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Purpose: Chronic inflammation is one of the key mechanisms of depression. Wenyang-Tianjin-Jie Decoction (WTJD) is an effective antidepressant found in the course of diagnosis and treatment, but the mechanism of therapeutic effect is not clear. The study aimed to evaluate the efficacy of WTJD in the kidney yang deficiency (KYD) type of depression rats and reveal its mechanisms.
Materials And Methods: We selected forty 6-week-old male Sprague-Dawley rats for the study. We established a KYD [Phellodendron amurense Rupr (Huangbai) solution oral gavage and 4°C environments; 8 weeks] type of depression (chronic unpredictable mild stimulus; 6 weeks) rat model first. After successful modeling, we used WTJD or fluoxetine on rats for 3 weeks. Then we evaluated the depression and KYD behavior. Finally, we observed the expression of key inflammatory factors and proteins in peripheral blood and hippocampus, and further investigated the immune balance of Th17/Treg and Th1/Th2 cells and the activity of their main regulatory pathways JAK2/STAT3 and TLR4/TRAF6/NF-κB.
Results: The imbalance of Th17/Treg and Th1/Th2 cells in rats were related to KYD and depressive symptoms. Through this study, we found that WTJD can inhibit the activity of JAK2/STAT3 and TLR4/TRAF6/NF-κB pathways, balance Th17/Treg and Th1/Th2 cell homeostasis, regulate the levels of inflammatory factors in the hippocampus and peripheral blood, and reverse KYD and depression.
Conclusion: This study confirmed that WTJD had a reliable effect on depression rats with KYD, and its mechanism was to regulate the immune homeostasis of hippocampal T cells and related inflammatory factors to improve KYD and depression symptoms in rats.
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http://dx.doi.org/10.2147/NDT.S445636 | DOI Listing |
Brain Behav
September 2025
School of Physical Education and Health, Henan University of Chinese Medicine, Zhengzhou, China.
Background: Clinical and basic research suggests that exercise is a safe behavioral intervention and effective in improving cognition in vascular dementia (VD). However, despite global efforts, there is still no effective method to completely cure VD. This study aimed to investigate the effects of long-term exercise pretreatment on typical VD pathology in a rat model, and further compare the neuroprotective impacts of different exercise modalities on VD rats.
View Article and Find Full Text PDFNeurochem Res
September 2025
Biology and Health Laboratory, Faculty of Sciences, Ibn Tofail University, Kenitra, Morocco.
Parkinson's disease (PD) is characterized by impairments in motor control following the degeneration of dopamine-producing neurons located in the substantia nigra pars compacta. Environmental pesticides such as Paraquat (PQ) and Maneb (MB) contribute to the onset of PD by inducing oxidative stress (OS). This study evaluated the therapeutic efficacy of moderate physical activity (PA) on both motor and non-motor symptoms in a Wistar rat model of Paraquat and Maneb (PQ/MB) induced PD.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2025
Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37240.
Major depressive disorder affects millions worldwide, yet current treatments require prolonged administration. In contrast, ketamine produces rapid antidepressant effects by blocking spontaneous N-Methyl-D-Aspartate (NMDA) receptor signaling, which lifts the suppression of protein synthesis and triggers homeostatic synaptic plasticity. Here, we identify a parallel signaling pathway involving metabotropic glutamate receptor 5 (mGluR5) that promotes rapid antidepressant-like effects.
View Article and Find Full Text PDFLife Sci
September 2025
Department of Pharmacology, Faculty of Medicine, University of Granada, 18016, Granada, Spain; Institute of Neuroscience, Biomedical Research Center, University of Granada, Armilla, 18100, Granada, Spain; Biosanitary Research Institute ibs.GRANADA, 18012, Granada, Spain. Electronic address: fnieto@u
The sigma-1 receptor (σ1R) is a chaperone involved in multiple physiological and pathological processes, including pain modulation, neuroprotection, and neurodegenerative diseases. Despite its functional significance, its precise roles remain unclear due to the lack of suitable models for detailed mechanistic studies. In this work, we describe the generation and phenotypic characterization of a novel σ1R knockout (σ1R KO) rat model.
View Article and Find Full Text PDFMol Psychiatry
September 2025
Obstetrics and Gynecology Hospital of Fudan University, Shanghai Key Lab of Reproduction and Development, Shanghai Key Lab of Female Reproductive Endocrine Related Diseases, Shanghai, China.
Dramatic drop in reproductive hormone, especially estrogen level, from pregnancy to postpartum period is known to contribute to postpartum depression (PPD), but the underlying mechanism and the role of the estrogen receptors (ERs) in this process were unclear. Here, we used an estrogen-withdrawal-induced PPD model following hormone simulated pregnancy (HSP) in female Sprague-Dawley rats to induce depressive-like behaviors. After estrogen withdrawal, we observe an up-regulation of astrocyte-specific potassium channel (Kir4.
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