Sotagliflozin attenuates cardiac dysfunction and depression-like behaviors in mice with myocardial infarction through the gut-heart-brain axis DOI Creative Commons

Lei Liao,

Lu Zhang,

Chengying Yang

et al.

Neurobiology of Disease, Journal Year: 2024, Volume and Issue: 199, P. 106598 - 106598

Published: July 11, 2024

Myocardial infarction (MI) and depression are leading causes of mortality morbidity globally, these conditions increasing recognized as being fundamentally interconnected. The recently gut-heart-brain axis offers insights into following MI, but effective treatments for this comorbidity remain lacking. To address medical need, we employed an animal model MI to investigate the potential repurposing sotagliflozin (SOTA), approved sodium-glucose cotransporter 1 2 (SGLT1/2) inhibitor diabetes, managing identifying SOTA-associated microbial mechanisms. SOTA treatment improved cardiac dysfunction alleviated depression-like behaviors induced by accompanied alterations in gut microbiota composition, such changes Prevotellaceae NK3B31 group, Alloprevotella, UCG-001. Moreover, fecal transplantation (FMT) using samples from SOTA-treated mice demonstrated that contributed beneficial effects on mice. Intriguingly, FMT-based intervention concordance analysis before after FMT suggested UCG-001 were associated with SOTA. Furthermore, functional prediction correlation support significance dynamic communities. In conclusion, findings suggest could serve a drug ameliorate depressive symptoms patients via through axis.

Language: Английский

Glucagon-like peptide-1 class drugs show clear protective effects in Parkinson's and Alzheimer's disease clinical trials: A revolution in the making? DOI Creative Commons
Christian Hölscher

Neuropharmacology, Journal Year: 2024, Volume and Issue: 253, P. 109952 - 109952

Published: April 25, 2024

Parkinson's disease (PD) is a complex syndrome for which there no disease-modifying treatment on the market. However, group of drugs from Glucagon-like peptide-1 (GLP-1) class have shown impressive improvements in clinical phase II trials. Exendin-4 (Bydureon), Liraglutide (Victoza, Saxenda) and Lixisenatide (Adlyxin), that are market as treatments diabetes, clear effects improving motor activity patients with PD In addition, has improvement cognition brain shrinkage trial Alzheimer (AD). Two III trials testing GLP-1 drug semaglutide (Wegovy, Ozempic, Rybelsus) ongoing. This perspective article will summarize results obtained so far this novel research area. We at crossroads where emerging new strategy AD. Newer been designed to enter easier being developed already show improved preclinical studies compared older had treat diabetes. The future looks bright AD PD.

Language: Английский

Citations

21
GLP-1 Receptor Agonist Use and Risk of Suicide Death DOI Creative Commons
Peter Ueda,

Jonas Söderling,

Viktor Wintzell

et al.

JAMA Internal Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 3, 2024

Importance Concerns have been raised regarding a link between use of glucagon-like peptide-1 (GLP-1) receptor agonists and increased risk suicidality self-harm. Objective To assess the association GLP-1 suicide death in routine clinical practice. Design, Setting, Participants This active-comparator new-user cohort study used nationwide register data from Sweden Denmark 2013 to 2021. Adults 18 84 years old who initiated treatment with or comparator sodium-glucose cotransporter-2 (SGLT2) inhibitors were included. Data analyzed March June 2024. Exposure Initiation agonist SGLT2 inhibitor. Main Outcomes Measures The primary outcome was recorded cause registers. Secondary outcomes composite nonfatal self-harm incident depression anxiety-related disorders. Using propensity score weighting, hazard ratios (HRs) 95% CIs calculated separately 2 countries pooled meta-analysis. Results In total, 124 517 adults 174 036 an inhibitor; among users, mean (SD) age 60 (13) years, 45% women. During follow-up 2.5 (1.7) 77 deaths occurred users 71 inhibitors: weighted incidences 0.23 vs 0.18 events per 1000 person-years (HR, 1.25; CI, 0.83-1.88), absolute difference 0.05 (95% −0.03 0.16) person-years. HR 0.83 0.70-0.97) for self-harm, 1.01 0.97-1.06) Conclusions Relevance study, including mostly patients type diabetes, does not show death, Suicide rare, upper limit confidence interval compatible increase no more than 0.16

Language: Английский

Citations

18
Vulnerability of the Hippocampus to Insults: Links to Blood–Brain Barrier Dysfunction DOI Open Access
Terry L. Davidson, Richard J. Stevenson

