Alogliptin Attenuates Lipopolysaccharide-Induced Neuroinflammation in Mice Through Modulation of TLR4/MYD88/NF-κB and miRNA-155/SOCS-1 Signaling Pathways.
Int J Neuropsychopharmacol
; 24(2): 158-169, 2021 02 15.
Article
en En
| MEDLINE
| ID: mdl-33125461
ABSTRACT
BACKGROUND:
Endotoxin-induced neuroinflammation plays a crucial role in the pathogenesis and progression of various neurodegenerative diseases. A growing body of evidence supports that incretin-acting drugs possess various neuroprotective effects that can improve learning and memory impairments in Alzheimer's disease models. Thus, the present study aimed to investigate whether alogliptin, a dipeptidyl peptidase-4 inhibitor, has neuroprotective effects against lipopolysaccharide (LPS)-induced neuroinflammation and cognitive impairment in mice as well as the potential mechanisms underlying these effects.METHODS:
Mice were treated with alogliptin (20 mg/kg/d; p.o.) for 14 days, starting 1 day prior to intracerebroventricular LPS injection (8 µg/µL in 3 µL).RESULTS:
Alogliptin treatment alleviated LPS-induced cognitive impairment as assessed by Morris water maze and novel object recognition tests. Moreover, alogliptin reversed LPS-induced increases in toll-like receptor 4 and myeloid differentiation primary response 88 protein expression, nuclear factor-κB p65 content, and microRNA-155 gene expression. It also rescued LPS-induced decreases in suppressor of cytokine signaling gene expression, cyclic adenosine monophosphate (cAMP) content, and phosphorylated cAMP response element binding protein expression in the brain.CONCLUSION:
The present study sheds light on the potential neuroprotective effects of alogliptin against intracerebroventricular LPS-induced neuroinflammation and its associated memory impairment via inhibition of toll-like receptor 4/ myeloid differentiation primary response 88/ nuclear factor-κB signaling, modulation of microRNA-155/suppressor of cytokine signaling-1 expression, and enhancement of cAMP/phosphorylated cAMP response element binding protein signaling.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Piperidinas
/
Uracilo
/
Proteínas Serina-Treonina Quinasas
/
Fármacos Neuroprotectores
/
MicroARNs
/
Receptor Toll-Like 4
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Factor 88 de Diferenciación Mieloide
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Inhibidores de la Dipeptidil-Peptidasa IV
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Disfunción Cognitiva
/
Proteína 1 Supresora de la Señalización de Citocinas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Int J Neuropsychopharmacol
Asunto de la revista:
NEUROLOGIA
/
PSICOFARMACOLOGIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Egipto