User:Tkadm30/Notebook/Endocannabinoids: Difference between revisions
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** Stimulation of GPR40-GPR55 receptor heteromer by DHA promotes heterosynaptic LTP through peroxisome proliferator-activated receptors (PPARs) activation. [http://jur.byu.edu/?p=18609 Link] [http://www.biomedcentral.com/1471-2202/13/109 doi:10.1186/1471-2202-13-109] | ** Stimulation of GPR40-GPR55 receptor heteromer by DHA promotes heterosynaptic LTP through peroxisome proliferator-activated receptors (PPARs) activation. [http://jur.byu.edu/?p=18609 Link] [http://www.biomedcentral.com/1471-2202/13/109 doi:10.1186/1471-2202-13-109] | ||
** FABP7 is a CB1/CB2 independent ligand for GPR55-mediated hippocampal plasticity. | ** FABP7 is a CB1/CB2 independent ligand for GPR55-mediated hippocampal plasticity. | ||
====Role of GPR40-GPR55 expression in neurodegenerative diseases: BDNF modulation of | ====Role of GPR40-GPR55 expression in neurodegenerative diseases: BDNF modulation of PPARγ by synaptamide promote neural differentiation and proliferation of progenitor cells==== | ||
* Receptor heteromerization of GPR40-GPR55 modulates hippocampal neurogenesis through PKA/CREB activation. | * Receptor heteromerization of GPR40-GPR55 modulates hippocampal neurogenesis through PKA/CREB activation. | ||
** Effects of PPARs agonists on BDNF expression: | ** Effects of PPARs agonists on BDNF expression: |
Revision as of 09:37, 1 September 2015
Introduction
The neuroprotective effects of the marijuana plant are still poorly understood. The aim of this study is to present a method for delivery of N-docosahexaenoyl ethanolamide (DHEA) to hippocampal progenitor cells using endocannabinoid-like mobilization of docosahexaenoic acid (DHA).
Neuroendopsychology of atypical endocannabinoids:
Endocannabinoids heteromerization may be a promising pharmacological target with neuroprotective properties in the treatment of neurological disorders through activation of PPARs and modulation of endocannabinoid transport. In particular, GPR40 and GPR55 may cooperatively regulate neuronal differentiation and proliferation via receptor heteromerization of synaptamide and astrocytes-expressed fatty acid-binding proteins (FABPs).
Development of endocannabinoid mobilized proneurogenic compounds:
In addition, the suppression of microglial activation by endocannabinoids may increase adult hippocampal neurogenesis and promote mBDNF expression. Thus the objective of the GPR40-GPR55 heteromer is to enhance hippocampal plasticity and neuroprotection via atypical endocannabinoid stimulation of endogenous BDNF in the hippocampus using DHA as the proneurogenic promoter to increase BDNF expression and inhibit microglial activation.
Synopsis
- Stimulation of endocannabinoid transport with polyunsaturated (22:6n-3) fatty acids (DHA, EPA) to target major depressive disorders (MDD) , epilepsy, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), posttraumatic stress disorder (PTSD), and Alzheimer's disease (AD).
- Distribution of endocannabinoid-dependent activity (LTP, synaptogenesis) in the hippocampus promoting brain-derived neurotrophic factor (BDNF) expression, a biological marker for learning-dependent synapse formation. PMID PMID
- Neuroprotective effects of the mitochondrial CB1 receptor on excitatory (glutamatergic) synapses and in particular astrocytes. PMID PMID
- Identification of a functional GPR40-GPR55 heteromer with potent anti-inflammatory, antiglutamatergic and neuroprotective properties.
- Effects of the endothelial CB2 receptor persistent activation on monocyte subpopulations/microglial activation PMID
Results
DHA stimulation of PPARs decreases brain anandamide levels and improves synaptic function through FABP5 expression
- http://www.sciencedaily.com/releases/2014/05/140502132458.htm
- Identification of DHA as a proneurogenic PPAR agonist for treatment of neurological disorders.
- Intrinsic role of BDNF expression in (retrograde) anandamide signaling: PPARs expression induce long-term potentiation (LTP) in the hippocampus. PMID
- Evidences that DHEA is a synaptogenic endocannabinoid and potent activator of hippocampal LTP.
- Stimulation of GPR40-GPR55 receptor heteromer by DHA promotes heterosynaptic LTP through peroxisome proliferator-activated receptors (PPARs) activation. Link doi:10.1186/1471-2202-13-109
- FABP7 is a CB1/CB2 independent ligand for GPR55-mediated hippocampal plasticity.
