TY - JOUR
T1 - Exposure to extremely low-frequency (50Hz) electromagnetic fields enhances adult hippocampal neurogenesis in C57BL/6 mice
AU - Cuccurazzu, Bruna
AU - Leone, Lucia
AU - Podda, Maria Vittoria
AU - Piacentini, Roberto
AU - Riccardi, Elisa
AU - Ripoli, Cristian
AU - Azzena, Gian Battista
AU - Grassi, Claudio
PY - 2010/11
Y1 - 2010/11
N2 - Throughout life, new neurons are continuously generated in the hippocampus, which is therefore a major site of structural plasticity in the adult brain. We recently demonstrated that extremely low-frequency electromagnetic fields (ELFEFs) promote the neuronal differentiation of neural stem cells in vitro by up-regulating Cav1-channel activity. The aim of the present study was to determine whether 50-Hz/1 mT ELFEF stimulation also affects adult hippocampal neurogenesis in vivo, and if so, to identify the molecular mechanisms underlying this action and its functional impact on synaptic plasticity. ELFEF exposure (1 to 7h/day for 7days) significantly enhanced neurogenesis in the dentate gyrus (DG) of adult mice, as documented by increased numbers of cells double-labeled for 5-bromo-deoxyuridine (BrdU) and doublecortin. Quantitative RT-PCR analysis of hippocampal extracts revealed significant ELFEF exposure-induced increases in the transcription of pro-neuronal genes (Mash1, NeuroD2, Hes1) and genes encoding Cav1.2 channel α1C subunits. Increased expression of NeuroD1, NeuroD2 and Cav1 channels was also documented by Western blot analysis. Immunofluorescence experiments showed that, 30days after ELFEF stimulation, roughly half of the newly generated immature neurons had survived and become mature dentate granule cells (as shown by their immunoreactivity for both BrdU and NeuN) and were integrated into the granule cell layer of the DG. Electrophysiological experiments demonstrated that the new mature neurons influenced hippocampal synaptic plasticity, as reflected by increased long-term potentiation. Our findings show that ELFEF exposure can be an effective tool for increasing in vivo neurogenesis, and they could lead to the development of novel therapeutic approaches in regenerative medicine.
AB - Throughout life, new neurons are continuously generated in the hippocampus, which is therefore a major site of structural plasticity in the adult brain. We recently demonstrated that extremely low-frequency electromagnetic fields (ELFEFs) promote the neuronal differentiation of neural stem cells in vitro by up-regulating Cav1-channel activity. The aim of the present study was to determine whether 50-Hz/1 mT ELFEF stimulation also affects adult hippocampal neurogenesis in vivo, and if so, to identify the molecular mechanisms underlying this action and its functional impact on synaptic plasticity. ELFEF exposure (1 to 7h/day for 7days) significantly enhanced neurogenesis in the dentate gyrus (DG) of adult mice, as documented by increased numbers of cells double-labeled for 5-bromo-deoxyuridine (BrdU) and doublecortin. Quantitative RT-PCR analysis of hippocampal extracts revealed significant ELFEF exposure-induced increases in the transcription of pro-neuronal genes (Mash1, NeuroD2, Hes1) and genes encoding Cav1.2 channel α1C subunits. Increased expression of NeuroD1, NeuroD2 and Cav1 channels was also documented by Western blot analysis. Immunofluorescence experiments showed that, 30days after ELFEF stimulation, roughly half of the newly generated immature neurons had survived and become mature dentate granule cells (as shown by their immunoreactivity for both BrdU and NeuN) and were integrated into the granule cell layer of the DG. Electrophysiological experiments demonstrated that the new mature neurons influenced hippocampal synaptic plasticity, as reflected by increased long-term potentiation. Our findings show that ELFEF exposure can be an effective tool for increasing in vivo neurogenesis, and they could lead to the development of novel therapeutic approaches in regenerative medicine.
KW - Ca1 channels
KW - Dentate gyrus
KW - Electromagnetic field
KW - Long-term potentiation
KW - Neural stem cells
KW - NeuroD
KW - Neurogenesis
KW - Neuronal differentiation
KW - Proliferation
UR - http://www.scopus.com/inward/record.url?scp=77957806490&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77957806490&partnerID=8YFLogxK
U2 - 10.1016/j.expneurol.2010.08.022
DO - 10.1016/j.expneurol.2010.08.022
M3 - Article
C2 - 20816824
AN - SCOPUS:77957806490
VL - 226
SP - 173
EP - 182
JO - Experimental Neurology
JF - Experimental Neurology
SN - 0014-4886
IS - 1
ER -