Sitagliptin, a dipeptidyl peptidase‐4 inhibitor, improves recognition memory, oxidative stress and hippocampal neurogenesis and upregulates key genes involved in cognitive decline

Gault, Victor; Lennox, Rachael; Flatt, Peter R.

doi:10.1111/dom.12432

Cited by 123 publications

(106 citation statements)

References 67 publications

(99 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…An increase in GLP-1 and GIP receptor mRNA in the hippocampus after sitagliptin administration was also found [70]. This supports the possibility that in addition to GLP-1, GIP may also have a neuroprotective effect, though further studies are required to explore this possibility.…”

Section: The Role Of Gip Glp-1 and Dpp4supporting

confidence: 65%

“…Insulin-resistance and subsequently object recognition in animals was improved by sitagliptin, as demonstrated by reduced plasma glucose, increased insulin concentrations and improved glucose tolerance [70]. Following treatment with sitagliptin, GLP-1 levels were increased by 60% in the plasma, and by 50% in the brain supporting the notion that DPP-4 effects are mediated via GLP-1 [70].…”

Section: The Role Of Gip Glp-1 and Dpp4mentioning

confidence: 88%

“…In addition to this, vildagliptin had an anti-apoptotic effect by inhibition of the intrinsic and extrinsic pathways of apoptosis, thus preserving striatal dopamine content [44]. In vitro studies using vildagliptin have demon- Vildagliptin and sitagliptin both decreased brain oxidative stress and improved mitochondrial function therefore improving learning and memory behaviours in insulin-resistance animal models [69,70]. Insulin-resistance and subsequently object recognition in animals was improved by sitagliptin, as demonstrated by reduced plasma glucose, increased insulin concentrations and improved glucose tolerance [70].…”

Section: The Role Of Gip Glp-1 and Dpp4mentioning

confidence: 99%

“…In vitro studies using vildagliptin have demon- Vildagliptin and sitagliptin both decreased brain oxidative stress and improved mitochondrial function therefore improving learning and memory behaviours in insulin-resistance animal models [69,70]. Insulin-resistance and subsequently object recognition in animals was improved by sitagliptin, as demonstrated by reduced plasma glucose, increased insulin concentrations and improved glucose tolerance [70]. Following treatment with sitagliptin, GLP-1 levels were increased by 60% in the plasma, and by 50% in the brain supporting the notion that DPP-4 effects are mediated via GLP-1 [70].…”

Section: The Role Of Gip Glp-1 and Dpp4mentioning

confidence: 99%

“…The up-regulation of other proteins such as synaptophysin (SYP) and vascular endothelial growth factor (VEGF) in the hippocampus following administration of sitagliptin, as well an increase in antioxidants such as superoxide dismutase 2 (SOD2) and NrF2, provide an interesting insight into the mechanisms underlying the improvement in cognition displayed using DPP-4 inhibitors [70]. As with GLP-1 analogues, DPP4 inhibitors have also shown promise in treatment of other conditions.…”

Section: The Role Of Gip Glp-1 and Dpp4mentioning

confidence: 99%

See 4 more Smart Citations

Parkinson';s Disease, Diabetes and Cognitive Impairment

Ashraghi¹,

Pagano²,

Polychronis³

et al. 2016

EMI

View full text Add to dashboard Cite

Patents published in the last 5 years could be used in novel approaches to Parkinson's treatment by targeting specific pathophysiology proteins, such as Nurr1, PINK1 and NrF2, while patents to improve penetration of the blood brain barrier could allow improved efficacy of existing treatments. Conclusion:Further studies using GLP-1 agonists and DPP-4 inhibitors to treat PD are warranted as they have shown promise.

