Dissertation
Dissertation > Medicine, health > Neurology and psychiatry > Psychiatry > Affective psychosis

Effects of Adenosine A1 and A2A Receptor Antagonists on ERK1/2 and pERK1/2 in Different Brain Subregions in Rats Treated with Sleep Deprivation

Author LiLing
Tutor XuChongTao
School Shantou University
Course Psychiatry and Mental Health
Keywords Rapid eye movement sleep deprivation Adenosine A1 receptor Adenosine A2A receptor ERK1 / 2 pERK1 / 2
CLC R749.4
Type Master's thesis
Year 2011
Downloads 47
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Background and purpose: both full night of sleep deprivation or sleep deprivation, two-thirds of patients with depression quickly play an antidepressant effect, but the neurobiological mechanisms are still unknown. Studies have shown that sleep deprivation can make extracellular adenosine concentration. Adenosine both a neuromodulator and a sleep factor, its monoamine neurotransmitters, especially the regulation of 5-HT perhaps the sleep deprivation fast play an important antidepressant effect factors. Therefore, in recent years, adenosine sleep deprivation rapid antidepressant mechanism of concern. With research on the molecular level of depression, ERK1/2-MAPK signal transduction system has also become the focus of the study. In this study, by 72 hours of rapid eye movement sleep deprivation and intraperitoneal injection of adenosine receptor antagonists on the rat prefrontal cortex and hippocampus ERK1 / 2 and p-ERK1 / 2 of the expression and phosphorylation level observed changes aims to explore the different subtypes of adenosine receptors in different brain regions of ERK1 / 2 signaling pathway provides a theoretical basis for adenosine and its receptors role in the mechanism of rapid antidepressant sleep deprivation. Materials and methods: the Experimental Animal Center of Sun Yat-sen University in experimental animals healthy adult male Sprague Dawley rats to 50, were randomly divided into normal control group (n = 10, hereinafter referred to as the normal control group), 72h REMSD group (n = 40, hereinafter referred to as sleep deprivation group). Small platform 72h rapid eye movement sleep deprivation sleep deprivation group to create a model of sleep deprivation, sleep deprivation rats were divided into four groups: 72h REMSD group (n = 10, hereinafter referred to as sleep deprivation group) randomized block the 72 h REMSD intraperitoneal injection of saline (n = 10, hereinafter referred to as the saline group), 72 h REMSD intraperitoneal injection of adenosine A1 receptor antagonist group (n = 10, hereinafter referred to as the adenosine A1 receptor antagonist group), 72 the h REMSD intraperitoneal injection the adenosine A2A receptor antagonist group (n = 10, hereinafter referred to as the adenosine A2A receptor antagonist). The process 72hREMSD 0h, 24h, 48h, 72h, respectively, in accordance with the the 2mg/kg and 1mg/kg pair of rat peritoneal adenosine A1 and A2A receptor antagonist injection of adenosine A1, A2A receptor antagonist, and the use of the abdominal cavity injection of saline as a control, to exclude intraperitoneal injection to rats. Opening experimental test observation of sleep deprivation, intraperitoneal injection of saline, adenosine A1 and A2A antagonists on the spontaneous activity of rats Western-blot method to detect the prefrontal cortex in rats hippocampal ERK1 / 2 protein phosphorylation level changes. The experimental results using Excel 2003 and SPSS 13.0 statistical software for statistical analysis and processing, the results are expressed as mean ± standard deviation (x_ ± S), the use of single-factor analysis of variance (ANOVA) and t-test (T-test) between groups mean compare (P lt; 0.05 for the difference was statistically significant, P lt; 0.01 for the difference was highly statistically significant). Results: 1) body weight of rats: 72h REMSD sleep deprivation rats with normal control group comparison, the weight difference was not statistically significance (P gt; 0.05); adenosine A1 receptor antagonist group with the control group weight loss (P lt; 0.05); adenosine A2A receptor antagonist group compared with the adenosine A1 receptor antagonist group, body weight decreased significantly (P lt; 0.01). After 72h REMSD, each treatment group and its than 72h REMSD before its own compared to the saline control group, body weight decreased significantly (P lt; 0.01); sleep deprivation group, adenosine A1 and A2A receptor antagonist group weight was no significant change (P gt; 0.05). 2) spontaneous activities: 72h REMSD after sleep deprivation in rats with normal control group compared to the total distance of the Central away, surrounding away no difference between statistical significance (P gt; 0.05); adenosine A2A receptor antagonist group with sleep deprived group compared to the decrease in total distance (P lt; 0.05), the surrounding away significantly reduced (P lt; 0.01); adenosine A2A receptor antagonist group compared with the control group, the decrease in total distance (P lt; 0.05 ), surrounding away significantly reduced (P lt; 0.01). 72h REMSD after each treatment group and its own 72h REMSD ago compared to the normal control group, spontaneous activity, no significant change (P gt; 0.05) increased (P lt; 0.05); sleep deprivation group surrounding away; adenosine A1 receptor antagonist The Group Central away significantly reduced (P lt; 0.01); decrease in total distance of the adenosine A2A receptor antagonist group (P lt; 0.01). 3) various processing methods on different brain regions of ERK1 / 2 protein (ERK1 / 2) and the level of phosphorylation (pERK1 / 2 and pERK1 / 2 / of ERK1 / 2) of: 1) the prefrontal cortex: 72h REMSD, treatment group compared pERK1/2/actin ERK1/2/actin and pERK1 / 2 / ERK1 / 2 the difference was not statistically significant (P gt; 0.05). The After 72h REMSD, compared to each treatment group and its own 72h REMSD ago, pERK1/2/actin ERK1/2/actin and pERK1 / 2 / of ERK1 / 2 difference had no statistical significance (P gt; 0.05). 2) the hippocampus: a variety of treatment the the hippocampus pERK1/2/actin and ERK1/2/actin impact difference had no statistical significance (P gt; 0.05), while the difference of of hippocampal pERK1/2/ERK1/2 impact height statistically significant (P lt; 0.01). Sleep deprivation group compared with the normal control group the hippocampus pERK1/2/actin, ERK1/2/actin and pERK1/2/ERK1/2 no significant difference (P gt; 0.05); saline control group, sleep deprivation group compared the hippocampus pERK1/2/ERK1/2 difference was highly statistically significant (P lt; 0.01); adenosine A1, A2A receptor antagonist group compared with the saline control group hippocampus pERK1/2/actin ERK1 / 2 of / actin pERK1/2/ERK1/2 of the difference was not statistically significant (P gt; 0.05); adenosine A1 and A2A receptor antagonist group compared to the the hippocampus pERK1/2/actin, ERK1/2/actin and pERK1 / 2/ERK1/2 the difference was not statistically significant (P gt; 0.05). Conclusion: 1. 72 h REMSD no effect on the weight of normal rats; intraperitoneal injection of adenosine A1 and A2A receptor antagonists may be the weight loss in rats, and the latter is more pronounced decline; intraperitoneal injection itself can also lead to the body weight of rats decline. Intraperitoneal injection of adenosine A2A receptor antagonists in rats can reduce total distance and Central away; 72h REMSD increase in rats surrounding away; a 72h REMSD and intraperitoneal injection of adenosine A1 receptor antagonist allows the rat central away significantly reduced; of 72h REMSD and intraperitoneal injection of adenosine A2A receptor antagonists decrease in the rats away. The 3. 72h REMSD of activation in the hippocampus and frontal cortex yet found a significant difference, but the hippocampus is more sensitive response to external stimuli, intraperitoneal injection of saline can lead to a decline in the level of pERK1 / 2. Sleep deprivation caused by the concentration of adenosine may duration is relatively short, it may not work through the MAPK pathway in the hippocampus and frontal cortex brain regions.

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