Blood harmane is correlated with cerebellar metabolism in essential tremor

Louis, Elan D.; Zheng, Wei; Mao, Xiangling; Shungu, Dikoma C.

doi:10.1212/01.wnl.0000266663.27398.9f

Cited by 32 publications

(18 citation statements)

References 39 publications

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“…This correlation was not found in other brain regions (e.g., thalamus, basal ganglia) or with other neurotoxins (e.g., lead) [159]. These findings suggest that increased blood harmane concentration could be associated with greater cerebellar neuronal damage, consistent with the animal study data that harmane and other β-carboline alkaloids produce cerebellar damage [121, 126, 127, 138–141].…”

Section: Possible Environmental Toxins In Etsupporting

confidence: 76%

“…Using magnetic resonance spectroscopic imaging, Louis et al[159] also demonstrated a strong inverse correlation between cerebellar N -acetyl aspartate to creatine ratio (a marker of neuronal damage) and blood harmane concentrations (p = 0.009, adjusting for age and gender) in a small study of 12 ET cases. This correlation was not found in other brain regions (e.g., thalamus, basal ganglia) or with other neurotoxins (e.g., lead) [159].…”

Section: Possible Environmental Toxins In Etmentioning

confidence: 99%

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Environmental Epidemiology of Essential Tremor

Louis

2008

Neuroepidemiology

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Background: Essential tremor (ET) is one of the most common neurological disorders. Despite this, the disease mechanisms and etiology are not well understood. While susceptibility genotypes undoubtedly underlie many ET cases, no ET genes have been identified thus far. As with many other progressive, degenerative neurological disorders, it is likely that environmental factors contribute to the etiology of ET. Environmental epidemiology is the study in specific populations or communities of the effect on human health of physical, biologic and chemical factors in the external environment. The purpose of this article is to review current knowledge with regards to the environmental epidemiology of ET. Results: As will be discussed, a series of preliminary case-control studies in recent years has begun to explore several candidate toxins/exposures, including harmane (1-methyl-9H-pyrido[3,4-b]indole), lead and agricultural exposures/pesticides. Conclusions: While several initial results are promising, as will be discussed, additional studies are needed to more definitively establish whether these exposures are associated with ET and if they are of etiological importance.

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Section: Possible Environmental Toxins In Etsupporting

confidence: 76%

Section: Possible Environmental Toxins In Etmentioning

confidence: 99%

Environmental Epidemiology of Essential Tremor

Louis

2008

Neuroepidemiology

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“…(1-methyl-9H-pyrido- [3,4-b]-indole), a tremor-producing b-carboline alkaloid (Louis et al 2007), is naturally present in hallucinogenic plants, such as Peganum harmala Linn (Zygophyllaceae), Banisteriopsis caapi (Spruce ex Grisb.) Morton (Malpighiaceae), and Tribulus terrestris Linn (Zygophyllaceae).…”

Section: Harmanementioning

confidence: 99%

Pharmacokinetic study of harmane and its 10 metabolites in rat after intravenous and oral administration by UPLC-ESI-MS/MS

Liu

et al. 2016

Pharmaceutical Biology

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Context The b-carboline alkaloid harmane is widely distributed in common foods, beverages and hallucinogenic plants. Harmane exerts potential in therapies for Alzheimer's and depression diseases. However, little information on its dynamic metabolic profiles and pharmacokinetics in vivo is currently available. Objective This study investigates the dynamic metabolic profiles and pharmacokinetic properties of harmane and its metabolites in rats in vivo. Materials and methods A highly selective, sensitive and rapid ultra-performance liquid chromatography combined with electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) method was developed and well-validated for simultaneous quantitative determination of harmane and its uncertain endogenous metabolite harmine, as well as for semiquantitative determination of 10 harmane metabolites in rats after intravenous injection and oral administration of harmane at 1.0 and 30.0 mg/kg, respectively. Results The calibration curves of harmane and harmine showed excellent linearity within the concentration range of 1-2000 ng/mL with acceptable accuracy, precision, selectivity, recovery, matrix effect and stability. Ten metabolites, including harmane but not harmine, were detected and identified after intravenous and oral administration of harmane. The absolute bioavailability of harmane following an oral dose was 19.41 ± 3.97%. According to the AUC 0-t values of all the metabolites, the metabolic levels of phase II metabolites were higher than those of phase I metabolites, and the sulphation pathways were the dominant metabolic routes for harmane in both routes of administration. Discussion and conclusion The pharmacokinetic properties of harmane and its 10 metabolites in rats were determined. Sulphate conjugation was the predominant metabolic process of harmane in rats.

