ArticleCNS neuroscience & therapeutics2024
GLT-1 downregulation in hippocampal astrocytes induced by type 2 diabetes contributes to postoperative cognitive dysfunction in adult mice.
Article in CNS neuroscience & therapeutics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Diabetes mellitus is associated with an increased risk of postoperative neurocognitive disorders: a systematic review.Frontiers in medicine · 2026Pooled it
- Cerebroprotective potential of ceftriaxone against cadmium chloride-induced cerebral inflammatory changes and oxidative insult.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Chronic alcohol exposure contributes to postoperative cognitive dysfunction via NR2B upregulation in the hippocampus of adult mice.Translational psychiatry · 2026Article
- Astrocytic GSTM2-STAT3 interaction ameliorates the diabetes associated cognitive dysfunction via targeting mitochondrial defects and oxidative stress.Redox biology · 2026Article
- Metabolic syndrome and perioperative neurocognitive disorders: epidemiology, mechanisms, and interventions.Frontiers in neuroscience · 2026Review
- Progress on exercise therapy in type 2 diabetes mellitus with cognitive impairment.Frontiers in sports and active living · 2026Review
- Chlorogenic Acid Alleviates the Detrimental Effects of Concurrent Hyperglycemia and Chronic Stress on Brain Homeostasis by Modulating Antioxidative Defense in Adult Zebrafish.Antioxidants (Basel, Switzerland) · 2025Article
- Unraveling the complexity of cognitive impairment following high-altitude exposure: from preclinical animal models to human organoids.Frontiers in neuroscience · 2025Review
- Structure and function of the blood-brain barrier in perioperative neurocognitive disorders.Frontiers in neuroscience · 2025Review
- GLT-1 downregulation in hippocampal astrocytes induced by type 2 diabetes contributes to postoperative cognitive dysfunction in adult mice.CNS neuroscience & therapeutics · 2024Article
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Abstract
aimsType 2 diabetes mellitus (T2DM) is related to an increased risk of postoperative cognitive dysfunction (POCD), which may be caused by neuronal hyperexcitability. Astrocyte glutamate transporter 1 (GLT-1) plays a crucial role in regulating neuron excitability. We investigated if T2DM would magnify the increased neuronal excitability induced by anesthesia/surgery (A/S) and lead to POCD in young adult mice, and if so, determined whether these effects were associated with GLT-1 expression.
methodsT2DM model was induced by high fat diet (HFD) and injecting STZ. Then, we evaluated the spatial learning and memory of T2DM mice after A/S with the novel object recognition test (NORT) and object location test (OLT). Western blotting and immunofluorescence were used to analyze the expression levels of GLT-1 and neuronal excitability. Oxidative stress reaction and neuronal apoptosis were detected with SOD2 expression, MMP level, and Tunel staining. Hippocampal functional synaptic plasticity was assessed with long-term potentiation (LTP). In the intervention study, we overexpressed hippocampal astrocyte GLT-1 in GFAP-Cre mice. Besides, AAV-Camkllα-hM4Di-mCherry was injected to inhibit neuronal hyperexcitability in CA1 region.
resultsOur study found T2DM but not A/S reduced GLT-1 expression in hippocampal astrocytes. Interestingly, GLT-1 deficiency alone couldn't lead to cognitive decline, but the downregulation of GLT-1 in T2DM mice obviously enhanced increased hippocampal glutamatergic neuron excitability induced by A/S. The hyperexcitability caused neuronal apoptosis and cognitive impairment. Overexpression of GLT-1 rescued postoperative cognitive dysfunction, glutamatergic neuron hyperexcitability, oxidative stress reaction, and apoptosis in hippocampus. Moreover, chemogenetic inhibition of hippocampal glutamatergic neurons reduced oxidative stress and apoptosis and alleviated postoperative cognitive dysfunction.
conclusionsThese findings suggest that the adult mice with type 2 diabetes are at an increased risk of developing POCD, perhaps due to the downregulation of GLT-1 in hippocampal astrocytes, which enhances increased glutamatergic neuron excitability induced by A/S and leads to oxidative stress reaction, and neuronal apoptosis.
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