Beneficial effect of a CNTF tetrapeptide on adult hippocampal neurogenesis, neuronal plasticity, and spatial memory in mice.
Beneficial effect of a CNTF tetrapeptide on adult hippocampal neurogenesis, neuronal plasticity, and spatial memory in mice.
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CNTF 四肽对成年海马神经发生、神经元可塑性和小鼠空间记忆的有益作用。
DOI：
10.3233/jad-2010-1000069
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
I. Grundke‐Iqbal
中科院分区：
文献类型：
--
作者：
J. Blanchard;M. Chohan;Bin Li;Fei Liu;K. Iqbal;I. Grundke‐Iqbal
治疗阿尔茨海默病等认知障碍的一种策略是利用大脑的再生能力和神经营养因子的特性，将平衡从神经退化转移到神经再生和神经元可塑性。虽然睫状神经营养因子(CNTF)具有一些必需的神经保护特性，但由于其副作用，如厌食、骨骼肌丧失、痛觉过敏、抽筋和肌肉疼痛，其临床应用尚未实现。在本研究中，我们报道了对应于CNTF氨基酸残基147-150的多肽6c(GDDL)可以增强小鼠齿状回的神经发生和神经元的可塑性，并改善小鼠的认知能力，而没有体重减轻或任何其他明显的副作用。正常成年C57BL6小鼠皮下植入含有载体或多肽6c的缓释库微丸，连续给药30天。通过表达神经元标记物、双皮质素和NeuN的细胞的体视学分析以及BrdU摄取来评估齿状回的神经发生。我们发现，多肽6c显著增加了新生前体细胞的早期神经元定位、分化和存活。由于c-fos的基础表达增强，神经元的可塑性增强，反映出MAP2a、b和突触素的高表达，这些新生神经元功能上整合到了海马网中。因此，多肽6c治疗改善了小鼠在空间参考记忆任务中对海马体依赖信息的编码。总体而言，这些发现证明了多肽6c对大脑再生和改善认知的治疗潜力。
A therapeutic strategy against cognitive disorders like Alzheimer's disease is to take advantage of the regenerative ability of the brain and the properties of neurotrophic factors to shift the balance from neurodegeneration to neurogenesis and neuronal plasticity. Although the ciliary neurotrophic factor (CNTF) has some of the required neuroprotective characteristics, its clinical use, due to its side effects, i.e., anorexia, skeletal muscle loss, hyperalgesia, cramps, and muscle pain, has not materialized. In the present study, we report that Peptide 6c (GDDL) that corresponds to CNTF amino acid residues 147-150, enhances the dentate gyrus neurogenesis and neuronal plasticity, and improves cognition without weight loss or any other apparent side effects in mice. Normal adult C57Bl6 mice received subcutaneous implants of extended release depot pellets containing vehicle or Peptide 6c for 30 days of continuous dosing. Dentate gyrus neurogenesis was assessed by stereological analysis of cells expressing neuronal markers, doublecortin and NeuN, and BrdU uptake. We found that Peptide 6c significantly increased early neuronal commitment, differentiation, and survival of newborn progenitor cells. These newborn neurons were functionally integrated into the hippocampal network, since basal expression of c-fos was enhanced and neuronal plasticity was increased, as reflected by higher expression of MAP2a,b and synaptophysin. Consequently, Peptide 6c treatment improved encoding of hippocampal-dependent information in a spatial reference memory task in mice. Overall, these findings demonstrated the therapeutic potential of Peptide 6c for regeneration of the brain and improvement of cognition.
影响因子：
2
作者：
Jessberger, Sebastian;Clark, Robert E.;Gage, Fred H.
通讯作者：
Gage, Fred H.
影响因子：
--
作者：
Hock, C;Heese, K;Otten, U
通讯作者：
Otten, U