The neurogenic effects of exogenous neuropeptide Y: early molecular events and long-lasting effects in the hippocampus of trimethyltin-treated rats.
The neurogenic effects of exogenous neuropeptide Y: early molecular events and long-lasting effects in the hippocampus of trimethyltin-treated rats.
复制标题
DOI：
10.1371/journal.pone.0088294
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Geloso MC
中科院分区：
文献类型：
--
作者：
Corvino V;Marchese E;Podda MV;Lattanzi W;Giannetti S;Di Maria V;Cocco S;Grassi C;Michetti F;Geloso MC
内源性神经发生的调节被认为是神经保护领域的一个有前途的挑战。在给予三甲基锡(TMT)(8 mg/kg)建立的大鼠海马神经变性模型中，以选择性锥体细胞丢失、神经发生增强、癫痫发作和认知障碍为特征，我们先前证明了外源性神经肽Y(NPY)在神经变性的早期阶段对齿状神经前体细胞具有增殖作用。为了研究新生神经元的功能整合，我们在成年大鼠侧脑室注射神经肽Y(2微克/2微克L，治疗后4天)，观察其对神经退行性变和癫痫的长期影响。结果表明，给予NPY 30d后，TMT+NPY组大鼠的新生神经元数量仍高于对照组+生理盐水组。作为新神经元整合到海马网的一个功能相关性，在没有GABAA受体阻断的情况下，TMT+NPY治疗组在齿状回(DG)记录的长时程增强高于所有其他组。此外，对DG神经元后期成熟所必需的转录因子Kruppel-like factor9和与新生神经元成熟和树突伸展密切相关的细胞周期蛋白依赖性激酶5进行的qPCR分析显示，与所有其他组相比，TMT+NPY处理组的这两个基因的表达都显著上调。为探讨NPY诱导的早期分子事件，用定量聚合酶链式反应(QPCR)检测NPY作用1、3、5d后参与维持海马神经源性生态位的Sonic Hedgehog(Shh)信号通路。与所有其他组相比，TMT+NPY组大鼠早期Shh表达显著上调，与下游基因的调节有关。我们的数据表明，在TMT诱导的神经变性过程中，NPY的神经发生作用涉及早期Shh通路的激活，并导致新生成的神经元功能整合到局部回路中。
Modulation of endogenous neurogenesis is regarded as a promising challenge in neuroprotection. In the rat model of hippocampal neurodegeneration obtained by Trimethyltin (TMT) administration (8 mg/kg), characterised by selective pyramidal cell loss, enhanced neurogenesis, seizures and cognitive impairment, we previously demonstrated a proliferative role of exogenous neuropeptide Y (NPY), on dentate progenitors in the early phases of neurodegeneration. To investigate the functional integration of newly-born neurons, here we studied in adult rats the long-term effects of intracerebroventricular administration of NPY (2 µg/2 µl, 4 days after TMT-treatment), which plays an adjuvant role in neurodegeneration and epilepsy. Our results indicate that 30 days after NPY administration the number of new neurons was still higher in TMT+NPY-treated rats than in control+saline group. As a functional correlate of the integration of new neurons into the hippocampal network, long-term potentiation recorded in Dentate Gyrus (DG) in the absence of GABAA receptor blockade was higher in the TMT+NPY-treated group than in all other groups. Furthermore, qPCR analysis of Kruppel-like factor 9, a transcription factor essential for late-phase maturation of neurons in the DG, and of the cyclin-dependent kinase 5, critically involved in the maturation and dendrite extension of newly-born neurons, revealed a significant up-regulation of both genes in TMT+NPY-treated rats compared with all other groups. To explore the early molecular events activated by NPY administration, the Sonic Hedgehog (Shh) signalling pathway, which participates in the maintenance of the neurogenic hippocampal niche, was evaluated by qPCR 1, 3 and 5 days after NPY-treatment. An early significant up-regulation of Shh expression was detected in TMT+NPY-treated rats compared with all other groups, associated with a modulation of downstream genes. Our data indicate that the neurogenic effect of NPY administration during TMT-induced neurodegeneration involves early Shh pathway activation and results in a functional integration of newly-generated neurons into the local circuit.
登录
查看更多内容
募集在电击性癫痫发作介导的成年大鼠海马神经发生调节中的声音刺猬信号级联。
DOI：
10.1111/j.1460-9568.2005.04317.x
发表时间：
2005-10
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Banerjee SB;Rajendran R;Dias BG;Ladiwala U;Tole S;Vaidya VA
通讯作者：
Vaidya VA
影响因子：
2.5
作者：
Dayer, AG;Ford, AA;Cameron, HA
通讯作者：
Cameron, HA
影响因子：
--
作者：
ABERCROMBIE, M
通讯作者：
ABERCROMBIE, M
影响因子：
25
作者：
Favaro, Rebecca;Valotta, Menella;Nicolis, Silvia K.
通讯作者：
Nicolis, Silvia K.
影响因子：
4.5
作者：
Florea, AM;Splettstoesser, F;Büsselberg, D
通讯作者：
Büsselberg, D