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Possible mechanisms for atrophy of the human hippocampus
1Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, NY 10021, USA. mcewen@rockvax.rockefeller.edu
Abstract:
Recently published work using MRI to image the human brain has revealed that the hippocampal formation undergoes a selective atrophy in diverse conditions such as Cushing's syndrome, post-traumatic stress disorder, recurrent depressive illness, normal aging preceding dementia and in Alzheimer's disease. Hippocampal shrinkage is usually accompanied by deficits in declarative, episodic, spatial and contextual memory performance and the hippocampal changes provide a neural substrate for changes in cognitive function that have been recognized to accompany these various conditions. The hippocampus has long been known as a target of stress hormones, and it is an especially plastic and vulnerable region of the brain. However, the prominence of the hippocampus as a glucocorticoid target has obscured the fact that other factors besides glucocorticoid hormones are involved in the process of hippocampal atrophy. Excitatory amino acids and NMDA receptors are prominent in their involvement in an animal model of hippocampal atrophy as well as in neuronal death. Further-more, the finding of hippocampal atrophy does not necessarily imply a permanent loss of cells, and this aspect deserves careful investigation, both to analyze the underlying anatomical changes and to investigate the possibility of pharmacological treatment to reverse the process. In cases where atrophy is due to cell loss, the time course of the disease process will provide much useful information about mechanism and offer the possibility of early intervention to arrest or slow the pathological process.
Insights
Hippocampal atrophy, or shrinkage, is observed in various conditions including aging and Alzheimer's disease, impacting memory. Research suggests factors beyond stress hormones contribute to this brain change.
Area of Science:
- Neuroscience
- Radiology
Background:
- The hippocampal formation shows selective atrophy in conditions like Cushing's syndrome, PTSD, depression, aging, and Alzheimer's disease.
- Hippocampal shrinkage correlates with memory deficits (declarative, episodic, spatial, contextual), indicating a neural basis for cognitive changes.
- The hippocampus is known for its plasticity and vulnerability, being a target of stress hormones, but other factors are also implicated in its atrophy.
Purpose of the Study:
- To investigate the neural substrates of cognitive decline associated with hippocampal atrophy.
- To explore factors beyond glucocorticoids involved in hippocampal atrophy.
- To examine whether hippocampal atrophy implies permanent cell loss and explore potential for reversal.
Main Methods:
- Magnetic Resonance Imaging (MRI) was used to image the human brain.
- Analysis of diverse conditions associated with hippocampal atrophy.
- Investigation of the role of excitatory amino acids and NMDA receptors in animal models.
Main Results:
- MRI reveals selective hippocampal atrophy across multiple neurological and psychiatric conditions.
- Hippocampal changes are linked to specific memory performance deficits.
- Excitatory amino acids and NMDA receptors are implicated in hippocampal atrophy and neuronal death in animal models.
Conclusions:
- Glucocorticoid hormones are not the sole cause of hippocampal atrophy; other factors like excitatory amino acids are involved.
- Hippocampal atrophy may not always involve permanent cell loss, suggesting potential for therapeutic intervention.
- Further research into anatomical changes and pharmacological treatments is warranted to potentially reverse hippocampal atrophy.