Lesion of the subthalamic nucleus reverses motor deficits but not death of nigrostriatal dopaminergic neurons in a rat 6-hydroxydopamine-lesion model of Parkinson's disease

V Rizelio,A.M Delattre,J.A Anselmo-Franci,A.C Ferraz,L.L Xavier,M Meneses,R.E Szawka,M Achaval,P Rigon,L Saur,F Matheussi

doi:10.1590/s0100-879x2010000100012

Abstract

The objective of the present study was to determine whether lesion of the subthalamic nucleus (STN) promoted by N-methyl-D-aspartate (NMDA) would rescue nigrostriatal dopaminergic neurons after unilateral 6-hydroxydopamine (6-OHDA) injection into the medial forebrain bundle (MFB). Initially, 16 mg 6-OHDA (6-OHDA group) or vehicle (artificial cerebrospinal fluid - aCSF; Sham group) was infused into the right MFB of adult male Wistar rats. Fifteen days after surgery, the 6-OHDA and SHAM groups were randomly subdivided and received ipsilateral injection of either 60 mM NMDA or aCSF in the right STN. Additionally, a control group was not submitted to stereotaxic surgery. Five groups of rats were studied: 6-OHDA/NMDA, 6-OHDA/Sham, Sham/NMDA, Sham/Sham, and Control. Fourteen days after injection of 6-OHDA, rats were submitted to the rotational test induced by apomorphine (0.1 mg/kg, ip) and to the open-field test. The same tests were performed again 14 days after NMDA-induced lesion of the STN. The STN lesion reduced the contralateral turns induced by apomorphine and blocked the progression of motor impairment in the open-field test in 6-OHDA-treated rats. However, lesion of the STN did not prevent the reduction of striatal concentrations of dopamine and metabolites or the number of nigrostriatal dopaminergic neurons after 6-OHDA lesion. Therefore, STN lesion is able to reverse motor deficits after severe 6-OHDA-induced lesion of the nigrostriatal pathway, but does not protect or rescue dopaminergic neurons in the substantia nigra pars compacta.

Highlights

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that results from a loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) [1]
We determined whether subthalamic nucleus (STN) lesion-induced motor recovery could be explained by the rescue of nigrostriatal dopaminergic neurons in a 6-OHDA-lesion rat model of PD
Our results show that STN lesion performed 15 days after 6-OHDA lesion of the nigrostriatal pathway reduced the apomorphine-induced rotational behavior

Summary

Introduction

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that results from a loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) [1]. The degeneration of mesencephalic dopaminergic cells causes significant dopamine (DA) depletion in the corpus striatum, leading to debilitating motor dysfunction when DA reduction is greater than 80% [2]. PD symptoms include akinesia, rigidity, resting tremor, slow movement, gait dysfunction, and postural instability [3]. The striatal DA deficit leads to the disinhibition of the indirect pathway of the basal ganglia circuit.

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