Open Access Review Article Sergio et al., Pharm Anal Acta 2015, 6:3 DOI: 10.4172/2153-2435.1000346 Volume 6 • Issue 3 • 1000346 Pharm Anal Acta ISSN: 2153-2435 PAA, an open access journal *Corresponding author: Rosales-Corral S, Neuroscience Division, Western Biomedical Research Center, Mexican Institute of Social Security, Guadalajara, Mexico, Tel: (+52) 33-36170060; E-mail: espiral17@gmail.com. Received February 05, 2015; Accepted February 23, 2015; Published March 03, 2015 Citation: Rosales-Corral S, Hernández L, Gallegos M (2015) Cannabinoids in Neuroinfammation, Oxidative Stress and Neuro Excitotoxicity. Pharm Anal Acta 6: 346. doi:10.4172/2153-2435.1000346 Copyright: © 2015 Rosales-Corral S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Research on cannabinoids has been growing signifcantly in the last fve years. More than ffty percent of this research corresponds to “cannabinoids and brain”, particularly about neurodegeneration. In this sense, there is evidence reporting that specifc phyto cannabinoids show some specifc action on each one of main pathogenic mechanisms involved in neurodegeneration such as oxidative stress, neuroinfammation and excitotoxicity. However, by using the same targets, cannabinoids may also induce the opposite effects, this is, excitotoxicity and infammation. In fact, both tetrahydro cannabinol and cannabidiol activate cannabinoid receptors, but they also may act as antagonists of those receptors. It seems to be a dose-dependent issue; nonetheless, as reviewed in this paper, many other factors such as timing, type of cell and its state of activity even the activation of different, non- cannabinoid receptorsseem to have a role related to those unexpected antagonic effects. Cannabinoids in Neuroinflammation, Oxidative Stress and Neuro Excitotoxicity Rosales-Corral S 1 *, Hernández L 2 and Gallegos M 2 1 Neuroscience Division, Western Biomedical Research Center, Mexican Institute of Social Security, Guadalajara, Mexico 2 Department of Physiology, University of Guadalajara Health Science Center,Guadalajara,Jalisco, Mexico Keywords: Cannabinoids; Neurodegeneration; Alzheimer; Excitotoxicity; Neuroinfammation Abbreviations: CB1R: cannabinoid receptor type 1; CB2R: cannabinoid receptor type 2; PPARs: peroxisome proliferator activated receptors; TPRV1: transient receptor potential vanilloid transmitter- gated channels; CNS: central nervous system; ATP: adenosine triphosphate; NLRP3:nucleotide-binding domain; leucine-rich-repeat- containing family; pyrin domain-containing 3; IL: interleukin; GPx: glutathione peroxidase; NADPH: nicotinamide adenine dinucleotide phosphate; O 2 -superoxide anion; H 2 O 2 : hydrogen peroxide; SO: superoxide dismutase; OH∙: hydroxyl radicals; NO: nitric oxide; ONOO-:peroxynitrite anion; ROS: reactive oxygen species; GSH: reduced glutathione; GSSG: glutathione disulfde; NMDA: N-Methyl- D-aspartic acid; IP 3 : inositol 1,4,5, triphosphate; TNF: tumor necrosis factor; AEA:anandamide; 2-arachidonylethanolamide (2-AG); 2-AGE: 2-Arachidonyl glyceryl ether; AD: Alzheimer disease; TBI: traumatic brain injury; GPRs: G protein coupled receptors; AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; THC: tetrahidro cannabinol; CBD: cannabidiol; CBN: cannabinol; CBC: Cannabichromen; CBG: Cannabigerol; VCAM-1: vascular cell adhesion molecule-1; NF-κB: nuclear factor kappa-B; PKA: protein kinase A; NOS: Nitric oxide synthase; FCCP: carbonyl cyanide-4- (trifuoromethoxy) phenylhydrazine Introduction Cannabinoids are a class of signaling lipids consisting of amides and esters of long-chain polyunsaturated fatty acids synthesized by Ca2+ or G-protein-dependent processes from lipid precursors in plasma membranes and exert their actions by binding to receptors [1]. Tese receptors can be 7-transmembrane receptors (CB1R, CB2R, GPR18, GPR55 and GPR119), nuclear receptors (PPARα, PPARβ/γ and PPARγ) and the transient receptor potential vanilloid transmitter- gated channels (TPRV1) [2]. Primary efects are mediated by CB1R and CB2R, which are coupled to G i or G o protein, modulating negatively to adenylyl cyclase, therefore cannabinoids attenuate the production of the second messenger cyclic adenosine monophosphate (cAMP). CB1R and CB2R are also coupled to ion channels via G protein signal transduction pathways [3]. Tere is a long list of undesirable efects of cannabis going from acute efects such as, impaired short-term memory and attention, reduced motor skills, anxiety, panic, even psychotic symptoms, to chronic efects such as, addiction, or subtle impairments of attention and memory [4]. Indeed, cannabis use has been related to psychosis or schizophrenia [5]. Certain cannabinoids, on the other hand, may induce neuroprotective pathways either by using cannabinoid receptors or by interacting with other receptors, such as the peroxisome proliferator-activated receptors (PPARs), as mentioned before. In such a manner that cannabinoids could go further and become involved in the promotion of neural stem cell proliferation, either through CB2R [6], or by activating PPARs [7]. It is the purpose of this short review to analyze the role of cannabinoids in the three key aspects of neurodegeneration: oxidative stress, neuroinfammation and glutamate-induced excitotoxicity. Neuroinfammation, Oxidative Stress and Excitotoxicity in Neurodegeneration Tere is a sophisticated scheme of vigilance of the environment by astrocytes and microglia, which maintain simultaneously a precise communication with neurons through specifc mediators. Tis isachieved through specifc mediators, such as Ca 2+ , cytokines and a group of molecules known as damage-associated molecular patterns (DAMPs) acting as stimulators of the immune system, similar to pathogen-associated molecular patterns (PAMPs). In such a manner that astrocytes and neurons regulate the activity of microglia during neuroinfammatory processes, while astrocyte calcium waves may modulate neuronal activity [8]. Minimal alterations in the redox P h a r m a c e u t i c a A n a l y t i c a A c t a ISSN: 2153-2435 Pharmaceutica Analytica Acta