Elan D Louis1, Pam Factor-Litvak, Xinhua Liu, Jean-Paul G Vonsattel, Monika Galecki, Wendy Jiang, Wei Zheng. 1. GH Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA. Electronic address: EDL2@columbia.edu.
Abstract
BACKGROUND: Harmane (1-methyl-9H-pyrido[3,4-β]indole), a potent neurotoxin that has tremor-producing properties in animal models, is present in many foods; although we have demonstrated a difference in tissue harmane concentrations in ET cases vs. controls, all work to date has involved blood samples. OBJECTIVES: We quantified harmane concentrations in human cerebellum, a brain region of particular pathogenic interest in essential tremor (ET), comparing ET to control brains. METHODS: Cerebellar cortex was snap frozen and stored at -80°C in aliquots for biochemical analyses. Harmane concentration was assessed using high performance liquid chromatography. RESULTS: Geometric mean brain harmane concentrations (adjusted for postmortem interval [PMI] and freezer time) were higher in ET cases than controls: 1.0824 (95% confidence interval=0.9405-1.2457) vs. 0.8037 (0.6967-0.9272), p=0.004. Geometric mean of brain harmane concentrations (adjusting for PMI and freezer time) was highest in ET cases who reported other relatives with tremor (1.2005 [0.8712-1.6541]), intermediate in ET cases without family history (1.0312 ([0.8879-1.1976]), and both were significantly higher than controls (p=0.02). CONCLUSIONS: This study provides additional evidence of a possible etiological importance of this toxin in some cases of the human disease ET.
BACKGROUND:Harmane (1-methyl-9H-pyrido[3,4-β]indole), a potent neurotoxin that has tremor-producing properties in animal models, is present in many foods; although we have demonstrated a difference in tissue harmane concentrations in ET cases vs. controls, all work to date has involved blood samples. OBJECTIVES: We quantified harmane concentrations in human cerebellum, a brain region of particular pathogenic interest in essential tremor (ET), comparing ET to control brains. METHODS: Cerebellar cortex was snap frozen and stored at -80°C in aliquots for biochemical analyses. Harmane concentration was assessed using high performance liquid chromatography. RESULTS: Geometric mean brain harmane concentrations (adjusted for postmortem interval [PMI] and freezer time) were higher in ET cases than controls: 1.0824 (95% confidence interval=0.9405-1.2457) vs. 0.8037 (0.6967-0.9272), p=0.004. Geometric mean of brain harmane concentrations (adjusting for PMI and freezer time) was highest in ET cases who reported other relatives with tremor (1.2005 [0.8712-1.6541]), intermediate in ET cases without family history (1.0312 ([0.8879-1.1976]), and both were significantly higher than controls (p=0.02). CONCLUSIONS: This study provides additional evidence of a possible etiological importance of this toxin in some cases of the human disease ET.
Authors: Elan D Louis; Phyllis L Faust; Jean-Paul G Vonsattel; Lawrence S Honig; Alex Rajput; Christopher A Robinson; Ali Rajput; Rajesh Pahwa; Kelly E Lyons; G Webster Ross; Sarah Borden; Carol B Moskowitz; Arlene Lawton; Nora Hernandez Journal: Brain Date: 2007-11-19 Impact factor: 13.501
Authors: Elan D Louis; Julian Benito-León; Sara Moreno-García; Saturio Vega; Juan Pablo Romero; Felix Bermejo-Pareja; Marina Gerbin; Amanda S Viner; Pam Factor-Litvak; Wendy Jiang; Wei Zheng Journal: Neurotoxicology Date: 2012-09-12 Impact factor: 4.294
Authors: Angela Cruz-Hernandez; Zeynep Sena Agim; Paola C Montenegro; George P McCabe; Jean-Christophe Rochet; Jason R Cannon Journal: Neurotoxicology Date: 2018-03 Impact factor: 4.294
Authors: Elan D Louis; Sheng-Han Kuo; Jie Wang; William J Tate; Ming-Kai Pan; Geoffrey C Kelly; Jesus Gutierrez; Etty P Cortes; Jean-Paul G Vonsattel; Phyllis L Faust Journal: Cerebellum Date: 2017-08 Impact factor: 3.847
Authors: Jie Wang; Geoffrey C Kelly; William J Tate; Yong-Shi Li; Michelle Lee; Jesus Gutierrez; Elan D Louis; Phyllis L Faust; Sheng-Han Kuo Journal: Parkinsonism Relat Disord Date: 2016-09-06 Impact factor: 4.891