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“…Although postmortem studies point towards cerebellar changes, PET and fMRI studies have revealed abnormalities in the cerebellum, thalamus, and triangle of Guillain-Mollaret, which is settled in the brain stem and inferior olive nucleus. Researchers argue that the postural tremor of ET arises from spontaneous firing of inferior olivary nucleus (ION), which connects the cerebellum and its output pathways to the cerebral cortex and then to the spinal cord through VIM of the thalamus (11,12,13,14,15,16,17). Studies have shown that ET amplitude could be significantly reduced with thalamic lesions or thalamic stimulation, and the thalamus has been suggested to play a major role in the formation or transmission of ET (18,19).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Thalamus Area In Essential Tremor Patients With Proton Magnetik Resonance Spectroscopy

Özkan¹,

Candan²,

Işık³

et al. 2015

tnd

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Objective: Although essential tremor (ET) is the most common movement disorder, its pathogenesis is poorly understood. It is suggested that the ventral intermediate (VIM) nucleus of the thalamus is important in the pathophysiology disease. Materials and Methods:The present study aimed to evaluate N-acetylaspartate (NAA), choline (cho), and creatinine (Cr) values via proton magnetic resonance spectroscopy (H-1 MRS) of the VIM of the thalamus in 16 control patients and 42 patients with ET. Results:The mean NAA/Cr and NAA/Cho values of the thalamus VIM nucleus region in patients with ET was statistically significantly lower than the control group (p=0.001, p=0.005, respectively). In patients with ET, no significant relation was found between NAA/Cr, NAA/Cho values, and age, family history, disease duration, tremor severity, dominant extremity localization of tremor, and history of drug use (p>0.05). Conclusion:Low NAA values in the thalamus region of patients with ET indicate neuron loss and cell death. Neuron loss in the thalamus region has been suggested to play a part in the pathophysiology of the disease, and may indicate that ET is a neurodegenerative disease. Keywords: Essential tremor, magnetic resonance spectroscopy, thalamusAmaç: Esansiyel tremor (ET) en sık görülen hareket bozukluğu olmasına rağmen patogenezi hala bilinmemektedir. Talamusun ventral intermediate (VİM) nükleusunun patofizyolojide rol oynadığı öne sürülmektedir. Gereç ve Yöntem:Bu çalışmada 42 ET tanısı almış hasta ve 16 kontrol olgusunun proton manyetik rezonans spektroskopi (H-1 MRS) tetkiki kullanarak talamus bölgesinin N-asetilaspartat (NAA), kolin ve kreatinin değerlerinin incelenmesi amaçlandı. Bulgular: ET hastalarında talamus VİM nükleus bölgesi ortalama NAA/Kreatinin ve NAA/Kolin değerleri kontrol grubuna göre istatistiksel olarak anlamlı derecede düşük olarak tespit edildi (sırasıyla p=0,001, p=0,005). ET hastalarının yaş, aile öyküsü, hastalık süresi, tremor şiddeti, tremor dominant ekstremite lokalizasyonu ve ilaç kullanım öyküsü ile NAA/Kreatinin, NAA/Kolin değerleri arasında anlamlı bir ilişki bulunmadı (p>0,05).Sonuç: ET hastalarının talamus bölgesindeki düşük NAA değerleri, bu bölgedeki nöron kaybı ve hücre yıkımını işaret etmektedir. Hastalığın patofizyolojisinde rol oynadığı öne sürülen talamus bölgesindeki nöron kaybı, ET'nin nörodejeneratif bir hastalık olduğunun göstergesi olabilir.

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Blood harmane is correlated with cerebellar metabolism in essential tremor

Abstract: This study provides additional support for the emerging link between harmane, a neurotoxin, and ET. Further studies are warranted to address whether cerebellar harmane concentrations are associated with cerebellar pathology in postmortem studies of the ET brain.

Cited by 32 publications

References 39 publications

Environmental Epidemiology of Essential Tremor

Environmental Epidemiology of Essential Tremor

Pharmacokinetic study of harmane and its 10 metabolites in rat after intravenous and oral administration by UPLC-ESI-MS/MS

Evaluation of Thalamus Area In Essential Tremor Patients With Proton Magnetik Resonance Spectroscopy

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