The Effects Of Aβ1-42 Monomers On Spatial Reference Memory In PS-1/PS-2 Conditional Double Knockout Mice

Alzheimer’s disease（AD）is a serious neurodegenerative disease.Amyloid cascade hypothesis shows that the overexpression and deposition of β-amyloid protein（Aβ）in brain tissue is an important factor leading to AD.So far,the research of AD therapeutic drugs aimed at the inhibition or clearance of Aβ aggregation has ended in failure.Aβ in cerebrospinal fluid of presenilin 1/2 conditional double knockout mice（cDKO mice）decreased,and cDKO mice showed a significant AD like phenotype.Therefore,we speculate that the decrease of Aβ may be the reason for the emergence of AD like phenotype in mice.Based on the above,this paper takes cDKO mice as the research object,mainly using in vivo multichannel electrophysiological recording technology and microinjection technology.The effect of exogenous Aβ1-42 monomer on spatial reference memory and neuroelectric activity in dorsal hippocampal CA1 in cDKO mice were studied.The main results are as follows:1.In the in the novel object place recognition task,cDKO mice not only showed significant impairment of spatial reference memory,but also significantly reduced the Theta oscillation power and Theta-Gamma oscillation phase amplitude coupling intensity in the dorsal hippocampal CA1.2.After adding exogenous Aβ1-42 monomer,in the in the novel object place recognition task,cDKO mice not only reversed the impairment of spatial reference memory,but also significantly improved the Theta oscillation power and Theta-Gamma oscillation phase amplitude coupling intensity in the dorsal hippocampal CA1.But the reversal effect of Aβ1-42 monomer will be blocked by alpha7 nicotinic acetylcholine receptor（a7-nAChR）antagonist（Methyllycaconitine）.In conclusion,exogenous addition of Aβ1-42 monomers can improve the impairment of reference memory and the abnormality of neuroelectric activity in dorsal hippocampus CAI of cDKO mice.Further study found that the role of Aβ1-42 monomers was related to a7-nAChR.