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.

Type 2 diabetes mellitus (T2DM) has been recognized as a known risk factor for cardiovascular diseases. Additionally, studies have shown the prevalence of depression among people with diabetes. Thus, the current study aimed to investigate the possible beneficial effects of escitalopram, a selective serotonin reuptake inhibitor, on metabolic changes and cardiac complications in type 2 diabetic rats. Diabetes was induced by feeding the rats high fat-high fructose diet (HFFD) for 8 weeks followed by a subdiabetogenic dose of streptozotocin (STZ) (35 mg/kg, i. p.). Treatment with escitalopram (10 mg/kg/day; p. o.) was then initiated for 4 weeks. At the end of the experiment, electrocardiography was performed and blood samples were collected for determination of glycemic and lipid profiles. Animals were then euthanized and heart samples were collected for biochemical and histopathological examinations. Escitalopram alleviated the HFFD/STZ-induced metabolic and cardiac derangements as evident by improvement of oxidative stress, inflammatory, fibrogenic and apoptotic markers in addition to hypertrophy and impaired conduction. These results could be secondary to its beneficial effects on the glycemic control and hence the reduction of receptor for advanced glycation end products content as revealed in the present study. In conclusion, escitalopram could be considered a favorable antidepressant medication in diabetic patients as it seems to positively impact the glycemic control in diabetes in addition to prevention of its associated cardiovascular complications.

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