Evaluation of gestational chronic mild stress as a valid animal model of postpartum depression

Abstract Postpartum depression (PPD) is a major health problem as it is undertreated and its pathophysiology is poorly understood. Although stress during pregnancy is a risk factor for PPD, currently there is no valid animal model of stress-induced PPO available to investigate its underlying mechanism. This thesis aimed to evaluate gestational chronic mild stress (CMS) as a valid animal model of PPD. Evaluation was done by addressing the construct, face and predictive validity. Specifically, the effect of gestational CMS in recapitulating hormone fluctuations, altering neurochemistry and behaviour, followed by reversal of CMS-induced behavioural changes by administration of chronic antidepressant drugs were assessed. Mice were either subjected to CMS or left undisturbed after the mating process until parturition. CMS involved sequential application of mild stressors (e.g. paired housing and 30° cage tilt). Exposure to gestational CMS increased the plasma corticosterone level at gestational day 13 and the level was found similarly high during late pregnancy. High-~ performance liquid chromatography analysis showed that gestational CMS altered the serotonergic levels in the hippocampus during late pregnancy. Investigation of postpartum behaviour showed no effect of CMS on maternal behaviour. However, CMS significantly increased the locomotor activity of the dams in the elevated plus maze one week after parturition and in the open field test after weaning of litters, and abolished anxiety-like behaviour in open field test. CMS impaired the retention of fear memory in contextual fear conditioning task. These results demonstrate that exposing pregnant mice to CMS resulted in changes reminiscent of PPD. Reversal of stress-induced behavioural changes could not be observed in a separate experiment, which some of the stressed mice were treated with oral clomipramine or fluoxetine at postpartum. Thus the predictive validity criterion of CMS remains to be established. In conclusion, CMS has the potential to be a valid animal model of PPD.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Antidepressant-like Effects of Polygonum minus Aqueous Extract in Chronic Ultra-Mild Stress-Induced Depressive Mice Model

Depression is the most common behavior disorder that leads to many disabilities. The main aim of this study was to evaluate the effects of a Polygonum minus (P. minus) aqueous extract on chronic ultra-mild stress (CUMS)-induced depressive mice model. Chronic ultra-mild stress can disturb the neurotransmitters levels and plasticity of the hippocampus. Balb/c male mice were used in this study, which consisted of six groups (n = 14). Treatment was given for eight weeks, and chronic ultra-mild stress was applied for six weeks. Commercially available P. minus extract (BioKesum®) was used in this study. The behavior and neurochemical parameters were investigated through behavioral Tests and ELISA assays. P. minus administration significantly (p < 0.05) restored CUMS-induced behavior abnormalities, decreased the immobility time, and increased the sucrose preference and increased the spatial memory. P. minus treatment also showed the decreased level of serum corticosterone and increased the level of hippocampal neurotransmitters (Serotonin and Norepinephrine) significantly (p < 0.05). The brain-derived neurotrophic factor (BDNF) level also increased significantly in both the prefrontal cortex and hippocampus (p < 0.05). P. minus treatment exhibited significant (p < 0.05) reduction of Monoamine Oxidase-A (MAO-A) in the hippocampus. These findings indicate that P. minus aqueous extract exhibits antidepressant effects, including decreased immobility time, increased spatial memory, reduced corticosterone, increased BDNF level, and reduced MAO-A enzyme level with increasing the monoamines (serotonin and norepinephrine) in the hippocampus

Proapoptotic and Antiangiogenic Activities of Arctium Lappa L. on Breast Cancer Cell Lines

In this study, the bioactivity-guided fractionation was conducted on the aerial parts of Arctium lappa L. and then the extracts were tested in vitro on breast cancer (MCF-7), colorectal cancer (HCT-116), and normal cells (EA.hy926). The n-hexane fraction (EHX) of the ethanolic extract showed strong activity against both MCF-7 and EA.hy926 cell lines (IC50 values: 14.08 ± 3.64 and 27.25 ± 3.45 μg/mL, respectively). The proapoptotic activity of EHX was assessed using MCF-7. Morphological alterations were visualized using Hoechst staining and a transmission electron microscope. Cancer cell signal transduction pathways were investigated, and EHX significantly upregulated p53, TGF-β, and NF-κB. Furthermore, EHX was found to disrupt the metastatic cascade of breast cancer cells by the inhibition of cell proliferation, migration, invasion, and colonization. The antiangiogenic activity of EHX fraction showed potent inhibition of rat aorta microvessels with IC50 value: 4.34 ± 1.64 μg/mL. This result was supported by the downregulation of VEGF-A expression up to 54%. Over 20 compounds were identified in EHX using GC-MS, of which stigmasterol, ß-sitosterol, and 3-O-acetyllupeol are the major active compounds. Phytochemical analysis of EHX showed higher phenolic and flavonoid contents with a substantial antioxidant activity. In conclusion, this work demonstrated that A. lappa has valuable anticancer activity and antiangiogenic properties that might be useful in breast cancer therapy