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Semaglutide Attenuates Anxious and Depressive-Like Behaviors and Reverses the Cognitive Impairment in a Type 2 Diabetes Mellitus Mouse Model Via the Microbiota-Gut-Brain Axis.
- Source :
-
Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology [J Neuroimmune Pharmacol] 2024 Jul 23; Vol. 19 (1), pp. 36. Date of Electronic Publication: 2024 Jul 23. - Publication Year :
- 2024
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Abstract
- Newly conducted research suggests that metabolic disorders, like diabetes and obesity, play a significant role as risk factors for psychiatric disorders. This connection presents a potential avenue for creating novel antidepressant medications by repurposing drugs originally developed to address antidiabetic conditions. Earlier investigations have shown that GLP-1 (Glucagon-like Peptide-1) analogs exhibit neuroprotective qualities in various models of neurological diseases, encompassing conditions such as Alzheimer's disease, Parkinson's disease, and stroke. Moreover, GLP-1 analogs have demonstrated the capability to enhance neurogenesis, a process recognized for its significance in memory formation and the cognitive and emotional aspects of information processing. Nonetheless, whether semaglutide holds efficacy as both an antidepressant and anxiolytic agent remains uncertain. To address this, our study focused on a mouse model of depression linked to type 2 diabetes induced by a High Fat Diet (HFD). In this model, we administered semaglutide (0.05 mg/Kg intraperitoneally) on a weekly basis to evaluate its potential as a therapeutic option for depression and anxiety. Diabetic mice had higher blood glucose, lipidic profile, and insulin resistance. Moreover, mice fed HFD showed higher serum interleukin (IL)-1β and lipopolysaccharide (LPS) associated with impaired humor and cognition. The analysis of behavioral responses revealed that the administration of semaglutide effectively mitigated depressive- and anxiety-like behaviors, concurrently demonstrating an enhancement in cognitive function. Additionally, semaglutide treatment protected synaptic plasticity and reversed the hippocampal neuroinflammation induced by HFD fed, improving activation of the insulin pathway, demonstrating the protective effects of semaglutide. We also found that semaglutide treatment decreased astrogliosis and microgliosis in the dentate gyrus region of the hippocampus. In addition, semaglutide prevented the DM2-induced impairments of pro-opiomelanocortin (POMC), and G-protein-coupled receptor 43 (GPR43) and simultaneously increased the NeuN + and Glucagon-like Peptide-1 receptor (GLP-1R+) neurons in the hippocampus. Our data also showed that semaglutide increased the serotonin (5-HT) and serotonin transporter (5-HTT) and glutamatergic receptors in the hippocampus. At last, semaglutide changed the gut microbiota profile (increasing Bacterioidetes, Bacteroides acidifaciens, and Blautia coccoides) and decreased leaky gut, improving the gut-brain axis. Taken together, semaglutide has the potential to act as a therapeutic tool for depression and anxiety.<br /> (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Subjects :
- Animals
Mice
Male
Diabetes Mellitus, Experimental complications
Diabetes Mellitus, Experimental drug therapy
Diabetes Mellitus, Experimental psychology
Diabetes Mellitus, Experimental metabolism
Disease Models, Animal
Antidepressive Agents pharmacology
Antidepressive Agents therapeutic use
Glucagon-Like Peptides pharmacology
Diabetes Mellitus, Type 2 complications
Diabetes Mellitus, Type 2 drug therapy
Diabetes Mellitus, Type 2 psychology
Diabetes Mellitus, Type 2 metabolism
Cognitive Dysfunction drug therapy
Cognitive Dysfunction prevention & control
Cognitive Dysfunction etiology
Cognitive Dysfunction metabolism
Depression drug therapy
Depression psychology
Depression metabolism
Anxiety drug therapy
Anxiety psychology
Anxiety etiology
Gastrointestinal Microbiome drug effects
Mice, Inbred C57BL
Brain-Gut Axis drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1557-1904
- Volume :
- 19
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 39042202
- Full Text :
- https://doi.org/10.1007/s11481-024-10142-w