title: Decreased HCN2 expression in STN contributes to abnormal high-voltage spindles in the cortex and globus pallidus of freely moving rats.
abstract: Abnormal oscillation in the cortical-basal ganglia loop is involved in the pathophysiology of parkinsonism. High-voltage spindles (HVSs), one of the main type abnormal oscillations in Parkinson's disease, are regulated by dopamine D2-like receptors but not D1-like receptors. However, little is known about how dopamine D2-like receptors regulate HVSs and the role of hyperpolarization-activated cyclic nucleotide-gated2 (HCN2) in HVSs regulation. We simultaneously recorded the local field potential (LFP) in globus pallidus (GP) and electrocorticogram (ECoG) in primary motor cortex (M1) in freely moving 6-hydroxydopamine (6-OHDA) lesioned or control rats. The expression of HCN2 and dopamine D2 receptor in the subthalamic nucleus (STN) was examined by immunochemical staining and Western blotting. We also tested the role of HCN2 in HVSs regulation by using pharmacological and shRNA methodology. We found that dopamine D2-like receptor agonists suppressed the increased HVSs in 6-OHDA lesioned rats. HCN2 was co-expressed with dopamine D2 receptor in the STN, and dopamine depletion decreased the expression of HCN2 as well as dopamine D2 receptor which contribute to the regulation of HVSs. HCN2 was down regulated by HCN2 shRNA, which thereby led to an increase in the HVSs in naïve rats while HCN2 agonist reduced the HVSs in 6-OHDA lesioned rats. These results suggest that HCN2 in the STN is involved in abnormal oscillation regulation between M1 cortex and GP.
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, People's Republic of China.
authors.forename: Chen
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Pathology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, People's Republic of China.
authors.forename: Jia-Rui
authors.initials: JR
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, People's Republic of China.
authors.forename: Shun-Nan
authors.initials: SN
authors.lastname: Ge
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, People's Republic of China.
authors.forename: Ju-Lei
authors.initials: JL
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710038, People's Republic of China.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Yan
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, People's Republic of China.
authors.forename: Dong
authors.initials: D
authors.lastname: Jia
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, People's Republic of China. Electronic address: zhujl65@fmmu.edu.cn.
authors.forename: Jun-Ling
authors.initials: JL
authors.lastname: Zhu
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, People's Republic of China. Electronic address: tdgguodong@163.com.
authors.forename: Guo-Dong
authors.initials: GD
authors.lastname: Gao
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use; D002317:Cardiovascular Agents / Q000494:pharmacology; D002540:Cerebral Cortex / Q000503:physiopathology*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005917:Globus Pallidus / Q000503:physiopathology*; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000235:genetics / Q000378:metabolism*; D007211:Indoles / Q000627:therapeutic use; D007736:Kynurenic Acid / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000473:pathology*; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D020531:Subthalamic Nucleus / Q000187:drug effects / Q000378:metabolism*; D014851:Wakefulness
chemical_list: D000978:Antiparkinson Agents; D002317:Cardiovascular Agents; D018691:Excitatory Amino Acid Antagonists; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007211:Indoles; D011743:Pyrimidines; D017448:Receptors, Dopamine D2; C046649:ropinirole; C082246:ICI D2788; D016627:Oxidopamine; D007736:Kynurenic Acid
keywords: Beta synchronization; Dopamine D2 receptor; ECoG; HCN2; High-voltage spindles; Parkinson’s disease