussion ePoster Session 28
Friday 31st August 2018
13:10 - 13:15 (ePoster Station 2)
Exhibition Hall
Animal Study Neuropathies: Central Physiology
1. Department of Functional Anatomy, Chiba University Graduate School of Medicine, Chiba, Japan, 2. Neurology Division, Department of Internal Medicine, Sakura Medical Center, Toho University, Sakura, Japan., 3. Department of Neurology, Chiba University Graduate School of Medicine, Chiba, Japan
Presenter
T

Tatsuya Yamamoto

Links

Poster

Abstract

Hypothesis / aims of study
The subthalamic nucleus deep brain stimulation (STN-DBS) is widely used for alleviating motor complications in the advanced stage of patients with Parkinson’s disease (PD). Although lower urinary tract symptoms (LUTS) such as overactive bladder (OAB) are also prevalent in advanced stage of PD, the efficacy of STN-DBS on LUTS are not well elucidated. 
The medial prefrontal cortex (mPFC) is known as higher micturition centre and receives output signal of basal ganglia which is highly modulated by STN-DBS. Therefore, STN-DBS might regulate bladder contraction by changing the activity of mPFC. We aimed to clarify the change in neuronal activity of mPFC induced by STN-DBS with relation to bladder contraction using PD model rat. We examined the neuronal activities of mPFC by recording local field potential (LFP) and measuring the levels of catecholamine which are important neurotransmitter in mPFC. We calculated beta power from LFP by performing spectral analysis, because STN-DBS is known to significantly reduce beta power in STN or cerebral cortex in PD patients . The reason for measuring catecholamine in mPFC is that the mPFC receives dense projections from ventral tegmental area and nucleus of raphe, which are known as producing dopamine and serotonin, respectively and also known as regulating micturition reflex.
Study design, materials and methods
Experiments were performed under urethane anesthesia in normal and 6-hydroxydopamine hemi-lesioned PD model rats. STN-DBS was applied to the left STN, and bladder contractions were monitored simultaneously. Local field potential (LFP) in mPFC was recorded before, during and after STN-DBS (n=6: normal rats, n=6: PD rats). Extracellular fluid in mPFC was collected before, during, and after STN-DBS (n=5: normal rats, n=6: PD rats).Each experiments were performed separately. Spectral analysis of LFP for calculating beta power was performed, and the levels of catecholamine were measured.
Results
STN-DBS significantly increased inter bladder contractions from 155.46 ± 23.45 sec (pre STN-DBS phase) to 260.43 ± 39.18 sec (during STN-DBS phase) in normal rat (SD rat) (p<0.01). (Table 1) STN-DBS also significantly increased inter bladder contractions interval from 175.28 ± 16.39 sec (pre STN-DBS phase) to 231.18 ± 26.32 sec (during STN-DBS phase) in PD rat (p<0.05). With regard to the difference in the inter bladder contractions interval between normal and PD rat, no significant differences were found.  
  In normal rat, power spectrum analysis revealed that STN-DBS significantly decreased the mean logarithmic power in beta frequency of mPFC from 7.50 ± 0.03 (a.u.) to 7.29 ± 0.04 (a.u.) (p<0.01). In PD rats, STN-DBS significantly decreased the mean logarithmic power in beta frequency of mPFC from 7.9 5± 0.04 (a.u.) to 7.57 ± 0.04 (a.u.) (p<0.01) 
 The levels of LDOPA (L-3,4-dihydroxyphenylalanine) , DOPAC (3,4-Dihydroxyphenylacetic acid) and dopamine were significantly decreased during and after STN-DBS (p<0.01), whereas the levels of HVA (homovanillic acid) were significantly decreased only after STN-DBS (p<0.01) in PD rats. The levels of 5-HIAA  (5-hydroxyindole acetic acid) and 5-HT(5-hydroxytryptamine)  were significantly decreased during STN-DBS (p<0.05) in PD rats The levels of serotonin and its metabolite and homovanillic acid (HVA) were significantly decreased after STN-DBS in normal rats .
Interpretation of results
The present study demonstrated that STN-DBS significantly increased the inter bladder contraction interval in normal and PD rats. The effect of STN-DBS on the inter bladder contraction interval was larger in normal rats (SD rats) than that in PD rats. The concomitant changes in mPFC induced by STN-DBS was significant reduction in the mean logarithmic power in beta frequency in normal and PD rats. Regarding the levels of catecholamine, 5-HIAA and 5-HT were significantly decreased after STN-DBS in normal rats (SD rat), whereas the both dopamine and serotonin and their metabolites were significantly decreased after STN-DBS in PD model rats.
 Because, several experimental studies and functional imaging studies suggested that the mPFC plays the important role in regulating micturition reflex in both human and animal [1,2], and the STN-DBS might significantly affect the function of mPFC via the output nuclei of basal ganglia (GPi/SNr) and thalamus, the present study indicated that STN-DBS increased the inter bladder contraction interval via decreasing the beta power of mPFC and the levels of catecholamines in mPFC in normal and PD rats. Furthermore, the present study also revealed that the effect of STN-DBS on the levels of catecholamines were different between normal and PD model rats.
Concluding message
STN-DBS could increase inter bladder contraction interval in normal and PD rats probably by changing the neural activity as evaluated by the beta power and catecholamine levels in mPFC. The effect of STN-DBS on the levels of catecholamine in mPFC was different between normal and PD rats.
Figure 1
Figure 2
References
  1. Griffiths D. Neural control of micturition in humans: a working model. Nat Rev Urol. 2015;12(12):695-705. doi: 10.1038/nrurol.2015.266
  2. Fowler CJ, Griffiths D, de Groat WC. The neural control of micturition. Nat Rev Neurosci. 2008;9(6):453-66. doi: 10.1038/nrn2401.
Disclosures
Funding JSPS KAKENHI Grant Number 26461306 Clinical Trial No Subjects Animal Species Rat Ethics Committee Chiba University Guideline for the Care and Use of Laboratory Animals