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.
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.
Rizelio
V
V
Laboratório de Neurofisiologia, Departamento de Fisiologia, Universidade Federal do Paraná, Curitiba, PR, Brasil.
Szawka
R E
RE
Xavier
L L
LL
Achaval
M
M
Rigon
P
P
Saur
L
L
Matheussi
F
F
Delattre
A M
AM
Anselmo-Franci
J A
JA
Meneses
M
M
Ferraz
A C
AC
D000818:Animals; D004298:Dopamine / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D016202:N-Methylaspartate; D009474:Neurons / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D014677:Pharmaceutical Vehicles; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000166:cytology* / Q000503:physiopathology; D020531:Subthalamic Nucleus / Q000187:drug effects / Q000293:injuries* / Q000473:pathology / Q000601:surgery; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D014677:Pharmaceutical Vehicles; D016202:N-Methylaspartate; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine