Consequences of NMDA receptor deficiency can be rescued in the adult brain.
Consequences of NMDA receptor deficiency can be rescued in the adult brain.
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NMDA受体缺乏症的后果可以在成人大脑中挽救。
DOI：
10.1038/s41380-020-00859-4
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发表时间：
2021-07
影响因子：
11
通讯作者：
Ramsey AJ
中科院分区：
文献类型：
--
作者：
Mielnik CA;Binko MA;Chen Y;Funk AJ;Johansson EM;Intson K;Sivananthan N;Islam R;Milenkovic M;Horsfall W;Ross RA;Groc L;Salahpour A;McCullumsmith RE;Tripathy S;Lambe EK;Ramsey AJ
N-甲基-D-天冬氨酸受体（NMDAR）是形成发育和成人大脑中活动依赖性连接所必需的。通过遗传或环境损伤受损的NMDAR信号传导导致一系列神经发育障碍，表现为智力残疾、癫痫、自闭症或精神分裂症。目前尚不清楚NMDAR功能障碍的发育影响是否可以通过成年期的干预措施来克服。这个问题对于由编码NMDAR亚基的GRIN基因突变和破坏NMDAR功能的更广泛突变引起的神经发育障碍至关重要。我们开发了一种小鼠模型，其中Grin 1的先天性功能丧失等位基因可以通过Cre重组酶的基因编辑恢复为野生型。在成年小鼠中拯救NMDAR产生了令人惊讶的认知功能的稳健改善，包括那些用当前药物治疗难治的认知功能。这些结果表明，NMDAR缺乏引起的神经发育障碍可以有效地治疗成人。
N-methyl-D-aspartate receptors (NMDARs) are required to shape activity-dependent connections in the developing and adult brain. Impaired NMDAR signalling through genetic or environmental insults causes a constellation of neurodevelopmental disorders that manifest as intellectual disability, epilepsy, autism, or schizophrenia. It is not clear whether the developmental impacts of NMDAR dysfunction can be overcome by interventions in adulthood. This question is paramount for neurodevelopmental disorders arising from mutations that occur in the GRIN genes, which encode NMDAR subunits, and the broader set of mutations that disrupt NMDAR function. We developed a mouse model where a congenital loss-of-function allele of Grin1 can be restored to wild type by gene editing with Cre recombinase. Rescue of NMDARs in adult mice yields surprisingly robust improvements in cognitive functions, including those that are refractory to treatment with current medications. These results suggest that neurodevelopmental disorders arising from NMDAR deficiency can be effectively treated in adults.
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影响因子：
64.5
作者：
LI, YQ;ERZURUMLU, RS;TONEGAWA, S
通讯作者：
TONEGAWA, S
影响因子：
64.8
作者：
Iwasato, T;Datwani, A;Itohara, S
通讯作者：
Itohara, S
影响因子：
25
作者：
Madisen L;Zwingman TA;Sunkin SM;Oh SW;Zariwala HA;Gu H;Ng LL;Palmiter RD;Hawrylycz MJ;Jones AR;Lein ES;Zeng H
通讯作者：
Zeng H
影响因子：
9.9
作者：
Lemke JR;Geider K;Helbig KL;Heyne HO;Schütz H;Hentschel J;Courage C;Depienne C;Nava C;Heron D;Møller RS;Hjalgrim H;Lal D;Neubauer BA;Nürnberg P;Thiele H;Kurlemann G;Arnold GL;Bhambhani V;Bartholdi D;Pedurupillay CR;Misceo D;Frengen E;Strømme P;Dlugos DJ;Doherty ES;Bijlsma EK;Ruivenkamp CA;Hoffer MJ;Goldstein A;Rajan DS;Narayanan V;Ramsey K;Belnap N;Schrauwen I;Richholt R;Koeleman BP;Sá J;Mendonça C;de Kovel CG;Weckhuysen S;Hardies K;De Jonghe P;De Meirleir L;Milh M;Badens C;Lebrun M;Busa T;Francannet C;Piton A;Riesch E;Biskup S;Vogt H;Dorn T;Helbig I;Michaud JL;Laube B;Syrbe S
通讯作者：
Syrbe S
影响因子：
8.2
作者：
Li, Liang;Du, Yi;Wu, Yanhong
通讯作者：
Wu, Yanhong