Altered function and maturation of primary cortical neurons from a 22q11.2 deletion mouse model of schizophrenia.
Altered function and maturation of primary cortical neurons from a 22q11.2 deletion mouse model of schizophrenia.
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DOI：
10.1038/s41398-018-0132-8
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发表时间：
2018-04-18
影响因子：
6.8
通讯作者：
Gogos JA
中科院分区：
文献类型：
--
作者：
Sun Z;Williams DJ;Xu B;Gogos JA
Given its high penetrance, clearly delineated and evolutionary conserved genomic structure, mouse models of the 22q11.2 deletion provide an ideal organism-based and cell-based model of this well-established disease mutation for schizophrenia. In this study we examined the development of changes in intrinsic properties, action potential firing and synaptic transmission using whole-cell patch-clamp recordings of cultured embryonic cortical neurons from Df(16)A+/− and WT mice at DIV7 and DIV14, respectively. Compared to neurons from the WT littermates, significantly increased input resistance and decreased rising rate of action potential was observed in Df(16)A+/− mice at DIV7 but not at DIV14 indicative of delayed neuronal maturation. Neurons from Df(16)A+/− mice also showed significantly higher cellular excitability at both DIV7 and DIV14. Evaluation of Ca2+ homeostasis perturbation caused by 22q11.2 deletion using calcium imaging revealed a significantly lower amplitude of calcium elevation and a smaller area under the curve after depolarization in neurons from Df(16)A+/− mice at both DIV7 and DIV14. Furthermore, the properties of inhibitory synaptic events were significantly altered in Df(16)A+/− mice. We identified changes in mRNA expression profiles, especially in ion channels, receptors, and transporters that may underlie the neurophysiological effects of this mutation. Overall, we show a number of alterations in electrophysiological and calcium homeostatic properties of embryonic cortical neurons from a 22q11.2 deletion mouse model at different culture times and provide valuable insights towards revealing disease mechanisms and discovery of new therapeutic compounds.
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影响因子：
25
作者：
Mukai, Jun;Dhilla, Alefiya;Drew, Liam J.;Stark, Kimberly L.;Cao, Luxiang;MacDermott, Amy B.;Karayiorgou, Maria;Gogos, Joseph A.
通讯作者：
Gogos, Joseph A.
影响因子：
5.3
作者：
Fenelon, Karine;Xu, Bin;Gogos, Joseph A.
通讯作者：
Gogos, Joseph A.
影响因子：
9.8
作者：
Edelmann, L;Pandita, RK;Morrow, BE
通讯作者：
Morrow, BE
影响因子：
2.5
作者：
Gittis, Aryn H.;Moghadam, Setareh H.;du Lac, Sascha
通讯作者：
du Lac, Sascha
影响因子：
2.5
作者：
Harvey, Michael;Lau, David;Contreras, Diego
通讯作者：
Contreras, Diego