Dynamic changes in dopamine neuron function after DNSP-11 treatment: Effects in vivo and increased ERK 1/2 phosphorylation in vitro
Dynamic changes in dopamine neuron function after DNSP-11 treatment: Effects in vivo and increased ERK 1/2 phosphorylation in vitro
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DOI：
10.1016/j.peptides.2013.12.007
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发表时间：
2014-04-01
期刊：
影响因子：
3
通讯作者：
Gerhardt, Greg A.
中科院分区：
文献类型：
--
作者：
Fuqua, Joshua L.;Littrell, Ofelia M.;Gerhardt, Greg A.
神经胶质细胞系源性神经营养因子（GDNF）对多巴胺（DA）神经元功能和存活有显著影响。人类GDNF蛋白的翻译后加工模型理论表明，从具有神经生物学功能的前区形成更小的修饰肽，包括一种名为多巴胺神经元刺激肽-11 （DNSP-11）的11氨基酸肽。将DNSP-11单次注入大鼠黑质，观察其对da神经元功能的影响。治疗4周后，采用微透析法观察纹状体钾（K+）和d -安非他明诱发DA释放。微透析检测DNSP-11治疗后da释放无明显变化。在DNSP-11治疗后1周、2周和4周，使用高速计时电流法进一步检测纹状体离散区域的多巴胺释放。在DNSP-11处理两周后，钾诱导的DA释放在纹状体的特定亚区增加。然而，DNSP-11治疗后自发性运动活动没有变化。此外，我们发现在MN9D多巴胺能神经元细胞系中单次处理DNSP-11会导致ERK1 /2的磷酸化，这表明一种新的细胞机制负责DA功能的增加。(c) 2014 Elsevier Inc.版权所有。
Glial cell-line derived neurotrophic factor (GDNF) has demonstrated robust effects on dopamine (DA) neuron function and survival. A post-translational processing model of the human GDNF proprotein theorizes the formation of smaller, amidated peptide(s) from the proregion that exhibit neurobiological function, including an 11-amino-acid peptide named dopamine neuron stimulating peptide-11 (DNSP-11). A single treatment of DNSP-11 was delivered to the substantia nigra in the rat to investigate effects on DA-neuron function. Four weeks after treatment, potassium (K+) and D-amphetamine evoked DA release were studied in the striatum using microdialysis. There were no significant changes in DA-release after DNSP-11 treatment determined by microdialysis. Dopamine release was further examined in discrete regions of the striatum using high-speed chronoamperometry at 1-, 2-, and 4-weeks after DNSP-11 treatment. Two weeks after DNSP-11 treatment, potassium-evoked DA release was increased in specific subregions of the striatum. However, spontaneous locomotor activity was unchanged by DNSP-11 treatment. In addition, we show that a single treatment of DNSP-11 in the MN9D dopaminergic neuronal cell line results in phosphorylation of ERK1 /2, which suggests a novel cellular mechanism responsible for increases in DA function. (c) 2014 Elsevier Inc. All rights reserved.