Activation of GPR55 increases neural stem cell proliferation and promotes early adult hippocampal neurogenesis.

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BACKGROUND AND Goal:

The cannabinoid method exerts functional regulation of neural stem cell (NSC) proliferation and adult neurogenesis, however not all effects of cannabinoid-like compounds noticed can be attributed to the cannabinoid 1 (CB1 ) or CBtwo receptor. The lately de-orphaned GPR55 has been shown to be activated by quite a few cannabinoid ligands suggesting that GPR55 is a third cannabinoid receptor. Right here, we examined the part of GPR55 activation in NSC proliferation and early adult neurogenesis.

EXPERIMENTAL Method:

The effects of GPR55 agonists (LPI, O-1602, ML184) on human (h) NSC proliferation in vitro have been assessed by flow cytometry. Human NSC differentiation was determined by flow cytometry, qPCR and immunohistochemistry. Immature neuron formation in the hippocampus of C57BL/six and GPR55-/- mice was evaluated by immunohistochemistry.

Essential Final results:

Activation of GPR55 considerably improved proliferation prices of hNSCs in vitro. These effects have been attenuated by ML193, a selective GPR55 antagonist. ML184 considerably promoted neuronal differentiation in vitro even though ML193 decreased differentiation prices as compared to car remedy. Continuous administration of O-1602 into the hippocampus by means of a cannula connected to an osmotic pump resulted in improved Ki67+ cells inside the dentate gyrus. O-1602 improved immature neuron generation, as assessed by DCX+ and BrdU+ cells, as compared to car-treated animals. GPR55-/- animals displayed decreased prices of proliferation and neurogenesis inside the hippocampus even though O-1602 had no impact as compared to car controls.

CONCLUSIONS AND IMPLICATIONS:

Collectively, these findings recommend GPR55 activation as a novel target and approach to regulate NSC proliferation and adult neurogenesis.

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