TRPM2 channel activation following in vitro ischemia contributes to male hippocampal cell death.
TRPM2 channel activation following in vitro ischemia contributes to male hippocampal cell death.
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DOI：
10.1016/j.neulet.2012.09.044
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发表时间：
2012-11-14
影响因子：
2.5
通讯作者：
Herson PS
中科院分区：
文献类型：
--
作者：
Verma S;Quillinan N;Yang YF;Nakayama S;Cheng J;Kelley MH;Herson PS
海马CA1区神经元对缺血损伤特别敏感，例如在心脏骤停和心肺复苏后经历的损伤。近年来，瞬时受体电位M2(TRPM2)通道被认为是缺血性损伤的介质。我们先前证明，针对TRPM2通道的神经保护策略在体外和体内都优先保护雄性大脑皮层神经元免受缺血损伤。确定TRPM2在海马神经元缺血性损伤中的作用非常重要，因为这类神经元对缺血性损伤特别敏感，是治疗的靶点。在这里，我们报告了在体外缺血后，使用TRPM2抑制剂或下调TRPM2表达，显著减少了雄性海马神经元的神经细胞死亡。性别分层培养的电生理学特征表明，在基础条件下，男性和女性海马神经元中功能TRPM2通道的表达水平相似。相反，在体外缺血后再灌流期间的记录显示，TRPM2通道只在雄性神经元中激活，导致快速而完全的去极化。这些发现为TRPM2作为男性脑缺血保护靶点提供了强有力的证据，并有助于确定一种在男性和女性神经元中差异参与的分子细胞死亡途径。
Hippocampal CA1 neurons are particularly sensitive to ischemic damage, such as experienced following cardiac arrest and cardiopulmonary resuscitation. In recent years transient receptor potential M2 (TRPM2) channels have been identified as mediators of ischemic damage. We previously demonstrated that neuroprotective strategies targeting TRPM2 channels preferentially protect male cortical neurons from ischemic injury both in vitro and in vivo. It is important to determine the role of TRPM2 in ischemic injury of hippocampal neurons as this population of neurons are particularly sensitive to ischemic injury and are therapeutic targets. Here we report significantly decreased neuronal cell death following in vitro ischemia preferentially in male hippocampal neurons using TRPM2 inhibitors or knockdown of TRPM2 expression. Electrophysiological characterization of sex-stratified cultures shows similar levels of functional TRPM2 channel expression in male and female hippocampal neurons under basal conditions. In contrast, recordings made during reperfusion following in vitro ischemia revealed that TRPM2 channels are activated only in male neurons, resulting in rapid and complete depolarization. These findings provide strong evidence for TRPM2 as a target for protection against cerebral ischemia in male brain and helps define a molecular cell death pathway that is differentially engaged in male and female neurons.
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影响因子：
37.8
作者：
Roger VL;Go AS;Lloyd-Jones DM;Benjamin EJ;Berry JD;Borden WB;Bravata DM;Dai S;Ford ES;Fox CS;Fullerton HJ;Gillespie C;Hailpern SM;Heit JA;Howard VJ;Kissela BM;Kittner SJ;Lackland DT;Lichtman JH;Lisabeth LD;Makuc DM;Marcus GM;Marelli A;Matchar DB;Moy CS;Mozaffarian D;Mussolino ME;Nichol G;Paynter NP;Soliman EZ;Sorlie PD;Sotoodehnia N;Turan TN;Virani SS;Wong ND;Woo D;Turner MB;American Heart Association Statistics Committee and Stroke Statistics Subcommittee
通讯作者：
American Heart Association Statistics Committee and Stroke Statistics Subcommittee
影响因子：
12.7
作者：
HORN, M;SCHLOTE, W
通讯作者：
SCHLOTE, W
影响因子：
16
作者：
Hara, Y;Wakamori, M;Mori, Y
通讯作者：
Mori, Y
影响因子：
5.5
作者：
Herson, PS;Ashford, MLJ
通讯作者：
Ashford, MLJ
影响因子：
5.5
作者：
Smith, MA;Herson, PS;Ashford, MLJ
通讯作者：
Ashford, MLJ