The Effect Of Human RPS23RG1 Overexpression In Astrocytes On Mouse Behaviors

Alzheimer’s disease(AD)is a most common neurodegenerative disease that severely impairs human cognition and health.The major pathologies and triggers of AD are extracellular amyloidal plaquescomposed of p-armloads(Aβ)andneurofibrillary tangles consisted of hyperphosphorylated tau proteins in the nerve cells.Therefore,identifying new genes/proteins that can effectively reduce A(βproduction and/ortau phosphorylation may provide new therapeutic targets for AD treatment.RPS23RG1 is newly identified gene and closely related to the occurrence of AD.In our previous work,we found that RPS23RG1 originated through retroposition of a conserved ribisomoal protein encoding gene RPS23,and encodes a single transmembrane protein RPS23RG1.We demonstrated that RPS23RG1 could regulate cAMP/PKA signaling through interacting with adenylate cyclase,further reducing the activity of GSK-3 kinas,thereby inhibiting the production of Aβ and the phosphorylation of tau protein.However,the exact physiological function of RPS23RG1 and its role in AD pathogenesis remains unknown.Since RPS23RG1 is ubiquitiously expressed in neurons,astrocytes and microglia,here we studied whether overexpression of human RPS23RG1(hRPS23RGl)in mouse astrocytes may affect mouse behaviors.By crossing an inducible hRPS23RG1 transgenic mouse line with the GFAP-Cre transgenic mice,we acquired hRPS23RG1xGFAP-Cre double transgenic mice and confirmed that hRPS23RGl overexpressed in astrocytes in these double transgenic mice.Moreover,we found that over expression of hRPS23RG1 in astrocytes did not affect the weight,sex,grasping and balance of mice,but could significantly increase learning and memory and reduce depression of mice.These results provided additional evidence to support targeting RPS23RG1 as AD therapeutics.