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首页> 外文期刊>The European Journal of Neuroscience >Acute cholinergic rescue of synaptic plasticity in the neurodegenerating cortex of anti-nerve-growth-factor mice.
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Acute cholinergic rescue of synaptic plasticity in the neurodegenerating cortex of anti-nerve-growth-factor mice.

机译：急性胆碱能抗神经生长因子小鼠神经变性皮层突触可塑性的抢救。

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摘要

Deficits in cholinergic systems innervating cerebral cortex are associated with cognitive impairment during senescence and in age-related neurodegenerative pathologies. However, little is known about the role of cholinergic pathways in modulating cortical plasticity. Basal forebrain cholinergic neurons are a major target for nerve-growth factor (NGF). In order to investigate the relationship between cholinergic innervation and cortical synaptic plasticity, we exploited a transgenic mouse model in which the activity of NGF in the adult nervous system is neutralized by the expression of blocking antibodies to NGF itself (anti-NGF mice) [Ruberti, F. et al. (2000). J. Neurosci. 20, 2589-2601]. In 6-month-old anti-NGF mice, we show that the reduction in cholinergic innervation of the cortex is associated with different forms of synaptic plasticity impairment. A local, acute increase in the availability of acetylcholine rescues these synaptic plasticity deficits, thus indicating that a cholinergic system mediates the impairment of cortical plasticity at this early stage of the neurodegenerative process triggered by NGF neutralization. Our results represent an important step in unveiling the pivotal role of cholinergic transmission in modulating adult cortical plasticity.
机译：支配大脑皮层的胆碱能系统的缺陷与衰老过程中以及年龄相关的神经退行性病变中的认知障碍有关。然而，关于胆碱能途径在调节皮层可塑性中的作用知之甚少。基底前脑胆碱能神经元是神经生长因子（NGF）的主要目标。为了研究胆碱能神经支配与皮质突触可塑性之间的关系，我们开发了一种转基因小鼠模型，其中成年神经系统中NGF的活性被针对NGF本身的阻断抗体（抗NGF小鼠）的表达所中和[Ruberti ，F。等。 （2000）。 J.神经科学。 20，2589-2601]。在6个月大的抗NGF小鼠中，我们显示皮质胆碱能神经支配的减少与不同形式的突触可塑性损伤相关。乙酰胆碱可用性的局部急剧增加可以挽救这些突触可塑性缺陷，从而表明在NGF中和引发的神经变性过程的这一早期阶段，胆碱能系统介导了皮质可塑性的损害。我们的结果代表了揭示胆碱能传递在调节成人皮质可塑性中的关键作用的重要一步。

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