Brouillard Charly, Carrive Pascal, Sévoz-Couche Caroline
Sorbonne Université, INSERM, UMRS1158 Neurophysiologie Respiratoire Expérimentale et Clinique, F-75005, Paris, France.
Blood Pressure, Brain and Behavior Laboratory, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
Neurobiol Stress. 2020 Aug 3;13:100245. doi: 10.1016/j.ynstr.2020.100245. eCollection 2020 Nov.
Previously, a sub-population of defeated anesthetized rats (Dlow) was characterized by persistent low blood levels of brain-derived neurotrophic factor (BDNF) at day 29 and autonomic alteration at day 30 after social challenge, while the other population (Dhigh) was similar to non-defeated (ND) animals. The aims of this study were to determine the time-course of autonomic dysfunction in awake animals, and whether Dhigh and/or Dlow were vulnerable to cardiac events. Defeated animals were exposed to four daily episodes of social defeats from day 1 to day 4. At day 30, anesthetized Dlow displayed decreased experimental and spontaneous reflex responses reflecting lower parasympathetic efficiency. In addition, Dlow but not Dhigh were characterized by left ventricular hypertrophy at day 30. Telemetric recordings revealed that Dlow had increased low frequency-to-high frequency ratio (LF/HF) and diastolic (DBP) and systolic (SBP) blood pressure, associated with decreased HF and spontaneous baroreflex responses (BRS) from day 3 to day 29. LF/HF, DBP and SBP recovered at day 5, and HF and BRS recovered at day 15 in Dhigh. Ventricular premature beats (VPBs) occurred in Dlow and Dhigh animals from day 5. Time course of VBP fluctuations in Dhigh mirrored that of HF and BRS, but not that of LF/HF, DBP and SBP. These results suggest that a psychosocial stress associated to low serum BDNF levels can lead to vulnerability to persistent autonomic dysfunction, cardiac hypertrophy and ventricular ectopic beats. The parasympathetic recovery seen in Dhigh may provide protection against cardiac events in this population.
此前,在遭受社交挑战后第29天,被击败的麻醉大鼠亚群(Dlow)的特征是脑源性神经营养因子(BDNF)的血液水平持续偏低,在第30天出现自主神经改变,而另一亚群(Dhigh)与未被击败(ND)的动物相似。本研究的目的是确定清醒动物自主神经功能障碍的时间进程,以及Dhigh和/或Dlow是否易发生心脏事件。从第1天到第4天,每天让被击败的动物经历4次社交失败。在第30天,麻醉状态下的Dlow表现出实验性和自发性反射反应降低,反映出副交感神经效率较低。此外,在第30天,Dlow而非Dhigh的特征是左心室肥大。遥测记录显示,从第3天到第29天,Dlow的低频与高频比值(LF/HF)、舒张压(DBP)和收缩压(SBP)升高,同时高频和自发性压力反射反应(BRS)降低。在Dhigh中,LF/HF、DBP和SBP在第5天恢复,高频和BRS在第15天恢复。从第5天起,Dlow和Dhigh动物均出现室性早搏(VPB)。Dhigh中VPB波动的时间进程与高频和BRS的相似,但与LF/HF、DBP和SBP不同。这些结果表明,与血清BDNF水平低相关的心理社会压力可导致易患持续性自主神经功能障碍、心脏肥大和室性异位搏动。Dhigh中观察到的副交感神经恢复可能为该亚群提供对心脏事件的保护。