| Objective: In the modern society, lack of sleep, insomnia and sleep deprivation have become even more prominent. Compared with acute sleep deprivation, chronic sleep deprivation damage is more serious. This experiment used the modified multiple platform sleep deprivation for chronic sleep deprivation model, analysis the effect of chronic sleep deprivation on Dopamine D 1receptors related signaling pathway(PKA, MAPK and phosphoinositide) and the regulation of SKF38393 in th ese signaling pathway.Methods: 35 healthy adult male SD rats were screened by Morris water maze and swimming training, then 24 rats were selected and randomly divided into 3 groups: big platform treatment control( TC) group, chronic sleep deprivation(CSD) group and chronic sleep deprivation treated with D 1receptor agonist SKF38393(SKF) group. Rats underwent sleep deprivation 18 h a day in consecutive 21 d. Besides CSD, the SKF group rats were administered SKF38393 from 15 d to 21 d in CSD protocol, wh ile TC group and CSD group were treated with equal volume PBS. Use Morris water maze and swimming exhaustive time to determine rats learning memory abilities and exercise ability. Western blot and Real-time PCR were used to analyze the expression of D1 receptors related signaling pathway key factors expression.Results: 1. Weight and exhaustion swimming time: compared with TC group, the CSD group and SKF group rats weight and the swimming exhaustive time decreased obviously(p<0.05). 2. Spatial learning and memory ability: compared with TC group, the CSD group and SKF group rats latency decreased obviously(p<0.05), but compared with CSD group, the latency of SKF group rats have improved(p<0.05).3. Receptor and transcription factors: compared with TC gro up, the CSD group and SKF group rats gene and protein expression of NMDAR1 、 CREB decreased obviously(p<0.05). Compared with CSD group, the SKF group gene and protein expression of CREB improved significantly(p<0.05). 4. PKA signaling pathway: compared with TC group, the CSD group and SKF group rats gene expression of Adcy5, Prkaca and Darpp32 decreased obviously(p<0.05), and the protein expression of PKAcα and its phosphorylation were significantly reduced(p<0.05). Compared with CSD group, the SKF group gene expression of Prkaca and Darpp32 improved significantly(p<0.05), the protein expression of PKAcα and its phosphorylation improved significantly(p<0.05). 5. MAPK signaling pathway: compared with TC group, the CSD group rats gene expression of Rap1 a 、 ERK1 and ERK2 decreased obviously(p<0.05), the SKF group rats gene expressi on of ERK2 decreased obviously too(p<0.05), and the protein expression of p-ERK1/2 was significantly reduced(p<0.05). Compared with CSD group, the SKF group gene expression of Rap1a、 Rap1 b and ERK1 improved significantly(p<0.05). 6. Phosphoinositide signaling pathway: compared with TC group, the CSD group rats gene expression of PLCβ1 、 Ca MK Ⅱ a and Ca MK Ⅳdecreased obviously(p<0.05), the SKF group rats gene expression of PLCβ1 and Ca MKⅡa decreased obviously too(p<0.05), and the protein expression of PLCβ1 and Ca MKⅣ were significantly reduced(p<0.05). Compared with CSD group, the SKF group gene expression of Ca MKⅣ improved significantly(p<0.05), the protein expression of p-Ca MK Ⅳ improved significantly(p<0.05).Conclusion: 1. CSD has hurt the ability of l earning and memory in rats, the reason maybe is CSD has serious damaged D 1 receptors 3 related signaling pathways in hippocampus. 2. SKF38393 can improv e the injury caused by CSD, the reason maybe is SKF38393 has improved D1 receptors related signaling pat hways in hippocampus. This adjustment process is mainly conducted by PKA pathways and phosphoinositide pathway. 3. p-Ca MK Ⅳ and pPKAcα may be plays an important role in theregulation of SKF38393 during in the CSD. |
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