Postnatal Loss of Mef2c Results in Dissociation of Effects on Synapse Number and Learning and Memory.
Postnatal Loss of Mef2c Results in Dissociation of Effects on Synapse Number and Learning and Memory.
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DOI：
10.1016/j.biopsych.2015.09.018
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发表时间：
2016-07-15
影响因子：
10.6
通讯作者：
Monteggia LM
中科院分区：
文献类型：
--
作者：
Adachi M;Lin PY;Pranav H;Monteggia LM
肌细胞增强因子2(MEF2)转录因子在中枢神经系统发育的多种细胞过程中发挥重要作用。试图解决MEF2在大脑中的作用的研究在很大程度上依赖于MEF2结构性结构的过度表达，该结构损害记忆形成或敲除MEF2功能，从而增加脊柱数量和增强记忆形成。胚胎发育过程中大脑中单个MEF2亚型的基因缺失表明，MEF2C缺失对脊柱数量产生负面调节，导致学习和记忆障碍，可能与其在发育中的重要作用有关。为了进一步研究MEF2C在脑中的功能，我们在小鼠出生后的发育过程中对MEF2C进行了基因缺失。我们用一系列行为范式描述了这些条件性MEF2C基因敲除小鼠的特征，并研究了出生后MEF2C基因缺失对长时程增强的影响。我们观察到条件性MEF2C基因敲除小鼠的海马区脊椎数量增加。然而，出生后MEF2C的丢失没有影响学习和记忆、长时程增强，或者社会和重复行为。我们的研究结果表明，MEF2C在调节脊椎数量、分离学习和记忆、突触可塑性以及出生后大脑中自闭症相关行为的测量方面发挥了关键作用。
Myocyte enhancer factor 2 (MEF2) transcription factors play critical roles in diverse cellular processes during CNS development. Studies attempting to address the role of MEF2 in brain have largely relied on overexpression of a constitutive MEF2 construct that impairs memory formation or knockdown of MEF2 function that increases spine numbers and enhances memory formation. Genetic deletion of individual MEF2 isoforms in brain during embryogenesis demonstrated Mef2c loss negatively regulates spine numbers resulting in learning and memory deficits, possibly due to its essential role in development. To further investigate Mef2c function in brain, we genetically deleted Mef2c during postnatal development in mice. We characterized these conditional Mef2c knockout mice in an array of behavioral paradigms and examined the impact of postnatal loss of Mef2c on long-term potentiation. We observed increased spine numbers in hippocampus of the conditional Mef2c knockout mice. However, the postnatal loss of Mef2c did not impact learning and memory, long-term potentiation, or social and repetitive behaviors. Our findings demonstrate a critical role for MEF2c in the regulation of spine numbers with a dissociation on learning and memory, synaptic plasticity and measures of autism-related behaviors in postnatal brain.