Trends in research on novel antidepressant treatments

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Янв. 27, 2025

Mood disorders, such as major depressive disorder and bipolar disorder, are among the most common mental illnesses a leading cause of disability worldwide. Key symptoms these conditions include depressed mood or anhedonia, sleep psychomotor disturbances, changes in appetite weight, fatigue loss energy. Prolonged cognitive disturbances further impair ability to think concentrate often accompanied by persistent feelings worthlessness excessive guilt. Collectively, underscore depression serious, long-term global health issue. In addition, clinical studies indicate growing number patients experiencing difficulties responding treatment, even long term. This phenomenon poses significant challenges for healthcare professionals, families, alike. As result, there is an urgent need therapies that both rapid-acting safe. review aims summarize prevailing trends research on novel antidepressants, emphasizing their diversity multi-directional mechanisms action. The development drugs increasingly focused achieving high efficacy, particularly treatment-resistant depression. Such advances offer potential rapid therapeutic effects without prolonged tedious administration older generation antidepressants. Findings from using animal models continue play crucial role predicting designing new strategies. These remain indispensable understanding physiological newly developed compounds, thereby guiding creation innovative treatments.

Язык: Английский

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Automated assessment of the mouse body-language reveals pervasive behavioral disruption in a two-hit model of psychiatric vulnerability

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 5, 2025

Abstract The influence of early-life experiences is widely acknowledged as a crafting tool that sculpts complex behavioral patterns and well-being living organisms. use preclinical models can provide invaluable insight into how negative environmental push interplays with genetic make-up in shaping psychiatric vulnerability. However, the assessment traits cross-species studies often relies on surrogate metrics proxy for internal state, limiting interpretation to context-dependent outcomes. In this work, we exploited validated computational digitalized ethological screening identify spontaneous hallmarks altered functioning dual-hit mouse model To do so, mice carrying heterozygous deletion gene coding Contactin-associated protein-like 2 ( Cntnap2 +/- ) their wild-type (WT) littermates were raised limited bedding nesting (LBN). These animals compared both WT standard conditions, mapping behavior during freely-moving exploration. Our data show descriptors motility state or anxiety indicators largely failed detecting subtle diversion from control conditions. By contrast, automated segmentation body-language revealed significant impact genotype experience programming. Thus, using unsupervised clustering, unveiled two alternative neurobehavioral profiles within our dataset. We found one identified overlapped LBN, while other was equally shared among controls. conclude coincidence adversity haploinsufficiency drastically reshapes structure rodents. SIGNIFICANCE STATEMENT Enhancing predictive face validity research remains challenge due inherent heterogeneity complexity these While animal are crucial understanding risk factors involved, replicating full conditions continues pose difficulties. study, investigate emotional double-hit (environmental genetic) vulnerability disorder, glimpsing subliminal disturbances not captured traditional assessments. findings highlight effectiveness novel tools identifying deviations support hypothesis gene-environment interaction contributes shape mice.

Язык: Английский

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Dorsal bed nucleus of the stria terminalis GABA neurons are necessary for chronic unpredictable stress-induced depressive behaviors in adolescent male mice

Journal of Psychiatric Research, Год журнала: 2025, Номер 182, С. 347 - 357

Опубликована: Янв. 18, 2025

Язык: Английский

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Bifidobacterium breve BB05 alleviates depressive symptoms in mice via the AKT/mTOR pathway

Frontiers in Nutrition, Год журнала: 2025, Номер 12

Опубликована: Янв. 30, 2025

Introduction This study investigates the potential of Bifidobacterium breve BB05 (BB05) in mitigating depressive symptoms a mouse model Chronic Unpredictable Mild Stress (CUMS), with fluoxetine as positive control. Methods and Results High-dose (1.0 × 10 9 CFU/kg, BB05H) significantly reduced anxiety- depression-like behaviors CUMS mice, measured by open field test, tail suspension forced swim test. treatment also pathological ileal damage, alleviated inflammation, lowered serum levels pro-inflammatory cytokines IL-6 TNF-α. Additionally, increased 5-HT decreased ACTH concentrations. Mechanistic analysis revealed that exerts antidepressant effects activating AKT/mTOR signaling pathway prefrontal cortex, promoting neuroprotection, neurogenesis, synaptic plasticity. Discussion These findings suggest BB05, particularly at higher doses, effectively alleviates CUMS-induced improves physiological outcomes, supporting use probiotics for depression targeting pathway.

Язык: Английский

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Depletion of MGO or Its Derivatives Ameliorate CUMS-Induced Neuroinflammation

