A NOVEL PERIPHERAL RAT MODEL OF PARKINSON’S DISEASE

Parkinson’s disease, the second most common neurodegenerative disorder, is characterized by degeneration of nigrostriatal dopaminergic neurons. Beyond motor symptoms, it causes non-motor issues including gastrointestinal and bladder dysfunctions, with poorly understood mechanisms and limited treatments. Interestingly, constipation most often precedes motor symptoms by years. This gut pathology has further inspired the gut-first (peripheral origin, spreading to brain) versus the brain-first (central origin, spreading to periphery) hypothesis, though the contributions of peripheral and central neurodegeneration in autonomic dysfunctions remain unclear.
While the central 6-OHDA rodent models elucidates brain dopamine loss, peripheral neurodegeneration is underexplored. This study aims to therefore develop a peripheral dopamine loss model using 6-OHDA, which does not cross the blood-brain barrier.
Rats were treated with 100 mg/kg 6-OHDA or vehicle intraperitonially for three consecutive days. Twenty-one days post-treatment, micturition patterns and in vitro functional assessment of bladder and distal colon smooth muscle contractility using organ bath were carried out. In addition, histological analysis of the brain and peripheral organs were performed.
Our data suggests that no dopaminergic loss was detected in the brain, while tyrosine hydroxylase expression was significantly reduced in the heart, indicating selective peripheral neurodegeneration. The distal colon also exhibited altered responses to cholinergic, serotonergic, and adrenergic stimuli. The bladder, in contrast showed altered responses primarily to adrenergic stimulation, while micturition patterns remained unchanged.
These findings support clinical evidence suggesting that peripheral neurodegeneration primarily affects gastrointestinal function, as observed in the gut-first phenotype, whereas bladder dysfunction appears to be strongly associated with central neurodegeneration.