A¹⁸[FDG] Micro-PET Imaging Study In Rat Brain Of Recurrent Depression Model

Depression disorder is a common neurobiological disorder, affecting over120million people worldwide. So far, depression has become the fourth major disablingdisease and a major global mental health problem in the world. Many studies suggestthat depression is a chronic and recurrent psychosis. Research show that at least50%ofthose who recover from a first episode of depression suffer from one or more additionalepisodes in their lifetime, and approximately80%of those with a history of twoepisodes are prone to a second. Therefore it is very important to prevent the recurrenceof depression. To the best of our knowledge, the pathogenesis of depression and itsrecurrence remains unclear, and there is little literature published about the recurrenceanimal model of depression. In recent years, with the emergence of small animal PET,new technology provides a new platform for metabolism studies of depression andrecurrent brain function. The present study focused on the establishment of the recurrentdepressive animal models, using small animal micro-PET to study changes of brainglucose metabolism in the recurrent depressive animal models, in hope of finding thebrain regions related to depression recurrence, and providing reference for the study ofdepression. The specific contents are as follows:1. Establishment of the recurrent depressive animal models induced by CUMSWe employed chronic unpredictable mild stress and fluoxetine intervention toestablish a rat model of recurrent depression. The present study used sucroseconsumption test, open-field test and body weight as animal behavior assessmentindicators.Before the experiment, all rats were given behavior tests after1week ofenvironment adaptation in the animal room. Healthly rats were randomly divided intocontrol group and experimental group. Control group rats in the modeling process werenormally fed, but the experimental group rats were given the following treatment.Firstly, they were exposed to chronic unpredictable mild stress for four weeks, followedby screening depression-like rats induced by CUMS. Secondly, depression-like rats were randomly divided into two groups, one group was given three weeks of salinetreatment, and the other group was given three weeks of fluoxetine treatment. Finally,rats that recovered with fluoxetine treatment were exposed to CUMS again. After4weeks of CUMS, depression-like rats were screened. Meanwhile, all experimental ratswere given behavioral assessment at baseline time, after4weeks of CUMS, fluoxetinetreatment and re-exposure to4weeks of CUMS.According to the result of behavior tests, compared to control rats and thosewithout depression, there was significant decrease in sucrose preference and totallocomotor activity in depressive-like rats after CUMS（P<0.01）;4weeks of CUMSinduced significant decrease in body weight gain in the stress rats compared to controlgroup（P<0.01）. After fluxetine or saline treatment, the recover rate of depressive-likerats in fluoxetine treatment group and saline treatment group was separately74%and72%. Meanwhile, body weight gain, sucrose preference test and open-field test did notdiffer significantly between recover rats and control rats（P>0.05）. After re-exposure toCUMS, the result showed again significant decrease in sucrose preference and totallocomotor activity in depressive-like rats after CUMS（P<0.05）; And4weeks ofRe-CUMS induced marked decrease in body weight gain in the stress rats. The resultsshowed we successfully had established a recurrent depressive rat model, and which canbe used for the next step experimental study.2.¹⁸[FDG] micro-PET imaging study in a rat recurrence model of depression¹⁸[FDG]-micro-PET indirectly reflect changes in the functional activity of brainregions as shown by changes in glucose metabolism. Our laboratory has studied the¹⁸FDG-PET imaging in a rat model of depression induced by CUMS. Based on theestablished recurrence animal model of depression, the study was to investigate changesof brain glucose metabolism in rats that recover and in rats re-exposed to CUMS.Firstly, we used¹⁸[FDG]-micro-PET to scan changes of brain glucose metabolismin CUMS-DE+FLX group, CUMS-DE+SAL group and control. We employedvoxel-based statistical analyses by SPM-2and used t-test for comparison between twogroups. Meanwhile, when Venn diagram analysis was made between CUMS-DE+FLXvs. Control and CUMS-DE+FLX vs. CUMS-DE+SAL, we found brain glucosemetabolism significantly increased in auditory cortex, hippocampus, thalamus,periaqueductal gray matter in CUMS-DE+FLX group, compared to Control and CUMS-DE+SAL group. In contrast, cingulate gyrus and striatum were deactivated inCUMS-DE+FLX group rats. The result suggested fluoxetine may affect changes offunctional activity in these brain regions.Secondly, we also used¹⁸[FDG]-micro-PET to scan brain glucose metabolism inRE-CUMS-DE group rats, CUMS-w/o-DE group rats and control rats. The resultshowed that when Venn diagram analysis was made between RE-CUMS-DE vs. Controland RE-CUMS-w/o-DE vs. Control, we found visual cortex, hippocampus,periaqueductal gray matter, motor cortex were significantly deactivated in CUMS-DEgroup and CUMS-w/o-DE group, but cerebellum was markedly activated in CUMS-DEgroup and CUMS-w/o-DE group. The result suggested changes in glucose metabolismof these brain regions may be closely related to chronic stress. What’s more, when Venndiagram analysis was made between RE-CUMS-DE vs. Control and RE-CUMS-DE vsRE-CUMS-w/o-DE, we found thalamus, hippocampus and striatum were significantlydeactivated in RE-CUMS-DE. Therefore, the three brain regions may be the key brainregions of recurrence in depressive-like rats.In conclution,1. We successfully established a recurrent depressive rat model byCUMS and fluoxetine intervention.2. Fluoxetine may affect glucose metabolism ofcingulate gyrus, hippocampus, striatum, thalamus, PAG and auditory cortex.3. Changesin glucose metabolism of hippocampus, cerebellum, PAG, motor cortex and visualcortex may be closely related to chronic stress.4. Thalamus, hippocampus and striatummay be the key brain regions of recurrence in depressive-like rats.