| Objective:1。To observe the emotional and cognitive-related behavioral phenotypes of 3xTg-AD and 5xFAD mice aged 4-5 months;2.To observe the improvement effect of electro-acupuncture on emotion and cognition-related behavior of 3xTg-AD and 5xFAD mice aged 4-5 months;3.To observe the effects of electro-acupuncture on memory function,amyloid plaques,astrocytes and neuralnetwork oscillations in 5xFAD mice aged 9-10 months.Methods:1.3xTg-AD mice,5xFAD mice and WT littermate mice of 4-5 months of age were selected as the study objects.Open field experiment and elevated cross maze were used to test whether they had anxiety-like behaviors.Three boxes of social experiments were used to evaluate their social function.The function of learning and memory was evaluated by new object recognition and conditional fear experiment.The olfactory functions were evaluated through buried food and wood block olfactory test.2.4-5 months old 3xTg-AD mice and 5xFAD mice were treated by electro-acupuncture on Baihui and Dazhui,the effects of electro-acupuncture on the emotions and cognition-related behaviors were evaluated.3.9-10 months old 5xFAD mice were treated by electro-acupuncture on Baihui and Dazhui,the effects of electro-acupuncture on learning and memory function were observed by using new object recognition.Immunofluorescence staining was used to observe the effects of electro-acupuncture on amyloid beta in the medial prefrontal cortex and hippocampus of the brain.The theta and gamma oscillations in the above two brain regions were recorded and analyzed by in vivo electrophysiology experiments to explore the influence of electro-acupuncture on the neural oscillations.Results:1.The results of the open-field and elevated cross maze experiments showed that both 3xTg-AD and 5xFAD mice aged 4-5 months had anxiety-like emotions.The results of the three-box social experiment showed that 3xTg-AD mice aged 4-5 months had impaired social interaction and social recognition,and 5xFAD mice had good social interaction,but their social recognition ability decreased.The results of the new object recognition and olfaction tests showed that the object recognition,memory and olfaction functions of the 4-5 months old 3xTg-AD and 5xFAD mice were impaired.The results of the conditioned fear experiment showed that the 4-5 months old 3xTg-AD mice had a normalfear memory of the sound which associared with amygdaloid nucleus,but the contextual fear memory associared with hippocampus significantly decrease.On the contrary,the sound fear memory associared with amygdaloid nucleus of 5xFAD mice significantly decrease while the contextual fear memory associared with hippocampus of 5xFAD mice had no change compared with WT mice.2.After electro-acupuncture,the results of the open field and elevated cross maze showed that the anxiety-like emotion of the 4-5 months old 3xTg-AD was not effectively improved,some aspects are worse.While part of the anxiety-like emotion of the 4-5 months old 5xFAD mice effectively improved after electroacupuncture treatment.The results of the three-box social experiment indicated that the social interaction and social recognition of 3xTg-AD mice were significantly improved,while the social recognition ability of 5xFAD mice was significantly improved,with no effect on their social interaction.The experimental results of new object recognition and new position recognition showed that the object recognition memory and position recognition memory of 4-5 months old 3xTg-AD and 5xFAD mice were significantly improved.The results of the conditioned fear experiment showed that the impaired episodic fear memory of 3xTg-AD mice and the impaired vocal fear memory of 5xFAD mice were significantly improved.3.After electroacupuncture treatment achieved a good effect on 4-5 months old AD mice,we further conducted electroacupuncture treatment on older 9-10 months old 5xFAD mice.The results showed that,the aspects of lraening and memory,amyloid beta and neural nerwork oscillations were all improved significantly after electroacupuncture treatment.The results of the novel object recognition experiment showed that the object recognition memory index of 5xFAD mice aged 9-10 months also be improved significantly.Immunofluorescence staining results showed that electro-acupuncture could effectively reduce the number and area of Aβ42 in medial prefrontal cortex and hippocampus.The results of electrophysiological experiments showed that the gamma oscillations in the medial prefrontal cortex and hippocampus had a significant improvement.Conclusion:1.4-5 months old 3xTg-AD and 5xFAD mice showed abnormal cognition-related behavioral phenotypes,manifested as anxiety-like mood changes;decline in social activity;learning and memory defects and olfactory dysfunction.2.Electro-acupuncture on Baihui and Dazhui had a certain effect on the improvement of social activities,learning and memory,and olfaction dysfunction in 4-5 months old 3xTg-AD and 5xFAD mice,but the improvement effect on anxiety-like emotion was not obvious.3.Electro-acupunctureon Baihui and Dazhui improved object recognition memory in older 9-10 months old 5xFAD mice.Electroacupucnture may eventually improve cognitive impairment by regulating gamma oscillations to increase the clearance level of abeta 42. |
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