Changes in the structural complexity of the aged brain
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Summary: Structural changes of neurons in the brain during aging are complex and not well understood. Neurons have significant homeostatic control of essential brain functions, including synaptic excitability, gene expression, and metabolic regulation. Any deviations from the norm can have severe consequences as seen in aging and injury. In this review, we present some of the structural adaptations that neurons undergo throughout normal and pathological aging and discuss their effects on electrophysiological properties and cognition. During aging, it is evident that neurons undergo morphological changes such as a reduction in the complexity of dendrite arborization and dendritic length. Spine numbers are also decreased, and because spines are the major sites for excitatory synapses, changes in their numbers could reflect a change in synaptic densities. This idea has been supported by studies that demonstrate a decrease in the overall frequency of spontaneous glutamate receptor‐mediated excitatory responses, as well as a decrease in the levels of α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid and N‐methyl‐d‐aspartate receptor expression. Other properties such as γ‐aminobutyric acid A receptor‐mediated inhibitory responses and action potential firing rates are both significantly increased with age. These findings suggest that age‐related neuronal dysfunction, which must underlie observed decline in cognitive function, probably involves a host of other subtle changes within the cortex that could include alterations in receptors, loss of dendrites, and spines and myelin dystrophy, as well as the alterations in synaptic transmission. Together these multiple alterations in the brain may constitute the substrate for age‐related loss of cognitive function.
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Neurite morphology is a substrate of neural function.
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The age-related decrease in cortical ODI is in line with histology showing age-related decreases of dendritic complexity and density.
“which is in line with histology showing age-related decreases of dendritic complexity and density (Dickstein et al., 2007).”
From NODDI in clinical research (2020) · cites this paper as Dickstein et al., 2007
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- Authors
- Dickstein, D. L., Kabaso, D., Rocher, A. B., Luebke, J. I., Wearne, S. L., & Hof, P. R.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Boston University (US)
- Corresponding author
- Dickstein, Dara L.
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2007-03-16
- Volume
- 6
- Issue
- 3
- Pages
- 275-284
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- PMC
- PMC2441530
- OpenAlex
- W2084792449
- Cited by
- 460
- References
- 9
- Citations by year
- 2026: 15 · 2025: 25 · 2024: 23 · 2023: 27 · 2022: 17 · 2021: 47 · 2020: 23 · 2019: 21 · 2018: 22 · 2017: 16 · 2016: 26 · 2015: 20 · 2014: 14 · 2013: 24 · 2012: 27
- FWCI
- 2.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Aging Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (AG-02219, AG 05138, P50AG005138, R01AG025062, P01AG000001, AG00001, P01AG002219)
- National Institute of Mental Health (R01MH071818, MH71818)
- National Institute on Deafness and Other Communication Disorders (DC05669, R01DC005669)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- brain aging, dendritic branching, dendritic spine loss, synaptic density, glutamate receptors, NMDA receptor, GABAA receptor, action potential firing rate, cognitive decline, synaptic transmission
- MeSH terms
- Action Potentials, Aged, Aging, Alzheimer Disease, Brain, Dendrites, Electrophysiology, gamma-Aminobutyric Acid, Homeostasis, Humans, Models, Biological, Models, Neurological, Neurons, Receptors, Glutamate, Dendritic Spines
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