Deep brain stimulation of the center median-parafascicular complex of the thalamus has efficient anti-parkinsonian action associated with widespread cellular responses in the basal ganglia network in a rat model of Parkinson's disease.
The thalamic centromedian-parafascicular (CM/Pf) complex, mainly represented by Pf in rodents, is proposed as an interesting target for the neurosurgical treatment of movement disorders, including Parkinson's disease. In this study, we examined the functional impact of subchronic high-frequency stimulation (HFS) of Pf in the 6-hydroxydopamine-lesioned hemiparkinsonian rat model. Pf-HFS had significant anti-akinetic action, evidenced by alleviation of limb use asymmetry (cylinder test). Whereas this anti-akinetic action was moderate, Pf-HFS totally reversed lateralized neglect (corridor task), suggesting potent action on sensorimotor integration. At the cellular level, Pf-HFS partially reversed the dopamine denervation-induced increase in striatal preproenkephalin A mRNA levels, a marker of the neurons of the indirect pathway, without interfering with the markers of the direct pathway (preprotachykinin and preprodynorphin). Pf-HFS totally reversed the lesion-induced changes in the gene expression of cytochrome oxidase subunit I in the subthalamic nucleus, the globus pallidus, and the substantia nigra pars reticulata, and partially in the entopeduncular nucleus. Unlike HFS of the subthalamic nucleus, Pf-HFS did not induce per se dyskinesias and directly, although partially, alleviated L-3,4-dihydroxyphenylalanine (L-DOPA)-induced forelimb dyskinesia. Conversely, L-DOPA treatment negatively interfered with the anti-parkinsonian effect of Pf-HFS. Altogether, these data show that Pf-DBS, by recruiting a large basal ganglia circuitry, provides moderate to strong anti-parkinsonian benefits that might, however, be affected by L-DOPA. The widespread behavioral and cellular outcomes of Pf-HFS evidenced here demonstrate that CM/Pf is an important node for modulating the pathophysiological functioning of basal ganglia and related disorders.
Jouve
Loréline
L
Developmental Biology Institute of Marseille Luminy, Unité Mixte de Recherche 6216 Centre National de la Recherche Scientifique-Université de la Méditerranée, 13288 Marseille, France.
Salin
Pascal
P
Melon
Christophe
C
Kerkerian-Le Goff
Lydia
L
D000818:Animals; D001479:Basal Ganglia / Q000473:pathology* / Q000503:physiopathology*; D046690:Deep Brain Stimulation; D003714:Denervation / Q000379:methods; D004195:Disease Models, Animal; D003576:Electron Transport Complex IV / Q000378:metabolism; D056228:Feedback, Sensory; D005917:Globus Pallidus / Q000378:metabolism; D007980:Levodopa / Q000008:administration & dosage / Q000378:metabolism; D008297:Male; D016627:Oxidopamine; D010300:Parkinson Disease / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000378:metabolism; D020531:Subthalamic Nucleus / Q000378:metabolism; D015320:Tachykinins / Q000235:genetics; D013788:Thalamus / Q000503:physiopathology*
D011498:Protein Precursors; D012333:RNA, Messenger; D015320:Tachykinins; C044206:preprotachykinin; D007980:Levodopa; D016627:Oxidopamine; D003576:Electron Transport Complex IV