Altered synaptic properties during integration of adult-born hippocampal neurons following a seizure insult.
Altered synaptic properties during integration of adult-born hippocampal neurons following a seizure insult.
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癫痫发作后，成年海马神经元整合过程中突触性质的改变。
DOI：
10.1371/journal.pone.0035557
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Ekdahl CT
中科院分区：
文献类型：
--
作者：
Jackson J;Chugh D;Nilsson P;Wood J;Carlström K;Lindvall O;Ekdahl CT
病理条件影响成人大脑神经发生的几个阶段，包括增殖、存活、细胞命运、迁移和功能整合。在这里，我们探讨了病理环境如何调节异质传入突触输入，形成新形成的神经元的功能特性。我们分析了在电诱导部分癫痫持续状态（pSE）后形成的成体海马神经元中粘附分子和其他突触蛋白的表达。pSE后一周用gfp逆转录病毒载体标记新细胞。1周和3周后，树突棘和树突轴上出现突触蛋白，但pSE组与对照组之间无差异。相比之下，在6周时，我们发现树突棘减少，棘上支架蛋白PSD-95的表达减少，而主要位于兴奋性突触的粘附分子n-钙粘蛋白或神经胶质素-1的表达没有变化。此外，我们检测到SE后新生神经元中抑制支架蛋白gephyrin的表达增加，而成熟神经元中没有。然而，这种增加并没有伴随着GABA表达的差异，甚至在新生和成熟神经元中，粘附分子神经胶质素-2的表达都有区域特异性的减少。神经胶质素-2簇与突触前胆囊收缩素末端共定位，也减少。神经胶质素-4和甘氨酸受体的表达没有变化。突触后卟啉聚类增加，而gaba能输入或神经素-2和-4表达不增加，后者分别对GABAA和甘氨酸受体的聚类很重要，这可能意味着新生神经元特异性的抑制性连接增加但改变。这种变化是短暂的，在se后3个月，gephyrin和NL-2的表达均恢复正常。我们的研究结果表明，癫痫引起的脑病理改变了突触粘附分子和支架蛋白的亚细胞表达，特别是抑制性突触和兴奋性突触，这可能对成年出生的神经元的整合产生功能后果。
Pathological conditions affect several stages of neurogenesis in the adult brain, including proliferation, survival, cell fate, migration, and functional integration. Here we explored how a pathological environment modulates the heterogeneous afferent synaptic input that shapes the functional properties of newly formed neurons. We analyzed the expression of adhesion molecules and other synaptic proteins on adult-born hippocampal neurons formed after electrically-induced partial status epilepticus (pSE). New cells were labeled with a GFP-retroviral vector one week after pSE. One and three weeks thereafter, synaptic proteins were present on dendritic spines and shafts, but without differences between pSE and control group. In contrast, at six weeks, we found fewer dendritic spines and decreased expression of the scaffolding protein PSD-95 on spines, without changes in expression of the adhesion molecules N-cadherin or neuroligin-1, primarily located at excitatory synapses. Moreover, we detected an increased expression of the inhibitory scaffolding protein gephyrin in newborn but not mature neurons after SE. However, this increase was not accompanied by a difference in GABA expression, and there was even a region-specific decrease in the adhesion molecule neuroligin-2 expression, both in newborn and mature neurons. Neuroligin-2 clusters co-localized with presynaptic cholecystokinin terminals, which were also reduced. The expression of neuroligin-4 and glycine receptor was unchanged. Increased postsynaptic clustering of gephyrin, without an accompanying increase in GABAergic input or neuroligin-2 and -4 expression, the latter important for clustering of GABAA and glycine receptors, respectively, could imply an increased but altered inhibitory connectivity specific for newborn neurons. The changes were transient and expression of both gephyrin and NL-2 was normalized 3 months post-SE. Our findings indicate that seizure-induced brain pathology alters the sub-cellular expression of synaptic adhesion molecules and scaffolding proteins related to particularly inhibitory but also excitatory synapses, which may yield functional consequences for the integration of adult-born neurons.
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影响因子：
82.9
作者：
Eriksson, PS;Perfilieva, E;Gage, FH
通讯作者：
Gage, FH
影响因子：
3.7
作者：
Ali, Afia B.;Thomson, Alex M.
通讯作者：
Thomson, Alex M.
DOI：
10.1007/978-1-4419-1170-4_8
发表时间：
2010-01-01
期刊：
STRUCTURE AND FUNCTION OF THE NEURAL CELL ADHESION MOLECULE NCAM
影响因子：
--
作者：
Gascon, Eduardo;Vutskits, Laszlo;Kiss, Jozsef Zoltan
通讯作者：
Kiss, Jozsef Zoltan
DOI：
10.1073/pnas.1006946108
发表时间：
2011-02-15
影响因子：
11.1
作者：
Hoon, Mrinalini;Soykan, Tolga;Varoqueaux, Frederique
通讯作者：
Varoqueaux, Frederique
突触时的钙粘蛋白和Catenin：突触发生和突触可塑性中的作用。
影响因子：
15.9
作者：
Arikkath, Jyothi;Reichardt, Louis F.
通讯作者：
Reichardt, Louis F.