Deep brain stimulation induces rapidly reversible transcript changes in Parkinson's leucocytes

Journal of Cellular and Molecular Medicine

Lilach Soreq²  Hagai Bergman²  Yael Goll¹  David S. Greenberg¹  Zvi Israel³ 

[1] Department of Biological Chemistry, The Life Sciences Institute, The Hebrew University of Jerusalem, Jerusalem, Israel;Department of Medical Neurobiology (Physiology), IMRIC, The Hebrew University-Hadassah Medical School, Jerusalem, Israel;Center for Functional & Restorative Neurosurgery, Department of Neurosurgery, Hadassah University Hospital, Jerusalem, Israel

关键词: blood leucocytes;    deep brain stimulation;    exon microarrays;    Parkinson's disease;    subthalamic nucleus;   

DOI  :  10.1111/j.1582-4934.2011.01444.x

来源: Wiley

【 摘 要 】

Abstract

Subthalamic deep brain stimulation (DBS) reversibly modulates Parkinson's disease (PD) motor symptoms, providing an unusual opportunity to compare leucocyte transcripts in the same individuals before and after neurosurgery and 1 hr after stimulus cessation (ON- and OFF-stimulus). Here, we report DBS-induced reversibility and OFF-stimulus restoration in 12 of 16 molecular functions and 3 of 4 biological processes shown in exon microarrays to be differentially expressed between PD patients and controls, post-DBS from pre-DBS and OFF from ON states. Intriguingly, 6 of 18 inflammation and immune-related functions exhibited reversibility, and the extent of stimulus-induced changes correlated with the neurological DBS efficacy, suggesting mechanistic implications. A minimal list of 29 transcripts that changed in all three comparisons between states discriminated pre-surgery and OFF states from post-surgery and controls. Six of these transcripts were found to be able to distinguish between PD patients and both healthy controls and patients with other neurological diseases in a previously published whole blood 3’ array data study of early PD patients. Our findings support the future use of this approach for identifying targets for therapeutic intervention and assessing the efficacy of current and new treatments in this and other neurological diseases.

【 授权许可】

Unknown   
© 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd