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Effects of Sleep Deprivation on Adenosine A1 Receptor and 5-HT1A Receptor in the Brain of Normal Rats and Rats Treated with Chronic Stresses

Author: ZhangJinLing
Tutor: XuChongTao
School: Shantou University
Course: Psychiatry and Mental Health
Keywords: Sleep deprivation Depression Adenosine A1 receptor 5-HT1A receptor
CLC: R749.4
Type: Master's thesis
Year: 2007
Downloads: 260
Quote: 4
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Abstract


Background: Adenosine is a sleep factor, it is mainly through its receptor to regulate sleep. Among them, the adenosine A 1 receptor plays a major role. In addition, adenosine as a nerve quenched and tempered, especially through its receptor adenosine A 1 receptor modulators variety of neurotransmitter release. Recently there have been found that adenosine and its receptors and depression and antidepressant process. Sleep deprivation can play fast antidepressant effect, but the neurobiological mechanisms are still not clear, the current study focused on monoamine neurotransmitter systems. Since adenosine and sleep, depression and a variety of neurotransmitters are closely related to the adenosine is involved in the the rapid antidepressant process of sleep deprivation? During this process, the adenosine receptor expression varies it ? There are currently no reports in this regard. The subjects in the study of normal rats for 72-hour rapid eye movement sleep deprivation (rapid eye Movement sleep deprivation, REMSD) adenosine A 1 receptor and 5-HT 1A receptor expression and neuronal activity changes based on the rat model of depression for 72-hour fast eye movement sleep deprivation rat brain regions adenosine A 1 receptor and 5-HT < sub> 1A receptor expression, and to explore the adenosine A 1 receptor rapid antidepressant mechanism of sleep deprivation may. Experiment: Objective: To observe the sleep deprivation on the spontaneous activity of normal rats and in different brain regions adenosine A 1 receptor and 5-HT 1A receptor expression and effects on neuronal activity. Materials and Methods: The experimental animals for 2-3 month-old Sprague Dawley male rats were randomly divided into normal 72 hours REMSD group (n = 8, hereinafter referred to as sleep deprivation group), the normal large platform control group (n = 8, hereinafter referred to as platform control group) and normal control group (n = 8, hereinafter referred to as the normal control group). Rapid eye movement sleep deprivation small platform water environmental law; water environment with a large platform control, eliminate water environment. The observed fast eye movement sleep deprivation under changes in spontaneous activity in rats, using reverse transcription - polymerase chain reaction (reverse transcription-polymerase chain reaction, RT-PCR) detection of hippocampus in each group, the prefrontal cortex, the brain, the hypothalamus striatal adenosine A 1 receptor and 5-HT 1A receptor mRNA expression changes, use of the Nissl staining techniques to observe the activity of neurons. The experimental results with Excel 2000 and SPSS 11.0 statistical software for analysis and processing. The results are mean ± standard mistake (X ± SE) said, using ANOVA analysis of variance (ANOVA) and t test (T-test) carried out between the two groups were the number of comparison, P <0.05 significant difference, P <0.01 for the difference highly significant. Results: 1. Normal rat 72 hours REMSD large platform of spontaneous activity from the control group (P <0.05); spontaneous activities in Central away and rest platform control group no significant change (P> 0.05). Normal rats treated by the water environment of a large platform, spontaneous activity from the central distance and rest time than normal control group (P> 0.05) were not significantly changed. 2. Normal rat 72 hours to compare hippocampal adenosine A after REMSD platform group 1 receptor mRNA transcription level was significantly lower (P <0.01), while the 5-HT 1A by body mRNA levels increased (P <0.05); large platform control group of normal rat hippocampal adenosine A 72-hour water environment treatment 1 receptor mRNA levels were significantly increased (P <0.01) , and 5-HT 1A receptor mRNA levels had no significant change (P> 0.05). 3.72 hours the REMSD itself can not make the normal rat prefrontal cortex adenosine A 1 receptor mRNA expression changed significantly (P> 0.05), while the 5-HT 1A receptor mRNA expression increased (P <0.05); 72 hours a large platform water environment treatment the normal rat prefrontal cortex adenosine A 1 receptor mRNA expression decreased (P <0.05); forehead cortical 5-HT 1A receptor mRNA expression had no significant effect (P> 0.05). 4. Normal rat 72 hours REMSD with a large platform control group than in the brain adenosine A 1 receptor mRNA expression and 5-HT 1A receptor mRNA expression were lower ( P <0.05); 72-hour water environment of a large platform processing, brain adenosine A 1 receptor mRNA expression in normal rats (P <0.05) reduction in brain 5-HT 1A receptor mRNA expression was increased (P <0.05). 5.72 hours REMSD the right normal rat hypothalamus the adenosine A 1- receptor and 5-HT 1A receptor mRNA expression were not significantly affected (P> 0.05) ; 72 hours platform water environment treatment did not change in normal rats hypothalamic adenosine A 1 receptor mRNA expression (P> 0.05), but allows the hypothalamic 5-the HT 1A receptor mRNA expression was increased (P <0.05). 6.72 hours REMSD large platform and 72-hour water environment treatment do not alter the striatal adenosine A 1 receptor and 5-HT 1A receptor mRNA expression (P> 0.05). 