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BackgroundDepression is a chronic mental disease which can be repeated several times and is characterized by depressive mood. It can seriously impact on20%of the global people’s physical and mental health and the quality of life. As we all know, its pathogenesis is still unclear. Researches which are focusing on plasticity of hippocampus is becoming one of the hot topics in depression pathogenesis in recent years. The postsynaptic density protein-95(postsynaptic density protein-95, the PSD-95), which is the main scaffolding protein in postsynaptic specialization region, plays an important role in the regulation of synapse growth and neural plasticity, and also participates in regulating functions such as learning and memory. In terms of current researches, it has been confirmed that PSD-95could participate in the mechanism of depression at the protein level. But researches are relatively seldom at the genetic level. This research was aimed to investigate the expression of hippocampus PSD-95and the structure change of neurons in hippocampus of depression rats, to figure out the effect of pharmacotherapy, and to explain the possible pathogenesis of depression.Objectives1. To explore changes in ability of learning and memory and the effect of drug intervention to these changes.2. To explore the morphological changes of neurons in hippocampal and drug intervention to these changes.3. To explore expression of PSD-95in hippocampal of depression model rats and the effect of drug interventionMethods1. Rats were divided into control group (n=16) and model group (n=48). All rats in model group were stimulated by chronic unpredictable mild stress.The model group were divided into three groups:depression model matched group (n=16, no gavage administration), depression model and saline group (n=16, Intragastric administration using physiological saline) and depression model and medication group (n=16, Intragastric administration using sertraline).2. Body weight measurement, sucrose water consumption test and open field test were used to detect the behavior of rats. Morris water maze was used to test the learning and memory ability of rats.3. HE staining was used to observe morphology of pyramidal neurons granulosa cell in rat hippocampal.4. Immunohistochemistry was used to detect the expression of PSD-95protein in rat hippocampal; and RT-PCR (reverse transcription and chain reaction) was used to detect the expression of PSD-95mRNA.Results1. Behavior results:Before the model established, here are the results.Rats weight (t=1.967, P>0.05). Sucrose water consumption(t=1.352, P>0.05). Open field test containing run-up time(t=0.073, P>0.05), horizontal behavior(t=-0.184, P>0.05), vertical behavior(t=-0.396, P>0.05).Y maze test containing error reaction times (t=-0.404, P>0.05), the correct reaction times(t=-0.805, P>0.05),and the total incubation time(t=-0.455, P>0.05).No statistical difference in all the items.All these suggest that CUS model could be established.After the model established, here are the results.Rats weight(t=18.909, P<0.05). Sucrose water consumption(t=20.414, P<0.05). Open field test containing run-up time(t=-10.420, P<0.05), horizontal behavior(t=11.859, P<0.05), vertical behavior(t=14.060, P<0.05. Y maze test containing error reaction times (t=-6.140, P<0.05), the correct reaction times (t=8.28, P<0.05), and the total incubation time(t=-17.66, P<0.05). Statistical differences were found in all the items. CUS model was successfully established.After pharmacotherapy, Behavioral comparison in these four groups are listing here. Rats weight (F=454.279, P<0.05). Sucrose water consumption (F=172.896, P<0.05). Open field test containing t run-up time (F=246.178, P<0.05), horizontal behavior (F=430.354, P<0.05), vertical behavior (F=1354.272, P<0.05). Y maze test containing error reaction times (F=23.150, P<0.01), the correct reaction times (F=40.258, P<0.05), and the total incubation time (F=129.083, P<0.05). Statistical differences were found in all the items.All these could tell that abilities of learning and Memory retrieval and preservation had decreased in depression rats, and these abilities could be improved by pharmacotherapy.2. HE staining results:Pathological changes of morphological structure of neurons pyramidal granulosa cell were found in hippocampal of depression model rats, and Drug intervention could improve this status. Parameters comparison of these pathological changes:Statistically significant differences The numbers of pyramidal and granulosa neurons cells in Hippocampal of these four groups (FCA1=8.228, P<0.05; FCA33=34.143, P<0.05; FDG=275.035, P<0.05), Neural cone pyramidal and granulosa cell gray value (FCA1=88.494, P<0.05; FCA3=89.398, P<0.05; FDG=236.085, P<0.05) Statistically significant differences were found.3. Immunohistochemical results:The results in Hippocampal of these four groups are listed here.PSD-95-positive cells number(FCA1=16.497, P<0.05; FCA3=23.494, P<0.05; FDG=37.628, P<0.05), the positive cells of integral optical density (FCA1=26.659, P<0.05; FCA3=13.556,.P<0.05; FDG=6.158, P<0.05). Statistically significant differences were found.And these results also indicated that expression of PSD-95was different in each group.4. RT-PCR results:The comparison of PSD-95mRNA expression in hippocampus of these four groups (F=290.951, P<0.05).The PSD-95mRNA expression of depression rats was lower than normal group (P<0.05). The PSD-95mRNA expression of medication group was higher than depression rats (P<0.05).5.Pearson correlation analysis results:four groups of rat hippocampal CA1region, the CA3area and DG PSD-95positive cells with Y-maze parameters correlation analysis model of depression in the hippocampal CA1of PSD-95-positive cells, the number of errors reaction times were negatively correlated (r=-0.769, P<0.05), and total escape latency was negatively correlated (r=-0.800, P<0.05), with the number of correct responses was positively correlated (r=0.800, P<0.05), model of depression in rat hippocampal CA3the number of PSD-95-positive cells and the number of error responses was negatively correlated (r=-0.751, P<0.05), with a total escape latency was negatively correlated (r=-0.832, P<0.05), and the number of correct responses was positively correlated (r=0.862, P<0.05), hippocampus of rat model of depression DG PSD-95positive cells and the number of error responses were negatively correlated (r=-0.699, P<0.05), and total escape latency time was negatively correlated (r=-0.869, P<0.05) were positively correlated, the number of correct responses was positively correlated (r=0.728, P<0.05).Conclusions1. Neural plasticity of hippocampal could be involved in regulation of emotion, learning and memory functions in depression. Morphological changes in numbers and structures of neurons in hippocampus could be the morphological basis of the onset of neural plasticity and depression.2. Sertraline could improve the abilities of learning and memory in depression rat model, reverse low expression of PSD-95in hippocampus and pathological changes of neurons’morphology.This could be one of the antidepressant mechanisms of Sertraline.
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