Role for Neuronal Nitric-Oxide Synthase in Cannabinoid-Induced Neurogenesis

@article{Kim2006RoleFN,
  title={Role for Neuronal Nitric-Oxide Synthase in Cannabinoid-Induced Neurogenesis},
  author={Sun Hee Kim and Seok Joon Won and Xiao Ou Mao and Catherine Ledent and Kunlin Jin and David A. Greenberg},
  journal={Journal of Pharmacology and Experimental Therapeutics},
  year={2006},
  volume={319},
  pages={150 - 154}
}
  • S. H. KimS. Won D. Greenberg
  • Published 1 October 2006
  • Biology, Chemistry
  • Journal of Pharmacology and Experimental Therapeutics
Cannabinoids, acting through the CB1 cannabinoid receptor (CB1R), protect the brain against ischemia and related forms of injury. This may involve inhibiting the neurotoxicity of endogenous excitatory amino acids and downstream effectors, such as nitric oxide (NO). Cannabinoids also stimulate neurogenesis in the adult brain through activation of CB1R. Because NO has been implicated in neurogenesis, we investigated whether cannabinoid-induced neurogenesis, like cannabinoid neuroprotection, might… 

Figures from this paper

Neuronal Nitric Oxide Synthase Critically Regulates the Endocannabinoid Pathway in the Murine Cerebellum During Development.

A novel role for nNOS/NO in regulating eCB signaling in the cerebellum is explored and expression of the eCB hydrolases fatty acid amide hydrolase and monoacylglycerol lipase were significantly downregulated in nN OS-/- cerebella compared to WT cerebellA at 7 W.

Cannabinoid receptor CB1 mediates baseline and activity-induced survival of new neurons in adult hippocampal neurogenesis

CB1 affected the stages of adult neurogenesis that involve intermediate highly proliferative progenitor cells and the survival and maturation of new neurons.

Disruption of IFN-gamma- mediated antiviral activity in neurons: the role of cannabinoids.

Activation of cells expressing CB(1) by endogenous (or exogenous) ligands may contribute to decreased inflammation and to increased viral replication in neurons and disease in the CNS.

Δ9-Tetrahydrocannabinol Prevents Methamphetamine-Induced Neurotoxicity

Results indicate that Δ9-THC reduces METH-induced brain damage via inhibition of nNOS expression and astrocyte activation through CB1-dependent and independent mechanisms, respectively.

Inducible Nitric Oxide Synthase Inhibition in the Medial Prefrontal Cortex Attenuates the Anxiogenic-Like Effect of Acute Restraint Stress via CB1 Receptors

The data suggest that iNOS inhibition may facilitate the local endocannabinoid signaling, attenuating stress effects, and be involved in the local ECB system, particularly the CB1 cannabinoid receptors.

The role of cannabinoids in adult neurogenesis

This timely review summarizes the evidence that the cannabinoid system is intricately associated with neuronal differentiation and maturation of NPCs and highlights intrinsic/extrinsic signalling mechanisms that are cannabinoid targets.
...

References

SHOWING 1-10 OF 50 REFERENCES

Molecular Mechanisms of Cannabinoid Protection from Neuronal Excitotoxicity

Cannabinoids seem to protect neurons againstNMDA toxicity at least in part by activation of CB1R and downstream inhibition of PKA signaling and NO generation, and cannabinoids might reduce NMDA toxicity by interfering with the generation of NO.

Cannabinoids and Neuroprotection in Global and Focal Cerebral Ischemia and in Neuronal Cultures

Cannabinoids may have therapeutic potential in disorders resulting from cerebral ischemia, including stroke, and may protect neurons from injury through a variety of mechanisms, including receptor-mediated neuroprotection.

Cannabinoids Promote Oligodendrocyte Progenitor Survival: Involvement of Cannabinoid Receptors and Phosphatidylinositol-3 Kinase/Akt Signaling

Oligodendrocyte progenitors undergo apoptosis with the withdrawal of trophic support, and both the selective CB1 agonist arachidonyl-2′-chloroethylamide/(all Z)-N-(2-cycloethyl)-5,8,11,14-eicosatetraenamide and the nonselective cannabinoid agonists HU210 and (+)-Win-55212-2 enhanced cell survival.

The central cannabinoid receptor (CB1) mediates inhibition of nitric oxide production by rat microglial cells.

Results indicate a functional linkage between the CB1 receptor and cannabinoid-mediated inhibition of NO production by rat microglial cells.

Defective adult neurogenesis in CB1 cannabinoid receptor knockout mice.

CB1 and VR1 receptors both seem to have roles in regulating adult neurogenesis.

Selective cannabinoid CB1 receptor‐mediated inhibition of inducible nitric oxide synthase protein expression in C6 rat glioma cells

The data suggest that selective cannabinoid CB1 receptor activation, by inhibiting iNOS expression and NO overproduction in glial cells, might be helpful in NO‐mediated inflammation leading to neurodegeneration.

Effects of CB(1) cannabinoid receptor activation on cerebellar granule cell nitric oxide synthase activity.

The hypothesis that activation of the CB(1) receptor in CGCs results in a decreased influx of calcium in response to membrane depolarization, resulting in a decrease activation of neuronal NOS is supported.

Cannabinoid receptor agonists protect cultured rat hippocampal neurons from excitotoxicity.

It is suggested that cannabimimetic drugs may slow the progression of neurodegenerative diseases by providing significant protection from excitotoxicity.

Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects.

It is shown that both embryonic and adult rat hippocampal NS/PCs are immunoreactive for CB1 cannabinoid receptors, indicating that cannabinoids could act on CB1 receptors to regulate neurogenesis and supports the hypothesis that chronic HU210 treatment produces anxiolytic- and antidepressant-like effects likely via promotion of hippocampal Neurogenesis.