User:Tkadm30/Notebook/Endocannabinoids

Notes

Hypothesis

1. DHA may potentiate synaptic plasticity (and cognition) via retrograde CB1 signaling.
   1. DHA activate the NMDA receptor and upregulate the release of glutamate. 1
   2. Hippocampal CA3 synapses facilitate synaptic plasticity, thus learning is enhanced. 2
      1. Induction of Long-Term Potentiation/Persistent synaptic plasticity (LTP). (Pathway)
2. Synaptic activation of neurotrophic GABA(B) receptor by endocannabinoids (CB1) promote synaptic function and learning. (Is activity-dependent synaptogenesis dependent on BDNF?) 3 4

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) 5
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 [1]

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

References

1. 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 |
2. 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 |
3. 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 |
4. Adermark L, Talani G, and Lovinger DM. Endocannabinoid-dependent plasticity at GABAergic and glutamatergic synapses in the striatum is regulated by synaptic activity. Eur J Neurosci. 2009 Jan;29(1):32-41. DOI:10.1111/j.1460-9568.2008.06551.x |
5. 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 |
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 |