GLP-1 agonist Liraglutide prevents MK‑801–induced schizophrenia‑like behaviors and BDNF, CREB, p-CREB, Trk-B expressions in the hippocampus and prefrontal cortex in Balb/c mice

Kutlu, Meltem Dönmez; Köse, Seda; Akıllıoğlu, Kübra

doi:10.1016/j.bbr.2023.114386

Behavioural Brain Research

2023

DOI: 10.1016/j.bbr.2023.114386

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GLP-1 agonist Liraglutide prevents MK‑801–induced schizophrenia‑like behaviors and BDNF, CREB, p-CREB, Trk-B expressions in the hippocampus and prefrontal cortex in Balb/c mice

Meltem Dönmez Kutlu

Seda Köse

Kübra Akıllıoğlu

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Cited by 11 publications

(1 citation statement)

References 48 publications

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“…Interestingly, a recent study has reported that metformin, which has been widely used as the first-line treatment for the management of type 2 diabetes for over 50 years, ameliorates schizophrenia-like symptoms caused by MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist, through the normalization of Akt-GSK-3 β signaling pathway (Wang et al, 2019). Similar results have been reported using liraglutide, a glucagon-like peptide-1 receptor agonist for type 2 diabetes treatment (Kutlu et al, 2023). In addition, metformin attenuated lipopolysaccharide-induced systemic and neuro-inflammation by reduced proinflammatory cytokines including TNF-α and IL-6 (Mudgal et al, 2019).…”

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confidence: 62%

Effect of D‐pinitol on MK‐801‐induced schizophrenia‐like behaviors in mice

Kim,

Kong,

Kim

et al. 2023

Phytotherapy Research

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Schizophrenia is a chronic brain disorder characterized by positive symptoms (delusions or hallucinations), negative symptoms (impaired motivation or social withdrawal), and cognitive impairment. In the present study, we explored whether D‐pinitol could ameliorate schizophrenia‐like behaviors induced by MK‐801, an N‐methyl‐D‐aspartate receptor antagonist. Acoustic startle response test was conducted to evaluate the effects of D‐pinitol on sensorimotor gating function. Social interaction and novel object recognition tests were employed to measure the impact of D‐pinitol on social behavior and cognitive function, respectively. Additionally, we examined whether D‐pinitol affects motor coordination. Western blotting was conducted to investigate the mechanism of action of D‐pinitol. Single administration of D‐pinitol at 30, 100, or 300 mg/kg improved the sensorimotor gating deficit induced by MK801 in the acoustic startle response test. D‐Pinitol also reversed social behavior deficits and cognitive impairments induced by MK‐801 without causing any motor coordination deficits. Furthermore, D‐pinitol reversed increased expression levels of pNF‐kB induced by MK‐801 treatment and consequently increased expression levels of TNF‐α and IL‐6 in the prefrontal cortex. These results suggest that D‐pinitol could be a potential candidate for treating sensorimotor gating deficits and cognitive impairment observed in schizophrenia by down‐regulating transcription factor NF‐κB and pro‐inflammatory cytokines in the prefrontal cortex.

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supporting

confidence: 62%

Effect of D‐pinitol on MK‐801‐induced schizophrenia‐like behaviors in mice

Kim,

Kong,

Kim

et al. 2023

Phytotherapy Research

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Liraglutide attenuates palmitate-induced apoptosis via PKA/β-catenin/Bcl-2/Bax pathway in MC3T3-E1 cells

Cheng

Long

et al. 2023

Naunyn-Schmiedeberg's Arch Pharmacol

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Liraglutide (LRG), one agonist of glucagon-like peptide-1, has multiple lipid-lowering effects in type 2 diabetes mellitus, however, studies on the role of LRG in saturated fatty acid-induced bone loss are limited. Therefore, our aim was to investigate whether LRG reduces palmitate (PA)-induced apoptosis and whether the mechanism involves PKA/β-catenin/Bcl-2/Bax in osteoblastic MC3T3-E1 cells. MC3T3-E1 cells were treated with different concentrations of PA, LRG, or pretreated with Exendin 9-39 and H89, cell viability, intracellular reactive oxygen species (ROS) and cAMP levels, apoptosis and the expression of protein kinase A (PKA), β-catenin, cleaved-Capase 3, Bcl2-Associated X Protein (Bax) and B-cell lymphoma-2 (Bcl-2) along with expression of Osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) were evaluated. PA treatment inhibited cell proliferation and cAMP levels, elevated intracellular ROS levels and promoted apoptosis, increased protein expressions of RANKL, Bax and Cleaved-Caspase3, meanwhile decreased protein expression of OPG and Bcl-2 in a dose-dependent manner. LRG inverted PA-induced apoptosis, increased cAMP levels, promoted expression of p-PKA, p-βcatenin and reversed these gene expression via increasing GLP1R expression. Pretreatment of the cells with Exendin 9-39 and H89 partially eradicated the protective effect of LRG on PA-induced apoptosis. Therefore, these ndings indicated that LRG attenuates PA-induced apoptosis possibly by GLP1Rmediated PKA/β-catenin/Bcl-2/Bax pathway in MC3T3-L1 cells. Our results point to LRG as a new strategy to attenuate bone loss associated with high fat diet beyond its lipid-lowering actions.

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The Impact of GLP-1 Receptor Agonists (GLP-1 RAs) on Mental Health: A Systematic Review

Tempia Valenta,

Nicastri,

Perazza

et al. 2024

Curr Treat Options Psych

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GLP-1 agonist Liraglutide prevents MK‑801–induced schizophrenia‑like behaviors and BDNF, CREB, p-CREB, Trk-B expressions in the hippocampus and prefrontal cortex in Balb/c mice

Cited by 11 publications

References 48 publications

Effect of D‐pinitol on MK‐801‐induced schizophrenia‐like behaviors in mice

Effect of D‐pinitol on MK‐801‐induced schizophrenia‐like behaviors in mice

Liraglutide attenuates palmitate-induced apoptosis via PKA/β-catenin/Bcl-2/Bax pathway in MC3T3-E1 cells

The Impact of GLP-1 Receptor Agonists (GLP-1 RAs) on Mental Health: A Systematic Review

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