Preliminary Analysis Of The Distribution Changes Of GABAergic Neurons In The Prefrontal Cortex Of Alzheimer’s Disease Mice

Alzheimer’s disease(AD)is one of the most common types of dementia,which is often clinically manifested as memory loss and ignorance.The prefrontal cortex plays an important role in memory,decision-making and emotional regulation and receives a lot of attention in the study of Alzheimer’s disease.As the most important inhibitory neurons in the prefrontal cortex,γ-aminobutyric acid ergic(GABAergic)neurons include somatostatin(SOM+),vasoactive intestinal peptide(VIP+),parvalbμmin(PV+)positive neurons and other different subtypes.The pathological changes of GABAergic neurons in the prefrontal cortex during Alzheimer’s disease are still unclear.In this thesis,I used 5×FAD mice as an experimental model to explore the changes of GABAergic neurons in the prefrontal cortex during the course of Alzheimer’s disease.The main results are as follows:Firstly,AD+ mice expressing different fluorescent protein in specific neurons were obtained by crossing 5×FAD mice with GAD67-GFP,SOM-cre: Ai14 and VIP-cre: Ai14 mice.The result of immunofluorescence staining certified the fluorescent protein expressed with neuron had specificity,while two-month-old AD mice had β-amyloid deposits in the prefrontal cortex.With typical behavioral paradigms(open field test,elevated plus maze and object recognition),I detected the ability,anxiety level and memory of those mice.The anxiety level of seven-month-old AD mice decreased significantly and those mice’s ability to remember new objects was weakened significantly.In conclusion,these AD mice constructed in this project had typical symptoms of Alzheimer’s disease.Secondly,the distribution changes of GABAergic neurons in AD mice were explored at different ages.Compared to the normal mice,the number of GABAergic neurons in the12-month-old AD mice did not change significantly in the anterior cingulate area and the agranular insular area,but decreased by 22%,18% and 36% in the prelimbic area,the infralimbic area and the orbital area respectively.The neurons distribution in different sublayers revealed that the number of GABAergic neurons decreased significantly in layer V of prelimbic area and infralimbic area(19% and 32% respectively).The results showed that the effect of AD lesions on the GABAergic neurons preferred to the medial orbital area and layer Ⅴ of the marginal cortex in the frontal cortex.Furthermore,the changes of the subtypes of GABAergic neurons,SOM+ and VIP+neurons,were investigated in the prefrontal cortex.The number of SOM+ neurons in the infralimbic area of 12-month-old AD mice reduced by nearly half,while the number of VIP+neurons reduced by 33% in the prelimbic area and infralimbic area.Among them,VIP+neurons changed significantly in layer Ⅱ/Ⅲ,while the number of SOM+ neurons had no significant differences among different sublayers.These results indicated that AD lesions had a subregional preference for different subtypes of GABAergic neurons.In summary,I explored the changes of GABAergic and their subtypes neurons in the prefrontal cortex of AD mice.The results showed that GABAergic neurons were more susceptible to AD lesions in the prelimbic area,infralimbic area of medial prefrontal cortex and orbital area of the lateral prefrontal cortex.VIP+ neurons were more susceptible to AD lesions in the infralimbic area of the medial prefrontal cortex and had a certain sublayer preference.These could provide anatomical data for understanding the role of GABAergic neurons in AD.