PNAS：天然海藻化合物有望治疗中风

2012年11月25日 讯 /生物谷BIOON/ --近日，一项新的研究证实海藻产生的一种化合物短裸甲藻毒素-2能刺激培养的小鼠神经元神经细胞的生长，增强可塑性。本研究提出一个潜在的新的药物治疗中风或其他脑外伤，恢复脑功能。

每年，在美国有超过795,000人患中风。中风是一种导致患者长期残疾的主要原因。
 
研究表明，化合物如短裸甲藻毒素-2可以增强神经元的可塑性，通过神经修复疗法对中风患者进行康复治疗。相关研究论文发表在PNAS杂志上。

短裸甲藻毒素是一种神经毒素，能刺激培养的小鼠神经细胞生长。这项新的研究表明短裸甲藻毒素增强培养皿中培养的小鼠神经元萌芽成长以及形成新的神经细胞之间的突触。

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Bidirectional influence of sodium channel activation on NMDA receptor-dependent cerebrocortical neuron structural plasticity.
Abstract
Neuronal activity regulates brain development and synaptic plasticity through N-methyl-D-aspartate receptors (NMDARs) and calcium-dependent signaling pathways. Intracellular sodium ([Na(+)](i)) also exerts a regulatory influence on NMDAR channel activity, and [Na(+)](i) may, therefore, function as a signaling molecule. In an attempt to mimic the influence of neuronal activity on synaptic plasticity, we used brevetoxin-2 (PbTx-2), a voltage-gated sodium channel (VGSC) gating modifier, to manipulate [Na(+)](i) in cerebrocortical neurons. The acute application of PbTx-2 produced concentration-dependent increments in both intracellular [Na(+)] and [Ca(2+)]. Pharmacological evaluation showed that PbTx-2-induced Ca(2+) influx primarily involved VGSC activation and NMDAR-mediated entry. Additionally, PbTx-2 robustly potentiated NMDA-induced Ca(2+) influx. PbTx-2-exposed neurons showed enhanced neurite outgrowth, increased dendritic arbor complexity, and increased dendritic filopodia density. The appearance of spontaneous calcium oscillations, reflecting synchronous neuronal activity, was accelerated by PbTx-2 treatment. Parallel to this response, PbTx-2 increased cerebrocortical neuron synaptic density. PbTx-2 stimulation of neurite outgrowth, dendritic arborization, and synaptogenesis all exhibited bidirectional concentration-response profiles. This profile paralleled that of NMDA, which also produced bidirectional concentration-response profiles for neurite outgrowth and synaptogenesis. These data are consistent with the hypothesis that PbTx-2-enhanced neuronal plasticity involves NMDAR-dependent signaling. Our results demonstrate that PbTx-2 mimics activity-dependent neuronal structural plasticity in cerebrocortical neurons through an increase in [Na(+)](i), up-regulation of NMDAR function, and engagement of downstream Ca(2+)-dependent signaling pathways. These data suggest that VGSC gating modifiers may represent a pharmacologic strategy to regulate neuronal plasticity through NMDAR-dependent mechanisms.