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

• Published in: Brazilian journal of medical and biological research 2010-01, Vol.43 (1), p.85-95
• Main Authors: Rizelio, V, Szawka, R E, Xavier, L L, Achaval, M, Rigon, P, Saur, L, Matheussi, F, Delattre, A M, Anselmo-Franci, J A, Meneses, M, Ferraz, A C
• Format: Article
• Language: English
• Subjects: 6-Hydroxydopamine; Animals; BIOLOGY; Dopamine - physiology; Immunohistochemistry; Male; MEDICINE, RESEARCH & EXPERIMENTAL; Motor Activity - drug effects; Motor Activity - physiology; N-Methylaspartate; Neurons - drug effects; Neurons - pathology; Neurons - physiology; Parkinson Disease, Secondary - chemically induced; Parkinson Disease, Secondary - pathology; Parkinson Disease, Secondary - physiopathology; Parkinson's disease; Pharmaceutical Vehicles; Random Allocation; Rats; Rats, Wistar; Substantia Nigra - cytology; Substantia Nigra - physiopathology; Substantia nigra pars compacta; Subthalamic nucleus; Subthalamic Nucleus - drug effects; Subthalamic Nucleus - injuries; Subthalamic Nucleus - pathology; Subthalamic Nucleus - surgery; Tyrosine 3-Monooxygenase - metabolism; Tyrosine hydroxylase immunohistochemistry
• ISSN: 0100-879X; 1414-431X; 1414-431X; 0100-879X
• DOI: 10.1590/S0100-879X2009007500020

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.