Inhibition of excessive glutamatergic transmission in the ventral thalamic nuclei by a selective adenosine A1 receptors agonist, 5'-chloro-5'-deoxy-(±)-ENBA underlies its tremorolytic effect in the harmaline-induced model of Essential Tremor.

07:00 EST 11th January 2020 | BioPortfolio

Summary of "Inhibition of excessive glutamatergic transmission in the ventral thalamic nuclei by a selective adenosine A1 receptors agonist, 5'-chloro-5'-deoxy-(±)-ENBA underlies its tremorolytic effect in the harmaline-induced model of Essential Tremor."

The primary cause of harmaline tremor, which is a model of essential tremor (ET) in animals, is excessive activation of olivocerebellar glutamatergic climbing fibers. Our recent study indicated that 5'-chloro-5'-deoxy-(±)-ENBA (5'Cl5'd-(±)-ENBA), a potent and selective adenosine A1 receptor agonist, inhibited harmaline tremor. The present study was aimed to evaluate the role of glutamatergic transmission system in 5'Cl5'd-(±)-ENBA tremorolytic action in the harmaline model in rats, by analyzing glutamate release in the motor nuclei of the thalamus and mRNA expression of glutamatergic neuron markers (vGlut1/2) in reference to the general neuronal activity marker (zif-268) in different brain structures. The extracellular glutamate level in the motor thalamus was evaluated by in vivo microdialysis and the vGlut1/vGlut2 and zif-268 mRNA expression was analyzed by in situ hybridization. The intensity of tremor was measured automatically using Force Plate Actimeters. 5'Cl5'd-(±)-ENBA (0.5mg/kg) given 30 min before harmaline (30mg/kg) decreased the harmaline-induced excessive glutamate release in the motor thalamus and reversed harmaline-induced molecular effects, such as elevation of the vGlut1 mRNA expression in the inferior olive and decrease in the motor cortex, as well as an increase of the zif-268 mRNA expression in the inferior olive, motor thalamus and motor cortex. Moreover, 5'Cl5'd-(±)-ENBA reduced harmaline tremor by lowering its power in 9-15 Hz frequency band. Our findings show that adenosine A1 receptor stimulation decreases glutamate release in the motor thalamic nuclei in a harmaline model of ET, suggesting that A1 receptors, especially in this structure, may be a potential therapeutic target in this disorder.


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This article was published in the following journal.

Name: Neuroscience
ISSN: 1873-7544


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Medical and Biotech [MESH] Definitions

A large group of nuclei lying between the internal medullary lamina and the internal capsule. It includes the ventral anterior, ventral lateral, and ventral posterior nuclei.

The largest of the medial nuclei of the thalamus. It makes extensive connections with most of the other thalamic nuclei.

A transitional diencephalic zone of the thalamus consisting of complex and varied cells lying caudal to the ventral posterolateral nucleus, medial to the rostal part of the pulvinar, and dorsal to the medial geniculate body. It contains the limitans, posterior, suprageniculate, and submedial nuclei.

Several groups of nuclei in the thalamus that serve as the major relay centers for sensory impulses in the brain.

The dorsal posterior subdivision of the diencephalon. The epithalamus is generally considered to include the habenular nuclei (HABENULA) and associated fiber bundles, the PINEAL BODY, and the epithelial roof of the third ventricle. The anterior and posterior paraventricular nuclei of the thalamus are included with the THALAMIC NUCLEI although they develop from the same pronuclear mass as the epithalamic nuclei and are sometimes considered part of the epithalamus.

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