Lorena Cuenca Bermejo¹, M.Pilar Almela Rojo², José Enrique Yuste³, Cristina Estrada Esteban¹, Vicente De Pablos Vicente¹, Victor Bautista-Hernández⁴, Emiliano FERNÁNDEZ VILLALBA¹, M. Luisa Laorden Carrasco⁵, Maria Trinidad Herrero Ezquerro¹

(1) NEUROCIENCIA CLÍNICA Y EXPERIMENTAL, IMIB, España
(2) FARMACOLOGÍA CLÍNICA Y EXPERIMENTAL, IMIB, España
(3) CEBAS-CSIC, España (Región de Murcia)
(4) Department of Cardiovascular Surgery. Integrated Management Area of A Coruña, España (Galicia)
(5)

Parkinson's disease (PD) is clinically featured by motor impairment caused by a decrease in dopamine levels in the nigrostriatal pathway. L-DOPA treatment is the gold therapy for PD, even if dyskinesias are the most unwanted side effect. Autonomic dysfunction is a well-known dominant symptom in the advanced stages of PD. However, the role of cardiac sympathetic nerves still needs to be elucidated.

The aim of our study was to evaluate the autonomic changes in parkinsonized monkeys (by MPTP intoxication) and L-DOPA-treated parkinsonized monkeys, focussing on cardiac sympathetic pathway. Additionally, the functional and molecular responses of the RV and LV to MPTP-induced neurotoxicity and the possible role of Hsp27 as an endogenous cytoprotective stress response protein were analysed. For this purpose, adult male monkeys were divided into groups (n=4/group): controls, MPTP-treated monkeys and MPTP+L-DOPA-treated animals. Noradrenaline (NA), its metabolite normetanephrine (NMN) and phospho-Hsp27 at Ser82 levels were analyzed in left (LV) and right ventricles (RV) of the heart. TH immunohistochemistry was performed in the ventral mesencephalon.

i) Dopaminergic neuronal death was significantly high in the SNpc of all MPTP-treated monkeys (groups 2 and 3); ii) MPTP intoxication decreased NMN levels and NA turnover in the RV; ii) L-DOPA treatment increased NMN levels and NA turnover in both ventricles; iii) NA turnover is decreased in both ventricles in Parkinsonian monkeys, but L-DOPA treatment induced an enhancement in NMN/NA ratio and increased Hsp27 activity.

L-DOPA does not protect against MPTP-induced neurotoxicity but its treatment could induce protective cardiac effects through the increased Hsp27 activity.