Epigenetic modulation of adult hippocampal neurogenesis by extremely low-frequency electromagnetic fields.

Lucia Leone, Salvatore Fusco, Roberto Piacentini, Giovambattista Pani, Maria Vittoria Podda, Claudio Grassi, Alessia Mastrodonato, Saviana Antonella Barbati, Salvatore Zaffina

Research output: Contribution to journalArticlepeer-review

48 Citations (Scopus)

Abstract

Throughout life adult neurogenesis generates new neurons in the dentate gyrus of hippocampus that have a critical role in memory formation. Strategies able to stimulate this endogenous process have raised considerable interest because of their potential use to treat neurological disorders entailing cognitive impairment. We previously reported that mice exposed to extremely low-frequency electromagnetic fields (ELFEFs) showed increased hippocampal neurogenesis. Here we demonstrate that the ELFEF-dependent enhancement of hippocampal neurogenesis improves spatial learning and memory. To gain insights on the molecular mechanisms underlying ELFEFs’ effects we extended our studies to an in vitro model of neural stem cells (NSCs) isolated from the hippocampi of newborn mice. We found that ELFEFs enhanced proliferation and neuronal differentiation of hippocampal NSCs by regulation of epigenetic mechanisms leading to pro-neuronal gene expression. Upon ELFEF stimulation of NSCs, we observed a significant enhancement of expression of the pro-proliferative gene Hes1 and the neuronal determination genes NeuroD1 and Neurogenin1. These events were preceded by increased acetylation of H3K9 and binding of the phosphorylated transcription factor cAMP response element-binding protein (CREB) on the regulatory sequence of these genes. Such ELFEF-dependent epigenetic modifications were prevented by the Cav1-channel blocker nifedipine, and were associated with increased occupancy of CREB binding protein (CBP) to the same loci within the analyzed promoters. Our results unravel the molecular mechanisms underlying the ELFEFs’ ability to improve endogenous neurogenesis, pointing to histone acetylation–related chromatin remodeling as a critical determinant. These findings could pave the way to the development of novel therapeutic approaches in regenerative medicine
Original languageEnglish
Pages (from-to)1472-1486
Number of pages15
JournalMolecular Neurobiology
Volume49
DOIs
Publication statusPublished - 2014

Keywords

  • CREB
  • Cav1 channels
  • Hes1
  • NeuroD1 and Neurogenin1 modulation
  • epigenetics
  • hippocampal neural stem cells

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