User:Tkadm30/Notebook/Endocannabinoids: Difference between revisions
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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. | 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. | ||
Thus "metaplasticity" is perhaps a biological activity relevant to hippocampal plasticity and may facilitate LTP through retrograde signaling of endocannabinoids release. | Thus "metaplasticity" is perhaps a biological activity relevant to hippocampal plasticity and may facilitate LTP through retrograde signaling of endocannabinoids release. [https://www.ncbi.nlm.nih.gov/pubmed/15363397 PMID] | ||
=== Mitochondrial function === | === Mitochondrial function === |
Revision as of 16:12, 21 August 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 neurons using endocannabinoid-like mobilization of docosahexaenoic acid (DHA).
Neuroendopsychology of endocannabinoids:
Endocannabinoids may be a promising therapeutic platform with neuroprotective properties in the treatment of neurological disorders including epilepsy, Alzheimer, and depression by inhibiting microglial activation and stress-induced neuroinflammation of the CNS.
Development of endocannabinoid mobilized pro-neurogenic compounds:
The suppression of microglial activation by endocannabinoids may increase adult hippocampal neurogenesis and promote mBDNF expression. The design of the GPR55-DHA heteromer aims to promote neurogenesis and neuroprotection through endocannabinoid stimulation of endogenous BDNF in the hippocampus using DHA as the pro-neurogenic promoter to increase BDNF expression and prevent 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, LTD, 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
- Putative GPR55-DHA heteromer (N-docosahexaenoyl ethanolamide) with potent anti-inflammatory, antiglutamatergic and neuroprotective properties
- Effects of the endothelial CB2 receptor persistent activation on monocyte subpopulations/microglial activation PMID
Results
2-arachidonoylglycerol (2-AG), a novel gliotransmitter controlled by the P2X7 receptor, exert neuroprotective effects on excitotoxic brain injury.
- 2-AG is an endogenous cannabinoid ligand synthesized by diacylglycerol lipase (DGL-α) and phospholipase C (PLC).
- Neuroprotective (anti-inflammatory) and a potent cytoprotective agent (antioxidant)
- retrograde 2-AG signaling
- modulate glutamatergic LTP/DSE PMID
- Anxiolytic
- ionotropic (permeable to calcium) P2X7 receptor control 2-AG production PMID
- monoacylglycerol lipase (MGL), a selective 2-AG hydrolase: http://www.uniprot.org/uniprot/Q99685
- calcium dependent biosynthesis
- ATP-induced 2-AG production from astrocytes PMID PMID
- 2-AG activate endogenous phospholipase C-dependent TRPV1 channel in the brain.
- doi:10.1038/srep04329
DHA stimulation of FABP7 increase brain anandamide levels
- Identification of anandamide as a potent immunomodulating compound for multiple sclerosis (MS).
- Intrinsic role of BDNF expression in (retrograde) anandamide signaling: FABP7 expression induce long-term potentiation (LTP) in the hippocampus.
- Evidences that DHA is a endocannabinoid promoter and potent activator of hippocampal LTP.
- Stimulation of GPR55 receptor by DHA promotes LTP/synaptic plasticity. Link
- FABP7 is a CB1/CB2 independent ligand for GPR55-mediated hippocampal plasticity.
Role of FABP7 expression in multiple sclerosis
- Heteromerization of GPR55-DHA modulates FABP7 function:
- Endocannabinoid mobilized LTP upregulate activity-dependent hippocampal neurogenesis and neural progenitor (NP) cell proliferation. (doi: 10.1074/jbc.M111.291294) PMID
NADA (N-arachidonoyl-dopamine)
- A putative endocannabinoid with potential atheroprotective properties.PMID PMID
- NADA modulate anti-inflammatory activation of the endothelium. PMID
- Full agonist at the CB1/CB2 receptors and TRPV1 ion channel.
- Pleiotropic role of the CB2 receptor: Immunomodulation of the endothelium. PMID PMID
- Structural analog of the dopamine conjugate of DHA.
Discussion
Endocannabinoid transport of pro-neurogenic 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.
Thus "metaplasticity" is perhaps a biological activity relevant to hippocampal plasticity and may facilitate LTP through retrograde signaling of endocannabinoids release. PMID
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/CB1 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
References
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A synaptogenic amide N-docosahexaenoylethanolamide promotes hippocampal development.
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N-Docosahexaenoylethanolamine is a potent neurogenic factor for neural stem cell differentiation.