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DPP4 regulates the inflammatory response in a rat model of febrile seizures
Qi Sun1, Yusong Zhang1, Jie Huang1
1Department of Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
Insights
Dipeptidyl peptidase IV (DPP4) plays a key role in neuroinflammation during febrile seizures (FS). Inhibiting DPP4 with sitagliptin reduced seizure severity and inflammation, suggesting potential therapeutic benefits for FS.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Febrile seizures (FS) are common in young children and can lead to temporal lobe epilepsy (TLE).
- Neuroinflammation is implicated in FS pathogenesis, but the underlying mechanisms are not fully understood.
- Previous research identified Dipeptidyl peptidase IV (DPP4) as a potentially relevant gene in FS.
Purpose of the Study:
- To investigate the role of DPP4 in neuroinflammation associated with hyperthermia-induced seizures.
- To evaluate the therapeutic potential of DPP4 inhibition in a rat model of FS.
Main Methods:
- Assessed DPP4 expression at protein and mRNA levels following hyperthermia induction in rats.
- Administered sitagliptin, a DPP4 inhibitor, to FS rats and monitored seizure severity.
- Measured inflammatory cytokine levels (IL-1β, TNF-α, IL-6, IL-10) and NF-κB activation.
Main Results:
- DPP4 expression significantly increased post-hyperthermia.
- Sitagliptin treatment attenuated seizure severity and suppressed hyperthermia-induced astrocytosis.
- Sitagliptin reduced levels of IL-1β, TNF-α, and IL-6, and inhibited NF-κB activation.
Conclusions:
- DPP4 is a critical regulator of neuroinflammation in hyperthermia-induced seizures.
- DPP4 inhibition demonstrates therapeutic potential for managing febrile seizures.
Abstract:
Febrile seizures (FS) are the most common seizure disorders in children aged 6 months to 5 years. Children suffering from complex FS have a high risk of developing subsequent temporal lobe epilepsy (TLE). Neuroinflammation is involved in the pathogenesis of FS although the mechanism remains unknown. Our previous study using the Whole Rat Genome Oligo Microarray determined that Dipeptidyl peptidase IV (DPP4) is potentially a related gene in FS rats. In this study, we demonstrated that DPP4 expression was significantly increased at both the protein and mRNA levels after hyperthermia induction. Sitagliptin, a specific enzyme inhibitor of DPP4, remarkably attenuated the severity of seizures in FS rats, and hyperthermia-induced astrocytosis was suppressed after DPP4 inhibition. Furthermore, sitagliptin significantly decreased the levels of the inflammatory cytokines IL-1β, TNF-α, and IL-6 but not IL-10. In addition, sitagliptin prevented NF-κB activation by decreasing phosphorylation of the p65 subunit. Taken together, our findings demonstrate that DPP4 functions as a critical regulator of neuroinflammation in hyperthermia-induced seizures and the DPP4 inhibitor may be a viable option for FS therapeutics.