# Dysregulation of Neurotransmission in the Bladder with Parkinson's Disease

> **NIH VA I21** · VA BOSTON HEALTH CARE SYSTEM · 2020 · —

## Abstract

Bladder dysfunction is highly prevalent and often debilitating in patients with Parkinson’s disease (PD), a
progressive movement disorder characterized by the appearance of abnormal aggregated α-synuclein in various
brain regions. Lower urinary tract symptoms (incontinence, urgency, nocturia, etc.) in patients with PD are
generally attributed to neurologic defects in the central inhibition of micturition centers in the brain that result in
detrusor overactivity. However, a direct effect of α-synuclein pathology on peripheral neural control of bladder
function has not been previously examined. Moreover, recent epidemiological evidence suggests that non-motor
symptoms may substantially precede the development of movement disorders in patients with PD. These factors
have prompted us to re-examine the pathophysiology of neurogenic bladder dysfunction in PD and address the
novel hypothesis that peripheral regulation of local neurotransmission in the bladder is significantly altered in
early stage PD, prior to the onset of motor deficits. Our first aim will be to demonstrate that pathologic α-synuclein
expression in PD causes temporal changes in bladder neurotransmission and contractile function that precede
somatomotor deficits. We will exploit transgenic animal models of PD that express either the wild-type human α-
synuclein gene or a mutant human α-synuclein gene found in a form of familial PD. The bladder phenotype of
these animals will be comprehensively characterized at increasing ages using in vitro and in vivo functional
assays. These studies will allow us to assess the physiologic role of local α-synuclein and determine the impact
of pathologic α-synuclein on bladder function. Our preliminary data indicate that α-synuclein is highly expressed
in human and mouse nerve fibers within the bladder and that the functional response to nerve stimulation is
dramatically altered in bladders from mice with α-synuclein mutation. These findings suggest an important role
for α-synuclein in synaptic vesicle transport, in a pathway that is shared by myosin Va, a processive motor protein
that we have previously shown to be involved in vesicular trafficking and neurotransmission in visceral organs.
Our preliminary data suggests a relevant intramolecular relationship between myosin Va and α-synuclein.
Therefore, in specific aim 2, we will determine the extent to which α-synuclein-myosin Va protein interactions
influence neurotransmission in the bladder. The interaction between myosin Va and α-synuclein will be assessed
in bladder tissue under physiologic conditions using molecular and cellular approaches. This physiologic protein-
protein interaction will be compared with the defective interaction in the bladder that occurs with PD and
correlated with changes in the level of neurotransmitters released from isolated bladder nerves. At the conclusion
of these studies, we will have: (1) provided new insights regarding the physiologic function of α- synuclein in
pe...

## Key facts

- **NIH application ID:** 10043894
- **Project number:** 5I21BX003680-03
- **Recipient organization:** VA BOSTON HEALTH CARE SYSTEM
- **Principal Investigator:** MARYROSE P SULLIVAN
- **Activity code:** I21 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-07-01 → 2020-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10043894

## Citation

> US National Institutes of Health, RePORTER application 10043894, Dysregulation of Neurotransmission in the Bladder with Parkinson's Disease (5I21BX003680-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10043894. Licensed CC0.

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