| Backgrounds and objective: Two thirds of depressed patients have the rapid antidepressant response to global sleep deprivation or partial sleep deprivation, but its neurobiological mechanisms are not clear so far. The study showed that sleep deprivation might elevate the levels of extracellular adenosine. Adenosine was both a endogenous modulator and a sleep factor,and that it modulated many monoamines especially 5-HT might be an important factor for the antidepressant response to sleep deprivation. Therefore, in these years, the role that adenosine played in the rapid antidepressant mechanisms of sleep deprivation draw more and more attention.With the study of molecule level in depression, ERK1/2-MAPK signaling pathways became the focus. In this study, we studied the effects of 72 hour rapid-eye-movement sleep deprivation (REMSD) and adenosine A1 and A2A receptor antagonists on ERK1/2 and P- ERK1/2 protein in hippocampus and prefrontal cortex of rats to investigate the effects of different adenosine receptors in different brain subreions on ERK1/2 pathway signal in REMSD model.Materials and methods: Experimental animals coming from Experimental Animal Center of Sun Yat-sen University which were fifty healthful adult male Sprague Dawley rats were divided into two groups randomly: 1) normal control group; 2) 72 hours rapid-eye-movement sleep deprivation group (72h REMSD group). The 72h REMSD group, which was used a small platform by water environment,was divided into four groups:1)72 hours rapid-eye-movement sleep deprivation group;2)72 hours rapid-eye-movement sleep deprivation + saline group;3)72 hours rapid-eye-movement sleep deprivation + adenosine A1 receptor antagonists group;4) 72 hours rapid-eye-movement sleep deprivation + adenosine A2A receptor antagonists group. Adenosine A1(2mg/kg),A2A (1mg/kg)receptor antagonist and saline(10ml/kg) were given into the rats by intraperitoneal injection at 0h, 24h, 48h, 72h respectively in 72h REMSD process.Using spontaneous movements test and sucrose consumption test to observe the change of behavior in rats.Using Western-blot analysis to examine ERK1/2 and phosphorylation levels in hippocampus and frontal cortex.Excel 2003 and SPSS 13.0 statistical software were used for the analysis.Results:1.Body weight:After 72 hours REMSD,72h REMSD group and normal control group have no statistic diffrences in body weight(P>0.05);adenosine A1 receptor antagonist group has lower body weight comparing with the saline control group(P<0.05);adenosine A2A receptor antagonist group has much lower body weight comparing with adenosine A1 receptor antagonist group(P<0.01). After 72 hours REMSD,comparing various treatment groups with themselves before 72h REMSD, the saline control group have even lower body weight (P<0.01);but 72h REMSD group , adenosine A1 receptor antagonist group and adenosine A2A receptor antagonist group all have no statistic diffrences (P>0.05)2. Spontaneous movements:After 72 hours REMSD, 72h REMSD group and normal control group have no statistic diffrences in total distance ,middle distance and border distance(P>0.05);comparing with 72h REMSD group ,adenosine A2A receptor antagonist group has less total distance(P<0.05)and much less border distance(P<0.01);adenosine A2A receptor antagonist group has less total distance(P<0.05)and even less border distance(P<0.01). After 72 hours REMSD, comparing various treatment groups with themselves before 72h REMSD, the normal control group has no statistic diffrences in spontaneous movements(P>0.05);72h REMSD group obtains more border distance(P<0.05);adenosine A1 receptor antagonist group attains much less middle distance(P<0.01);adenosine A2A receptor antagonist group acquires less total distance(P<0.01).3.Effects on ERK1/2 and phosphorylation levels(pERK1/2 and pERK1/2/ ERK1/2) in different brain regions by various treatments:1) Frontal cortex: After 72 hours REMSD,all the various treatments groups have no statistic diffrences in pERK1/2/actin, ERK1/2/actin and pERK1/2/ ERK1/2 (P>0.05). After 72 hours REMSD, comparing with themselves before 72h REMSD, various treatment groups attain no statistic diffrences in pERK1/2/actin, ERK1/2/actin and pERK1/2/ ERK1/2 (P>0.05).2) Hippocampus: Various treatments groups attain no statistic diffrences in pERK1/2/actin and ERK1/2/actin (P>0.05),but have significant statistic diffrences in pERK1/2/ERK1/2(P<0.01). 72h REMSD group and normal control have no statistic diffrences in pERK1/2/actin, ERK1/2/actin and pERK1/2/ ERK1/2 (P>0.05);the saline control group and 72h REMSD group acquire significant statistic diffrences in pERK1/2/ERK1/2(P<0.01); adenosine A1 receptor antagonist group,adenosine A2A receptor antagonist group and saline control group have no statistic differences(P>0.05);adenosine A1 receptor antagonist group attains no statistic differences in pERK1/2/actin,ERK1/2/actin and pERK1/2/ERK1/2 comparing with adenosine A2A receptor antagonist group(P>0.05).Conclusions:1. 72 hours rapid-eye-movement sleep deprivation has no effect on body weight of normal rats;adenosine A1 and A2A receptors antagonist by i.p. decrease body weight of rats, and the behind less;intraperitoneal itself decreases body weight of rats.2. Adenosine A2A receptors antagonist by i.p. may reduce total distances and middle distances; 72 hours rapid-eye-movement sleep deprivation can increase border distances of rats;both 72 hours rapid-eye-movement sleep deprivation and adenosine A1 receptors antagonist lessen middle distances significantly; both 72 hours rapid-eye-movement sleep deprivation and adenosine A2A receptors antagonist decrease total distances of rats.3. 72h REMSD can't activated hippocampus and frontal cortex differently, but the response to of hippocampus external stimulus is a susceptivity, and ventro-injection itself can decrease pERK1/2 in hippocampus.4. The high concentration after sleep deprivation may persist shortly, and may not make effect on MAPK signaling pathway in hippocampus and frontal cortex. |
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