The Study On Emotional Abnormalities Of APP/PS1/Tau Triple Transgenic Alzheimer’s Disease Model Mice

Alzheimer’s disease(AD)is a neurodegenerative disease whose incidence rate increases with age.It is the fourth major cause of death after cancer,cardiovascular disease and stroke.The disease is clinically mainly manifested as cognitive impairment such as learning and memory impairment.In addition to cognitive impairment,patients are often accompanied by anxiety,depression,apathy and other neuropsychiatric symptoms.These emotional symptoms not only seriously affect the quality of life of patients and caregivers,but also accelerate the cognitive decline of patients.However,up to now,the neural mechanism of emotional abnormalities in AD patients is still unclear.In recent years,studies have found that the medial prefrontal cortex(mPFC)is closely related to emotions such as anxiety and depression,but there has been no report on whether the mPFC brain region is involved in the occurrence of neuropsychiatric symptoms in AD patients.For this reason,this article intends to use APP/PS1/Tau three transgenic Alzheimer’s disease(Triple-transgenic AD,3×Tg-AD model mice were used as animal research models.Using techniques such as holistic behavior,molecular biology,and in vitro brain patch clamp techniques,the brain regions of mPFC were studied in 3×Possible mechanisms involved in the occurrence of emotional abnormalities in Tg-AD mice.The main research results are as follows:1.3×Tg-AD mice showed significant anxiety-like behavior at 6 months of age,but no significant depression-like behavior.2.Alpha-amino-3-hydroxy-5-methyl-4-isoxazol-propionicacid receptor(α-amino-3-hydroxy-5-methyl-4-isoxazol-propionicacid receptor)in mPFC brain of 3×Tg-AD mice aged 6 months.There is no significant change in Glu A1 and Glu A2 subunit expressions of AMPAR,whileγ-aminobutyric acid receptor A,GABA_A receptor(receptor A)receptorα1 subunit expression decreases.3.Abnormal balance of excitatory/inhibitory synaptic transmission in the brain region of mPFC in 3×Tg-AD mice aged 6 months.4.In 6-month-old 3×Tg-AD mice,the resting membrane potential of pyramidal neurons in mPFC brain region tended to be depolarized,the release of action potential increased,and the intrinsic excitability increased.To sum up,this study observed that 6-month-old 3×Tg-AD mice have shown significant anxiety like behavior.Further studies found that 6-month-old 3×Tg-AD mice have significantly decreased the expression of GABA_Aα1 receptor in the mPFC brain region,and abnormal balance of excitatory/inhibitory synaptic transmission.These results suggest that the mPFC brain region may play an important role in the occurrence of anxiety-like behaviors in 3×Tg-AD mice,and may be involved in the occurrence of anxiety-like behaviors in 3×Tg-AD mice through the increased excitability of the neural network mediated by the expression of GABA_Aα1 receptor.Our study provides new insights into the pathogenesis of neuropsychiatric symptoms of AD and provides a theoretical basis for intervention strategies for neuropsychiatric disorders of AD.