Overexpression of serotonin receptor 5b expression rescues neuronal and behavioral deficits in a mouse model of Kabuki syndrome
Overexpression of serotonin receptor 5b expression rescues neuronal and behavioral deficits in a mouse model of Kabuki syndrome
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血清素受体 5b 的过度表达可挽救歌舞伎综合症小鼠模型的神经元和行为缺陷
DOI：
10.1016/j.ibror.2020.07.005
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发表时间：
2020-07
期刊：
影响因子：
--
通讯作者：
Liu Chang-Mei
中科院分区：
文献类型：
--
作者：
Tang Gang-Bin;Mi Ting-Wei;Sun Man-Lian;Xu Ya-Jie;Yang Shu-Guang;Du Hong-Zhen;Saijilafu;Gao Jun;Liu Chang-Mei
5-羟色胺受体5 B（5-HT 5 B）是编码G蛋白偶联受体（GPCR）的基因，其在几种神经发育障碍中起关键作用。我们的前期研究表明，赖氨酸（K）特异性脱甲基酶6A（Kdm 6a，也称为Utx）条件性敲除（cKO）诱导的小鼠海马5-HT 5 B的破坏与Kabuki综合征（KS）的认知障碍相关，KS是一种与多种先天性和发育异常，尤其是神经行为异常相关的罕见疾病。在这里，我们表明，Utx敲除（KO）在培养的海马神经元导致受损的神经元兴奋性和钙稳态。此外，我们发现5-HT 5 B过表达逆转了培养的UtxKO海马神经元和海马切片中神经元兴奋性、细胞内钙稳态和长时程增强（LTP）的失调。更重要的是，5-HT 5 B在Utx cKO小鼠中的过表达导致异常焦虑样行为和受损的空间记忆能力的逆转。因此，我们的研究结果表明，5-HT 5 B，作为Utx的下游目标，功能调节电生理结果，从而影响KS小鼠模型的行为活动。
5-hydroxytryptamine receptor 5B (5-HT5B) is a gene coding for a G protein-coupled receptor (GPCR) that plays key roles in several neurodevelopmental disorders. Our previous study showed that disruption of 5-HT5B induced by lysine (K)-specific demethylase 6A (Kdm6a, also known asUtx) conditional knockout (cKO) in mouse hippocampus was associated with cognition deficits underlying intellectual disability in Kabuki syndrome (KS), a rare disease associated with multiple congenital and developmental abnormalities, especially neurobehavioral features. Here we show thatUtxknockout (KO) in cultured hippocampal neurons leads to impaired neuronal excitability and calcium homeostasis. In addition, we show that 5-HT5B overexpression reverses dysregulation of neuronal excitability, intracellular calcium homeostasis, and long-term potentiation (LTP) in culturedUtxKO hippocampal neurons and hippocampal slices. More importantly, overexpression of 5-HT5B in Utx cKO mice results in reversal of abnormal anxiety-like behaviors and impaired spatial memory ability. Our findings therefore indicate that 5-HT5B, as a downstream target of Utx, functions to modulate electrophysiological outcomes, thereby affecting behavioral activities in KS mouse models.
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组蛋白 H3K27 去甲基化酶 UTX 调节小鼠突触可塑性和认知行为
影响因子：
4.8
作者：
Tang GB;Zeng YQ;Liu PP;Mi TW;Zhang SF;Dai SK;Tang QY;Yang L;Xu YJ;Yan HL;Du HZ;Teng ZQ;Zhou FQ;Liu CM
通讯作者：
Liu CM
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
3.4
作者：
Bickmeyer, U;Heine, M;Richter, DW
通讯作者：
Richter, DW
影响因子：
3.5
作者：
K. Tada;K. Kasamo;Tadashi Suzuki;Y. Matsuzaki;T. Kojima
通讯作者：
K. Tada;K. Kasamo;Tadashi Suzuki;Y. Matsuzaki;T. Kojima
影响因子：
5
作者：
COSTALL, B;DOMENEY, AM;EGLEN, RM
通讯作者：
EGLEN, RM