Disordered autonomic function during exposure to moderate heat or exercise in a mouse model of Dravet syndrome.
Disordered autonomic function during exposure to moderate heat or exercise in a mouse model of Dravet syndrome.
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DOI：
10.1016/j.nbd.2020.105154
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发表时间：
2021-01
影响因子：
6.1
通讯作者：
Kalume F
中科院分区：
文献类型：
--
作者：
Sahai N;Bard AM;Devinsky O;Kalume F
在Dravet综合征（DS）小鼠模型中，研究对适度升高的环境温度或适度体育锻炼的核心体温、心率（HR）和呼吸频率（BR）的自主调节。我们研究了视频脑电图，心电图，呼吸和温度与全球杂合子Scn1a基因敲除（KO）（DS小鼠），interneuron特异性Scn1a基因敲除，野生型（WT）小鼠在暴露于环境温度升高和中度跑步机运动。WT和DS小鼠的核心体温在基线期间相似。热暴露15分钟后，DS小鼠的峰值低于WT小鼠。在接下来的几分钟的热暴露中，WT小鼠的体温缓慢恢复至接近基线水平，而DS小鼠的体温仍然升高。敲除GABA能神经元中的Scn1a可导致小鼠出现类似的体温调节缺陷。在运动期间，DS小鼠的HR增加不如WT小鼠显著。运动后，DS的HR明显受到抑制。DS小鼠的心率变异性（HRV）在基线期低于WT小鼠，而在运动恢复期高于WT小鼠。我们发现了新的异常，扩大频谱发作间期，发作，发作后自主神经失调DS小鼠。在轻度热应激期间，DS小鼠的体温校正明显减弱，心率和呼吸速率的抑制程度低于WT小鼠。在GABA能神经元中选择性KO Scn1A的小鼠中观察到这些效应。在运动应激期间，与对照组相比，DS小鼠的HR增加减少，随后在恢复期间HR抑制和HRV升高加剧。这些研究结果表明，不同的环境应激源可以揭示不同的自主神经紊乱在DS小鼠。中间神经元在体温调节中起重要作用。了解DS中自主神经紊乱的频谱和机制可能有助于制定更有效的策略来预防癫痫发作和SUDEP。
To examine autonomic regulation of core body temperature, heart rate (HR), and breathing rate (BR) in response to moderately elevated ambient temperature or moderate physical exercise in a mouse model of Dravet syndrome (DS). We studied video-EEG, ECG, respiration, and temperature in mice with global heterozygous Scn1a knockout (KO) (DS mice), interneuron specific Scn1a KO, and wildtype (WT) mice during exposure to increased environmental temperature and moderate treadmill exercise. Core body temperatures of WT and DS mice were similar during baseline. After 15 mins of heat exposure, the peak value was lower in DS than WT mice. In the following mins of heat exposure, the temperature slowly returned close to baseline level in WT, whereas it remained elevated in DS mice. KO of Scn1a in GABAergic neurons caused similar thermoregulatory deficits in mice. During exercise, the HR increase was less prominent in DS than WT mice. After exercise, the HR was significantly more suppressed in DS. The heart rate variability (HRV) was lower in DS than WT mice during baseline and higher in DS during exercise-recovery periods. We found novel abnormalities that expand the spectrum of interictal, ictal, and postictal autonomic dysregulation in DS mice. During mild heat stress, there was a significantly blunted correction of body temperature, and a less suppression of both HR and respiration rate in DS than WT mice. These effects were seen in mice with selective KO of Scn1A in GABAergic neurons. During exercise stress, there was diminished increase in HR, followed by an exaggerated HR suppression and HRV elevation during recovery in DS mice compared to controls. These findings suggest that different environmental stressors can uncover distinct autonomic disturbances in DS mice. Interneurons play an important role in thermoregulation. Understanding the spectrum and mechanisms of autonomic disorders in DS may help develop more effective strategies to prevent seizures and SUDEP.
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影响因子：
3.7
作者：
Auerbach DS;Jones J;Clawson BC;Offord J;Lenk GM;Ogiwara I;Yamakawa K;Meisler MH;Parent JM;Isom LL
通讯作者：
Isom LL
影响因子：
2.2
作者：
Cooper, Monica S.;Mcintosh, Anne;Scheffer, Ingrid E.
通讯作者：
Scheffer, Ingrid E.
DOI：
10.1590/s0100-879x2002000800018
发表时间：
2002-08-01
影响因子：
2.3
作者：
Javorka, M.;Zila, I.;Javorka, K.
通讯作者：
Javorka, K.
影响因子：
37.8
作者：
ALGRA, A;TIJSSEN, JGP;LUBSEN, J
通讯作者：
LUBSEN, J
影响因子：
1.3
作者：
Dogan, Sait M.;Yidirim, Nesligul;Cam, Fatih
通讯作者：
Cam, Fatih