Alogliptin Attenuates Lipopolysaccharide-Induced Neuroinflammation in Mice Through Modulation of TLR4/MYD88/NF-κB and miRNA-155/SOCS-1 Signaling Pathways

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 (AD) models. Thus, the present study aimed to investigate whether alogliptin, a dipeptidyl peptidase-4 (DPP-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/day; p.o.) for 14 days, starting 1 day prior to intracerebroventricular (ICV) LPS injection (8 μg/μl in 3μl). Results Alogliptin treatment alleviated LPS-induced cognitive impairment as assessed by Morris water maze (MWM) and novel object recognition (NOR) tests. Moreover, alogliptin reversed LPS-induced increases in toll-like receptor 4 (TLR4) and myeloid differentiation primary response 88 (MYD88) protein expression, nuclear factor-κB (NF-κB) p65 content, and microRNA-155 (miRNA-155) gene expression. It also rescued LPS-induced decreases in suppressor of cytokine signaling (SOCS-1) gene expression, cyclic adenosine monophosphate (cAMP) content, and phosphorylated cAMP response element binding protein (pCREB) expression in the brain. Conclusion The present study sheds light on the potential neuroprotective effects of alogliptin against ICV LPS-induced neuroinflammation and its associated amyloidogenesis, apoptosis, and memory impairment via inhibition of TLR4/MYD88/NF-κB signaling, modulation of miRNA-155/SOCS-1 expression, and enhancement of cAMP/pCREB signaling.

Milrinone Ameliorates the Neuroinflammation and Memory Function of Alzheimer’s Disease in an APP/PS1 Mouse Model

“…Meanwhile, milrinone treatment expectedly repressed the expression of this pathway. Some previous studies on AD inflammation suggested that the inhibition of TLR4/MyD88/NF-κB signalling is crucial for the reduction of neuroinflammation in AD, 42 , 43 which validated our experimental data that milrinone inhibited neuroinflammation through suppression of TLR4/MyD88/NF-κB signalling pathway.…”

Novel Luteolin-Loaded Chitosan Decorated Nanoparticles for Brain-Targeting Delivery in a Sporadic Alzheimer’s Disease Mouse Model: Focus on Antioxidant, Anti-Inflammatory, and Amyloidogenic Pathways

“…Mice were anesthetized with i.p. thiopental (50 mg/kg) [ 38 ], and the head of the mouse was stabilized using downward pressure above the ears. The needle was inserted directly through the skin and skull into the lateral ventricle, which was targeted by visualizing an equilateral triangle between the eyes and the center of the skull to locate the bregma.…”

Therapeutic Potential of Allicin and Aged Garlic Extract in Alzheimer’s Disease

“…Alternatively, TLR can interact with MyD88, triggering NF-κB stimulation, thus provoking the secretion of TNF-α and IL-6 [68,[78][79][80].…”

“…A comparison between raw and steamed garlic has been performed in terms of anti-inflammatory activities in LPS-stimulated BV2 microglial cells. It was found that only raw garlic, in which the generation of allicin was preserved, was able to reduce proinflammatory cytokines such as IL-1 Alternatively, TLR can interact with MyD88, triggering NF-κB stimulation, thus provoking the secretion of TNF-α and IL-6 [68,[78][79][80].…”