User:Tkadm30/Notebook/Endocannabinoids: Difference between revisions
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** Effects of PPARs agonists on FABP7-Pax6 expression: | ** Effects of PPARs agonists on FABP7-Pax6 expression: | ||
*** Neuroprotection? | *** Neuroprotection? | ||
*** Neuron-astrocyte cell migration and differentiation | *** Neuron-astrocyte cell migration and differentiation [https://www.ncbi.nlm.nih.gov/pubmed/18467663 PMID] | ||
*** Proliferation of neural progenitor cells | *** Proliferation of neural progenitor cells | ||
*** DHA activation of PPARs inhibit amyloid-beta (Abeta) generation in astrocytes. (Alzheimer) [https://www.ncbi.nlm.nih.gov/pubmed/20413894 PMID] [https://www.ncbi.nlm.nih.gov/pubmed/25048111 PMID] | *** DHA activation of PPARs inhibit amyloid-beta (Abeta) generation in astrocytes. (Alzheimer) [https://www.ncbi.nlm.nih.gov/pubmed/20413894 PMID] [https://www.ncbi.nlm.nih.gov/pubmed/25048111 PMID] |
Revision as of 04:49, 26 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 atypical endocannabinoids:
Novel 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 proneurogenic compounds:
The suppression of microglial activation by endocannabinoids may increase adult hippocampal neurogenesis and promote mBDNF expression. The objective of the GPR55-GPR120 heteromer is to enhance hippocampal plasticity and neuroprotection through 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, 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-GPR120 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
DHA stimulation of PPARs increase brain anandamide levels
- Identification of DHA as a potent proneurogenic compound 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 atypical endocannabinoid and potent activator of hippocampal LTP.
- Stimulation of GPR55-GPR120 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 GPR55-GPR120 expression in neurodegenerative diseases: PPARs modulation of FABP7 by retrograde endocannabinoid signaling promote hippocampal neurogenesis
- Heteromerization of GPR55-GPR120 modulates FABP7-mediated neurogenesis through Pax6 activation.
- Effects of PPARs agonists on FABP7-Pax6 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
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