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Pharmacological inhibition of fatty acid amide hydrolase as a therapeutic target to reduce excitotoxic damage in a huntingtonand#8217;s disease model in rat

Journal of Neurology & Neurophysiology

ISSN - 2155-9562

Pharmacological inhibition of fatty acid amide hydrolase as a therapeutic target to reduce excitotoxic damage in a huntington’s disease model in rat

Joint Event on International Conference on Neuroimmunology, Neurological disorders and Neurogenetics & 28th World Summit on Neurology, Neuroscience and Neuropharmacology

September 26-27, 2018 | Montreal, Canada

Abel Santamaria-Del Angel

National Institute of Neurology and Neurosurgery, Mexico

Posters & Accepted Abstracts: J Neurol Neurophysiol

Abstract :

The endocannabinoid system (ECS) participates in physiological processes within the Central Nervous System [1]. Its involvement in the downregulation of the N-methyl-D-aspartate receptor (NMDAr) through a modulatory input at the cannabinoid receptors (CBr) has been described [2]. Quinolinic acid (QUIN) acts as an excitotoxin through the selective overactivation of NMDAr, thus participating in the development of neurological disorders [3]. Here we evaluated if the pharmacological inhibition of fatty acid amide hydrolase (FAAH) by URB597, and the consequent increase in endogenous levels of anandamide, can prevent the excitotoxic damage induced by QUIN. URB597 (0.3 mg/kg/day x 7 days, administered before, during and after the striatal lesion) exerted protective effects on the QUIN-induced motor (asymmetric behavior) and biochemical (lipid peroxidation and protein carbonylation) alterations in rats. URB597 also preserved the structural integrity of the striatum and prevented the neuronal loss (assessed as microtubule-associated protein-2 and glutamate decarboxylase localization) induced by QUIN (1 ?¼L intrastriatal, 240 nmol/?¼L), while modified the early localization patterns of CBr1 and NMDAr subunit 1 (NR1), suggesting a reduced risk of excitotoxic damage. Altogether, these findings support the concept that the pharmacological stimulation of the ECS may play a neuroprotective role against excitotoxic insults in the CNS.

Biography :

Abel Santamaria is Professor in the Laboratory of Excitatory Amino Acids at the National Institute of Neurology and Neurosurgery, Mexico. His laboratory currently studies the mechanisms by which quinolinic acid exert their effects in the Central Nervous System, trying to find additional and not-excluding components of neurodegeneration, including oxidative stress, novel inflammatory signals, and synergic toxicity. Through the evaluation of these events, the use of potential agents with therapeutic profiles, such as cannabinoids, serve to model deleterious events potentially taking place in the brains of patients with excitotoxic events. He has published several scientific papers on this topic and keeps working on alternative explanations for toxic mechanisms involving excitotoxicity and oxidative stress.

E-mail: [email protected]

 

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