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Rescue of neurogenesis and age‐associated cognitive decline in SAMP8 mouse: Role of transforming growth factor‐alpha
Neuropathological aging is associated with memory impairment and cognitive decline, affecting several brain areas including the neurogenic niche of the dentate gyrus of the hippocampus (DG). In the healthy brain, homeostatic mechanisms regulate neurogenesis within the DG to facilitate the continuous...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10265154/ https://www.ncbi.nlm.nih.gov/pubmed/37177826 http://dx.doi.org/10.1111/acel.13829 |
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author | Gómez‐Oliva, Ricardo Martínez‐Ortega, Sergio Atienza‐Navarro, Isabel Domínguez‐García, Samuel Bernal‐Utrera, Carlos Geribaldi‐Doldán, Noelia Verástegui, Cristina Ezzanad, Abdellah Hernández‐Galán, Rosario Nunez‐Abades, Pedro Garcia‐Alloza, Monica Castro, Carmen |
author_facet | Gómez‐Oliva, Ricardo Martínez‐Ortega, Sergio Atienza‐Navarro, Isabel Domínguez‐García, Samuel Bernal‐Utrera, Carlos Geribaldi‐Doldán, Noelia Verástegui, Cristina Ezzanad, Abdellah Hernández‐Galán, Rosario Nunez‐Abades, Pedro Garcia‐Alloza, Monica Castro, Carmen |
author_sort | Gómez‐Oliva, Ricardo |
collection | PubMed |
description | Neuropathological aging is associated with memory impairment and cognitive decline, affecting several brain areas including the neurogenic niche of the dentate gyrus of the hippocampus (DG). In the healthy brain, homeostatic mechanisms regulate neurogenesis within the DG to facilitate the continuous generation of neurons from neural stem cells (NSC). Nevertheless, aging reduces the number of activated neural stem cells and diminishes the number of newly generated neurons. Strategies that promote neurogenesis in the DG may improve cognitive performance in the elderly resulting in the development of treatments to prevent the progression of neurological disorders in the aged population. Our work is aimed at discovering targeting molecules to be used in the design of pharmacological agents that prevent the neurological effects of brain aging. We study the effect of age on hippocampal neurogenesis using the SAMP8 mouse as a model of neuropathological aging. We show that in 6‐month‐old SAMP8 mice, episodic and spatial memory are impaired; concomitantly, the generation of neuroblasts and neurons is reduced and the generation of astrocytes is increased in this model. The novelty of our work resides in the fact that treatment of SAMP8 mice with a transforming growth factor‐alpha (TGFα) targeting molecule prevents the observed defects, positively regulating neurogenesis and improving cognitive performance. This compound facilitates the release of TGFα in vitro and in vivo and activates signaling pathways initiated by this growth factor. We conclude that compounds of this kind that stimulate neurogenesis may be useful to counteract the neurological effects of pathological aging. |
format | Online Article Text |
id | pubmed-10265154 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-102651542023-06-15 Rescue of neurogenesis and age‐associated cognitive decline in SAMP8 mouse: Role of transforming growth factor‐alpha Gómez‐Oliva, Ricardo Martínez‐Ortega, Sergio Atienza‐Navarro, Isabel Domínguez‐García, Samuel Bernal‐Utrera, Carlos Geribaldi‐Doldán, Noelia Verástegui, Cristina Ezzanad, Abdellah Hernández‐Galán, Rosario Nunez‐Abades, Pedro Garcia‐Alloza, Monica Castro, Carmen Aging Cell Research Articles Neuropathological aging is associated with memory impairment and cognitive decline, affecting several brain areas including the neurogenic niche of the dentate gyrus of the hippocampus (DG). In the healthy brain, homeostatic mechanisms regulate neurogenesis within the DG to facilitate the continuous generation of neurons from neural stem cells (NSC). Nevertheless, aging reduces the number of activated neural stem cells and diminishes the number of newly generated neurons. Strategies that promote neurogenesis in the DG may improve cognitive performance in the elderly resulting in the development of treatments to prevent the progression of neurological disorders in the aged population. Our work is aimed at discovering targeting molecules to be used in the design of pharmacological agents that prevent the neurological effects of brain aging. We study the effect of age on hippocampal neurogenesis using the SAMP8 mouse as a model of neuropathological aging. We show that in 6‐month‐old SAMP8 mice, episodic and spatial memory are impaired; concomitantly, the generation of neuroblasts and neurons is reduced and the generation of astrocytes is increased in this model. The novelty of our work resides in the fact that treatment of SAMP8 mice with a transforming growth factor‐alpha (TGFα) targeting molecule prevents the observed defects, positively regulating neurogenesis and improving cognitive performance. This compound facilitates the release of TGFα in vitro and in vivo and activates signaling pathways initiated by this growth factor. We conclude that compounds of this kind that stimulate neurogenesis may be useful to counteract the neurological effects of pathological aging. John Wiley and Sons Inc. 2023-05-12 /pmc/articles/PMC10265154/ /pubmed/37177826 http://dx.doi.org/10.1111/acel.13829 Text en © 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Gómez‐Oliva, Ricardo Martínez‐Ortega, Sergio Atienza‐Navarro, Isabel Domínguez‐García, Samuel Bernal‐Utrera, Carlos Geribaldi‐Doldán, Noelia Verástegui, Cristina Ezzanad, Abdellah Hernández‐Galán, Rosario Nunez‐Abades, Pedro Garcia‐Alloza, Monica Castro, Carmen Rescue of neurogenesis and age‐associated cognitive decline in SAMP8 mouse: Role of transforming growth factor‐alpha |
title | Rescue of neurogenesis and age‐associated cognitive decline in SAMP8 mouse: Role of transforming growth factor‐alpha |
title_full | Rescue of neurogenesis and age‐associated cognitive decline in SAMP8 mouse: Role of transforming growth factor‐alpha |
title_fullStr | Rescue of neurogenesis and age‐associated cognitive decline in SAMP8 mouse: Role of transforming growth factor‐alpha |
title_full_unstemmed | Rescue of neurogenesis and age‐associated cognitive decline in SAMP8 mouse: Role of transforming growth factor‐alpha |
title_short | Rescue of neurogenesis and age‐associated cognitive decline in SAMP8 mouse: Role of transforming growth factor‐alpha |
title_sort | rescue of neurogenesis and age‐associated cognitive decline in samp8 mouse: role of transforming growth factor‐alpha |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10265154/ https://www.ncbi.nlm.nih.gov/pubmed/37177826 http://dx.doi.org/10.1111/acel.13829 |
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