[en] 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.
Gómez Oliva, Ricardo ; Université de Liège - ULiège > GIGA > GIGA Neurosciences - Molecular Regulation of Neurogenesis ; Área de Fisiología, Facultad de Medicina, Universidad de Cádiz, Cádiz, Spain ; Instituto de Investigación e Innovación Biomédica de Cádiz (INIBICA), Cádiz, Spain
Martínez-Ortega, Sergio; Área de Fisiología, Facultad de Medicina, Universidad de Cádiz, Cádiz, Spain ; Instituto de Investigación e Innovación Biomédica de Cádiz (INIBICA), Cádiz, Spain
Atienza-Navarro, Isabel ; Área de Fisiología, Facultad de Medicina, Universidad de Cádiz, Cádiz, Spain ; Instituto de Investigación e Innovación Biomédica de Cádiz (INIBICA), Cádiz, Spain
Domínguez-García, Samuel ; Área de Fisiología, Facultad de Medicina, Universidad de Cádiz, Cádiz, Spain ; Instituto de Investigación e Innovación Biomédica de Cádiz (INIBICA), Cádiz, Spain
Bernal-Utrera, Carlos ; Instituto de Investigación e Innovación Biomédica de Cádiz (INIBICA), Cádiz, Spain ; Departamento de Fisioterapia, Universidad de Sevilla, Seville, Spain
Geribaldi-Doldán, Noelia ; Instituto de Investigación e Innovación Biomédica de Cádiz (INIBICA), Cádiz, Spain ; Departamento de Anatomía y Embriología Humanas, Facultad de Medicina, Universidad de Cádiz, Cádiz, Spain
Verástegui, Cristina ; Instituto de Investigación e Innovación Biomédica de Cádiz (INIBICA), Cádiz, Spain ; Departamento de Anatomía y Embriología Humanas, Facultad de Medicina, Universidad de Cádiz, Cádiz, Spain
Ezzanad, Abdellah ; Instituto de Investigación e Innovación Biomédica de Cádiz (INIBICA), Cádiz, Spain ; Departamento de Química Orgánica, Universidad de Cádiz, Puerto Real, Spain
Hernández-Galán, Rosario ; Instituto de Investigación e Innovación Biomédica de Cádiz (INIBICA), Cádiz, Spain ; Departamento de Química Orgánica, Universidad de Cádiz, Puerto Real, Spain
Nunez-Abades, Pedro ; Instituto de Investigación e Innovación Biomédica de Cádiz (INIBICA), Cádiz, Spain ; Departamento de Fisiología, Universidad de Sevilla, Sevilla, Spain
Garcia-Alloza, Monica ; Área de Fisiología, Facultad de Medicina, Universidad de Cádiz, Cádiz, Spain ; Instituto de Investigación e Innovación Biomédica de Cádiz (INIBICA), Cádiz, Spain
Castro, Carmen ; Área de Fisiología, Facultad de Medicina, Universidad de Cádiz, Cádiz, Spain ; Instituto de Investigación e Innovación Biomédica de Cádiz (INIBICA), Cádiz, Spain
Language :
English
Title :
Rescue of neurogenesis and age-associated cognitive decline in SAMP8 mouse: Role of transforming growth factor-alpha.
This work was supported by the Spanish Agencia Estatal de Investigación (grant number RTI‐2018‐099908‐B‐C21 and RTI‐2018‐099908‐B‐C22 granted to Carmen Castro). This work has been co‐financed by the European Union under the 2014‐2020 ERDF Operational Programme and by the Department of Economic Transformation, Industry, Knowledge, and Universities of the Regional Government of Andalusia. Project reference: (grant number FEDER‐UCA18‐106647 granted to Carmen Castro). This work has been co‐financed and by the Consejería de Salud y Familias and by EDRF ITI regional funds (80%) (Grant number: ITI‐Cadiz‐0042‐2019 granted to Carmen Castro).We thank the Servicio de experimentación y producción animal (SEPA) de la Universidad de Cádiz as well as the Servicios Centrales de apoyo a la investigación en Ciencias de la Salud (SCICS) and Servicios centrales de Ciencia y tecnología (SC-ICYT) de la Universidad de Cádiz.
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