Leptin counteracts the hypoxia-induced inhibition of spontaneously firing hippocampal neurons: a microelectrode array study.
Leptin counteracts the hypoxia-induced inhibition of spontaneously firing hippocampal neurons: a microelectrode array study.
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DOI：
10.1371/journal.pone.0041530
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Carabelli V
中科院分区：
文献类型：
--
作者：
Gavello D;Rojo-Ruiz J;Marcantoni A;Franchino C;Carbone E;Carabelli V
除了调节能量平衡和减轻体重外，脂肪因子瘦素最近被证明具有神经保护和抗凋亡作用，通过促进兴奋毒性和氧化损伤后的神经元存活。在此，我们研究了小鼠海马神经元的放电特性以及瘦素预处理对缺氧损伤（2小时，3% O2）的影响。实验采用微电极阵列（MEA）技术，在体外培养11 ~ 18 d （DIV）监测海马神经元活动。在常压条件下，海马神经元自发放电，要么以普遍孤立和随机分布的尖峰放电（11 DIV），要么以同步脉冲放电（18 DIV）为特征。缺氧严重损害了海马神经元的自发活动，在11和18 DIV时，海马神经元的放电频率分别降低了54%和69%，并使海马神经元的放电活动同步。50nm瘦素预处理降低了常氧神经元的放电频率，并通过限制放电频率降低（两个年龄）或将其增加到126%（年轻神经元）来对比缺氧诱导的抑郁作用。为了了解瘦素是否通过激活大电导Ca2+激活的K+通道（BK）来发挥作用，如在大鼠海马神经元上所示，我们使用了BK通道阻滞剂paxilline（1µM）。我们的数据显示，paxilline逆转了瘦素对常氧和缺氧神经元的作用，这表明脂肪因子通过激活小鼠海马神经元中的BK通道来抵消缺氧。
Besides regulating energy balance and reducing body-weight, the adipokine leptin has been recently shown to be neuroprotective and antiapoptotic by promoting neuronal survival after excitotoxic and oxidative insults. Here, we investigated the firing properties of mouse hippocampal neurons and the effects of leptin pretreatment on hypoxic damage (2 hours, 3% O2). Experiments were carried out by means of the microelectrode array (MEA) technology, monitoring hippocampal neurons activity from 11 to 18 days in vitro (DIV). Under normoxic conditions, hippocampal neurons were spontaneously firing, either with prevailing isolated and randomly distributed spikes (11 DIV), or with patterns characterized by synchronized bursts (18 DIV). Exposure to hypoxia severely impaired the spontaneous activity of hippocampal neurons, reducing their firing frequency by 54% and 69%, at 11 and 18 DIV respectively, and synchronized their firing activity. Pretreatment with 50 nM leptin reduced the firing frequency of normoxic neurons and contrasted the hypoxia-induced depressive action, either by limiting the firing frequency reduction (at both ages) or by increasing it to 126% (in younger neurons). In order to find out whether leptin exerts its effect by activating large conductance Ca2+-activated K+ channels (BK), as shown on rat hippocampal neurons, we applied the BK channel blocker paxilline (1 µM). Our data show that paxilline reversed the effects of leptin, both on normoxic and hypoxic neurons, suggesting that the adipokine counteracts hypoxia through BK channels activation in mouse hippocampal neurons.
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影响因子：
120.7
作者：
Lieb, Wolfgang;Beiser, Alexa S.;Vasan, Ramachandran S.;Tan, Zaldy S.;Au, Rhoda;Harris, Tamara B.;Roubenoff, Ronenn;Auerbach, Sanford;DeCarli, Charles;Wolf, Philip A.;Seshadri, Sudha
通讯作者：
Seshadri, Sudha
影响因子：
5.3
作者：
Hu, H;Shao, LR;Storm, JF
通讯作者：
Storm, JF
影响因子：
3.2
作者：
Galan, Roberto Fernandez;Dick, Thomas E.;Baekey, David M.
通讯作者：
Baekey, David M.
DOI：
10.3109/14767058.2011.565834
发表时间：
2012-02-01
影响因子：
1.8
作者：
Kumral, Abdullah;Yesilirmak, Didem Cemile;Ozkan, Hasan
通讯作者：
Ozkan, Hasan
DOI：
10.1016/j.bbrc.2011.09.050
发表时间：
2011-10-14
影响因子：
3.1
作者：
Greco, Steven J.;Hamzelou, Ashkan;Johnston, Jane M.;Smith, Mark A.;Ashford, J. Wesson;Tezapsidis, Nikolaos
通讯作者：
Tezapsidis, Nikolaos