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

Neurotoxicology. 2013 Sep:38:131-5. doi: 10.1016/j.neuro.2013.07.002. Epub 2013 Aug 2.

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.

Keywords: Brain; Epidemiology; Essential tremor; Harmane; Pathology; Toxicant.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Cerebellar Cortex / chemistry*
  • Essential Tremor / chemically induced*
  • Family Health
  • Female
  • Harmine / analogs & derivatives*
  • Harmine / analysis
  • Humans
  • Male
  • Neurotoxins / analysis*

Substances

  • Neurotoxins
  • Harmine
  • harman