Deep brain stimulation in a rat model modulates TH, CaMKIIa and Homer1 gene expression.
High-frequency stimulation (HFS) of subthalamic nucleus (STN) is a therapy for late-stage Parkinson's disease. Its mechanisms of action are not yet fully understood. In the present study, gene expression analyses were performed in a rat model of Parkinson's disease, i.e. striatal 6-hydroxydopamine (6-OHDA) lesion. Using microarrays, gene expression was analysed in 1-mm-thick sagittal brain slices, including basal ganglia of five groups of male Wistar rats. These were unmanipulated rats (group A), unlesioned rats with implanted electrode but without stimulation (group B), unlesioned, stimulated rats (group C), 6-OHDA-lesioned rats with implanted electrode but without stimulation (group D), and finally 6-OHDA-lesioned and stimulated rats (group E). A statistically significant downregulation of tyrosine hydroxylase (TH) mRNA expression induced by 6-OHDA lesion and an HFS-induced TH upregulation in 6-OHDA-lesioned rats could be detected. It could be hypothesized that the HFS-induced upregulation of TH is the result of neuronal STN modulation and mediated via projections from STN to substantia nigra pars compacta. Furthermore, a downregulation of calcium/calmodulin-dependent protein kinase type IIA and Homer1 was observed. This downregulation could result in a reduced sensitivity towards glutamate in basal ganglia downstream of STN.
Henning
Jeannette
J
Department of Neurology, University of Rostock, Gehlsheimer Str. 20, 18147 Rostock, Germany.
Koczan
Dirk
D
Glass
Anne
A
Karopka
Thomas
T
Pahnke
Jens
J
Rolfs
Arndt
A
Benecke
Reiner
R
Gimsa
Ulrike
U
D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D046690:Deep Brain Stimulation; D004195:Disease Models, Animal; D007839:Functional Laterality; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects*; D000072233:Homer Scaffolding Proteins; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000378:metabolism / Q000628:therapy; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; C000606624:Homer1 protein, rat; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases