Sodium-Glucose Cotransporter-2 Inhibitor, Dapagliflozin, Reverses Depressive-Like Behavior in a mouse model of Post-Traumatic Stress Disorder

Brain Research Bulletin, Год журнала: 2025, Номер unknown, С. 111414 - 111414

Опубликована: Июнь 1, 2025

Post-traumatic stress disorder (PTSD) is a psychological condition characterized by consistent 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 significant concern they have only limited efficacy symptomatic treatment PTSD. Moreover, no effect on core underlying causes PTSD Studies reported potential neuroprotective Sodium-Glucose Cotransporter-2 Inhibitors (SGLTi). This study utilized single-prolonged (SPS) mouse model which involved sequential exposure to different stressors (2hours restraint, 20minutes forced swimming, 15minutes rest, 1-2minutes diethyl ether exposure), investigate therapeutic Dapagliflozin (DAPA), novel SGLTi, in mitigating SPS-induced depressive-like behavior. Male mice were randomly assigned four experimental groups: Control group, SPS DAPA group (dapagliflozin; 1mg/kg/day oral gavage 7 days), SPS+DAPA group. Behavioral assessments behaviors evaluated using swim test tail suspension test. Blood brain tissue samples collected analysis markers. SPS-treated showed behavior seventh day post-treatment, was reversed (1mg/kg/day). Significant increases mRNA expression Crh, Bax, Il1b, Bdnf, well serum corticosterone, observed while these effects. data indicates that (1mg/kg) has PTSD-induced symptoms.

Язык: Английский

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Social isolation induces hyperactivity and exploration in aged female mice

PLoS ONE, Год журнала: 2021, Номер 16(2), С. e0245355 - e0245355

Опубликована: Фев. 3, 2021

Prolonged social isolation is associated with poor physical and mental health outcomes, findings observed in both humans, rodent models of isolation. Humans, like mice, may engage enhanced exploratory behaviour following isolation, which protect against subsequent cognitive decline psychological distress. Understanding how these effects impact older adults particularly relevant, as this population likely to experience periods late-life We report that female mice did not lead robust depressive-like symptomology, altered interaction behaviour, sensitivity context fear acquisition memory, or alterations inflammatory cytokines ( IL-6 , IL-1β Tnf-α) microglial activation (Itgam) within the hippocampus. Rather, increased hyperactivity exploration behaviours. These have translational value first mouse model provide evidence inform development interventions aimed at promoting functional recovery late-life.

Язык: Английский

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An Automated, Home-Cage, Video Monitoring-based Mouse Frailty Index Detects Age-associated Morbidity in C57BL/6 and Diversity Outbred Mice

The Journals of Gerontology Series A, Год журнала: 2023, Номер 78(5), С. 762 - 770

Опубликована: Янв. 27, 2023

Abstract Frailty indexes (FIs) provide quantitative measurements of nonspecific health decline and are particularly useful as longitudinal monitors morbidity in aging studies. For mouse studies, frailty assessments can be taken noninvasively, but they require handling direct observation that is labor-intensive to the scientist stress inducing animal. Here, we implement, evaluate, a refined digital FI composed entirely computational analyses home-cage video compare it manually obtained scores both C57BL/6 genetically heterogeneous Diversity Outbred mice. We show assigned by our index correlate with chronological age. Thus, an automated tool for assessment collected reproducibly, at scale, without substantial labor cost.

Язык: Английский

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Effects of maternal social isolation on adult rodent offspring cognition

Scientific Reports, Год журнала: 2023, Номер 13(1)

Опубликована: Май 12, 2023

Abstract Prenatal experiences can influence offspring physiology and behaviour through the lifespan. Various forms of prenatal stress impair adult learning memory function lead to increased occurrence anxiety depression. Clinical work suggests that maternal depression similar outcomes in children adolescents, however long-term effects are less established, particularly well controlled animal models. Social isolation is common depressed individuals during recent COVID-19 pandemic. Accordingly, for this study we were interested induced via social on cognitive functions including spatial, stimulus–response, emotional mediated by different networks centered hippocampus, dorsal striatum, amygdala, respectively. Tasks included a discriminative contextual fear conditioning task cue-place water task. Pregnant dams group single housed prior throughout gestation. Once reached adulthood male trained which rats associate one two contexts with an aversive stimulus opposing context remained neutral. Afterwards was performed they required navigate both visible invisible platform. Fear results revealed socially isolated mothers, but not controls, impaired associating specific fear-inducing as assessed conditioned freezing avoidance. Results from indicate mothers showed place deficits stimulus-response habit same These impairments, dams, occurred absence elevated hormone levels, anxiety, or altered mothering. Some evidence suggested blood-glucose levels Our provide further support idea networks, amygdala hippocampus susceptible negative impacts these occur without glucocorticoid associated other stress.

Язык: Английский

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Sex matters in neuroscience and neuropsychopharmacology

European Journal of Neuroscience, Год журнала: 2020, Номер 52(1), С. 2423 - 2428

Опубликована: Июнь 24, 2020

Abstract Prevalence and symptoms of most psychiatric neurological disorders differ in men women there is substantial evidence that their neurobiological basis treatment also by sex. This special issue sought to bring together a series empirical papers targeted reviews highlight the diverse impact sex neuroscience neuropsychopharmacology. emphasizes neuropsychopharmacology, including 9 review 17 research articles highlighting investigation different species (zebrafish, mice, rats, humans). Each contribution covers scientific topics overlap with genetics, endocrinology, cognition, behavioral neuroscience, neurology, pharmacology. Investigating extent which differences can brain behavior key moving forward research.

Язык: Английский

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