Changes Of Pineal Per1 And Bmal1 Gene Expression And Plasma Melatonin Concentration In HIBD Neonatal Rat

Background Neonatal hypoxic-ischemic brain damage(HIBD) is induced by perinatal oxygen deficiency. The survivals may show disorders of psychomotor development and sleep-waking cycle disorder. Circadian rhythm is known as the initiative adaptation of the organism to the rhythmic environment, which can ensure proper temporal organization of physiological,biochemistry and locomotor activity,and is related to the pathologic processes of many diseases. The mammalian pineal gland, not only acts as a neuroendocrine organ, like an central circadian oscillator, but also presents the effect of a peripheral circadian oscillator, so it is considered as a neuroendocrine translator. The pineal gland regulates the circadian rhythm by synthesizing and secreting melatonin, which reaches to the target organs of the body through the circulation system and causes 24h phase-shift. The basic circadian structure is the intracellular circadian oscillator, which is made up of core clock genes. These genes and their expression products form interlocked feedback loops of transcription/translation, two significant genes among which are Per1 and Bmal1.However,studies about circadian disturbance in HIBD are so few that the mechanism of circadian disorders in HIBD is indefinite. Objective To explore the effects of clock genes on circadian disorder in hypoxic-ischemic brain damage(HIBD) by studying the expression of Per1 mRNA,Bmal1 mRNA in neonatal rat pineal gland and plasma melatonin.Methods 7-day-old Sprague-Dawley (SD) rats were randomly divided into 2 groups (36 pups each). HIBD models were set up according to modified Levine euthanized 0,2,12,24,36,48 hours afterwards. Semi-quantitative Reverse Transcriptase Polymerase Chain Reaction(RT-PCR)analysis was used to measure the expression profiles of Per1 and Bmal1 in pineal gland and Radioimmunoassay(RIA) for plasma melatonin(Mel) concentrations, respectively.Results 1,The amount of per1 mRNA 24h after HIBD began to decline, and that of 36h and 48h displayed significantly lower than the control groups, respectively(p<0.01).2,Comparing with each corresponding control group,the expression of Bmal1 mRNA in HIBD group increased at 36 hour(sp<0.05), decreased at 48 hour(sp<0.05),and there was no difference between 0 hour,2 hours and 12 hours (p>0.05).3,The plasma melatonin concentration began to decline 12h after HIBD, reached their minimi 24h after HIBD and returned to the normal levels at 48h after HIBD.4,The control groups'plasma melatonin concentration had no difference among each time (P>0.05).Conclusion HIBD indeed affects the expression of Per1 mRNA and Bmal1 mRNA level in the neonatal pineal gland and the melatonin concentration in the plasma. These results reveal the existence of changes of Per1 mRNA and Bmal1 mRNA expression patterns and melatonin concentration, suggest the presumed regulatory mechanism of circadian disorder in HIBD.