ArticleDiabetologia2023
Disruption of cortical cell type composition and function underlies diabetes-associated cognitive decline.
Article in Diabetologia, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 19 citations in OpenAlex.
- Diabetic cerebral microvascular disorder: from key pathologies to targeted interventions.Annals of medicine · 2026Review
- Integrating GLP-1 Receptor Agonists into Modern Stroke Prevention: Evidence, Mechanisms, and Clinical Consideration-A Narrative Review.Biomedicines · 2026Review
- Differential pericyte pathology in the human retina and brain in diabetes mellitus and Alzheimer's disease.Frontiers in neuroscience · 2026Article
- Border-associated macrophages: an emerging perspective from physiological basis and multi-disease roles to the mechanism of vascular cognitive impairment and dementia.Journal of neuroinflammation · 2025Review
- Trelagliptin Ameliorates Memory Decline in Diabetic Rats through the AMPK/AKT/GSK-3β Pathway in the Cerebral Cortex.ACS omega · 2025Article
- Single-Cell Analysis in Cerebrovascular Research: Primed for Breakthroughs and Clinical Impact.Stroke · 2025Review
- SGK1 drives hippocampal demyelination and diabetes-associated cognitive dysfunction in mice.Nature communications · 2025Article
- Alzheimer's disease and diabetes-associated cognitive dysfunction: the microglia link?Metabolic brain disease · 2025Article
- Identification of common biomarkers in diabetic kidney disease and cognitive dysfunction using machine learning algorithms.Scientific reports · 2024Article
- Insights into the Pathobiology of GM1 Gangliosidosis from Single-Nucleus Transcriptomic Analysis of CNS Cells in a Mouse Model.International journal of molecular sciences · 2024Article
- New Insights in ATP Synthesis as Therapeutic Target in Cancer and Angiogenic Ocular Diseases.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2024Review
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Authors and funding
16 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisType 2 diabetes is associated with increased risk of cognitive decline although the pathogenic basis for this remains obscure. Deciphering diabetes-linked molecular mechanisms in cells of the cerebral cortex could uncover novel therapeutic targets.
methodsSingle-cell transcriptomic sequencing (scRNA-seq) was conducted on the cerebral cortex in a mouse model of type 2 diabetes (db/db mice) and in non-diabetic control mice in order to identify gene expression changes in distinct cell subpopulations and alterations in cell type composition. Immunohistochemistry and metabolic assessment were used to validate the findings from scRNA-seq and to investigate whether these cell-specific dysfunctions impact the neurovascular unit (NVU). Furthermore, the behavioural and cognitive alterations related to these dysfunctions in db/db mice were assessed via Morris water maze and novel object discrimination tests. Finally, results were validated in post-mortem sections and protein isolates from individuals with type 2 diabetes.
resultsCompared with non-diabetic control mice, the db/db mice demonstrated disrupted brain function as revealed by losses in episodic and spatial memory and this occurred concomitantly with dysfunctional NVU, neuronal circuitry and cerebral atrophy. scRNA-seq of db/db mouse cerebral cortex revealed cell population changes in neurons, glia and microglia linked to functional regulatory disruption including neuronal maturation and altered metabolism. These changes were validated through immunohistochemistry and protein expression analysis not just in the db/db mouse cerebral cortex but also in post-mortem sections and protein isolates from individuals with type 2 diabetes (74.3 ± 5.5 years) compared with non-diabetic control individuals (87.0 ± 8.5 years). Furthermore, metabolic and synaptic gene disruptions were evident in cortical NVU cell populations and associated with a decrease in vascular density. CONCLUSIONS/
interpretationTaken together, our data reveal disruption in the cellular and molecular architecture of the cerebral cortex induced by diabetes, which can explain, at least in part, the basis for progressive cognitive decline in individuals with type 2 diabetes. DATA AVAILABILITY: The single-cell sequencing data that supports this study are available at GEO accession GSE217665 ( https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE217665 ).
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