The Change Of GABAergic Neurons In The Mouse Brain Of Schizophrenia

Objective In this study, observed the stereotyped and ataxia behavior, and the changesin the prefrontal cortex (PFC) and hippocampus (HIP) CA1, CA2, and CA3within of GABAin models of schizophrenia mouse.Methods Experiments were carried out on C57BL/6mice and GAD67-GFP knock inmice. Animals were injected with NMDAR antagonist MK801(Dizocilpine)(0.3mg/kg,0.6mg/kg,1mg/kg, respectively) for two weeks to induce schizophrenia. To examine thestereotyped movement, we have scored for stereotyped movement using scales on3,5,7,10and14d after MK801injecton. Using immunofluorescence methods, the morphology ofGABAergic subpopulation markers, calcium-binding protein(CB)、 calretinin (CR)、parvalbumin (PV) were observed, and RT-PCR were used to examine the mRNA level.Result (1) behavior change.○1Stereotyped behavior assessment will be0.3mg/kg,0.6mg/kg,1mg/kg three doses of mouse stereotyped behavior scale score compared. Theresults showed that,0.6mg/kg,1mg/kg doses of mouse stereotyped behavior score issignificantly higher than that of0.3mg/kg dose group, respectively37.9%,38.1%, and0.6mg/kg doses groups and1mg/kg doses no obvious difference between groups score; After thetreatment of3,5,7,10and14days, along with the increase of drugs for days, each dosegroup of stereotyped behavior score were in mouse reduced gradually.○2Ataxia assessmentwill be0.3mg/kg,0.6mg/kg,1mg/kg three doses of mouse ataxia scale score compared, theresults showed that1mg/kg doses of mouse stereotyped behavior score significantly higherthan0.3mg/kg dose group, increased36.4%. It is no obvious difference between0.3mg/kg doses group and0.6mg/kg doses group,1mg/kg doses group and0.6mg/kg doses groupsscore; After the treatment of3,5,7,10and14days, with the increase of drugs for days, eachdose group of mouse ataxia scores were gradually reduced in mouse.(2) Changes of GABAneurons. Morphological change. In the prefrontal cortex, GFP positive cells are visible oneach layer of the model group and control group, but there was no significant differencebetween the two groups; PV positive cells distributed in III-V layers, CB and CR positivecells were mainly distributed in layer II-III, but there were no significant changes betweenthe model and control group. In the CA1, CA2, CA3regions of hippocampus, GFP positivecells distribute in each layer of unit area, but the number of positive cells were no significantchange; PV, CB positive cells were mainly distributed in the CA1starting layer, the numberof positive cells in the unit area was no significant difference between the model and controlgroup; CR positive cells in CA1zone increased significantly, while in the CA2and CA3area,the number of positive cells in per unit area was no significant difference. The results ofRT-PCR. In the prefrontal cortex of schizophrenia model mice, GAD67mRNA expressiondecreased significantly compared to saline control group, while in the hippocampus, GAD67mRNA expression was not changed between model and saline control group.Conclusion Stereotyped movements and ataxia behavior in mouse injected withMK801in a dose-dependent; long-term may weaken the stereotyped movement and ataxiabehavior of mouse given1mg/kg and less than dose of MK801, which may be the mouseneurotransmitters self-regulation and the behavior of mouse to adapt to the inhibition in thePFC and HIP CA1, CA2, CA3of brain regions; the neurotransmitter GABA was nosignificant change at the protein level; the expression level of GABA mRNA decreased in thePFC in schizophrenia. The relationship between these changes and schizophrenia still remainsfurther study.