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The melatonin analog IQM316 may induce adult hippocampal neurogenesis and preserve recognition memories in mice

AuthorsFigueiro-Silva, Joana ; Antequera, Desiree; Pascual, Consuelo; Fuente Revenga, Mario de la; Volt, H.; Acuña-Castroviejo, D.; Rodríguez-Franco, María Isabel ; Carro, Eva
Long-term memory
Adult neurogenesis
Neural stem cells
Issue Date2018
PublisherCognizant Communication Corporation
CitationCell Transplantation 27: 423-437 (2018)
AbstractNeurogenesis 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.
Publisher version (URL)http://dx.doi.org/10.1177/0963689717721217
Identifiersdoi: 10.1177/0963689717721217
issn: 0963-6897
e-issn: 1555-3892
Appears in Collections:(IQM) Artículos
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