Genetic suppression of agrin reduces mania‐like behavior in Na+, K+‐ATPase α3 mutant mice
Genetic suppression of agrin reduces mania‐like behavior in Na+, K+‐ATPase α3 mutant mice
复制标题
Na+、K+-ATPase α3 突变小鼠的集聚蛋白躁狂样行为的基因抑制
DOI：
10.1111/j.1601-183x.2012.00800.x
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发表时间：
2012
期刊：
影响因子：
3.5
通讯作者：
J. Roder
中科院分区：
文献类型：
--
作者：
G. Kirshenbaum;S. Clapcote;J. Petersen;B. Vilsen;M. Ralph;J. Roder
神经元特异性Na+，K+ - atp酶α3亚型失活突变杂合的梅什金小鼠表现出类似躁狂的行为，包括异常的内源性昼夜节律周期。Agrin是一种蛋白多糖，被认为是突触的调节因子，可以抑制Na+，K+‐atp酶α3的活性。我们研究了是否可以通过基因敲除减少agrin的表达来挽救梅什金小鼠的躁狂症相关行为。抑制agin减少了过度活动和孔板探索，恢复了焦虑样行为（或减少了冒险行为），改善了脉冲前抑制，缩短了昼夜节律周期。因此，agrin对于调节躁狂样行为和昼夜节律是重要的。在Myshkin小鼠中，抑制agrin使脑内Na+，K+‐atp酶活性增加了11±4%，而在没有Myshkin突变的小鼠中，抑制agrin对Na+，K+‐atp酶活性没有影响。这些结果介绍了agin作为治疗躁狂症和其他与Na+，K+‐atp酶活性降低和神经元高兴奋性相关的神经系统疾病的潜在治疗靶点。
Myshkin mice heterozygous for an inactivating mutation in the neuron‐specific Na+,K+‐ATPase α3 isoform show behavior analogous to mania, including an abnormal endogenous circadian period. Agrin is a proteoglycan implicated as a regulator of synapses that has been proposed to inhibit activity of Na+,K+‐ATPase α3. We examined whether the mania‐related behavior of Myshkin mice could be rescued by a reduction in the expression of agrin through genetic knockout. The suppression of agrin reduced hyperambulation and holeboard exploration, restored anxiety‐like behavior (or reduced risk‐taking behavior), improved prepulse inhibition and shortened the circadian period. Hence, agrin is important for regulating mania‐like behavior and circadian rhythms. In Myshkin mice, the suppression of agrin increased brain Na+,K+‐ATPase activity by 11 ± 4%, whereas no effect on Na+,K+‐ATPase activity was detected when agrin was suppressed in mice without the Myshkin mutation. These results introduce agrin as a potential therapeutic target for the treatment of mania and other neurological disorders associated with reduced Na+,K+‐ATPase activity and neuronal hyperexcitability.
与正常对照相比，躁狂双相情感障碍患者的内源性地高辛样免疫反应因子（DLIF）血清浓度降低。
影响因子：
6.6
作者：
Grider,G;El-Mallakh,RS;Huff,MO;Buss,TJ;Miller,J;ValdesJr,R
通讯作者：
ValdesJr,R
概念化冲动性和风险服用双相情感障碍：酗酒史的重要性。
影响因子：
5.4
作者：
Kathleen Holmes M;Bearden CE;Barguil M;Fonseca M;Serap Monkul E;Nery FG;Soares JC;Mintz J;Glahn DC
通讯作者：
Glahn DC
DOI：
10.1073/pnas.0503584102
发表时间：
2005-06-28
影响因子：
11.1
作者：
McClung, CA;Sidiropoulou, K;Nestler, EJ
通讯作者：
Nestler, EJ