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) 1 2 3
3. The Vector:
   1. FAAH/anandamide hydrolysis of DHEA (a endocannabinoid like molecule)
   2. Activation of Ca2+ dependent BDNF via the TrkB pathway

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/

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, fatty acids, THC, neurogenesis, synaptogenesis

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. 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 |
4. 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 |