Detalle Publicación


Short- and long-term effects induced by repeated 6-OHDA intraventricular administration: A new progressive and bilateral rodent model of Parkinson's disease

Título de la revista: NEUROSCIENCE
ISSN: 0306-4522
Volumen: 361
Páginas: 144 - 156
Fecha de publicación: 2017
The pathological hallmark of Parkinson's disease (PD) is the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc), and the resulting striatal dopamine deficiency, which are responsible for the classic motor features. Although a diagnosis of PD relies on the clinical effects of dopamine deficiency, this disease is also associated with other neurotransmitter deficits that are recognized as causing various motor and non-motor symptoms. However, the cause of dopaminergic nigral neurodegeneration in PD and the underlying mechanisms remain unknown. While animal models are considered valuable tools with which to investigate dopaminergic cell vulnerability, rodent models usually fail to mimic the neurodegeneration progression that occurs in human PD. To find a convenient rat model for studying the progression of dopaminergic cell degeneration and motor signs, we have developed a progressive rodent model using a repeated daily, intraventricular administration of the neurotoxin 6-hydroxydopamine (6-OHDA) (100 mu g/day) in awakened rats for 1 to 10 consecutive days. The short-(6-day) and long-term (32-day) progression of motor alterations was studied. This model leads to a bilateral and progressive increase in catalepsy (evident from the 3rd infusion in the short-term groups (p < 0.01) and from the 7th infusion in the long-term groups (p < 0.01), which was associated with a progressive nigrostriatal dopaminergic deficit. All together this makes the new model an interesting experimental tool to investigate the mechanisms involved in the progression of dopaminergic neurodegeneration. (C) 2017 Published by Elsevier Ltd on behalf of IBRO.