Re: [DIYbio] Re: THC legislation is next week

This is by the at least one of the same authors as the last paper I
posted, but is open and published within the past month:

http://www.cell.com/neuron/abstract/S0896-6273(12)00855-0

Endocannabinoid Signaling and Synaptic Function

Neuron, Volume 76, Issue 1, 70-81, 4 October 2012
Copyright © 2012 Elsevier Inc. All rights reserved.
10.1016/j.neuron.2012.09.020

Authors
Pablo E. Castillo, Thomas J. Younts, Andrés E. Chávez, Yuki Hashimotodani

Endocannabinoids are key modulators of synaptic function. By
activating cannabinoid receptors expressed in the central nervous
system, these lipid messengers can regulate several neural functions
and behaviors. As experimental tools advance, the repertoire of known
endocannabinoid-mediated effects at the synapse, and their underlying
mechanism, continues to expand. Retrograde signaling is the principal
mode by which endocannabinoids mediate short- and long-term forms of
plasticity at both excitatory and inhibitory synapses. However,
growing evidence suggests that endocannabinoids can also signal in a
nonretrograde manner. In addition to mediating synaptic plasticity,
the endocannabinoid system is itself subject to plastic changes.
Multiple points of interaction with other neuromodulatory and
signaling systems have now been identified. In this Review, we focus
on new advances in synaptic endocannabinoid signaling in the mammalian
brain. The emerging picture not only reinforces endocannabinoids as
potent regulators of synaptic function but also reveals that
endocannabinoid signaling is mechanistically more complex and diverse
than originally thought.

On Thu, Nov 1, 2012 at 1:07 PM, Nathan McCorkle <nmz787@gmail.com> wrote:
> This paper also looks pretty good, but I can't get it:
> http://www.annualreviews.org/doi/pdf/10.1146/annurev.neuro.29.051605.112834
>
> ENDOCANNABINOID-MEDIATED SYNAPTIC PLASTICITY IN THE CNS
> Annual Review of Neuroscience
> Vol. 29: 37-76 (Volume publication date July 2006)
> First published online as a Review in Advance on March 15, 2006
> DOI: 10.1146/annurev.neuro.29.051605.112834
> Vivien Chevaleyre, Kanji A. Takahashi, and Pablo E. Castillo
> Department of Neuroscience, Albert Einstein College of Medicine,
> Bronx, New York 10461; email: pcastill@aecom.yu.edu
>
> Changes in synaptic efficacy are thought to be crucial to
> experience-dependent modifications of neural function. The diversity
> of mechanisms underlying these changes is far greater than previously
> expected. In the last five years, a new class of use-dependent
> synaptic plasticity that requires retrograde signaling by
> endocannabinoids (eCB) and presynaptic CB1 receptor activation has
> been identified in several brain structures. eCB-mediated plasticity
> encompasses many forms of transient and long-lasting synaptic
> depression and is found at both excitatory and inhibitory synapses. In
> addition, eCBs can modify the inducibility of non-eCB-mediated forms
> of plasticity. Thus, the eCB system is emerging as a major player in
> synaptic plasticity. Given the wide distribution of CB1 receptors in
> the CNS, the list of brain structures and synapses expressing
> eCB-mediated plasticity is likely to expand.
>
> On Thu, Nov 1, 2012 at 12:52 PM, Nathan McCorkle <nmz787@gmail.com> wrote:
>> On Thu, Nov 1, 2012 at 11:57 AM, Josiah Zayner <josiah.zayner@gmail.com> wrote:
>>> It is great that you want to study this plant scientifically apart from the
>>> millions of others that can be studied legally. The benefit is that we have
>>> the Cannabis genome/transcriptome, what genes are you interested in
>>> studying? Have you tried to clone them recombinantly?
>>
>> I never said I wanted to study it, but I do think there are people out
>> there that would... well established neuroscientists who could
>> theorize more than me. I'm primarily interested in DNA as a
>> chemical/molecule, rather than the much higher level neuroscience
>> field.
>>
>>> What do you think about using synthetic cannibinoids? Why not just use that
>>> for treatment?
>>
>> Sure, but I think I read a while ago that we have signatures for more
>> than 80 biosynthetic active molecules in marijuana, and probably about
>> the same number or more in a synthetic library that the JWH guy came
>> up. So if the whole political atmosphere changed from 'hippies' to '1
>> of a million things that has some effect on your brain' I think
>> progress would be less hindered for sure.
>>
>>>
>>> You say marijuana could perhaps be used to help brain plasticity, what
>>> signalling pathway/mechanism do you suggest this works by and how would you
>>> suggest one plan on testing it?
>>
>> There are tons of results if you type marijuana plasticity into google
>> or google scholar, lots this year even. To cherry pick an open one:
>> Allele-specific Differences in Activity of a Novel Cannabinoid
>> Receptor 1 (CNR1) Gene Intronic Enhancer in Hypothalamus, Dorsal Root
>> Ganglia, and Hippocampus*
>> http://www.jbc.org/content/287/16/12828.short
>>
>> Polymorphisms within intron 2 of the CNR1 gene, which encodes
>> cannabinoid receptor 1 (CB1), have been associated with addiction,
>> obesity, and brain volume deficits. We used comparative genomics to
>> identify a polymorphic (rs9444584-C/T) sequence (ECR1) in intron 2 of
>> the CNR1 gene that had been conserved for 310 million years. The
>> C-allele of ECR1 (ECR1(C)) acted as an enhancer in hypothalamic and
>> dorsal root ganglia cells and responded to MAPK activation through the
>> MEKK pathway but not in hippocampal cells. However, ECR1(T) was
>> significantly more active in hypothalamic and dorsal root ganglia
>> cells but, significantly, and in contrast to ECR1(C), was highly
>> active in hippocampal cells where it also responded strongly to
>> activation of MAPK. Intriguingly, rs9444584 is in strong linkage
>> disequilibrium with two other SNPs (rs9450898 (r2 = 0.841) and
>> rs2023239 (r2 = 0.920)) that have been associated with addiction,
>> obesity (rs2023239), and reduced fronto-temporal white matter volumes
>> in schizophrenia patients as a result of cannabis misuse (rs9450898).
>> Considering their high linkage disequilibrium and the increased
>> response of ECR1(T) to MAPK signaling when compared with ECR1(C), it
>> is possible that the functional effects of the different alleles of
>> rs9444584 may play a role in the conditions associated with rs9450898
>> and rs2023239. Further analysis of the different alleles of ECR1 may
>> lead to a greater understanding of the role of CNR1 gene misregulation
>> in these conditions as well as chronic inflammatory pain.
>>
>> -----
>>
>> I guess I would suggest testing it on those people who don't seem to
>> have any reliable or clear cut options in the existing repertoire of
>> medicine, or on mice or monkeys. If the political and social taboo was
>> removed, some decent survey association studies could be done, but as
>> it stands I doubt self-reporting is complete and true.
>
>
>
> --
> -Nathan



--
-Nathan

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