Herrmann Gudrun, Hlushchuk Ruslan, Baum Oliver, Scotti Alessandra L
Department of Anatomy, University of Bern, CH-3012 Bern, Switzerland.
J Chem Neuroanat. 2007 Mar;33(2):87-96. doi: 10.1016/j.jchemneu.2007.01.004. Epub 2007 Jan 19.
Homozygous mutations in the Reelin gene result in severe disruption of brain development. The histogenesis of layered regions, like the neocortex, hippocampus and the cerebellum, is most notably affected in mouse reeler mutants and similar traits are also present in mice lacking molecular components of the Reelin signalling pathway. Moreover, there is evidence for an additional role of Reelin in sustaining synaptic plasticity in adult networks. Nitric oxide is an important gaseous messenger that can modulate neuronal plasticity both in developing and mature synaptic networks and has been shown to facilitate synaptic changes in the hippocampus, cerebellum and olfactory bulb. We studied the distribution and content of neuronal nitric oxide synthase in the olfactory bulbs of reeler and wildtype mice. Immunocytochemistry reveals that Reelin and neuronal nitric oxide synthase containing interneurons are two distinct, non overlapping cell populations of the olfactory bulb. We show by in situ hybridization that both nitrergic and Reelin expressing cells represent only a subset of olfactory bulb GABAergic neurons. Immunoblots show that neuronal nitric oxide synthase protein content is decreased by two thirds in reeler mice causing a detectable loss of immunolabelled cells throughout the olfactory bulb of this strain. However, neuronal nitric oxide synthase mRNA levels, essayed by quantitative real-time RT-PCR, are unaffected in the reeler olfactory bulb. Thus, disruption of the Reelin signalling pathway may modify the turnover of neuronal nitric oxide synthase in the olfactory bulb and possibly affects nitric oxide functions in reeler mice.
Reelin基因的纯合突变会导致大脑发育严重紊乱。在小鼠reeler突变体中，像新皮层、海马体和小脑等分层区域的组织发生受到最显著影响，并且在缺乏Reelin信号通路分子成分的小鼠中也存在类似特征。此外，有证据表明Reelin在维持成年神经网络的突触可塑性方面还有额外作用。一氧化氮是一种重要的气体信使，它可以在发育中和成熟的突触网络中调节神经元可塑性，并且已被证明能促进海马体、小脑和嗅球中的突触变化。我们研究了reeler小鼠和野生型小鼠嗅球中神经元型一氧化氮合酶的分布和含量。免疫细胞化学显示，含有Reelin和神经元型一氧化氮合酶的中间神经元是嗅球中两个不同的、不重叠的细胞群体。我们通过原位杂交表明，表达一氧化氮能和Reelin的细胞仅代表嗅球GABA能神经元的一个子集。免疫印迹显示，reeler小鼠中神经元型一氧化氮合酶蛋白含量降低了三分之二，导致该品系小鼠整个嗅球中可检测到免疫标记细胞的减少。然而，通过定量实时RT-PCR检测，reeler小鼠嗅球中神经元型一氧化氮合酶mRNA水平未受影响。因此，Reelin信号通路的破坏可能会改变嗅球中神经元型一氧化氮合酶的周转，并可能影响reeler小鼠中的一氧化氮功能。
