Figure 4
From: The CB1 cannabinoid receptor signals striatal neuroprotection via a PI3K/Akt/mTORC1/BDNF pathway
CB1 receptor antagonism attenuates BDNF upregulation induced by pharmacogenetic activation of striatal neurons. (a) STHdhQ7/Q7 cells were nucleofected with a construct expressing hM3Dq-mCherry (or mCherry alone as control). Two days after, cells were treated with 50-μM CNO (or H2O as vehicle) plus 0.25-μM SR141716 (or 0.1% DMSO as vehicle) for 4 h, and the levels of exon IV-containing and total BDNF transcripts were determined by qPCR (n=3–4 experiments). KCl (25 mM) was used as a control of activity-dependent BDNF expression upregulation. (b) Eight-week-old C57BL/6J mice were injected stereotactically into the dorsolateral striatum with a recombinant adeno-associated virus encoding hM3Dq-mCherry (or only mCherry as control) under the control of the CaMKIIα promoter (n=6–8 animals per group). Left: Example of a mouse brain injected with the mCherry construct. The site of infection in the striatum is outlined. Right: Levels of exon IV-containing and total BDNF transcripts in the dorsolateral striatum as determined by qPCR 4 h after i.p. injection of CNO (10 mg/kg body weight) with or without SR141716 (1 mg/kg body weight) or the corresponding vehicles. Data were analyzed using unpaired Student’s t-test. *P<0.05 and **P<0.01 from the corresponding Veh/Veh group; #P<0.05 and ##P<0.01 from the corresponding Veh/CNO group
