Neuropeptide Y protects rat cortical neurons against β-amyloid toxicity and re-establishes synthesis and release of nerve growth factor - PubMed (original) (raw)

. 2012 Apr 18;3(4):312-8.

doi: 10.1021/cn200127e. Epub 2012 Jan 30.

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Neuropeptide Y protects rat cortical neurons against β-amyloid toxicity and re-establishes synthesis and release of nerve growth factor

Nicoletta Croce et al. ACS Chem Neurosci. 2012.

Abstract

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 β-peptide (Aβ) 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 Aβ's pathogenic fragment 25-35 (Aβ(25-35)). 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 Aβ(25-35), 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 Aβ, 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 Aβ alone. This study in primary cortical neurons supports the hypothesis that NPY may be a neuroprotective agent against β-amyloid neurotoxicity. These data also suggest that NPY may influence the synthesis and the release of NGF by cortical neurons.

Keywords: NGF; NPY; cerebral cortex; cortical neurons; primary cells; β-amyloid.

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Figures

Figure 1

Figure 1

NPY effects on cell viability in cultured rat cortical neurons exposed to Aβ25–35. Cortical neurons were preincubated alone (a) or with three concentrations of NPY [(b) 2 mM, (c) 1 mM, and (d) 0.5 mM] for 24 h and then exposed to Aβ25–35 (50 μM) or Aβ35–25 (50 μM) for 48 h (number of experiments performed = 4). After 24 and 48 h, cells were tested with MTS assay. NPY treatment restored normal cell survival. Cell viability is expressed as percent of the mean absorbance value of untreated cells at each time point. Data represent means ± SEM

Figure 2

Figure 2

NGF protein [(a) synthesis, (b) release] and mRNA (c) in cortical neurons incubated with Aβ25–35 (50 μM) or its inactive control Aβ35–25 (50 μM). Cell pellets were collected at 24 and 48 h. NGF protein levels are expressed in pg/g total proteins. NGF mRNA was measured by real time PCR and expressed as amount of target gene normalized to an endogenous reference (β-actin) and relative to a calibrator (ΔΔCt) Data represent means ± SEM. Asterisks indicate statistical level of significance (*p < 0.05; **p < 0 01).

Figure 3

Figure 3

NGF protein [(a) synthesis, (b) release] and mRNA (c) in cortical neurons pretreated with NPY (1 mM) for 24 h and then exposed to toxic concentration (50 μM) of Aβ25–35 or its inactive control Aβ35–25 (50 μM). Cell pellets were collected at 24 and 48 h. NGF protein levels are expressed in pg/g total protons. NGF mRNA was measured by real time PCR and expressed as amount of target gene normalized to an endogenous reference (β-actin) and relative to a calibrator (ΔΔCt). Data represent means ± SEM. Asterisks indicate statistical level of significance (*p < 0.05).

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