The role of nitric oxide synthase in cortical plasticity is sex specific.

The role of nitric oxide synthase in cortical plasticity is sex specific.
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一氧化氮合酶在皮质可塑性中的作用是性别特异性的。

DOI:
10.1523/jneurosci.3189-12.2012
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发表时间:
2012-10-24
期刊:
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子:
--
通讯作者:
Fox K
Fox K
中科院分区:
其他
文献类型:
--
作者:
Dachtler J;Hardingham NR;Fox K

文献摘要

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一氧化氮合酶-1(NOS 1)参与多种形式的可塑性,包括海马依赖性学习和记忆,桶皮质中的经验依赖性可塑性以及海马和新皮质中的LTP。NOS 1也有助于中风期间的缺血性损伤,并且在男性中比女性具有更强的有害作用。因此,我们研究了NOS 1在可塑性中的作用是否也具有性别特异性。我们测试了LTP在层(L)IV到II/III之间的桶柱和经验依赖性可塑性在α NOS 1基因敲除小鼠和野生型同窝小鼠的桶皮质通路。我们发现雄性α NOS 1基因敲除小鼠LTP不存在,而雌性小鼠则不存在,雌性小鼠的LTP残留不依赖于NO。我们还发现,在α NOS 1基因敲除的男性中,由单须经验引起的经验依赖性增强显著降低,但在女性中不受影响。α NOS 1敲除对桶的发育有很小的影响,与野生型相比,桶的大小减少了20%,但这种影响不是性别特异性的。因此,我们得出结论,新皮质可塑性机制在突触水平上在男性和女性之间存在差异,无论是在其基本的可塑性诱导途径还是在其补偿α NOS 1损失的能力方面。
Nitric oxide synthase-1 (NOS1) is involved in several forms of plasticity including hippocampal-dependent learning and memory, experience-dependent plasticity in the barrel cortex and LTP in the hippocampus and neocortex. NOS1 also contributes to ischaemic damage during stroke and has a stronger deleterious effect in males than females. We therefore investigated whether NOS1’s role in plasticity might also be sex specific. We tested LTP in the layer (L)IV to II/III pathway between barrel-columns and experience-dependent plasticity in the barrel cortex of αNOS1 knockout mice and their wild-type littermates. We found that LTP was absent in male αNOS1 knockout mice but not in females and that the residual LTP in females was not NO-dependent. We also found that experience-dependent potentiation due to single whisker experience was significantly reduced in male αNOS1 knockouts but unaffected in females. The αNOS1 knockout had a small effect on development of the barrels, which were reduced in size by 20% compared to wild-types but this effect was not sex specific. We therefore conclude that neocortical plasticity mechanisms differ between males and females at the synaptic level, either in their basic plasticity induction pathways or in their ability to compensate for loss of αNOS1.