CB2 cannabinoid receptors promote mouse neural stem cell proliferation

Area of Science:

• Neuroscience
• Cell Biology
• Pharmacology

Background:

• Neurospheres are cultures of neural stem/precursor cells.
• CB1 cannabinoid receptors on these cells promote proliferation.
• CB2 cannabinoid receptors' role in neural stem cells is less understood.

Purpose of the Study:

• Investigate CB2 cannabinoid receptor expression in neurospheres.
• Determine the effect of exogenous cannabinoids on neural stem/precursor cell proliferation.
• Elucidate the signaling pathways involved in cannabinoid-mediated proliferation.

Main Methods:

• Cultured neurospheres expressing nestin and sn-1 diacylglycerol lipase alpha.
• Applied selective and non-selective CB1 and CB2 cannabinoid receptor agonists and antagonists.
• Utilized bromodeoxyuridine incorporation assays and neurosphere formation assays.
• Investigated the role of phosphoinositide-3 kinase/Akt signaling using BML-257.

Main Results:

• Neurospheres express both CB1 and CB2 cannabinoid receptors.
• Non-selective, CB1-selective, and CB2-selective cannabinoid agonists stimulated proliferation.
• CB1 and CB2 antagonists blocked basal proliferation, suggesting endogenous cannabinoid involvement.
• Cannabinoid-stimulated proliferation was attenuated by an Akt translocation inhibitor.

Conclusions:

• Cannabinoids stimulate neural stem/precursor cell proliferation via both CB1 and CB2 receptors.
• Endogenous cannabinoids appear to regulate basal neurosphere proliferation.
• The phosphoinositide-3 kinase/Akt pathway mediates cannabinoid-induced proliferation in neural stem cells.