Haneen Amawi , Tayma Makhlouf , Alaa M. Hammad , Sahar Alsheyab , Rawan Alhazaimeh , F. Scott Hall , Joyeeta T. Khan , Bahaa Al-Trad , Amit K. Tiwari
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引用次数: 0
Abstract
Background
Post-traumatic stress disorder (PTSD) is a psychological condition characterized by consistent psychological distress resulting from the experience of intense traumatic events, such as warfare or natural disasters. Benzodiazepines and selective serotonin reuptake inhibitors (SSRIs) are widely prescribed treatments for PTSD, but their adverse side effects are a significant concern and they have only limited efficacy as a symptomatic treatment for PTSD. Moreover, they have no effect on the core underlying causes of PTSD Studies have reported a potential neuroprotective effect for Sodium-Glucose Cotransporter-2 Inhibitors (SGLTi). This study utilized the single-prolonged stress (SPS) mouse model of PTSD, which involved sequential exposure to different stressors (2 hours of restraint, 20 minutes of forced swimming, 15 minutes of rest, and 1–2 minutes of diethyl ether exposure), to investigate the therapeutic potential of Dapagliflozin (DAPA), a novel SGLTi, in mitigating the SPS-induced depressive-like behavior.
Methods
Male mice were randomly assigned to four experimental groups: Control group, SPS group, DAPA group (dapagliflozin; 1 mg/kg/day by oral gavage for 7 days), and SPS+DAPA group. Behavioral assessments for depressive-like behaviors were evaluated using the forced swim test and the tail suspension test. Blood and brain tissue samples were collected for analysis stress markers.
Results
SPS-treated mice showed significant depressive-like behavior on the seventh day post-treatment, which was reversed by DAPA treatment (1 mg/kg/day). Significant increases in brain tissue mRNA expression of Crh, Bax, Il1b, and Bdnf, as well as serum corticosterone, were observed in the SPS group, while DAPA reversed these effects.
Conclusion
This data indicates that DAPA (1 mg/kg) has potential therapeutic effects for the treatment of PTSD-induced depressive-like symptoms.
期刊介绍:
The Brain Research Bulletin (BRB) aims to publish novel work that advances our knowledge of molecular and cellular mechanisms that underlie neural network properties associated with behavior, cognition and other brain functions during neurodevelopment and in the adult. Although clinical research is out of the Journal''s scope, the BRB also aims to publish translation research that provides insight into biological mechanisms and processes associated with neurodegeneration mechanisms, neurological diseases and neuropsychiatric disorders. The Journal is especially interested in research using novel methodologies, such as optogenetics, multielectrode array recordings and life imaging in wild-type and genetically-modified animal models, with the goal to advance our understanding of how neurons, glia and networks function in vivo.