Role of GPR40-GPR55 expression in neurodegenerative diseases: BDNF modulation of PPARγ by synaptamide promote neural differentiation and proliferation of progenitor cells
- Receptor heteromerization of GPR40-GPR55 modulates hippocampal neurogenesis through PKA/CREB activation.
- Effects of PPARs agonists on BDNF expression:
- Neuroprotection?
- Neuron-astrocyte cell migration and differentiation PMID
- Proliferation of neural stem/progenitor cells (NSPCs)
- DHA activation of PPARs inhibit amyloid-beta (Abeta) generation in astrocytes. (Alzheimer) PMID PMID
- Neuroimmune modulation (ie: endogenous remyelination) PMID PMC PMC
- BDNF-induced synaptogenesis
- Effects of PPARs agonists on BDNF expression:
- Endocannabinoid mobilized LTP upregulate activity-dependent hippocampal neurogenesis and neural progenitor (NP) cell proliferation. (doi: 10.1074/jbc.M111.291294) PMID
Discussion
Endocannabinoid transport of proneurogenic compounds
DHA is an effective promoter of long-term potentiation (LTP) and new evidences suggest its effects on synaptic plasticity as a potent endocannabinoid-like transporter of synaptogenic amides. (N-acyl ethanolamide)
Endocannabinoids and synaptic plasticity
Anandamide and 2-AG may exert a synergistic effect on DHA regulation, glutamatergic transport, and synaptic plasticity through retrograde signaling. Thus the modulation of DHA with endogenous cannabinoids may provide a persistent supply of endocannabinoids to neurons.
Is hippocampal plasticity an evidence of proneurogenic endocannabinoid transport ?
"Metaplasticity" is perhaps a biological activity relevant to hippocampal plasticity and may facilitate heterosynaptic LTP through retrograde endocannabinoid signaling and diffusion in the hippocampus. PMID
The evidences of GPR55 expression in the hippocampus therefore indicate a promising proneurogenic promoter to mediate hippocampal plasticity in neurodegenerative diseases. Hence, intracellular anandamide trafficking by GPR55 may enhance BDNF expression and promote synaptic function.
Mitochondrial function
DHA supplementation may increase mitochondrial function and enhance CB1/CB2 dependent neuroprotection through endocannabinoids mobilization.
Neuroprotective effects of endocannabinoids
Endocannabinoids may protect on-demand neurons from excitotoxicity and neuroinflammation upon exposure to stress-induced excitotoxic insults. PMID PMID
Intracellular anandamide/GPR55 signaling
Endocannabinoids constitute a family of intracellular lipid signaling molecules with potent anti-inflammatory, anti-oxidative and anti-excitotoxic bioactivity to reduce microglial activation during neuroinflammation of the CNS.
Keywords
endocannabinoids, hippocampus, anandamide, 2-AG, CB1, CB2, CBD, FAAH, DHA, DHEA, THC, TRPV1, neurogenesis, synaptogenesis, GABA, synaptamide, BDNF, LTP, ATP, P2X7, NADA, purinergic signaling, adenosine, acetylcholine, synaptic plasticity, heterosynaptic metaplasticity, astrocytes, cytokines, neuroinflammation, Alzheimer, endothelium, microglial activation, mitochondrial phospholipids, cardioprotection, synaptamide, ethanolamide, FABP7, PPAR, GPCR, receptor heteromerization, CREB, GPR40, GPR55, arachidonic acid, neural stem/progenitor cells
References
- Kim HY, Spector AA, and Xiong ZM. A synaptogenic amide N-docosahexaenoylethanolamide promotes hippocampal development. Prostaglandins Other Lipid Mediat. 2011 Nov;96(1-4):114-20. DOI:10.1016/j.prostaglandins.2011.07.002 |
A synaptogenic amide N-docosahexaenoylethanolamide promotes hippocampal development.
- Cao D, Kevala K, Kim J, Moon HS, Jun SB, Lovinger D, and Kim HY. Docosahexaenoic acid promotes hippocampal neuronal development and synaptic function. J Neurochem. 2009 Oct;111(2):510-21. DOI:10.1111/j.1471-4159.2009.06335.x |
Docosahexaenoic acid promotes hippocampal neuronal development and synaptic function.
- Chevaleyre V and Castillo PE. Endocannabinoid-mediated metaplasticity in the hippocampus. Neuron. 2004 Sep 16;43(6):871-81. DOI:10.1016/j.neuron.2004.08.036 |
Endocannabinoid-mediated metaplasticity in the hippocampus.
