title: Neuropeptide Y protects rat cortical neurons against β-amyloid toxicity and re-establishes synthesis and release of nerve growth factor.
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.
authors.affiliation: IRCCS Santa Lucia Foundation, Rome, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Croce
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Ciotti
authors.forename: Francesca
authors.initials: F
authors.lastname: Gelfo
authors.forename: Silvia
authors.initials: S
authors.lastname: Cortelli
authors.forename: Giorgio
authors.initials: G
authors.lastname: Federici
authors.forename: Carlo
authors.initials: C
authors.lastname: Caltagirone
authors.forename: Sergio
authors.initials: S
authors.lastname: Bernardini
authors.forename: Francesco
authors.initials: F
authors.lastname: Angelucci
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000818:Animals; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism*; D005333:Fetus; D020932:Nerve Growth Factor / Q000096:biosynthesis* / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009478:Neuropeptide Y / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016229:Amyloid beta-Peptides; D009478:Neuropeptide Y; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D020932:Nerve Growth Factor