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 1991 - 1991

Published: Feb. 6, 2024

The hippocampus is a critical brain substrate for learning and memory; events that harm the can seriously impair mental behavioral functioning. Hippocampal pathophysiologies have been identified as potential causes effects of remarkably diverse array medical diseases, psychological disorders, environmental sources damage. It may be more vulnerable than other areas to insults are related these conditions. One purpose this review assess vulnerability most prevalent types in multiple biomedical domains (i.e., neuroactive pathogens, neurotoxins, neurological conditions, trauma, aging, neurodegenerative disease, acquired injury, health endocrine developmental disabilities, nutrition) evaluate whether affect first prominently compared loci. A second consider role hippocampal blood–brain barrier (BBB) breakdown either causing or worsening harmful each insult. Recent research suggests BBB fragile also prone disruption transport mechanisms act maintain internal milieu. Moreover, compromised could factor common many different insults. Our analysis indicates parts brain, developing interventions protect help prevent ameliorate on memory cognition.

Language: Английский

Citations

15
The SGLT2 inhibitor Empagliflozin promotes post-stroke functional recovery in diabetic mice DOI Creative Commons
Ellen Vercalsteren, Dimitra Karampatsi, Carolina Buizza

et al.

Cardiovascular Diabetology, Journal Year: 2024, Volume and Issue: 23(1)

Published: Feb. 29, 2024

Abstract Type-2 diabetes (T2D) worsens stroke recovery, amplifying post-stroke disabilities. Currently, there are no therapies targeting this important clinical problem. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) potent anti-diabetic drugs that also efficiently reduce cardiovascular death and heart failure. In addition, SGLT2i facilitate several processes implicated in recovery. However, the potential efficacy of to improve recovery T2D has not been investigated. Therefore, we determined whether a intervention with Empagliflozin could mice. was induced C57BL6J mice by 8 months high-fat diet feeding. Hereafter, animals were subjected transient middle cerebral artery occlusion treated vehicle or SGLTi (10 mg/kg/day) starting from 3 days after stroke. A similar study non diabetic conducted. Stroke assessed using forepaw grip strength test. To identify mechanisms involved Empagliflozin-mediated effects, metabolic parameters assessed. Additionally, neuronal survival, neuroinflammation, neurogenesis vascularization analyzed immunohistochemistry/quantitative microscopy. significantly improved but non-diabetic Improvement functional associated lowered glycemia, increased serum levels fibroblast growth factor-21 (FGF-21), normalization T2D-induced aberration parenchymal pericyte density. The global T2D-epidemic fact is major risk factor for drastically increasing number people need efficacious Our data provide strong incentive use treatment sequelae T2D.

Language: Английский

Citations

12
Exploring the Potential Impact of GLP-1 Receptor Agonists on Substance Use, Compulsive Behavior, and Libido: Insights from Social Media Using a Mixed-Methods Approach DOI Creative Commons
Davide Arillotta, Giuseppe Floresta,

Guy Pelletier

et al.

Brain Sciences, Journal Year: 2024, Volume and Issue: 14(6), P. 617 - 617

Published: June 20, 2024

Glucagon-like peptide-1 (GLP-1) is involved in a range of central and peripheral pathways related to appetitive behavior. Hence, this study explored the effects glucagon-like receptor agonists (GLP-1 RAs) on substance behavioral addictions, including alcohol, caffeine, nicotine, cannabis, psychostimulants, compulsive shopping, sex drive/libido. Data were collected from various social platforms. Keywords GLP-1 RAs substance/behavioral addiction used extract relevant comments. The employed mixed-methods approach analyze online discussions posted December 2019 June 2023 using specialized web application. Reddit entries focus here due limited data other platforms, such as TikTok YouTube. A total 5859 threads comments extracted six subreddits, which included about drugs associated brand names. To obtain posts, keywords potential use behavior selected. Further analysis two main steps: (1) manually coding posts based users’ references impact non-substance habits, excluding irrelevant or unclear comments; (2) performing thematic dataset keywords, AI-assisted techniques followed by manual revision generated themes. Second, was performed keyword-related dataset, In total, 29.75% alcohol-related; 22.22% caffeine-related; 23.08% nicotine-related clearly stated cessation intake these substances following start prescription. Conversely, mixed results found for cannabis intake, only limited, anecdotal made available cocaine, entactogens, dissociative drugs’ misuse. Regarding 21.35% reported shopping interruption, whilst sexual drive/libido elements reportedly increased several users. current appeared be useful tool gaining insight into complex topics addiction-related disorders; some RA-related mental health benefits could also inferred here. Overall, it that may show target both craving maladaptive/addictive behaviors, although further empirical research needed.