7. Nissl staining showed that normal rat 72 hours after sleep deprivation the big platform control group Bihaimani's small staining optical density increased (P <0.05); platform control group and normal control group Bihaimani's staining no significant change in optical density (P> 0.05). Experiment II: Objective: To observe the sleep deprivation Chronic Stress Depression Rats spontaneous activity in different brain regions adenosine A 1 receptor and 5-HT 1A receptor expression the impact. Materials and Methods: The experimental animals for 2-3 month-old Sprague Dawley male rats were randomly divided into normal control group (n = 10, hereinafter referred to as the normal control group) stress model group (n = 48). Stress-made module chronic unpredictable mild stress (chronic mild unpredicted stress, CMUS) and points raised combination of two classic models to create a model of depression, randomized block successful modeling rats were divided into 3 groups: depression model group (n = 8, hereinafter called depression model group) model of depression in 72 hours REMSD group (n = 8, hereinafter called sleep deprivation group) model of depression large platform control group (n = 7, the following said a large platform control group). Small platform water environment rat model of depression, rapid eye movement sleep deprivation, and the water environment of the large platform control. Observed rapid eye movement sleep deprivation role in the rat model of depression changes in spontaneous activity, using reverse transcription - polymerase chain reaction (reverse transcription-polymerase chain reaction, RT-PCR) was used to detect the rats prefrontal cortex, hippocampus, hypothalamus, in brain areas of the brain adenosine A 1 receptor and 5-HT 1A receptor mRNA content changes, the use of immunohistochemical techniques on the adenosine A 1 receptor protein expression to locate and analyze. The experimental results with Excel 2000 and SPSS 11.0 statistical software for analysis and processing. The results are expressed as mean ± standard error (X ± SE), using single-factor analysis of variance (ANOVA) and t test (T-test) between the two groups were compared, P <0.05 as significant difference. Results: 1. Rats after 21 days of mild chronic unpredictable stress treatment, the total distance of the spontaneous activity of the Central away than the normal control group significantly reduced rest time (P <0.05); depression model rats after 72 hours REMSD after the spontaneous activities from the central from the platform control group compared to a significant increase in rest time (P <0.05). (That part of the experiments carried out by the 2003 graduate of the professional Inami) 2.21 days of chronic stress in rats hippocampal adenosine A , 1 receptor mRNA levels in the normal control group compared increased (P <0.01); 72-hour REMSD hippocampal adenosine A 1 receptor mRNA expression with a large platform compared to the control group (P <0.05) lower; 72 hour platform water environment treatment of depression model the the rat hippocampal adenosine A 1 receptor mRNA levels did not affect (P> 0.05). The 3.21 days chronic stress can affect the normal rat prefrontal cortex adenosine A 1 receptor mRNA levels decreased significantly (P <0.01); 72 hours REMSD is the impact of this change is not obvious ( P> 0.05); 72 hour platform water environment handle this change has no significant effect (P> 0.05). 4.21 days of chronic stress does not significantly change the part of the brain in normal rats the Adenosine A 1 receptor mRNA transcription level (P> 0.05); the 72 hour REMSD and water environment itself on the model of depression rat brain parts adenosine A 1 receptor mRNA levels were not significantly affected (P> 0.05). 5.21 days of chronic stress, the hypothalamus part of the normal rat adenosine A 1 receptor mRNA levels in the normal control group compared with no significant difference (P> 0.05); 72 hours REMSD Adenosine A 1 receptor mRNA levels with a large platform group increased (P <0.05), 72 hours a large platform water environment treatment on hypothalamic adenosine A rat model of depression 1 receptor mRNA expression had no effect (P> 0.05). 6. Immunohistochemical results showed that adenosine A 1 receptor-positive cells were mainly distributed in brain regions such as the hippocampus, cerebellum, and other brain regions were seldom. After 21 days of chronic stress, increased (P <0.05) compared to the rat hippocampal adenosine A 1 receptor protein levels with normal control group; 72-hour REMSD hippocampal adenosine A 1 receptor expression platform group decreased (P <0.05); platform control group 72 hours water environment treatment model of depression in rat hippocampal adenosine A 1 receptor protein The expression levels did not affect (P> 0.05). 7. Sleep deprivation Chronic Stress Depression Rats in different brain regions 5-HT 1A receptor expression results are shown in Appendix (the part of the testing and analysis by the brothers Zhang Inami) Conclusion: 72 hours The rapid reversal REMSD 21-day chronic stress result in behavioral depression. Hippocampal adenosine A 1 receptor mRNA level of transcription and protein expression levels and the prefrontal cortex adenosine A 1 receptor mRNA levels may be involved in the pathogenesis of depression process. In the mechanism of antidepressant sleep deprivation may hippocampal adenosine A 1 receptor mRNA transcription and protein expression levels of recovery decreased and hypothalamus the adenosine A 1 by -mRNA transcription elevated levels play an important role. Adenosine A 1 receptor in sleep deprivation the rapid antidepressant process may be associated with 5-HT system.

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