The endocannabinoid signaling system and new experimental approaches to the treatment of movement disorders

Cover Page


Cite item

Full Text

Abstract

Reviewed are modern concepts concerning physiological role and mechanisms of brain functioning of the endocannabinoid signaling system comprising cannabinoid receptors, endocannabinoids and proteins participating in their synthesis, transport and degradation. The results of recent experimental studies showing an important role of the endocannabinoid system in motor control and mechanisms of movement disorders in multiple sclerosis, Parkinson’s disease and Huntington’s chorea are presented. In this context, investigation of possibilities of pharmacological correction of the endocannabinoid transmission should be considered as a novel and important field in experimental neurology with significant therapeutic potential.

 
 

About the authors

V. P. Barkhatova

Research Center of Neurology, Russian Academy of Medical Sciences

Author for correspondence.
Email: platonova@neurology.ru
Россия, Moscow

References

  1. Бархатова В.П., Завалишин И.А., Переседова А.В. Спастичность: патогенез и современные подходы к лечению. Русский мед. журн. 2005; 22: 1503–1505.
  2. Бархатова В.П., Пантелеева Е.А., Алферова В.П. и др. Нейротрансмиттерные механизмы двигательных нарушений при рассеянном склерозе. Журн. неврол. и психиатрии им. С.С. Корсакова 2007; 2: 43–48.
  3. Хаспеков Л.Г., Бобров М.Ю. Эндогенная каннабиноидная система и ее защитная роль при ишемическом и цитотоксическом повреждении нейронов головного мозга. Нейрохимия 2006; 2: 85–105.
  4. Battista N., Fezza F., Finazzi-Agro A. et al. The endocannabinoid system in neurodegeneration. Int. J. Biochem. 2006; 55: 283–289.
  5. Caranian D.A., Bahr B.A. Cannabinoid drugs and enhancement of endocannabinoid response: strategies for a wide array of disease states. Curr. Mol. Med. 2006; 6: 677–684.
  6. Centonze D., Rossi S., Prosperetti C. et al. Abnormal sensitivity to cannabinoid receptor stimulation might contribute to altered gamma-aminobutyric acid transmission in the striatum of R6/2 Huntington’s disease mice. Biol. Psychiatry 2005; 57: 1583–1589.
  7. Degroot A., Nomikos G.G. In vivo neurochemical effects induced by changes in endocannabinoid neurotransmission. Curr. Opin. Pharmacol. 2007; 7: 62–68.
  8. De Lago E., Fernandez-Ruiz J., Ortega-Gutierrez Z. et al. UCM707, an inhibitor of the anandamide uptake, behaves as a symptom control agent in models of Huntington s disease and multiple sclerosis, but fails to delay/arrest the progression of different motor-related disorders. Eur. Neuropsychopharmacol. 2006; 16: 7–18.
  9. Eljaschewitsch E., Witting A., Mawrin C. et al. The endocannabinoid anandamide protects neurons during CNS inflammation by induction of MKP-1 in microglial cells. Neuron 2006; 5: 67–79.
  10. Fernandez-Espejo E., Caraballo I., Rodriguez de Fonseca F. et al. Experimental parkinsonism alters anandamide precursor synthesis, and functional deficits are improved by AM404: a modulator of endocannabinoid function. Neuropsychopharmacology 2004; 29: 1134–1142.
  11. Fernandez-Ruiz J., Gonzales S. Cannabinoid control of motor function at the basal ganglia. Handb. Exp. Pharmacol. 2005; 168: 479–507.
  12. Fusco F.R., Martorana A., Giampa C. et al. Immunolocalization of CB1 receptor in rat striatal neurons: a confocal microscopy study. Synapse 2004; 53: 159–167.
  13. Garcia-Arencibia M., Gonzalez S., de Lago E. Evaluation of the neuroprotective effect of cannabinoids in rat model of Parkinson’s disease: importance of antioxidant and cannabinoid receptor-independent properties. Brain Res. 2007; 1134: 162–170.
  14. Kreitzer A.C., Malenka R.C. Dopamine modulation of state dependent endocannabinoid release and long term depression in the striatum. J. Neurosci. 2005; 25: 10537–10545.
  15. Kreitzer A.C., Malenka R.C. Endocannabinoid-mediated rescue of striatal LTD and motor deficits in Parkinson’s disease models. Nature 2007; 445: 643–647.
  16. Lee J., Di Marzo V., Brotchie J.M. A role for vanilloid receptor 1 (TRPV1) and endocannabinoid signalling in the regulation of spontaneous and L-Dopa induced locomotion in normal and reserpine-treated rats. Neuropharmacology 2006; 51: 557–565.
  17. Mackie K. Mechanisms of CB1 receptor signaling: endocannabinoid modulation of synaptic strength. Int. J. Obes. (Lond.) 2006; 30 (Suppl.1): 19–23.
  18. Melis M., Pillolla G., Bisogno T. et al. Protective activation of the endocannabinoid system during ischemia in dopamine neurons. Neurobiol. Dis. 2006; 24: 15–27.
  19. Mestre L., Correa F., Arevalo-Martin A. et al. Pharmacological modulation of the endocannabinoid system in a viral model of multiple sclerosis. J. Neurochem. 2005; 92: 1327–1339.
  20. Narushima M., Uchigashima M., Fucaya M. et al. Tonic enhancement of endocannabinoid-mediated retrograde suppression of inhibition by cholinergic interneuron activity in the striatum. J. Neurosci. 2007; 27: 496–506.
  21. Pacher P., Batkai S., Kunos G. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol. Rev. 2006; 58: 389–462.
  22. Perez J. Combined cannabinoid therapy via an oromucosal spray. Drugs of Today 2006; 42: 495–501.
  23. Pertwee R.G. Pharmacology of cannabinoid CB1 and CB2 receptors. Pharmacol. Ther. 1997; 74: 129–180.
  24. Pickel V.M., Chan J., Kearn C.S. et al. Targeting dopamine D2 and cannabinoid-1 (CB1) receptors in rat nucleus accumbens. J. Comp. Neurol. 2006; 495: 299–313.
  25. Rinaldi-Carmona M., Calandra B., Shire D. et al. Characterization of two cloned human CB1 cannabinoid receptor isoforms. J. Pharmacol. Exp. Ther. 1996; 278: 871–878.
  26. Rodriguez de Fonseca F., Del Arco I., Bermudez-Silva F.J. et al. The endocannabinoid system: physiology and pharmacology. Alcohol Alkohol 2005; 40: 2–14.
  27. Safo P.K., Regehr W.G. Endocannabinoids control of cerebellar LTD. Neuron. 2005; 48: 647–659.
  28. Sharkey K.A., Cristino L., Oland L.D. et al. Arvanil, anandamid and N-arachidonoilldopamine (NADA) inhibit emesis through cannabinoid CB1 and vanilloid TRPV1 receptors in the ferret. Eur. J. Neurosci. 2007; Apr. 25 [E-pub. ahead of print].
  29. Singh J., Budhiraja S. Therapeutic potential of cannabinoid receptor ligands: current status. Methods Find. Exp. Clin. Pharmacol. 2006; 28: 177–183.
  30. van der Stelt M., Fox S.H., Hill M. et al. A role for endocannabinoids in the generation of parkinsonism and levodopa-induced dyskinesia in MPTP-lesioned non-human primate models of Parkinson’s disease. FASEB J. 2005; 19: 1140–1142.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2008 Barkhatova V.P.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77-83204 от 12.05.2022.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies