ArticleJournal of neuroinflammation2021
The effect of dipeptidyl peptidase IV on disease-associated microglia phenotypic transformation in epilepsy.
Article in Journal of neuroinflammation, 2021. 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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Who cites it
11 citing papers in PubMed, 22 citations in OpenAlex.
- Neurovascular Actions of Dipeptidyl Peptidase-4 Inhibitors and Their Implications for Cognitive Dysfunction in Type 2 Diabetes Mellitus.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2026Review
- Lipid metabolism, microglia, and stroke.Neural regeneration research · 2026Article
- TSC-associated microglial hyperactivity: enhanced calcium signaling, metabolism, and phagocytosis.Acta neuropathologica · 2026Article
- Exploring the role of interleukin-6 receptor blockade in epilepsy and associated neuropsychiatric conditions through a mendelian randomization study.World journal of psychiatry · 2024Article
- Comparative analysis of hippocampal extracellular space uncovers widely altered peptidome upon epileptic seizure in urethane-anaesthetized rats.Fluids and barriers of the CNS · 2024Article
- Shear-induced phenotypic transformation of microglia in vitro.Biophysical journal · 2023Article
- CD11cCell death & disease · 2023Article
- Blockade of Kv1.3 Potassium Channel Inhibits Microglia-Mediated Neuroinflammation in Epilepsy.International journal of molecular sciences · 2022Article
- Nicotinic Acetylcholine Receptors and Microglia as Therapeutic and Imaging Targets in Alzheimer's Disease.Molecules (Basel, Switzerland) · 2022Review
- Inhibition of Transient Receptor Potential Vanilloid 4 (TRPV4) Mitigates Seizures.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Article
- Semaglutide attenuates seizure severity and ameliorates cognitive dysfunction by blocking the NLR family pyrin domain containing 3 inflammasome in pentylenetetrazole‑kindled mice.International journal of molecular medicine · 2021Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundAccumulating evidence suggests that disease-associated microglia (DAM), a recently discovered subset of microglia, plays a protective role in neurological diseases. Targeting DAM phenotypic transformation may provide new therapeutic options. However, the relationship between DAM and epilepsy remains unknown.
methodsAnalysis of public RNA-sequencing data revealed predisposing factors (such as dipeptidyl peptidase IV; DPP4) for epilepsy related to DAM conversion. Anti-epileptic effect was assessed by electroencephalogram recordings and immunohistochemistry in a kainic acid (KA)-induced mouse model of epilepsy. The phenotype, morphology and function of microglia were assessed by qPCR, western blotting and microscopic imaging.
resultsOur results demonstrated that DPP4 participated in DAM conversion and epilepsy. The treatment of sitagliptin (a DPP4 inhibitor) attenuated KA-induced epilepsy and promoted the expression of DAM markers (Itgax and Axl) in both mouse epilepsy model in vivo and microglial inflammatory model in vitro. With sitagliptin treatment, microglial cells did not display an inflammatory activation state (enlarged cell bodies). Furthermore, these microglia exhibited complicated intersections, longer processes and wider coverage of parenchyma. In addition, sitagliptin reduced the activation of NF-κB signaling pathway and inhibited the expression of iNOS, IL-1β, IL-6 and the proinflammatory DAM subset gene CD44.
conclusionThe present results highlight that the DPP4 inhibitor sitagliptin can attenuate epilepsy and promote DAM phenotypic transformation. These DAM exhibit unique morphological features, greater migration ability and better surveillance capability. The possible underlying mechanism is that sitagliptin can reduce the activation of NF-κB signaling pathway and suppress the inflammatory response mediated by microglia. Thus, we propose DPP4 may act as an attractive direction for DAM research and a potential therapeutic target for epilepsy.
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