Elevated brain harmane (1-methyl-9H-pyrido[3,4-b]indole) in essential tremor cases vs. controls


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Abstract

BackgroundHarmane (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.ObjectivesWe quantified harmane concentrations in human cerebellum, a brain region of particular pathogenic interest in essential tremor (ET), comparing ET to control brains.MethodsCerebellar cortex was snap frozen and stored at −80 °C in aliquots for biochemical analyses. Harmane concentration was assessed using high performance liquid chromatography.ResultsGeometric 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).ConclusionsThis study provides additional evidence of a possible etiological importance of this toxin in some cases of the human disease ET.HighlightsEnvironmental correlates for essential tremor (ET) are largely unexplored.Harmane (1-methyl-9H-pyrido[3,4-b]indole) is a potent tremor-producing toxin.Brain (cerebellar) harmane levels were quantified by high performance liquid chromatography.Brain harmane levels were elevated in ET cases vs. controls, and highest in familial ET cases.This study provides additional evidence of a possible etiological importance of this toxin in ET.

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