ArticleBioscience reports2016
Diabetes negatively affects cortical and striatal GABAergic neurons: an effect that is partially counteracted by exendin-4.
Article in Bioscience reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Investigating the functional connectivity between central glucagon-like peptide-1 (GLP-1) and glutamatergic signaling: a systematic review.CNS spectrums · 2026Pooled it
- Excitation-inhibition homeostasis in Alzheimer's disease: a selective multiscale review of mechanisms, sex differences, and therapeutic opportunities.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- Role of γ-Aminobutyric Acid (GABA) as an Inhibitory Neurotransmitter in Diabetes Management: Mechanisms and Therapeutic Implications.Biomolecules · 2025Review
- Normalisation of glucose metabolism by exendin-4 in the chronic phase after stroke promotes functional recovery in male diabetic mice.British journal of pharmacology · 2022Article
- Article
- GLP-1 Receptor Agonists: Beyond Their Pancreatic Effects.Frontiers in endocrinology · 2021Review
- Article
- Diabetes Mellitus-Related Dysfunction of the Motor System.International journal of molecular sciences · 2020Review
- Region-specific brain area reductions and increased cholecystokinin positive neurons in diabetic OLETF rats: implication for anxiety-like behavior.The journal of physiological sciences : JPS · 2020Article
- Long-Lasting Exendin-4 Fusion Protein Improves Memory Deficits in High-Fat Diet/Streptozotocin-Induced Diabetic Mice.Pharmaceutics · 2020Article
- Aging and Central Auditory Disinhibition: Is It a Reflection of Homeostatic Downregulation or Metabolic Vulnerability?Brain sciences · 2019Review
- Comprehensive transcriptomic analysis indicates brain regional specific alterations in type 2 diabetes.Aging · 2019Article
- Sitagliptin and Liraglutide Modulate L-dopa Effect and Attenuate Dyskinetic Movements in Rotenone-Lesioned Rats.Neurotoxicity research · 2019Article
- Type 2 Diabetes Leads to Axon Initial Segment Shortening inFrontiers in cellular neuroscience · 2018Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Type 2 diabetic (T2D) patients often develop early cognitive and sensorimotor impairments. The pathophysiological mechanisms behind these problems are largely unknown. Recent studies demonstrate that dysfunctional γ-aminobutyric acid (GABAergic) neurons are involved in age-related cognitive decline. We hypothesized that similar, but earlier dysfunction is taking place under T2D in the neocortex and striatum (two brain areas important for cognition and sensorimotor functions). We also hypothesized that the T2D-induced effects are pharmacologically reversible by anti-diabetic drugs targeting the glucagon-like peptide-1 receptor (GLP-1R). We determined the effect of T2D on cortical and striatal GABAergic neurons positive for glutamic acid decarboxylase-67 (GAD67), calbindin (CB), parvalbumin (PV) and calretinin (CR) by using immunohistochemistry and quantitative microscopy. Young and middle-aged T2D Goto-Kakizaki (GK) (a model of spontaneous T2D) and Wistar rats were used. Furthermore, we determined the therapeutic potential of the GLP1-R agonist exendin-4 (Ex-4) by treating middle-aged GK rats for 6 weeks with 0.1 μg/kg Ex-4 twice daily. We show that T2D reduced the density of GAD67-positive neurons in the striatum and of CB-positive neurons in both striatum and neocortex. T2D also increased the average volume of PV-positive interneurons in the striatum. Ex-4 treatment increased the density of CB-positive neurons in the striatum of GK rats. Our data demonstrate that T2D negatively affects GAD67 and CB-positive GABAergic neurons in the brain during aging, potentially identifying some of the pathophysiological mechanisms to explain the increased prevalence of neurological complications in T2D. We also show a specific, positive effect of Ex-4 on striatal CB-positive neurons, which could be exploited in therapeutic perspective.
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Registered trials
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