harmine and Cognition-Disorders

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.. 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.. 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.

Topics: Cognition Disorders; Disease Susceptibility; Environmental Exposure; Environmental Health; Essential Tremor; Harmine; Humans; Lead Poisoning; Pesticides; Risk Factors

The aim of the study was to isolate the harmine alkaloids from the seeds of Peganum harmala (TAPH) and its cerebroprotective effect on cognitive deficit mice. The tested doses of TAPH were screened for Sodium nitrite induced hypoxia and Ethanol induced neurodegeneration using behavioral models. The TAPH was found to be non-neurotoxic and Psychoactive by preventing the motor impairment and increasing the locomotion activity of animals in Rota rod and Actophotometer respectively. TAPH (5, 2.5 and 1.25 mg kg(-1) p.o.) significantly (p < 0.001) protected the Sodium nitrite induced memory impairment by decreasing the time require to find the water bottle in special water bottle case model. In Elevated Plus Maze (EPM) and Passive Shock Avoidance paradigm (PSA) the TAPH shown improved acquisition and retention memory significantly (p < 0.001) by decreasing the Transverse Latency Time (TLT) and increasing the Step Down Latency (SDL), respectively in dose dependent manner. The results were well supported by biochemical parameters, by inhibiting the Acetylcholinestrase (p < 0.01) activity, increasing the GSH (p < 0.001) level and decreasing the TBARS (p < 0.001) level of whole brain. Moreover TAPH has shown the significant Monoamine oxidase-A (MAO-A) inhibition action (p < 0.001), hence it reduces the metabolism of epinephrine, 5-HT and other monoamines and enhances the action of these neurotransmitters indirectly; this adrenergic system plays an important role in learning and memory. Further, TAPH (5 mg kg(-1)) protect the DNA fragmentation of frontotemporal cortex of the brain from hypoxic effect induced by Sodium nitrite in Gel Electrophoresis studies. The results were comparable to their respective standards. Hence, harmine alkaloids are potential enough to utilize in the management of Neurodegenerative disorders of the type Alzheimer's diseases.

Topics: Acetylcholinesterase; Animals; Apoptosis; Behavior, Animal; Brain; Cognition; Cognition Disorders; Cytoprotection; Disease Models, Animal; Dose-Response Relationship, Drug; Ethanol; Glutathione; GPI-Linked Proteins; Harmine; Hypoxia, Brain; Male; Mice; Monoamine Oxidase; Motor Activity; Nerve Degeneration; Neuroprotective Agents; Peganum; Phytotherapy; Plant Extracts; Plants, Medicinal; Reaction Time; Seeds; Sodium Nitrite; Thiobarbituric Acid Reactive Substances; Time Factors

Harmane (1-methyl-9H-pyrido[3,4-b]indole), a neurotoxin, may be an environmental risk factor for essential tremor (ET). Harmane and related chemicals are toxic to the cerebellum. Whether it is through this mechanism (cerebellar toxicity) that harmane leads to ET is unknown. Impaired olfaction may be a feature of cerebellar disease.. To determine whether blood harmane concentrations correlate with olfactory test scores in patients with ET.. Blood harmane concentrations were quantified using high performance liquid chromatography. Odor identification testing was performed with the University of Pennsylvania Smell Identification Test (UPSIT).. In 83 ET cases, higher log blood harmane concentration was correlated with lower UPSIT score (rho=-0.46, p<0.001). 25/40 (62.5%) cases with high log blood harmane concentration (based on a median split) had low UPSIT scores (based on a median split) vs. 12/43 (27.9%) ET cases with low log blood harmane concentration (adjusted odd ratios (OR) 4.04, 95% confidence intervals (CI) 1.42-11.50, p=0.009). When compared with the low log blood harmane tertile, the odds of olfactory dysfunction were 2.64 times higher in cases in the middle tertile and 10.95 times higher in cases in the high tertile. In 69 control subjects, higher log blood harmane concentration was not correlated with lower UPSIT score (rho=0.12, p=0.32).. Blood harmane concentrations were correlated with UPSIT scores in ET cases but not controls. These analyses set the stage for postmortem studies to further explore the role of harmane as a cerebellar toxin in ET.

Topics: Aged; Cerebellar Diseases; Cognition Disorders; Essential Tremor; Female; Harmine; Humans; Male; Middle Aged; Neuropsychological Tests; Neurotoxins; Psychomotor Performance; Smell