The Neurotoxic Effect Of Amyloid Beta-peptide 42 Oligomers On The Thalamus Of Mice

Purpose: To observe the neurotoxic effect of amyloid beta-peptides(Aβ)42 oligomer on the thalamus of mice,and to establish a new animal model of Alzheimer’s disease(AD).Method: 150 male C57BL/6 mice were randomly divided into the normal group,the solvent group and the Aβ group.Each group contained 50 samples.The Aβ42 oligomer was injected into the bilateral thalamus by stereotaxtic technique in the Aβ group,and the solvent group was injected into the thalamus by equal volume solvent.At 3d,7d,14 d and 28 d after the operation,Morris water maze,paste removal experiment and forelimb grasping experiment were used to evaluate the nerve function of animals.Besides,Immunohistochemistry and Western blot were used to detect the protein expression of GFAP,Neu N,Iba1,P-tau(Ser396)and Tau-5 in the thalamus of mice.Result: 1.Morris water maze: In place navigation experiment,the average escape latency of mice in the Aβ group was significantly longer than that in the normal group and the solvent group.However,compared with 28-33 d,the Morris water maze experiment conducted 7-12 d and 14-19 d after the operation had a greater difference from the normal group and the solvent group.In spatial probe test,the frequency of crossing the original platform and the swimming time in the quadrant of the original platform of mice in the Aβ group were significantly reduced compared with those in the control group and the solvent group(P < 0.05).2.The paste removal time of mice in the Aβ group was significantly longer than that in the normal group and the solvent group,reaching a peak at 14d(P < 0.01),but the difference in forelimb grasping force was not statistically significant.3.Compared with the normal group and solvent group,expression of GFAP,Iba1 and P-tau(Ser396)in the Aβ group was significantly increased.GFAP and Iba1 peaked on day 14,and P-tau(Ser396)peaked on day 28,expression of Neu N in the Aβ group was significantly decreased,and the expression of Neu N was the lowest on day 28,but the difference in expression of Tau-5 in all three groups was not statistically significant at all time points after the operation.Conclusion: 1.Aβ42 oligomer had obvious neurotoxic effect on the thalamus of mice,and could significantly reduce the number of neurons.Microglia and astrocytes proliferated significantly,and phosphorylated Tau protein was up-regulated.However,there was no significant change in total Tau protein.2.The neurotoxic effects of Aβ42 oligomer on the thalamus could impair the cognitive and sensory functions of mice.3.Bilateral thalamic injection of Aβ42 oligomer might be a new method for the preparation of the AD sample animal models.