User:Tkadm30/Notebook/Endocannabinoids

Notes

Hypothesis

1. DHA may potentiate synaptic plasticity (and cognition) via retrograde CB1 signaling.
   1. DHA activate the (presynaptic) NMDA receptor and upregulate the release of glutamate. [1]
      1. DHA-induced synapses (CA3) enhance synaptic plasticity, thus learning is enhanced. [2]
      2. Induction of Long-Term Potentiation/Persistent synaptic plasticity (LTP). (Pathway)
   2. Synaptic activation of neurotrophic GABA(B) receptor by endocannabinoids (CB1/DHA) promote synaptic function and learning. [3]

Model

1. The Promoter: omega 3 (fish oil supplement) fatty acids
   1. DHA (docosahexaenoic acid) conjugate (in the hippocampus?) is docosahexaenoyl ethanolamide (DHEA).
2. The Wet Blanket:
   1. Role: Protect the hippocampus and neurons from glutamate excitoxicity.
   2. CB1: A synaptogenic receptor? (most likely) [4]
3. The Vector:
   1. FAAH/anandamide hydrolysis of DHEA (a endocannabinoid like molecule)
   2. TrkB (2.7.10.1) potentiate GABAergic synaptic activation:
      1. BDNF expression is Ca2+ and CREB dependent [5]

Documentation

Protocol:

• http://www.ncbi.nlm.nih.gov/pubmed/23103355
• http://www.ncbi.nlm.nih.gov/pubmed/11470906
• http://www.ncbi.nlm.nih.gov/pubmed/9842734/
• http://www.ncbi.nlm.nih.gov/pubmed/15111006/
• http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1253627/
• http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3035504/
• http://www.ncbi.nlm.nih.gov/pubmed/22959887
• http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2219532/
• http://www.ncbi.nlm.nih.gov/pubmed/21288475
• http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2661034/
• http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2773444/
• http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3687658/
• http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769341/
• http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1160357/
• http://www.ncbi.nlm.nih.gov/pubmed/23426383
• http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1574086/
• http://www.ncbi.nlm.nih.gov/pubmed/17525344

Cannabinoids and hippocampal neurogenesis:

• http://www.truthonpot.com/2013/07/13/scientists-discover-another-way-marijuana-helps-the-brain-grow/

DHA:

• http://www.ncbi.nlm.nih.gov/pubmed/19682204

Anandamide signaling:

• http://www.hindawi.com/journals/ije/2013/361895/

FAAH (fatty acid amide hydrolase):

• http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.5.1.99

Introduction to fatty amides:

• http://lipidlibrary.aocs.org/Lipids/amides/index.htm

Synaptic Plasticity:

• http://neuroscience.uth.tmc.edu/s1/chapter07.html

Keywords

hippocampus, anandamide, FAAH, DHA, THC, neurogenesis, synaptogenesis, GABA, synaptamide, BDNF, LTP

References

1. 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 |
2. Hagena H and Manahan-Vaughan D. Learning-facilitated synaptic plasticity at CA3 mossy fiber and commissural-associational synapses reveals different roles in information processing. Cereb Cortex. 2011 Nov;21(11):2442-9. DOI:10.1093/cercor/bhq271 |
3. 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 |
4. Chen AI, Nguyen CN, Copenhagen DR, Badurek S, Minichiello L, Ranscht B, and Reichardt LF. TrkB (tropomyosin-related kinase B) controls the assembly and maintenance of GABAergic synapses in the cerebellar cortex. J Neurosci. 2011 Feb 23;31(8):2769-80. DOI:10.1523/JNEUROSCI.4991-10.2011 |
6. 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 |