- Gaiarsa JL and Porcher C. Emerging neurotrophic role of GABAB receptors in neuronal circuit development. Front Cell Neurosci. 2013;7:206. DOI:10.3389/fncel.2013.00206 |
Emerging neurotrophic role of GABAB receptors in neuronal circuit development.
- Wu A, Ying Z, and Gomez-Pinilla F. Docosahexaenoic acid dietary supplementation enhances the effects of exercise on synaptic plasticity and cognition. Neuroscience. 2008 Aug 26;155(3):751-9. DOI:10.1016/j.neuroscience.2008.05.061 |
Docosahexaenoic acid dietary supplementation enhances the effects of exercise on synaptic plasticity and cognition.
- Düster R, Prickaerts J, and Blokland A. Purinergic signaling and hippocampal long-term potentiation. Curr Neuropharmacol. 2014 Jan;12(1):37-43. DOI:10.2174/1570159X113119990045 |
Purinergic signaling and hippocampal long-term potentiation.
- Kim HY and Spector AA. Synaptamide, endocannabinoid-like derivative of docosahexaenoic acid with cannabinoid-independent function. Prostaglandins Leukot Essent Fatty Acids. 2013 Jan;88(1):121-5. DOI:10.1016/j.plefa.2012.08.002 |
Synaptamide, endocannabinoid-like derivative of docosahexaenoic acid with cannabinoid-independent function.
- Monory K, Massa F, Egertová M, Eder M, Blaudzun H, Westenbroek R, Kelsch W, Jacob W, Marsch R, Ekker M, Long J, Rubenstein JL, Goebbels S, Nave KA, During M, Klugmann M, Wölfel B, Dodt HU, Zieglgänsberger W, Wotjak CT, Mackie K, Elphick MR, Marsicano G, and Lutz B. The endocannabinoid system controls key epileptogenic circuits in the hippocampus. Neuron. 2006 Aug 17;51(4):455-66. DOI:10.1016/j.neuron.2006.07.006 |
The Endocannabinoid System Controls Key Epileptogenic Circuits in the Hippocampus.
- Pertwee RG, Howlett AC, Abood ME, Alexander SP, Di Marzo V, Elphick MR, Greasley PJ, Hansen HS, Kunos G, Mackie K, Mechoulam R, and Ross RA. International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB₁ and CB₂. Pharmacol Rev. 2010 Dec;62(4):588-631. DOI:10.1124/pr.110.003004 |
International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid Receptors and Their Ligands: Beyond CB1 and CB2.
- Zogopoulos P, Vasileiou I, Patsouris E, and Theocharis S. The neuroprotective role of endocannabinoids against chemical-induced injury and other adverse effects. J Appl Toxicol. 2013 Apr;33(4):246-64. DOI:10.1002/jat.2828 |
The neuroprotective role of endocannabinoids against chemical-induced injury and other adverse effects.
- Meijerink J, Balvers M, and Witkamp R. N-Acyl amines of docosahexaenoic acid and other n-3 polyunsatured fatty acids - from fishy endocannabinoids to potential leads. Br J Pharmacol. 2013 Jun;169(4):772-83. DOI:10.1111/bph.12030 |
N-Acyl amines of docosahexaenoic acid and other n-3 polyunsatured fatty acids - from fishy endocannabinoids to potential leads.
- Rashid MA, Katakura M, Kharebava G, Kevala K, and Kim HY. N-Docosahexaenoylethanolamine is a potent neurogenic factor for neural stem cell differentiation. J Neurochem. 2013 Jun;125(6):869-84. DOI:10.1111/jnc.12255 |
N-Docosahexaenoylethanolamine is a potent neurogenic factor for neural stem cell differentiation.
- Yu S, Levi L, Casadesus G, Kunos G, and Noy N. Fatty acid-binding protein 5 (FABP5) regulates cognitive function both by decreasing anandamide levels and by activating the nuclear receptor peroxisome proliferator-activated receptor β/δ (PPARβ/δ) in the brain. J Biol Chem. 2014 May 2;289(18):12748-58. DOI:10.1074/jbc.M114.559062 |
Fatty Acid-binding Protein 5 (FABP5) Regulates Cognitive Function Both by Decreasing Anandamide Levels and by Activating the Nuclear Receptor Peroxisome Proliferator-activated Receptor β/δ (PPARβ/δ) in the Brain