User:Tkadm30/Notebook/Endocannabinoids/Synopsis

Synopsis

• Key concept 1:Endogenous activation of retrograde endocannabinoid signaling 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), Parkinson's disease (PD), Alzheimer's disease (AD), and drug-induced neuronal damage.
• Key concept 2:Neuroprotection!
• Identification of CREB phosphorylation in the hippocampus promoting brain-derived neurotrophic factor (BDNF) expression, a molecular marker for learning-dependent synapse formation. [1] [2]
• Intracellular CB1/BDNF signaling mediate on-demand neuroprotection on excitatory (glutamatergic) synapses and in particular astrocytes. [3]
  • DHA supplementation improves mitochondrial function and neuronal survival (homeostasis). [4]
• Identification of a functional GPR40-GPR55 receptor heteromer with potent anti-inflammatory, antiglutamatergic and neuroprotective properties.
  • Anti-proliferative effects of DHEA on prostate cancer cell lines. [5]
  • A synaptogenic endocannabinoid promoting synaptogenesis.
  • Antioxidant (cytoprotective) properties of GPR40-GPR55 heteromer.
• Inhibitory effect of the CB2 receptor on monocyte subpopulations and microglial activation. [6]
  • Anti-inflammatory role of anandamide and 2-AG signaling in LPS-stimulated microglial activation of endogenous CB2 receptor. [7]
  • Neuroprotection by inhibition of microglial activation. [8]
  • CB2 stimulation is proneurogenic on adult hippocampal neurogenesis PMC
• Caffeine is a adenosine antagonist which potentiate CB1 receptor activation in the hippocampus PMID PMID

References

1. https://www.ncbi.nlm.nih.gov/pubmed/21035522

   Complementary synaptic distribution of enzymes responsible for synthesis and inactivation of the endocannabinoid 2-arachidonoylglycerol in the human hippocampus.

2. https://www.ncbi.nlm.nih.gov/pubmed/24360280

   Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor.

3. https://www.ncbi.nlm.nih.gov/pubmed/14526074

   CB1 cannabinoid receptors and on-demand defense against excitotoxicity.

4. https://www.ncbi.nlm.nih.gov/pubmed/22248591

   Update on lipids and mitochondrial function: impact of dietary n-3 polyunsaturated fatty acids.

5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930808/

6. https://www.ncbi.nlm.nih.gov/pubmed/21350020

   Cannabidiol and other cannabinoids reduce microglial activation in vitro and in vivo: relevance to Alzheimer's disease.

7. http://www.hindawi.com/journals/np/2015/130639/

8. https://www.ncbi.nlm.nih.gov/pubmed/16343349

   Stimulation of cannabinoid receptor 2 (CB2) suppresses microglial activation.