Elevated brain harmane (1-methyl-9H-pyrido3,4-bindole) in essential tremor cases vs. controls.
Harmane (1-methyl-9H-pyrido3,4-βindole), 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. We quantified harmane concentrations in human cerebellum, a brain region of particular pathogenic interest in essential tremor (ET), comparing ET to control brains. Cerebellar cortex was snap frozen and stored at -80°C in aliquots for biochemical analyses. Harmane concentration was assessed using high performance liquid chromatography. Geometric mean brain harmane concentrations (adjusted for postmortem interval PMI and freezer time) were higher in ET cases than controls 1.0824 (95% confidence interval0.9405-1.2457) vs. 0.8037 (0.6967-0.9272), p0.004. 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 (p0.02). This study provides additional evidence of a possible etiological importance of this toxin in some cases of the human disease ET.