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The Melatonin Analog IQM316 May Induce Adult Hippocampal Neurogenesis and Preserve Recognition Memories in Mice

Neurogenesis in the adult hippocampus is a unique process in neurobiology that requires functional integration of newly generated neurons, which may disrupt existing hippocampal network connections and consequently loss of established memories. As neurodegenerative diseases characterized by abnormal...

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Autores principales: Figueiro-Silva, Joana, Antequera, Desireé, Pascual, Consuelo, de la Fuente Revenga, Mario, Volt, Huayqui, Acuña-Castroviejo, Darío, Rodríguez-Franco, María Isabel, Carro, Eva
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2018
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6038050/
https://www.ncbi.nlm.nih.gov/pubmed/29873251
http://dx.doi.org/10.1177/0963689717721217
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author Figueiro-Silva, Joana
Antequera, Desireé
Pascual, Consuelo
de la Fuente Revenga, Mario
Volt, Huayqui
Acuña-Castroviejo, Darío
Rodríguez-Franco, María Isabel
Carro, Eva
author_facet Figueiro-Silva, Joana
Antequera, Desireé
Pascual, Consuelo
de la Fuente Revenga, Mario
Volt, Huayqui
Acuña-Castroviejo, Darío
Rodríguez-Franco, María Isabel
Carro, Eva
author_sort Figueiro-Silva, Joana
collection PubMed
description Neurogenesis in the adult hippocampus is a unique process in neurobiology that requires functional integration of newly generated neurons, which may disrupt existing hippocampal network connections and consequently loss of established memories. As neurodegenerative diseases characterized by abnormal neurogenesis and memory dysfunctions are increasing, the identification of new anti-aging drugs is required. In adult mice, we found that melatonin, a well-established neurogenic hormone, and the melatonin analog 2-(2-(5-methoxy-1H-indol-3-yl)ethyl)-5-methyl-1,3,4-oxadiazole (IQM316) were able to induce hippocampal neurogenesis, measured by neuronal nuclei (NeuN) and 5-bromo-2′-deoxyuridine (BrdU) labeling. More importantly, only IQM316 administration was able to induce hippocampal neurogenesis while preserving previously acquired memories, assessed with object recognition tests. In vitro studies with embryonic neural stem cells replicated the finding that both melatonin and IQM316 induce direct differentiation of neural precursors without altering their proliferative activity. Furthermore, IQM316 induces differentiation through a mechanism that is not dependent of melatonergic receptors (MTRs), since the MTR antagonist luzindole could not block the IQM316-induced effects. We also found that IQM316 and melatonin modulate mitochondrial DNA copy number and oxidative phosphorylation proteins, while maintaining mitochondrial function as measured by respiratory assays and enzymatic activity. These results uncover a novel pharmacological agent that may be capable of inducing adult hippocampal neurogenesis at a healthy and sustainable rate that preserves recognition memories.
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spelling pubmed-60380502018-07-11 The Melatonin Analog IQM316 May Induce Adult Hippocampal Neurogenesis and Preserve Recognition Memories in Mice Figueiro-Silva, Joana Antequera, Desireé Pascual, Consuelo de la Fuente Revenga, Mario Volt, Huayqui Acuña-Castroviejo, Darío Rodríguez-Franco, María Isabel Carro, Eva Cell Transplant Original Articles Neurogenesis in the adult hippocampus is a unique process in neurobiology that requires functional integration of newly generated neurons, which may disrupt existing hippocampal network connections and consequently loss of established memories. As neurodegenerative diseases characterized by abnormal neurogenesis and memory dysfunctions are increasing, the identification of new anti-aging drugs is required. In adult mice, we found that melatonin, a well-established neurogenic hormone, and the melatonin analog 2-(2-(5-methoxy-1H-indol-3-yl)ethyl)-5-methyl-1,3,4-oxadiazole (IQM316) were able to induce hippocampal neurogenesis, measured by neuronal nuclei (NeuN) and 5-bromo-2′-deoxyuridine (BrdU) labeling. More importantly, only IQM316 administration was able to induce hippocampal neurogenesis while preserving previously acquired memories, assessed with object recognition tests. In vitro studies with embryonic neural stem cells replicated the finding that both melatonin and IQM316 induce direct differentiation of neural precursors without altering their proliferative activity. Furthermore, IQM316 induces differentiation through a mechanism that is not dependent of melatonergic receptors (MTRs), since the MTR antagonist luzindole could not block the IQM316-induced effects. We also found that IQM316 and melatonin modulate mitochondrial DNA copy number and oxidative phosphorylation proteins, while maintaining mitochondrial function as measured by respiratory assays and enzymatic activity. These results uncover a novel pharmacological agent that may be capable of inducing adult hippocampal neurogenesis at a healthy and sustainable rate that preserves recognition memories. SAGE Publications 2018-06-06 2018-03 /pmc/articles/PMC6038050/ /pubmed/29873251 http://dx.doi.org/10.1177/0963689717721217 Text en © The Author(s) 2017 http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Articles
Figueiro-Silva, Joana
Antequera, Desireé
Pascual, Consuelo
de la Fuente Revenga, Mario
Volt, Huayqui
Acuña-Castroviejo, Darío
Rodríguez-Franco, María Isabel
Carro, Eva
The Melatonin Analog IQM316 May Induce Adult Hippocampal Neurogenesis and Preserve Recognition Memories in Mice
title The Melatonin Analog IQM316 May Induce Adult Hippocampal Neurogenesis and Preserve Recognition Memories in Mice
title_full The Melatonin Analog IQM316 May Induce Adult Hippocampal Neurogenesis and Preserve Recognition Memories in Mice
title_fullStr The Melatonin Analog IQM316 May Induce Adult Hippocampal Neurogenesis and Preserve Recognition Memories in Mice
title_full_unstemmed The Melatonin Analog IQM316 May Induce Adult Hippocampal Neurogenesis and Preserve Recognition Memories in Mice
title_short The Melatonin Analog IQM316 May Induce Adult Hippocampal Neurogenesis and Preserve Recognition Memories in Mice
title_sort melatonin analog iqm316 may induce adult hippocampal neurogenesis and preserve recognition memories in mice
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6038050/
https://www.ncbi.nlm.nih.gov/pubmed/29873251
http://dx.doi.org/10.1177/0963689717721217
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