Hippocampal transplants of fetal GABAergic progenitors regulate adult neurogenesis in mice with temporal lobe epilepsy.
Hippocampal transplants of fetal GABAergic progenitors regulate adult neurogenesis in mice with temporal lobe epilepsy.
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胎儿GABA能祖细胞的海马移植可调节颞叶癫痫的小鼠成人神经发生。
DOI：
10.1016/j.nbd.2022.105879
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发表时间：
2022-11
影响因子：
6.1
通讯作者：
Naegele, Janice R.
中科院分区：
文献类型：
--
作者：
Arshad, Muhammad N.;Oppenheimer, Simon;Jeong, Jaye;Buyukdemirtas, Bilge;Naegele, Janice R.
GABA能中间神经元在调节海马齿状回（DG）内的成年神经发生中发挥作用。神经发生发生在DG的亚颗粒区（SGZ）的干细胞龛内。在这个生态位中，神经祖细胞群产生颗粒细胞，这些颗粒细胞径向迁移到DG的颗粒细胞层（GCL）中。颞叶癫痫（TLE）中神经发生的改变与新生神经元增殖的短暂增加和1型祖细胞的异常倒置有关，导致3型祖细胞异位迁移到DG门。这些异位细胞在门部成熟为颗粒细胞，变得过度兴奋并促进自发性复发性癫痫发作的发展。为了测试DG中GABA能细胞的移植物是否恢复突触抑制，先前的工作集中于将GABA能祖细胞移植到DG的门部。这种基于细胞的治疗方法被证明可以通过改善匹鲁卡品诱导的TLE小鼠的自发性癫痫发作来改变疾病表型。先前的光遗传学和免疫组织化学研究表明，移植的GABA能中间神经元通过与成人出生的颗粒细胞建立抑制性突触接触来增加突触抑制水平，这与观察到的癫痫发作抑制一致。GABA能祖细胞移植到DG是否能改善TLE引起的成人神经发生的潜在异常尚不清楚。作为解决这一问题的第一步，我们在未处理的非癫痫小鼠中使用细胞类型特异性分子标记物比较了GABA能祖细胞移植对干细胞龛中1型、2型和3型祖细胞的影响。祖细胞移植增加了DG中的GABA能中间神经元，并导致2型祖细胞的显著减少和3型祖细胞的伴随增加。接下来，我们比较了GABA能中间神经元移植在癫痫小鼠中的作用。GABA能祖细胞的移植导致倒置的1型、2型和门部异位的3型细胞减少，伴随着3型祖细胞向GCL的径向迁移增加。因此，在毛果芸香碱诱导的TLE小鼠中，GABA中间神经元的肝门移植可能逆转成人神经发生的异常模式，这可能改善癫痫发作的结果。
GABAergic interneurons play a role in regulating adult neurogenesis within the dentate gyrus (DG) of the hippocampus. Neurogenesis occurs within a stem cell niche in the subgranular zone (SGZ) of the DG. In this niche, populations of neural progenitors give rise to granule cells that migrate radially into the granule cell layer (GCL) of the DG. Altered neurogenesis in temporal lobe epilepsy (TLE) is linked to a transient increase in the proliferation of new neurons and the abnormal inversion of Type 1 progenitors, resulting in ectopic migration of Type 3 progenitors into the hilus of the DG. These ectopic cells mature into granule cells in the hilus that become hyperexcitable and contribute to the development of spontaneous recurrent seizures. To test whether grafts of GABAergic cells in the DG restore synaptic inhibition, prior work focused on transplanting GABAergic progenitors into the hilus of the DG. This cell-based therapeutic approach was shown to alter the disease phenotype by ameliorating spontaneous seizures in mice with pilocarpine-induced TLE. Prior optogenetic and immunohistochemical studies demonstrated that the transplanted GABAergic interneurons increased levels of synaptic inhibition by establishing inhibitory synaptic contacts with adult-born granule cells, consistent with the observed suppression of seizures. Whether GABAergic progenitor transplantation into the DG ameliorates underlying abnormalities in adult neurogenesis caused by TLE is not known. As a first step to address this question, we compared the effects of GABAergic progenitor transplantation on Type 1, Type 2, and Type 3 progenitors in the stem cell niche using cell type-specific molecular markers in naïve, non-epileptic mice. The progenitor transplantation increased GABAergic interneurons in the DG and led to a significant reduction in Type 2 progenitors and a concomitant increase in Type 3 progenitors. Next, we compared the effects of GABAergic interneuron transplantation in epileptic mice. Transplantation of GABAergic progenitors resulted in reductions in inverted Type 1, Type 2, and hilar ectopic Type 3 cells, concomitant with an increase in the radial migration of Type 3 progenitors into the GCL. Thus, in mice with Pilocarpine induced TLE, hilar transplants of GABA interneurons may reverse abnormal patterns of adult neurogenesis, an outcome that may ameliorate seizures.
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DOI：
10.1007/978-1-0716-0830-2_15
发表时间：
2021-01-01
期刊：
CHANNELRHODOPSIN
影响因子：
--
作者：
Arshad, Muhammad N.;Aaron, Gloster B.;Naegele, Janice R.
通讯作者：
Naegele, Janice R.
影响因子：
3.6
作者：
Catavero C;Bao H;Song J
通讯作者：
Song J
影响因子：
2.5
作者：
Dayer, AG;Ford, AA;Cameron, HA
通讯作者：
Cameron, HA
DOI：
10.3233/bpl-170056
发表时间：
2018-08-10
期刊：
Brain plasticity (Amsterdam, Netherlands)
影响因子：
--
作者：
Danzer SC
通讯作者：
Danzer SC
影响因子：
3.5
作者：
Dieni CV;Chancey JH;Overstreet-Wadiche LS
通讯作者：
Overstreet-Wadiche LS