Prominent decline of newborn cell proliferation, differentiation, and apoptosis in the aging dentate gyrus, in absence of an age-related hypothalamus–pituitary–adrenal axis activation
Abstract
Neurogenesis and apoptosis in the hippocampal dentate gyrus (DG) occur during development and adulthood. However, little is known about how these two processes relate to each other during aging. In this study, we examined apoptosis, proliferation, migration, and survival of newborn cells in the young (2 weeks), young-adult (6 weeks), middle-aged (12 months), and old (24 months) rat DG. We also measured dentate volume and cell numbers, along with basal corticosterone and stress response parameters. We show that new cell proliferation and apoptosis slow down profoundly over this time period. Moreover, migration and differentiation into a neuronal or glial phenotype was strongly reduced from 6 weeks of age onwards; it was hardly present in middle-aged and old rats as confirmed by confocal analysis. Surprisingly, we found no correlation between cell birth and corticosterone levels or stress response parameters in any age group.
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It is well accepted that neurogenesis sharply decreases in the aged mammalian nervous system, with no new neurons detectable in mice by 10 months of age.
“It is well accepted that neurogenesis sharply decreases in the aged mammalian nervous system29–31, with no new neurons detectable in mice by 10 months of age29,31.”
From Therapeutically viable generation of neurons with antisense oligonucleotide suppression of PTB (2021) · cites this paper as [31]
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- Authors
- Heine, V. M., Maslam, S., Joëls, M., & Lucassen, P. J.
- Affiliations
- University of Amsterdam (NL)
- Corresponding author
- Heine, Vivi M
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2004-03
- Volume
- 25
- Issue
- 3
- Pages
- 361-375
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2157252680
- Cited by
- 318
- References
- 7
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 6 · 2023: 4 · 2022: 11 · 2021: 10 · 2020: 9 · 2019: 7 · 2018: 8 · 2017: 12 · 2016: 13 · 2015: 11 · 2014: 18 · 2013: 17 · 2012: 12
- FWCI
- 4.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- UvA-DARE (University of Amsterdam) (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- dentate gyrus, hippocampal neurogenesis, aging, cell proliferation, apoptosis, neuronal differentiation, glial differentiation, corticosterone, hypothalamic-pituitary-adrenal axis, stress response
- MeSH terms
- Aging, Animals, Cell Count, Cell Differentiation, Cell Division, Cell Movement, Cell Survival, Corticosterone, Hypothalamo-Hypophyseal System, Male, Nerve Tissue Proteins, Neuroglia, Neurons, Phenotype, Pituitary-Adrenal System, Stem Cells, Stress, Physiological, Biomarkers, Rats, Wistar, Apoptosis, Dentate Gyrus, Rats
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