Role Of The Cannabinoid Receptors 2 In Controlling The Senescence Of Neural Stem/Progenitor Cells Induced By Aβ_1-42

Cannabinoid(CB)receptors play an important role in the maintenance of NSPCs proliferation,and more and more researchers pay attention on it.Both CB1 receptor and CB2 receptor were found on the surface of NSPCs.We didi this subject to confirm the effect of CB1 and CB2 receptors in NSPCs.We found that the number of amyloid plaques was increased in the brain of APP-PS1 transgenic mice during aging by immunohistochemical experiment.There existed the negative relationship between the number of amyloid plaques and nestin positive cells in the brain slices of APP-PS1 transgenic mice.The amyloid deposits were colocalized with senescence-associated β-galactosidase(SA-β-gal)plaques in the brain of APP-PS1 transgenic mice.After that we decided to use Amyloidl-42 to set up the model of senescence.Amyloidl-42 promoted cell viability of NSPCs after 6 days incubation and inhibited cell viability after 12 days incubation.In addition,amyloidl-42 significantly promoted the number of SA-β-gal positive NSPCs after 9 days incubation.Aβ1-42 dose-dependently increased the expression of prosenescence molecules p16 and Rb in NSPCs after 9 days incubation,which remind that Amyloidl-42 can imitate the senescence of NSPCs in APP-PS1 transgenic mice.NsTyr,an anandamide(AEA)analogue is similar to AEA.In the previous research,we found that NsTyr has neuroprotect effect.In this study,we found that NsTyr can inhibit the expression of p16 and Rb.We added the inhibitors of CB1 and CB2 in NSPCs,and just CB2 inhibitor can reverse the effect of NsTyr.It’s reminds that NsTyr inhibit the senescence via CB2 receptors.Autophagy plays an important role in cells senescence.It also influenced by CB receptors.To further confirm the mechanism of NsTyr,we studied the autophagy of cells in different situation.Ap 1-42 significantly inhibited the autophagy after 9 days incubation.NsTyr can recover the level of autophagy.These indicate that NsTyr can reduce the senescence cells by increasing autophagy levelIn addition,JWH133,one of the agonists of CB2,significantly increased autophagy.NsTyr has the same effect.In brief,CB2 receptors play an important role in the senescence of NSPCs.