Language: Английский

Citations

12
GLP-1 programs the neurovascular landscape DOI
Bandy Chen, Xiaofei Yu,

Claudia Horvath-Diano

et al.

Cell Metabolism, Journal Year: 2024, Volume and Issue: 36(10), P. 2173 - 2189

Published: Oct. 1, 2024

Language: Английский

Citations

10
Albumin-based delivery systems: Recent advances, challenges, and opportunities DOI Creative Commons
Gillian Murphy, David J. Brayden, David W. Cheung

et al.

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: 380, P. 375 - 395

Published: Feb. 9, 2025

Language: Английский

Citations

1
Exploring the Role of GLP-1 Receptor Agonists in Alzheimer’s Disease: A Review of Preclinical and Clinical Evidence DOI Creative Commons
Lívia Cristina Ribeiro Teixeira, Marcelo R. Luizon, Karina Braga Gomes

et al.

Receptors, Journal Year: 2025, Volume and Issue: 4(1), P. 2 - 2

Published: Jan. 26, 2025

Glucagon-like peptide-1 receptor agonists (GLP-1RAs), including dulaglutide, liraglutide, semaglutide, and exenatide, are effective treatments for type 2 diabetes mellitus (T2DM) obesity. These agents mimic the action of endogenous incretin glucagon-like (GLP-1) by enhancing insulin secretion, inhibiting glucagon release, promoting weight loss through appetite suppression. GLP-1RAs have recently been suggested to neuroprotective effects, suggesting their potential as treatment neurodegenerative disorders, such Alzheimer’s disease (AD). AD T2DM share several common pathophysiological mechanisms, resistance, chronic inflammation, oxidative stress, mitochondrial dysfunction. shared mechanisms suggest that therapeutic targeting metabolic dysfunction may also be beneficial conditions. Preclinical studies on in models, both vitro vivo, demonstrated promising reductions amyloid-beta accumulation, decreased tau hyperphosphorylation, improved synaptic plasticity, enhanced neuronal survival. Despite encouraging results from preclinical challenges need addressed before can widely used treatment. Ongoing clinical trials investigating cognitive benefits patients, aiming establish role a option AD. This review aimed examine current literature GLP-1

Language: Английский

Citations

1
An analysis on the role of glucagon-like peptide-1 receptor agonists in cognitive and mental health disorders DOI Creative Commons
Riccardo De Giorgi, Ana Ghenciulescu,

Oliwia Dziwisz

et al.

Nature Mental Health, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 13, 2025

Abstract Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are novel drugs approved for diabetes and obesity. They acknowledged as a major scientific breakthrough. In addition to their metabolic effects, these medications act on other bodily systems involved in the physiopathology of various neurological psychiatric disorders. Several stakeholders calling more research investigate repurposing potential GLP-1RAs cognitive mental disorders, while others advocate better assessment safety profile from neuropsychiatric perspective. this Analysis, we searched relevant literature effects across range illnesses, gathering describing available pre-clinical mechanistic (278 studies) clinical (96 evidence substance-use psychotic mood anxiety eating others. By leveraging translational insights data, consider implications practice propose avenues further research.

Language: Английский

Citations

1
Current Therapeutic Landscape for Metabolic Dysfunction-Associated Steatohepatitis DOI Open Access

Arun George Devasia,

Adaikalavan Ramasamy, Chen Huei Leo

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1778 - 1778

Published: Feb. 19, 2025

In recent years, “metabolic dysfunction-associated steatotic liver disease” (MASLD) has been proposed to better connect disease metabolic dysfunction, which is the most common chronic worldwide. MASLD affects more than 30% of individuals globally, and it diagnosed by combination hepatic steatosis obesity, type 2 diabetes, or two risk factors. begins with buildup extra fat, often greater 5%, within liver, causing hepatocytes become stressed. This can proceed a severe form, steatohepatitis (MASH), in 20–30% people, where inflammation causes tissue fibrosis, limits blood flow over time. As fibrosis worsens, MASH may lead cirrhosis, failure, even cancer. While pathophysiology not fully known, current “multiple-hits” concept proposes that dietary lifestyle factors, genetic epigenetic factors contribute elevated oxidative stress inflammation, fibrosis. review article provides an overview pathogenesis evaluates existing therapies as well pharmacological drugs are currently being studied clinical trials for MASH.

Language: Английский

Citations

1