What is the Dentate Gyrus?
The dentate gyrus (DG) is a critical subregion of the hippocampus, involved in memory formation. Shaped like a tooth, the DG processes information entering the hippocampal formation.
The Role of Pattern Separation
A key function of the DG is pattern separation, the ability to distinguish between similar pieces of information to create unique memories. Impaired pattern separation can lead to confusion between similar past and present events, for example, forgetting where you parked today versus yesterday. This function is crucial for accurate episodic memory encoding and retrieval.
The Age-Related Decline in Neurogenesis
Aging significantly impacts neurogenesis, the creation of new neurons, in the dentate gyrus. The subgranular zone (SGZ) of the DG is one of the few brain areas producing new neurons throughout life. However, with age, the proliferation of neural stem cells decreases, and the survival of new neurons is reduced. This decline in neurogenesis correlates with age-related cognitive changes, although the extent in healthy aging humans compared to animals is debated.
Structural and Functional Changes
Aging causes various structural and functional changes in the DG:
- Synaptic Changes: While some studies note synapse loss, others suggest remaining synapses enlarge. Overall, the efficiency of synaptic transmission is reduced, and long-term potentiation (LTP), vital for encoding new information, is harder to induce.
- Hilar Neuron Loss: Aging leads to a significant loss of hilar neurons, interneurons important for regulating DG information flow. This loss increases susceptibility to damage and impairs filtering.
- Impaired Filter Function: The DG's ability to filter excitatory input from other brain regions declines with age. This contributes to reduced spatial learning and memory.
- Neuroinflammation: Aging involves increased brain inflammation ('inflammaging'), including inflammatory cell invasion and changes in glial cells within the DG. This neuroinflammation can decrease neurogenesis and worsen age-related cognitive problems.
Age-related vs. Alzheimer's Pathology
Normal age-related changes in the DG differ from Alzheimer's disease (AD) pathology. While the DG is affected by aging, the entorhinal cortex, its primary input source, is the region most severely and earliest impacted by AD (tau tangles and amyloid-beta plaques). {Link: ScienceDirect https://www.sciencedirect.com/science/article/abs/pii/S0079612307630374}
Factors Influencing and Mitigating Age-Related Effects
Lifestyle factors can influence the impact of aging on the DG.
The Impact of Physical Activity
{Link: ScienceDirect https://www.sciencedirect.com/science/article/pii/S0197458005002605}
- Increased Neurogenesis: Regular exercise, particularly aerobic, can increase the number of proliferating precursor cells and support the survival of new neurons.
- Improved Cognition: Exercise is linked to increased hippocampal volume and better memory in humans, potentially via increased brain-derived neurotrophic factor (BDNF).
Mental Stimulation and Cognitive Reserve
Mentally stimulating activities build cognitive reserve, buffering against age-related changes.. Engaging in new challenges may stimulate hippocampal function and promote neural plasticity.
The Role of Diet and Stress
- Diet: Poor glucose control negatively affects the DG, emphasizing the importance of a healthy diet.
- Stress: Chronic stress and high stress hormone levels can inhibit DG neurogenesis.
Comparison of Healthy Dentate Gyrus vs. Aged Dentate Gyrus
| Feature | Healthy Dentate Gyrus | Aged Dentate Gyrus |
|---|---|---|
| Neurogenesis | Robust production of new neurons in the subgranular zone. | Significant decline in the proliferation of neural stem cells and neuron production. |
| Synaptic Plasticity (LTP) | Strong, easily induced long-term potentiation, facilitating new memory formation. | Increased threshold for LTP induction and decreased durability, hindering memory encoding. |
| Hilar Neurons | Stable population of hilar neurons, crucial for regulated network activity. | Significant reduction in hilar neurons, increasing vulnerability to damage. |
| Pattern Separation | Efficiently distinguishes between similar patterns and memories. | Impaired pattern separation, leading to difficulty discriminating between similar experiences. |
| Neuroinflammation | Low levels of inflammation, balanced immune environment. | Increased neuroinflammation and reactive glial cells, potentially inhibiting neurogenesis. |
| Overall Function | Optimal cognitive function, especially for learning and memory. | Suboptimal cognitive function, contributing to age-related memory decline. |
Conclusion
Aging significantly impacts the dentate gyrus, causing cellular and functional changes. Key impacts include reduced adult neurogenesis, compromised synaptic plasticity, and increased neuroinflammation, all affecting its crucial pattern separation function. While these are normal age-related changes, lifestyle factors like exercise, mental stimulation, and stress management can mitigate these effects and support cognitive health. {Link: ScienceDirect https://www.sciencedirect.com/science/article/abs/pii/S0079612307630374}
For more information on the critical role of physical activity, visit the National Institutes of Health page on the topic: Brain-Derived Neurotrophic Factor and the Aging Hippocampus.
