NPY modulates miR-30a-5p and BDNF in opposite direction in an in vitro model of Alzheimer disease: a possible role in neuroprotection?
Using in vitro models of Alzheimer's disease (AD), we found that the toxic effects of amyloid beta 25-35 (Aβ(25-35)) on the neurotrophin brain-derived neurotrophic factor (BDNF) were counteracted by pre-incubation with neuropeptide Y (NPY), a neuropeptide expressed within the central nervous system. Nonetheless, the mechanism of action of NPY on BDNF neuronal production in the presence of Aβ is not known. BDNF expression might be directly regulated by microRNA (miRs), small non-coding DNA fragments that regulate the expression of target genes. Thus, there is the possibility that miRs alterations are present in AD-affected neurons and that NPY influences miR expression. To test this hypothesis, we exposed NPY-pretreated primary rat cortical neurons to Aβ(25-35) and measured miR-30a-5p (a member of the miR-30a family involved in BDNF tuning expression) and BDNF mRNA and protein expression after 24 and 48 h. Our results demonstrated that pre-treatment with NPY decreased miR-30a-5p expression and increased BDNF mRNA and protein expression at 24 and 48 h of incubation with Aβ. Therefore, this study demonstrates that NPY modulates BDNF and its regulating microRNA miR-30a-5p in opposite direction with a mechanism that possibly contributes to the neuroprotective effect of NPY in rat cortical neurons exposed to Aβ.
Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy.
Nicoletta
N
Croce
Francesca
F
Gelfo
Maria Teresa
MT
Ciotti
Giorgio
G
Federici
Carlo
C
Caltagirone
Sergio
S
Bernardini
Francesco
F
Angelucci
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002525:Cerebellar Cortex / Q000166:cytology / Q000196:embryology; D005786:Gene Expression Regulation / Q000187:drug effects; D035683:MicroRNAs / Q000378:metabolism*; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009478:Neuropeptide Y / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; C556157:MIRN30 microRNA, rat; D035683:MicroRNAs; D009478:Neuropeptide Y; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35)