Uric acid and uridine exert neuroprotective effect in a transgenic mouse model of Huntington’s disease
Plangar I, Zadori D, Vecsei L, Klivenyi P
Introduction: Huntington’s disease (HD) is a progressive neurodegenerative disorder caused by an expanded poly-glutamine repeat in the huntingtin protein and characterized by motor, cognitive and psychiatric deficits. Neutopathologically in HD can be observed early loss of medium spiny neurons in the striatum and abnormal folding of the huntingtin protein that results in the formation of neuronal intranuclear inclusions in the striatum and cortex. The mitochondrial dysfunction, oxidative damage, excitotoxicity and altered membrane transport may play a crucial role in the pathogenesis of HD.
Our object was to examine the effects of uric acid (UA) and uridine (URD) on the survival.
Behavioural test and immunohistochemistry were performed in the N171-82Q transgenic mouse model of HD.
Materials and methods: The N171-82Q mice and their normal littermates received
intraperitoneal injections of UA (10 mg/kg/day), URD (100 mg/kg/day) or the vehicle at the same time each day on 5 days per week from 7 weeks of age until death occurred. We
investigated spontaneous locomotor activity of the mice therefore we applied open-field tests.
The brain was removed and serial sections were processed for immunostaining with a polyclonal antibody.
Results: Duration of survival after UA administration improved by 25.15% and after URD administration increased by 17.62%. As compared with the control transgenic group the locomotor activity was not significantly changed. UA and URD treatment reduced the number of neuronal intranuclear aggregates.
Conclusion: We could have demonstrated that UA and URD administration to N171-82Q transgenic mice extends the survival time and decreases the number of intranuclear huntingtin aggregates. UA and URD may develop its effect through decreasing the oxidative damage.
While the exact mechanism responsible for the beneficial effects of UA and URD in N171- 82Q mice is uncertain, our data suggest that these drugs are neuroprotective and may possibly be beneficial in the treatment of HD.
Keywords: Huntington’s disease, N171-82Q mice, survival time, behavioural test, immunohistochemistry
Acknowledgement: the abstract was supported by the TAMOP-4.2.2/B-10/1-2010-0012 project: “Broadening the knowledge base and supporting the long term professional sustainability of the Research University Center of Excellence at the University of Szeged by ensuring the rising generation of excellent scientists.” European Union grant.
