User:Tkadm30/Notebook/Endocannabinoids

Introduction

Medicinal marijuana has been for centuries a medicinal herb to cure many diseases naturally, and its effects are still subject of intense controversial debates. In this study is presented a method to induce cognitive enhancements through the combination of medicinal marijuana with fatty acids supplements (omega 3), and to stimulate neuronal activity and shape brain connectivity with natural products. Furthermore the functions of metabolic endocannabinoids ligands are investigated to identify key evidences of endocannabinoid-dependent LTP and synaptic plasticity in the hippocampus.

Endocannabinoid-dependent activity promote persistent synaptic plasticity in the hippocampus.

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. Activation of inhibitory GABAergic synapse (GABA(B) receptor ?) by endocannabinoids (DHA) may promote synaptic function and learning. [3]
      1. TrkB receptor regulate activity-dependent synaptogenesis and BDNF expression [4]

Model

1. The Promoter: omega 3 (fish oil supplement) fatty acids
   1. DHA (docosahexaenoic acid) conjugate (in the hippocampus?) is docosahexaenoyl ethanolamide (DHEA).
      1. FAAH hydrolysis of DHEA (a endocannabinoid like molecule)
2. The Wet Blanket:
   1. Role: Protect the hippocampus and neurons from glutamate excitoxicity.
   2. CB1: A synaptogenic receptor? (most likely)
3. The Suppression of Inhibition:
   1. TrkB (2.7.10.1) potentiate GABAergic synaptic activation:
      1. BDNF expression is Ca2+ and CREB dependent
   2. DSI (CB1-mediated inhibition of GABAergic transmission/Depolarization-induced Suppression of Inhibition) -> EPSC (excitatory post-synaptic currents) -> NMDA-dependent(?) LTP at excitatory, and glutamatergic synapses
      1. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1574086
      2. http://www.ncbi.nlm.nih.gov/pubmed/12080342
      3. http://www.ncbi.nlm.nih.gov/pubmed/17392410
      4. http://www.sciencedirect.com/science/article/pii/S0896627304005732
      5. endocannabinoids-mediated metaplasticity : http://www.ncbi.nlm.nih.gov/pubmed/15363397 http://www.ncbi.nlm.nih.gov/pubmed/18523004
4. metaplastic control of synaptic transmission

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
• http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3208643/
• http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1574086/
• http://www.ncbi.nlm.nih.gov/pubmed/12649318

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. Huang ZJ. Activity-dependent development of inhibitory synapses and innervation pattern: role of GABA signalling and beyond. J Physiol. 2009 May 1;587(Pt 9):1881-8. DOI:10.1113/jphysiol.2008.168211 |
5. 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 |
6. 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 |