The GABA System Regulates The Effects Of Alzheimer's Disease And Normal Aging

Alzheimer’s disease(AD),also known as senile dementia,is a chronic progressive neurodegenerative disease.It is insidious and common in the elderly,however the pathogenesis is unclear and no drugs are proved effective.As a whole brain process,aging can be divided into physiological brain senescence and pathological brain senescence,and pathological changes in brain is related with AD and other neurodegenerative diseases.AD and aging processes are accompanied with memory loss,abnormal neurotransmitter level and neural activity,which suggests that the two have a similar neuropathological basis.GABA is the most important inhibitory neurotransmitter in the central nervous system and plays an important role in senescence and neurodegenerative diseases such as AD.The GABA system regulates the entire neural network system by inhibiting the excitatory neurons.Electroencephalogram(EEG)is a much sensitive method for monitoring brain activity in real time,and has important clinical value in the diagnosis and treatment of various neurological and psychiatric diseases.This study focused on the effects of agitation or antagonism of GABAergic system on spatial recognition memory and EEG in AD mice and aging mice.The study was performed by using GABAA receptor agonist Muscimol and antagonist Bicuculline.The EEG recording sites were hippocampus,prefrontal cortex and cortex.First,we used the low,medium and high dose of drugs in young mice on the dose screening experiments,used mine experimental analysis on mouse activities,evaluated mouse spatial identification memory through the exploration of the Y-maze paradigm,and researched brain activity changes by recording three brain spontaneous state EEG Then,an effective dose of the drug was applied to AD model mice and aging mice to study the differences between the two groups of mice on their activity,spatial recognition memory,spontaneous EEG,and we also studied the similarities and differences among three brain areas of EEG of the two groups of mice on the exploratory Y maze experiment under the effective dose.The results were as follows:First,low dose of Muscimol(0.1 mg/kg)slightly increased the activity of young mice and clearly promoted their spatial recognition memory in the Y-maze experiment in dose screening experiment for the young animal.The spontaneous EEG activicities of the three local brain areas were significantly affected after two hours’s drug administration.The same dose of Bicuculline had no significant effect on the activity and the memory of spatial recognition of the mice,but within two hours after drug administration,the same dose of Bicuculline significantly affected the spontaneous EEG activity of the prefrontal cortex.Later,we used the two drugs in AD model mice and aged mice(≈12 months)and no significant effect to the two groups mice’s activity were founded under this dose.However,the Muscimol significantly affected the young mice,hippocampus and spontaneous EEG activity of cortex,while Bicuculline significantly affected the spontaneous EEG activity of three local brain.The significant differences in spontaneous EEG activity between the two groups were mainly manifested in hippocampus and prefrontal cortex.In particular,the spatial recognition memory capacity of AD mice was significantly lower than that of senescent mice,whereas 0.1 mg/kg Muscimol and Bicuculline significantly increased the spatial recognition of AD mice.Muscimol has no significant effect in senescent mice,while Bicuculline has a damaging effect.At the same time,Y maze task EEG activity analysis showed that the two drugs mainly affect the prefrontal activity of the two groups of mice.Finally,combined with AD mice and aging mice in different administration group data,the results showed that in the aging mice,Y maze task state of the three brain regions of the five basic frequency bands(2-100 Hz)EEG activity and its spatial identification(P<0.05).In AD mice,only the low frequency delta(2-4 Hz)EEG activity of hippocampus and prefrontal cortex was significantly correlated with its spatial recognition memory ability.Conclusion:Positive or negative pharmacological regulation of low-dose GABAergic system can promote the spatial recognition and memory ability of AD mice,which may have relation to the decrease of low-frequency EEG activity in hippocampus and prefrontal cortex.Both regulations have different roles in AD and aging mice,and have connection with the correspondence changes of EEG activities of a number of brain areas.This study is of great clinical significance in revealing the occurrence and development of AD and aging,and the effective diagnosis and treatment.GABA system is expected to become AD,aging and other neurodegenerative diseases related to memory repair effective target.