Neuropeptide Y Protects Rat Cortical Neurons against 尾-Amyloid Toxicity and Re-establishes Synthesis and Release of Nerve Growth Factor
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- 作者：Nicoletta Croce ; Maria Teresa Ciotti ; Francesca Gelfo ; Silvia Cortelli ; Giorgio Federici ; Carlo Caltagirone ; Sergio Bernardini ; Francesco Angelucci
- 刊名：ACS Chemical Neuroscience
- 出版年：2012
- 出版时间：April 18, 2012
- 年：2012
- 卷：3
- 期：4
- 页码：312-318
- 全文大小：295K
- 年卷期：v.3,no.4(April 18, 2012)
- ISSN：1948-7193
文摘
Neuropeptide Y (NPY) is a 36 amino acid peptide, widely distributed within central nervous system neurons. More recently, it has been shown that NPY is involved in Alzheimer's disease (AD), a disorder characterized by accumulation of amyloid 尾-peptide (A尾) in neurons. In a previous study, we investigated the effect of NPY on neuronal damage by exposing SH-SY5Y cells (an established human derived neuroblastoma cell line) to A尾鈥檚 pathogenic fragment 25鈥?5 (A尾25鈥?5). We found a NPY-neuroprotective action associated with changes in intracellular production of nerve growth factor (NGF), a member of the neurotrophin family. Since our results were encouraging, we decided to replicate our data using primary cortical neurons cultured in presence of A尾25鈥?5, and investigated whether NPY had similar neuroprotective action. Moreover, since cortical neurons are able to produce and release NGF, we investigated whether the synthesis and release of NGF were modified in such experimental conditions. Our results showed that a preincubation with NPY counteracted the toxic effect of A尾, as measured by increased cell viability. Moreover, NPY pretreatment had an effect on NGF since its intracellular synthesis was increased, release was normalized, and mRNA expression was downregulated. Notably, these effects on NGF were in the opposite direction of those produced by incubating the cells with A尾 alone. This study in primary cortical neurons supports the hypothesis that NPY may be a neuroprotective agent against 尾-amyloid neurotoxicity. These data also suggest that NPY may influence the synthesis and the release of NGF by cortical neurons.