| Background and purpose: Autism, which is a kind of pervasive developmentaldisorder, is commonly seen in clinical practices. In has serious impact on the patients’ qualityof life, and provide tremendous burden for families and the society. The pathogenesis ofautism is unknown, which draws strong attention of the researchers. Cognitive impairment isan important aspect of autism clinical characteristics, the research of which is more onclinical observation than on animal model. Bumetanide, which is believed to improve thesymptoms of autism, is widely used clinically, but the research on its mechanism is limited.We use VPA to produce autism rats model, and invite a variety of behavioral testing researchof autism behavior characteristics, especially the cognitive behavioral characteristics. Forpart of autism rats, we give bumetanide for intervention therapy, and observe on theimprovement of their behavior. At last, we make morphological observation on the brainareas concerning brain development and cognition, and test the level of5-HT, GABA andother related transmitters in serum, to investigate the pathogenesis of cognitive impairmentin autism and the mechanism of the effect of bumetanide.Method: In our study, we inject pregnant Wistar rat at E12.5with VPA (600mg/kg), andselect male offspring as the autism model. In different stage of growth, we observe the indexof the growth and development, such as body weight gained and the eye opening. We alsoobserve the stereotyped behavior, social interaction, learning and memory behavior. After allthe behavior tests, we test the level of5-HT and other related transmitters in serum, andtake the brain pathology slice to make morphological observation. All the data are statisticalanalyzed under SPSS Statistics19.0software.Results: In our study, the experimental rats were divided into normal control group,model control group and bumetanide treatment group. Comparison between three groups:(1)in terms of growth and development, autistic rats (including those treated withbumetanide) compared with the normal rats, showing significant growth retardation,including low body weight, eyes open delay, vestibular and movement function delay;(2) interms of behavioral and cognitive function, autistic rats compared with normal rats showedobvious repeat stereotyped behavior, narrowed interest, decreased exploration ability，social cognition and communication disorders, learning and memory disorders, while, those treatedwith bumetanide showed obvious improvement in behavioral and cognitive aspects;(3)autistic rats compared with normal rats had increased serum5-HT and GABA concentration,while those treated with bumetanide showed obviously decrease in the level. there was noevident difference between the three groups in the serum concentrations of Glu;(4) in termsof nerve pathology, autistic rats compared with normal rats showed low levels of brainfunction, such as smaller neurons with fewer and shortened synapses in the lobes, especiallyin the temporal lobe and hippocampus, neurons there were increased in number, anddisordered arrangement. Purkinje cells in cerebellar were reduced and sparse arranged.Bumetanide treatment showed no obvious improvement in nerve pathology.Conclusion:(1)VAP autism model rats showed typical behavior and cognitivedysfunction such as obvious repeat stereotyped behavior, narrowed interest, decreasedexploration ability, social cognition and communication disorders, learning and memorydisorders.(2) Autisitic rats showed obvious nerve pathological change, and5-HT and GABAconcentration in serum were significantly increased, which may be the cause of its behaviorand cognitive dysfunction.(3) Bumetanide can significantly improve autism behavior and cognitive dysfunction,its mechanism may be inhibit NKCC1transporter, which can reduce the concentration of Cl-in the cell, and adjust the function of GABA. |
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