RT journal article
T1 Rescue of neurogenesis and age-associated cognitive decline in SAMP8 mouse: Role of transforming growth factor-alpha
A1 Gómez Oliva, Ricardo
A1 Martínez Ortega, Sergio
A1 Atienza Navarro, Isabel
A1 Domínguez García, Samuel
A1 Bernal Utrera, Carlos
A1 Geribaldi Doldán, Noelia
A1 Verástegui Escolano, Cristina
A1 Ezzanad, Abdellah
A1 Hernández Galán, Rosario
A1 Nunez Abades, Pedro
A1 García Alloza, Mónica
A1 Castro González, Carmen
A1 martinez, sergio
A2 Anatomía y Embriología Humana
A2 BiomedicinaBiotecnología y Salud Pública
A2 Química Orgánica
A2 Tecnologías del Medio Ambiente
K1 adult hippocampal neurogenesis
K1 aging
K1 dentate gyrus
K1 diterpenes
K1 memory
K1 neuroregeneration
K1 transforming growth factor-alpha
AB 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.
PB Wiley
SN 1474-9718
YR 2023
FD 2023-05-12
LK http://hdl.handle.net/10498/29687
UL http://hdl.handle.net/10498/29687
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 08-nov-2026