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Published on: March 23, 2011
Mapping the transcriptomic changes of endothelial compartment in human hippocampus across aging and mild cognitive
Daniel V Guebel1,2, Néstor V Torres2, Ángel Acebes3
1Program Agustín de Betancourt, Universidad de La Laguna, Tenerife 38200, Spain.
Insights
This study computationally analyzed hippocampal vascular molecular signatures in young adults, aged individuals, and those with mild cognitive impairment (MCI). Aged individuals showed significant vascular endothelial cell dysfunction, impacting brain health and neurodegeneration.
Area of Science:
- Neuroscience
- Vascular Biology
- Genomics
Background:
- Vascular compromise significantly impacts cognitive function and neurodegeneration.
- Understanding hippocampal vascular molecular signatures is crucial for addressing these pathologies.
- Direct hippocampal vascular experimentation is challenging.
Purpose of the Study:
- To computationally identify molecular signatures in human hippocampal blood vessels across different age groups.
- To compare vascular changes in young adults, aged individuals, and those with mild cognitive impairment (MCI).
Main Methods:
- Utilized publicly available whole microarray data from human hippocampal homogenates.
- Computationally disaggregated data for three conditions: 'Young Adults', 'Aged', and 'aged with Mild Cognitive Impairment' (MCI).
- Validated identified genes against two independent datasets.
Main Results:
- Endothelial cells in 'Young Adults' exhibited an 'activated stage'.
- In 'Aged' individuals, endothelial cells displayed reduced shear stress response, altered adhesion molecules, increased inflammation, brain-insulin resistance, lipid alterations, and extracellular matrix changes.
- Specific vascular changes were noted in the MCI group.
Conclusions:
- Aged hippocampal vasculature shows significant functional and molecular alterations, including loss of shear stress response and increased inflammation.
- Observed features like high tortuosity and smooth muscle proliferation in aged individuals require further study to differentiate arteriogenesis from vascular remodeling.
- Findings provide a molecular basis for understanding age-related cognitive decline and neurodegeneration linked to vascular health.
Abstract:
Compromise of the vascular system has important consequences on cognitive abilities and neurodegeneration. The identification of the main molecular signatures present in the blood vessels of human hippocampus could provide the basis to understand and tackle these pathologies. As direct vascular experimentation in hippocampus is problematic, we achieved this information by computationally disaggregating publicly available whole microarrays data of human hippocampal homogenates. Three conditions were analyzed: 'Young Adults', 'Aged', and 'aged with Mild Cognitive Impairment' (MCI). The genes identified were contrasted against two independent data-sets. Here we show that the endothelial cells from the Younger Group appeared in an 'activated stage'. In turn, in the Aged Group, the endothelial cells showed a significant loss of response to shear stress, changes in cell adhesion molecules, increased inflammation, brain-insulin resistance, lipidic alterations, and changes in the extracellular matrix. Some specific changes in the MCI group were also detected. Noticeably, in this study the features arisen from the Aged Group (high tortuosity, increased bifurcations, and smooth muscle proliferation), pose the need for further experimental verification to discern between the occurrence of arteriogenesis and/or vascular remodeling by capillary arterialization. This article has an associated First Person interview with the first author of the paper.