Cells, Год журнала: 2025, Номер 14(6), С. 397 - 397

Опубликована: Март 8, 2025

Advanced glycation end products (AGEs) are a series of structurally complex and harmful compounds formed through the reaction between carbonyl group reducing sugars (such as glucose fructose) free amino groups proteins, lipids, or nucleic acids. Excessive accumulation AGEs in body can trigger oxidative stress, induce inflammatory responses, contribute to development diabetes, atherosclerosis, neurological disorders. Within category dicarbonyl compounds, methylglyoxal (MGO)—a byproduct resulting from degradation—serves pivotal precursor formation induction neurotoxicity. Specifically, generated MGO display significant cytotoxicity toward cells central nervous system. Therefore, we aimed investigate role MGO-AGEs neuroinflammation mediated by CUMS. Interestingly, found that overexpression glyoxalase 1 (GLO1) reduced levels corticosterone-treated microglia, thereby alleviating response. Furthermore, GLO1 hippocampus chronically stressed mice levels, mitigating CUMS-induced cognitive impairment. Additionally, when using receptor for advanced (RAGE) inhibitor FPS-ZM1 primary microglia cells, observed despite corticosterone-induced elevation MGO, no response occurred. This suggests RAGE clearance reduce MGO-AGE-mediated Subsequently, used treat it significantly ameliorated dysfunction. These results suggest targeting metabolism could serve therapeutic approach manage stress-related mental

Язык: Английский

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Music Therapy in Depression: Exploring Mechanisms and Efficacy in Rat Models

Brain Sciences, Год журнала: 2025, Номер 15(4), С. 338 - 338

Опубликована: Март 25, 2025

Background/Objectives: Depression is a common mental disorder, and traditional treatments are often associated with side effects, making it particularly important to identify safe effective alternative therapies. As non-invasive intervention, music therapy has attracted increasing attention in the field of health recent years. Methods: This study aimed explore effectiveness interventions alleviating depressive symptoms through systematic review their effects on rat model depression. The databases PubMed, Embase, Medline, PsycINFO, Scopus, Web Science, Cochrane Library, Google Scholar, Ovid MEDLINE were searched for publications dated between January 2010 November 2024. Results: First, construction methods behavioral test approaches used models introduced analyzed. Second, physiological biochemical indexes, as well neural structure function depressed rats, discussed. types influencing behaviors rats also summarized Finally, current concerns challenges translating into clinical applications depression reviewed, alongside future prospects its development. Conclusions: It anticipated that this will pave way both basic research application treatment

Язык: Английский

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The Behavioral and Neuroinflammatory Impact of Ketamine in a Murine Model of Depression and Liver Damage

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(8), С. 3558 - 3558

Опубликована: Апрель 10, 2025

Non-alcoholic fatty liver disease (NAFLD) has been associated with depression and inadequate response to antidepressants. While ketamine demonstrated efficacy in treating depression, its impact on pre-existing injury remains unclear. This study aimed evaluate the effects of treatment a murine model damage, considering age-related differences. Young aged male C57BL/6N mice were submitted chronic unpredictable mild stress (CUMS) methionine–choline-deficient (MCD) diet induce depressive-like behavior NAFLD. Behavioral testing (sucrose preference test, open field novel object recognition Crawley’s sociability test) used assess ketamine’s (50 mg/kg) effect behavior. Hepatic ultrasonography was utilized status. The cortical hippocampal NeuN+, GFAP+, Iba1+ signals quantified for each animal. Ketamine administration proved effective relieving anhedonia anxiety-like behavior, regardless damage. Although did not improve memory animals it enhanced sociability, particularly subjects. acute affect severity injury, but seems astrogliosis neuronal loss. animal models only replicate certain clinical features condition, they remain valuable evaluating complex varied ketamine. By applying such models, we could demonstrate therapeutic versatility, also indicate that responses may differ across different age groups.

Язык: Английский

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Restoration of mitochondrial energy metabolism by electroconvulsive therapy in adolescent and juvenile mice

Frontiers in Psychiatry, Год журнала: 2025, Номер 16

Опубликована: Апрель 10, 2025

Background Adolescent depression is an increasingly serious public health issue, and traditional treatment methods often have side effects or limited efficacy. Electroconvulsive therapy (ECT), a widely used for severe depression, has recently gained attention its potential in treating adolescent depression. Previous studies suggest that mitochondrial dysfunction closely related to the onset of Therefore, investigating mechanism by which ECT alleviates depressive symptoms through improvement energy metabolism great significance. Methods This study employed chronic unpredictable mild stress (CUMS) mouse model assess on depression-like behaviors sucrose preference test, open field tail suspension test. Additionally, markers, including ATP levels, oxygen consumption rate (OCR), lactate, pyruvate, were measured both human plasma evaluate function. Results The results showed significantly improved anxiety-like mice, as evidenced reversal abnormal Analysis markers revealed increased restored OCR, reduced lactate accumulation, pyruvate levels. These findings restoring improving brain supply. Conclusion systematically explored metabolism. indicate not only effectively but also provides new insights experimental evidence function restoration. Future research could further investigate how combine drug treatments enhance function, improve efficacy, different subtypes, providing guidance personalized clinical treatment.

Язык: Английский

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SEP-363856 attenuates CUMS-induced depression-like behaviours and reverses hippocampal neuronal injuries

The World Journal of Biological Psychiatry, Год журнала: 2024, Номер unknown, С. 1 - 18

Опубликована: Ноя. 29, 2024

Objectives This study employed a chronic unpredictable mild stress (CUMS) model to examine the antidepressant properties of SEP-363856.

Язык: Английский

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Subanesthetic propofol alleviates chronic stress-induced anxiety by enhancing VTADA neurons’ activity

Neuropharmacology, Год журнала: 2024, Номер unknown, С. 110264 - 110264

Опубликована: Дек. 1, 2024

Язык: Английский

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