title: Role of cyclic nucleotide-gated channels in the modulation of mouse hippocampal neurogenesis.
abstract: Neural stem cells generate neurons in the hippocampal dentate gyrus in mammals, including humans, throughout adulthood. Adult hippocampal neurogenesis has been the focus of many studies due to its relevance in processes such as learning and memory and its documented impairment in some neurodegenerative diseases. However, we are still far from having a complete picture of the mechanism regulating this process. Our study focused on the possible role of cyclic nucleotide-gated (CNG) channels. These voltage-independent channels activated by cyclic nucleotides, first described in retinal and olfactory receptors, have been receiving increasing attention for their involvement in several brain functions. Here we show that the rod-type, CNGA1, and olfactory-type, CNGA2, subunits are expressed in hippocampal neural stem cells in culture and in situ in the hippocampal neurogenic niche of adult mice. Pharmacological blockade of CNG channels did not affect cultured neural stem cell proliferation but reduced their differentiation towards the neuronal phenotype. The membrane permeant cGMP analogue, 8-Br-cGMP, enhanced neural stem cell differentiation to neurons and this effect was prevented by CNG channel blockade. In addition, patch-clamp recording from neuron-like differentiating neural stem cells revealed cGMP-activated currents attributable to ion flow through CNG channels. The current work provides novel insights into the role of CNG channels in promoting hippocampal neurogenesis, which may prove to be relevant for stem cell-based treatment of cognitive impairment and brain damage.
authors.affiliation: Institute of Human Physiology, Medical School, Università Cattolica, Rome, Italy.
authors.forename: Maria Vittoria
authors.initials: MV
authors.lastname: Podda
authors.forename: Roberto
authors.initials: R
authors.lastname: Piacentini
authors.forename: Saviana Antonella
authors.initials: SA
authors.lastname: Barbati
authors.forename: Alessia
authors.initials: A
authors.lastname: Mastrodonato
authors.forename: Daniela
authors.initials: D
authors.lastname: Puzzo
authors.forename: Marcello
authors.initials: M
authors.lastname: D'Ascenzo
authors.forename: Lucia
authors.initials: L
authors.lastname: Leone
authors.forename: Claudio
authors.initials: C
authors.lastname: Grassi
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000494:pharmacology*; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology*; D055495:Neurogenesis / Q000502:physiology*; D018408:Patch-Clamp Techniques
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels; D006152:Cyclic GMP