Sex-Specific Neurogenic and Cognitive Responses in a Murine Model of Accelerated Aging.
5 affiliations
- 1Área de Fisiología, Facultad de Medicina, Universidad de Cádiz, Cádiz, Spain.
- 2Instituto de Investigación e Innovación Biomédica de Cádiz, Cádiz, Spain.
- 3Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, Sevilla, Spain.
- 4Hospital Universitario Puerta del Mar de Cádiz, Cádiz, Spain.
- 5Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Cádiz, Cádiz, Spain.
Abstract
Aging is associated with cognitive deterioration accompanied by a reduction in hippocampal neurogenesis. Murine models have been widely used to study aging and age-related cognitive decline, as they recapitulate many of the key features of the degenerative process. Among these, the SAMP8 strain represents a well-established model of accelerated aging, characterized by early-onset and progressive cognitive impairment, Alzheimer's disease-like neuropathology, and an initial increase in hippocampal neurogenesis that ultimately depletes the neural stem cell pool. Notably, most studies using murine models of aging or neurodegeneration have focused on males or mixed-sex cohorts, leaving sex-specific differences in neurogenesis and cognitive decline largely unexplored. Recent evidence indicates that diterpenoid treatment is associated with improved cognitive performance and enhanced neurogenesis in 6-month-old male SAMP8 mice. However, whether females exhibit similar responses remains unknown. In this study, we characterized sex differences in hippocampal neurogenesis in 6-month-old SAMP8 mice and examined potential sex-dependent effects of diterpenoid therapy. Our findings reveal sex-specific differences in physiological and pathological hippocampal neurogenesis and in responsiveness to ER272 treatment. Male SAMR1 mice displayed higher baseline neurogenesis than females, while male and female SAMP8 mice followed distinct neurogenic aging trajectories. ER272 was associated with improved cognitive performance and preservation of multiple neurogenic parameters in males but showed limited effects in females. These results suggest sex-specific mechanisms of brain aging and indicate that mixed-sex analyses may mask biologically relevant differences, highlighting the importance of considering sex in aging studies and therapeutic development.
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BibTeX
@article{gomezoliva2026sexspecific,
title = {{Sex-Specific Neurogenic and Cognitive Responses in a Murine Model of Accelerated Aging.}},
author = {Ricardo Gómez-Oliva and Andrea Chamorro-Francisco and Isabel Atienza-Navarro and Livia Carrascal and María D Freire-Aragón and Rosario Hernández-Galán and Pedro Nunez-Abades and Mónica García-Alloza and Carmen Castro},
journal = {Aging cell},
year = {2026},
month = oct,
doi = {10.1111/acel.70663},
url = {https://europepmc.org/article/MED/42853103},
note = {CC BY},
}
RIS
TY - JOUR
TI - Sex-Specific Neurogenic and Cognitive Responses in a Murine Model of Accelerated Aging.
AU - Ricardo Gómez-Oliva
AU - Andrea Chamorro-Francisco
AU - Isabel Atienza-Navarro
AU - Livia Carrascal
AU - María D Freire-Aragón
AU - Rosario Hernández-Galán
AU - Pedro Nunez-Abades
AU - Mónica García-Alloza
AU - Carmen Castro
PY - 2026
DA - 2026/10/01
JO - Aging cell
DO - 10.1111/acel.70663
UR - https://europepmc.org/article/MED/42853103
AB - Aging is associated with cognitive deterioration accompanied by a reduction in hippocampal neurogenesis. Murine models have been widely used to study aging and age-related cognitive decline, as they recapitulate many of the key features of the degenerative process. Among these, the SAMP8 strain represents a well-established model of accelerated aging, characterized by early-onset and progressive cognitive impairment, Alzheimer's disease-like neuropathology, and an initial increase in hippocampal neurogenesis that ultimately depletes the neural stem cell pool. Notably, most studies using murine models of aging or neurodegeneration have focused on males or mixed-sex cohorts, leaving sex-specific differences in neurogenesis and cognitive decline largely unexplored. Recent evidence indicates that diterpenoid treatment is associated with improved cognitive performance and enhanced neurogenesis in 6-month-old male SAMP8 mice. However, whether females exhibit similar responses remains unknown. In this study, we characterized sex differences in hippocampal neurogenesis in 6-month-old SAMP8 mice and examined potential sex-dependent effects of diterpenoid therapy. Our findings reveal sex-specific differences in physiological and pathological hippocampal neurogenesis and in responsiveness to ER272 treatment. Male SAMR1 mice displayed higher baseline neurogenesis than females, while male and female SAMP8 mice followed distinct neurogenic aging trajectories. ER272 was associated with improved cognitive performance and preservation of multiple neurogenic parameters in males but showed limited effects in females. These results suggest sex-specific mechanisms of brain aging and indicate that mixed-sex analyses may mask biologically relevant differences, highlighting the importance of considering sex in aging studies and therapeutic development.
SN - 1474-9718
SN - 1474-9726
ER -