ArticleBritish journal of pharmacology2016
PPARγ agonists regulate bidirectional transport of amyloid-β across the blood-brain barrier and hippocampus plasticity in db/db mice.
Article in British journal of pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
- Observational
- Novel Insights into the Mechanism and Treatment of Diabetes-Related Brain Complications: Focusing on the Blood-Brain Barrier Impairment.Aging and disease · 2025Review
- Exploring the molecular mechanisms of PPARγ agonists in modulating memory impairment in neurodegenerative disorders.Molecular biology reports · 2024Review
- New insights toward molecular and nanotechnological approaches to antidiabetic agents for Alzheimer's disease.Molecular and cellular biochemistry · 2023Review
- Review
- PHPB Attenuated Cognitive Impairment in Type 2 Diabetic KK-Ay Mice by Modulating SIRT1/Insulin Signaling Pathway and Inhibiting Generation of AGEs.Pharmaceuticals (Basel, Switzerland) · 2023Article
- CoQJournal of clinical medicine · 2020Article
- Berberine Improves Inflammatory Responses of Diabetes Mellitus in Zucker Diabetic Fatty Rats and Insulin-Resistant HepG2 Cells through the PPM1B Pathway.Journal of immunology research · 2020Article
- Impairment of cognitive flexibility in type 2 diabetic db/db mice.Behavioural brain research · 2019Article
- Low-dose pioglitazone can ameliorate learning and memory impairment in a mouse model of dementia by increasing LRP1 expression in the hippocampus.Scientific reports · 2019Article
- Leptin receptor deficiency induces early, transient and hyperglycaemia-independent blood-brain barrier dysfunction.Scientific reports · 2019Article
- Albumin Exchange in Alzheimer's Disease: Might CSF Be an Alternative Route to Plasma?Frontiers in neurology · 2019Article
- Inhibiting the NLRP3 Inflammasome Activation with MCC950 Ameliorates Diabetic Encephalopathy in db/db Mice.Molecules (Basel, Switzerland) · 2018Article
- Type 2 Diabetes Leads to Axon Initial Segment Shortening inFrontiers in cellular neuroscience · 2018Article
- 1, 25-DFrontiers in cellular neuroscience · 2018Article
- Pancreatic islet regeneration through PDX-1/Notch-1/Ngn3 signaling after gastric bypass surgery in db/db mice.Experimental and therapeutic medicine · 2017Article
- Effect of rosiglitazone on amyloid precursor protein processing and Aβ clearance in streptozotocin-induced rat model of Alzheimer's disease.Iranian journal of basic medical sciences · 2017Article
- The restorative role of annexin A1 at the blood-brain barrier.Fluids and barriers of the CNS · 2016Review
- PPARγ agonists regulate bidirectional transport of amyloid-β across the blood-brain barrier and hippocampus plasticity in db/db mice.British journal of pharmacology · 2016Article
- Antidiabetic Drugs for the Risk of Alzheimer Disease in Patients With Type 2 DM Using FAERS.American journal of Alzheimer's disease and other dementiasArticle
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeThere is emerging evidence suggesting that abnormal transport of amyloid-β (Aβ) across the blood-brain barrier (BBB) is involved in diabetes-associated cognitive decline. We investigated whether PPARγ agonists restore Aβ transport across the BBB and hippocampal plasticity in db/db mice. EXPERIMENTAL APPROACH: Efflux and influx of Aβ across the BBB were determined by stereotaxic intra-cerebral or i.a. infusion of [(125) I]-Aβ1-40 respectively. Receptor for advanced glycation end products (RAGE) and low-density lipoprotein receptor-related protein 1 (LRP1), which are involved in Aβ influx and efflux, PPARγ and NF-κB p65 at the BBB, as well as hippocampal Aβ, caspase-3, Bax and Bcl-2 were assayed by Western blot, immunohistochemistry and RT-PCR. In vivo, hippocampal LTP was recorded, and Morris water maze and Y-maze tasks were performed. KEY
resultsTreatment with PPARγ agonists, rosiglitazone (0.8 mg·kg(-1) ) and pioglitazone (9.0 mg·kg(-1) ), for 6 weeks significantly increased Aβ efflux and decreased Aβ influx across the BBB in db/db mice. Concomitantly, they decreased hippocampal Aβ1-40 and Aβ1-42 , suppressed neuronal apoptosis, as indicated by decreased caspase-3 activity and increased ratio of Bcl-2/Bax, and increased hippocampal plasticity, characterized by an enhanced in vivo LTP and better performance in behavioural tests. Furthermore, the PPARγ agonists induced the expression of LRP1 gene by activation of PPARγ and suppressed RAGE gene expression by inactivation of NF-κB signalling at the BBB of db/db mice. CONCLUSIONS AND IMPLICATIONS: PPARγ agonists modify abnormal Aβ transport across the BBB and this is accompanied by amelioration of β-amyloidosis and an improvement in hippocampal plasticity in diabetic mice.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.