Beta <sub> 2 </ Sub> Adrenergic Receptor In The Restraint Stress Lead Role In The Mouse Brain Amyloidosis Research

Background and aims Individuals prone to experience psychological distress are twice likely to develop Alzheimer's disease(AD) and exhibit quicker decline in episodic memory;it is probable that C-fos exerts neurotoxic effect as an indicator of stress reaction. As one of the pathology characteristics in AD,amyloid-β(Aβ) can be termed as an initial factor followed by other characteristics or clinical manifestations.Activation ofβ₂-adrenergic receptor(β₂-AR) may accelerate amyloid plaque formation.To better understand the interactions betweenβ₂-AR and C-fos,we analyzed the C-fos expression in the hippocampus of mice,which were randomly divided into a control group and an acute restraint stress mice model group.Subunit(n = 8) of each group was respectively given saline,β₂-AR agonist clenbuterol hydrochloride andβ₂-AR antagonist ICI 118,551. Aβproductions(1-40/42) were tested to assess the effect ofβ₂-adrenergic receptor on the mice hippocampus with amyloidosis caused by acute restraint stress.Methods 48 C57 mice were randomly divided into a control group(C) and an acute restraint stress model group(S),each of which was divided into solvent subunit(SN,n=8; CN,n = 8) interfered by saline,β₂-AR agonist subunit(SC,n = 8;CC,n = 8) interfered by clenbuterol hydrochloride,andβ₂-AR antagonist subunit(SI,n = 8;CI,n = 8) interfered by ICI 118,551.Mice were given reagents before restrained in self-made equipments for 14 days(5 h/day).Reverse transcription of RNA from mice hippocampus, followed by SYBR Green I Real Time Polymerase Chain Reaction(PCR),was used to detect the C-fos gene expression.Aβ1-40/42 productions in the tissue extraction buffer after BCA protein assay were examined with sandwich enzyme linked immunosobent assay(ELISA).Results 1.The expression level of SN group C-fos mRNA was 1.8901 times as much as CN group(p<0.01),caused by acute restraint stress.In the acute restraint stress group, compared with the solvent subunit,clenbuterol increased C-fos mRNA level(p<0.05); ICI 118,551 decreased C-fos mRNA level(p<0.01).In the control group,C-fos mRNA level was increased by clenbuterol(p<0.01),and reduced by ICI 118,551(p<0.05)2.Compared with CN group,Aβ1-40/42 in SN group were increased significantly(p <0.01) as results of stress.In the same stress condition,clenbuterol led to increased Aβ1-40(p<0.05)/1-42(p<0.01) productions,or vice versa due to ICI 118,551.The same is true in the control group under the effects of clenbuterol/ICI 118,551.Conclusions 1.We demonstrate that expression level of C-fos mRNA was elevated by the self-made restraint equipment and the acute restraint stress mice model is successful.The activation ofβ₂-AR facilitates the expression of C-fos mRNA or vice versa,which supports the hypothesis that neuron function in stress condition could be improved byβ₂-AR antagonist.2.Our findings reveal that aggravation of amyloidosis arising from acute restraint stress can be lessened byβ₂-AR antagonist.These datas may have implications for therapeutic strategies aiming at prevention of AD and identify potential new targets for drug development.