ABSTRACT
Objective To investigate the behavioral characteristics of circadian rhythm disturbance in 3xTg-AD mice.Methods The free-running period,average activity per hour,total amount of exercise and circadian amplitude were examined with voluntary wheel-running test in 3-to 9-month-old C57BL/6 and 3xTg-AD mice under 12 h light/12 h dark cycle and constant darkness environment.Results In constant darkness environment,the free-running period in 3-month-old 3xTg-AD mice was (23.2±0.4) h,and shorter than the period((23.5±0.2) h) in C57BL/6 mice.In 6-and 9-month-old 3xTg-AD mice,activity pattern was disorganized,without clear boundary between activity and rest phase.The free-running period was unavailable.The circadian amplitude and total exercise amount were(40.6± 11.5) counts/5 min and(2.6±0.1) × 104 counts/d,(37.0±20.8) counts/5 min and(2.3±0.4) × 104 counts/d,(29.3± 11.0) counts/5 min and(1.6± 0.9) × 104 counts/d in 3-,6-and 9-month-old 3xTg-AD mice,respectively,which was significantly lower than that in age-matched C57BL/6 mice.In 12 h light/12 h dark cycle,the circadian amplitude and total exercise amount of 3-,6-and 9-month-old 3xTg-AD mice were (87.0 ± 37.8) counts/5 min and (2.2 ± 0.8) × 104 counts/d,(25.9± 6.3) counts/5 min and (1.1 ± 0.2) × 104 counts/d,(14.3 ± 5.7) counts/5 min and (0.6 ± 0.3)× 104 counts/d respectively,and with a significant decrease from the age of 6 months.Meanwhile,the locomotor activity decreased at night and increased during the day.Conclusion The endogenous circadian rhythm disturbance emerges in 3xTg-AD mice at 3-month-old,while the exogenous circadian rhythm disorder appears at 6-month-old;the degree of disorder in circadian rhythm is gradually aggravated with the increase of age in of the AD mice.
ABSTRACT
Objective To investigate the effect of Shenfu injection on the expressions of endoplasmic reticulum stress-related factors oxygen-regulated protein 150 (ORP150),X-box binding protein 1 (XBP1),and C/EBP homologous protein (CHOP) mRNAs in cerebral cortical neurons after hypoxic-ischemic brain damage (HIBD) in neonatal rats.Methods The 7 day-newborn Sprague-Dawley rats were randomly divided into sham operation,normal saline and Shenfu treatment (Shenfu injection,10 ml/kg per day,peritoneal injection,for 3 days) groups.They were redivided into 3 h,6 h,12 h,24 h,3 d and 7 d subgroups at different time points after modeling (n =8 in each group).A HIBD model of the neonatal rats was induced.Reverse transcription-polymerase chain reaction was used to detect the expressions of ORP150,XBP1,and CHOP mRNAs in rat cerebral cortex.Results The expressions of ORP150,XBP1 and CHOP mRNAs of the sham operation group was very week.The expressions of ORP150,XBP1 and CHOP mRNAs in the normal saline group and the Shenfu treatment group were significantly upregulated compared to those in the sham operation group at 3 h after modeling (all P ＜0.05); the expressions of XBP1 and CHOP mRNAs reached the peak at 6 and 12 h,respectively.Then they decreased mildly and closed to the level in the sham operation group at day 7.The expressions of XBP1 and CHOP mRNAs in the Shenfu treatment group at 12,24 h and day 3 after modeling were significantly lower than those in the normal saline group (all P ＜0.05).The XBP1 mRNA expression was significantly positively correlated with the CHOP mRNA expression in the normal saline group (r =0.649,P ＜0.05).Conclusions HIBD in neonatal rats induces endoplasmic reticulum stress response.ORP150,XBP1 and CHOP may be involved in the delayed neuronal damage process after HIBD in neonatal rats.Shenfu injection downregulates the expression of XBP1 and CHOP mRNAs and inhibits endoplasmic reticulum stress response.