| Depression (minor depression) is a series of diseases characterized by remarkable and permanent depressive mood or mental changes. The incidence of depression has increased progressively for more and more social challenges these years. Depression has become a major health care not only because of personal distress, excessive mind pressure, impaired interpersonal relationships and restriction of work ability but also because of more and more economic burdens.At present, the study of depression pathogenesis and antidepressant is closely associated with monoamine transmitters and neuroendocrinological system. In depression, the 5-hydroxytryptamine (5-HT, serotonin) plasma concentration is lower, based on this mechanism, the selective serotonin reuptake inhibitors (SSRIs), an important and widely used class of antidepressant, can improve depression mood. Although these hypotheses and theories play an important role in prevention and cure of depression , the mechanism of depression remains to be explored. The G-protein-gated inwardly rectifying K+ channels (GIRKs) that are linked to a pertussis toxin sensitive G protein, a member of the family of inwardly rectifying K+ channels, can be directly activated by Gpy. GIRK channels play an important role in the modulation of not only the heart rate but also neurotransmitters releasing and neuronal excitability. It has been believed that the GIRK channels are coupled to numerous inhibited neurotransmitters receptors in brain and heart. One of the neurotransmitters known to activate GIRKs is 5-HT, through interaction with the 5-HTia receptor, The 5-HTia receptor can directly activate GIRK channels. In the hippocampus corticosterone can alter neural activity through which 5-HTia receptor increases the conductance of an GIRK.The GIRKi gene contains a number of consensus elements for transcription factors including a potential binding site for the glucocorticoid receptor (GRE). Corticosterone activation of GR can directly alter transcription of GIRKt. In the stress depression rats model, the hypothalamic-pituitary-adrenal axis is stimulated, stress-induced high circulating plasma corticosterone concentration can regulate GIRK gene expression through two receptor subtypes, i.e., the mineralocorticoidreceptor (MR) and glucocorticoid receptors (GR). Therefore, the GIRK study in the stress depression pathogenesis has a future meaning.The aim of this study is to test the hippocampus and parietal cortex GIRK1-4 mRNA expression changes via in situ hybridization after phasic blockade of brain MR and/or GR by intracerebroventricular administration of the MR antagonist and/or GR antagonist respectively, So as to determine the underlying mechanism of corticosterone on GIRKs.The main results are as follows:1. The changes of the number and morphology of neurons in hippocampus andparietal cortex in experimental depression ratsNissl staining showed that the number of neurons in parietal cortex and hippocampal CA1, CA2, CA3 areas and dendate gyrus did not significantly decrease compared with control (p>0.05). In parietal cortex and pyramidal cells, inner granular cells, multiform cells layer of hippocampus, the arrangement of neurons was not turbulent, the amounts of Nissl bodies did not decrease,. And did not find that some certain cellullar nucleus were pycnosis or vacuolened.2. The alteration of GIRKm mRNA expression in the brain of depression rats.ISH showed that GIRK1-4 mRNA expression significantly decreased in the CA1, CA2, CA3 and dentate gyrus of hippocampus and parietal cerebral cortex compared with control (P<0.05).3. The changes of the number and morphology of neurons in hippocampus and parietal cortex in experimental depression rats after intracerebroventricular administration of mineralocorticoid receptor antagonist (spironolactone, SPI) and glucocorticoid receptors antagonist (mifepristone, MIF)Nissl staining showed that in NS depression, SPI depression, MIF depression and SPI+MIF depression groups, the number of neurons in parietal cort... |
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