show abstract

Section: The Role Of Gip Glp-1 and Dpp4supporting

confidence: 65%

Section: The Role Of Gip Glp-1 and Dpp4mentioning

confidence: 88%

Section: The Role Of Gip Glp-1 and Dpp4mentioning

confidence: 99%

Section: The Role Of Gip Glp-1 and Dpp4mentioning

confidence: 99%

Section: The Role Of Gip Glp-1 and Dpp4mentioning

confidence: 99%

See 3 more Smart Citations

Parkinson';s Disease, Diabetes and Cognitive Impairment

Ashraghi¹,

Pagano²,

Polychronis³

et al. 2016

EMI

View full text Add to dashboard Cite

show abstract

Glucagon‐like peptide‐1 receptor differentially controls mossy cell activity across the dentate gyrus longitudinal axis

et al. 2022

View full text Add to dashboard Cite

Understanding the role of dentate gyrus (DG) mossy cells (MCs) in learning and memory has rapidly evolved due to increasingly precise methods for targeting MCs and for in vivo recording and activity manipulation in rodents. These studies have shown MCs are highly active in vivo, strongly remap to contextual manipulation, and that their inhibition or hyperactivation impairs pattern separation and location or context discrimination. What is not well understood is how MC activity is modulated by neurohormonal mechanisms, which might differentially control the participation of MCs in cognitive functions during discrete states, such as hunger or satiety. In this study, we demonstrate that glucagon-like peptide-1 (GLP-1), a neuropeptide produced in the gut and the brain that regulates food consumption and hippocampal-dependent mnemonic function, might regulate MC function through selective expression of its receptor, GLP-1R. RNA-seq demonstrated that most Glp1r in hippocampal principal neurons is expressed in MCs, and in situ hybridization revealed strong expression of Glp1r in hilar neurons. Glp1rires-Cre mice crossed with Ai14D reporter mice followed by co-labeling for the MC marker GluR2/3 revealed that almost all MCs in the ventral DG expressed Glp1r and that almost all Glp1r-expressing hilar neurons were MCs. However, only ~60% of dorsal DG MCs expressed Glp1r, and Glp1r was also expressed in small hilar neurons that were not MCs. Consistent with this expression pattern, peripheral administration of the GLP-1R agonist exendin-4 (5 μg/kg) increased cFos expression in ventral but not dorsal DG hilar neurons. Finally, whole-cell patch-clamp recordings from ventral MCs showed that bath application of exendin-4 (200 nM) depolarized MCs and increased action potential firing. Taken together, this study identifies a potential neurohormonal mechanism linking a critically important satiety signal with activity of MCs in the ventral DG that might have functional effects on learning and memory during distinct states.

show abstract

Antioxidative potential of antidiabetic agents: A possible protective mechanism against vascular complications in diabetic patients

Yaribeygi

Butler

Barreto

et al. 2018

Journal Cellular Physiology

View full text Add to dashboard Cite

Many vascular complications are related to exposure of tissues to elevated levels of glucose, a condition that promotes oxidative stress. The primary goal of antidiabetic medication is for normalization of blood glucose. However, antidiabetic medications may have antioxidant effects that go beyond their hypoglycemic influences. Therefore, antidiabetic drugs may be doubly beneficial in preventing diabetic complications. Vascular dysfunction due to uncontrolled diabetes is a serious complication of the disease and one which has a severe impact on quality of life. Readjustment of the oxidative balance in subjects with diabetes, and the positive effects thereof is a topic of intense interest at present. In the current review, we highlight the antioxidant effects of antidiabetic medications which may prevent or delay the onset of vascular dysfunction.

show abstract

Sitagliptin, a dipeptidyl peptidase‐4 inhibitor, improves recognition memory, oxidative stress and hippocampal neurogenesis and upregulates key genes involved in cognitive decline

Cited by 123 publications

References 67 publications

Parkinson';s Disease, Diabetes and Cognitive Impairment

Parkinson';s Disease, Diabetes and Cognitive Impairment

Glucagon‐like peptide‐1 receptor differentially controls mossy cell activity across the dentate gyrus longitudinal axis

Antioxidative potential of antidiabetic agents: A possible protective mechanism against vascular complications in diabetic patients

Contact Info

Product

Resources

About