2014 Nov 20;15(12):786-801. doi: 10.1038/nrn3846.
Programming of neural cells by (endo)cannabinoids: from physiological rules to emerging therapies.
Abstract
Among the many signalling lipids, endocannabinoids are increasingly recognized for their important roles in neuronal and glial development. Recent experimental evidence suggests that, during neuronal differentiation, endocannabinoid signalling undergoes a fundamental switch from the prenatal determination of cell fate to the homeostatic regulation of synaptic neurotransmission and bioenergetics in the mature nervous system. These studies also offer novel insights into neuropsychiatric disease mechanisms and contribute to the public debate about the benefits and the risks of cannabis use during pregnancy and in adolescence.
- PMID:
25409697
[PubMed – as supplied by publisher]
Publication Types, MeSH Terms, Substances, Grant Support
Publication Types
MeSH Terms
- Animals
- Cannabis/adverse effects*
- Cell Differentiation/drug effects
- Cell Differentiation/physiology
- Endocannabinoids/metabolism*
- Female
- Humans
- Neurogenesis/drug effects
- Neurogenesis/physiology*
- Neurons/cytology
- Neurons/drug effects
- Neurons/metabolism*
- Pregnancy
Substances
Grant Support
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Full Text Sources
- Figure 1: Molecular architecture of the endocannabinoid system during synaptogenesis and at mature synapses.
Neuronal and glial components of developing and mature synapses are shown. The molecular architecture shown here is for a ‘stereotypical’ synapse that uses endocannabinoid signalling. There are differences in neurotransmitter system-spe…Figure 2: Molecular architecture of endocannabinoid signalling during corticogenesis, including neurogenesis and neuronal migration.
a | During mid or late gestation in rodents, 2-arachidonoylglycerol (2-AG)-rich cortical microdomains are thought to repulse postmitotic neurons that express cannabinoid 1 receptors (CB1Rs), including radially migrating pyramidal cells…Figure 3: Design logic of endocannabinoid signalling during neurite outgrowth and synaptogenesis.
a | Signal transduction mechanisms implicated in the cannabinoid 1 receptor (CB1R)-mediated control of cortical neuron specification and morphological differentiation are shown. Activation of tyrosine kinase receptors (particularly the…Figure 4: Defective development of the corticofugal system following genetic manipulation of CB1Rs.
Conditional deletion204 of cannabinoid 1 receptors (CB1Rs) from mouse cortical pyramidal cells results in errant corticofugal axon fasciculation compared with wild-type controls (shown by arrows). Note that enlarged axon fascicles (enci…Figure 5: Dysregulation of cannabinoid receptor signalling in glioma cells.
a | In neural progenitor cells, endocannabinoid (eCB) binding to cannabinoid receptors couples to the phosphatidylinositol 3-kinase (PI3K)–AKT–mammalian target of rapamycin complex 1 (mTORC1) pathway via Giproteins. Receptor tyrosine k…
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