scholarly journals Effects of Vitamin D3 in Long-Term Ovariectomized Rats Subjected to Chronic Unpredictable Mild Stress: BDNF, NT-3, and NT-4 Implications

Nutrients ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1726 ◽  
Author(s):  
Alexandra Koshkina ◽  
Tatyana Dudnichenko ◽  
Denis Baranenko ◽  
Julia Fedotova ◽  
Filippo Drago

The purpose of this study was to explore the antidepressant-like effects of vitamin D3 at different doses (1.0, 2.5, and 5.0 mg/kg sc) on a model of depression produced by chronic unpredictable mild stress (CUMS) for 28 days in long-term (3 months) ovariectomized (OVX) adult rats. Sucrose preference (SPT), forced swimming (FST) and open-field (OFT) tests were conducted to examine the depression-like state. Serum corticosterone/adrenocorticotrophic hormone (ACTH) levels and hippocampal brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-3/NT-4 expressions by ELISA kits and/or western blotting were determined to assess the possible mechanisms of the vitamin D3 effects on the depression-like profile in long-term OVX rats subjected to CUMS. The results showed that vitamin D3 (5.0 mg/kg), as well as fluoxetine treatment, considerably reversed the depression-like state in the SPT and FST, decreased serum corticosterone/ACTH levels, and increased BDNF and NT-3/NT-4 levels in the hippocampus of long-term OVX rats compared to OVX rats with CUMS (p < 0.05). Thus, a high dose of vitamin D3 (5.0 mg/kg sc) could improve the depression-like profile in long-term OVX adult female rats subjected to the CUMS procedure, which might be mediated by the regulation of BDNF and the NT-3/NT-4 signaling pathways in the hippocampus, as well as the corticosterone/ACTH levels of the blood serum.

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Hye Ryeong Kim ◽  
Young-Ju Lee ◽  
Tae-Wan Kim ◽  
Ri-Na Lim ◽  
Dae Youn Hwang ◽  
...  

Abstract Background Depression is a serious and common psychiatric disorder generally affecting more women than men. A woman’s risk of developing depression increases steadily with age, and higher incidence is associated with the onset of menopause. Here we evaluated the antidepressant properties of Asparagus cochinchinensis (AC) extract and investigated its underlying mechanisms in a rat menopausal depression model. Methods To model this menopausal depression, we induced a menopause-like state in rats via ovariectomy and exposed them to chronic unpredictable mild stress (CUMS) for 6 weeks, which promotes the development of depression-like symptoms. During the final 4 weeks of CUMS, rats were treated with either AC extract (1000 or 2000 mg/kg, PO), which has been reported to provide antidepressant effects, or with the tricyclic antidepressant imipramine (10 mg/kg, IP). Results We report that CUMS promotes depression-like behavior and significantly increases serum corticosterone and inflammatory cytokine levels in the serum of ovariectomized (OVX) rats. We also found that CUMS decreases the expression of brain-derived neurotrophic factor (BDNF) and its primary receptor, tropomyosin receptor kinase B (TrkB), in OVX rats, and treatment with AC extract rescues both BDNF and TrkB expression levels. Conclusion These results suggest that AC extract exerts antidepressant effects, possibly via modulation of the BDNF-TrkB pathway, in a rat model of menopausal depression.


1998 ◽  
Vol 12 (1) ◽  
pp. 76-81 ◽  
Author(s):  
T. Sasaki ◽  
N.S. Ramamurthy ◽  
L.M. Golub

The effect of a new non-antimicrobial analog of tetracycline (CMT-8) on bone loss in ovariectomized (OVX) rats was examined. Three-month-old female rats were ovariectomized, and one week later, were distributed into 3 groups: sham-operated non-OVX controls, vehicle-treated OVX controls, and CMT-8-treated OVX rats. After 145 days of daily CMT-8 administration, the intact femurs were dissected and examined by several histological and histomorphometric techniques. OVX significantly (p < 0.01) decreased trabecular bone volume by 53.4% in the metaphyses compared with sham-operated controls. CMT-8 therapy produced a significant (p < 0.05) inhibition of trabecular bone loss and also induced bone formation in the OVX rats. Of interest, the newly synthesized bone in the CMT-treated OVX rats was found to increase the "connectivity" of the trabecular "struts" by bridging the adjacent longitudinal bone trabeculae, forming dense, platelike bone trabeculae. These results strongly suggest that long-term CMT-8 therapy effectively inhibits bone loss after OVX, not only by inhibiting bone resorption but also by inducing new bone formation in the trabecular areas of long bones.


2020 ◽  
Vol 8 (1) ◽  
pp. 29-46
Author(s):  
Julia Fedotova

Background: Vitamin D3 (VD3) is involved in the pathophysiological mechanisms of affective-related disorders and controls the functional activity of various hormonal systems. The complex interaction between estrogen and VD3 creates a neurobiological basis for their participation in similar behavioral disorders. Objectives: This study aimed to evaluate whether VD3 (5.0 mg/kg, s.c.) facilitates the antidepressant-like action of fluoxetine (10.0 mg/kg, i.p.) or paroxetine (10.0 mg/kg, i.p.) by enhancing the antidepressant-like activity of these drugs in adult long-term Ovariectomized (OVX) rats subjected to Chronic Unpredictable Mild Stress (CUMS) protocol for 6 weeks. Methods: Sucrose Preference (SPT) and Forced Swim (FST) tests were performed to evaluate the anhedonia state and depressive symptoms, respectively. The Open-Field Test (OFT) was carried out to measure locomotor activity as well as grooming behavior produced by CUMS in long-term OVX rats. Corticosterone (CS)/estradiol (E2) in the serum was tested by rat ELISA kits. NF-kB, 5-HT/5-HIIA, and pro-inflammatory cytokine levels in the hippocampus were also examined by rat ELISA kits. Results: The results of this study suggest that combined treatment with fluoxetine (10.0 mg/kg, i.p.) or paroxetine (10.0 mg/kg, i.p.) along with VD3 (5.0 mg/kg, s.c.) produces distinct effects on the depression-like behavior in long-term OVX/CUMS rats. Co-administration of fluoxetine (10.0 mg/kg, i.p.) with VD3 did not facilitate the antidepressant-like effects of fluoxetine in the long-term OVX rats with CUMS. On the other hand, co-treatment with paroxetine with VD3 resulted in faster and marked antianhedonic- and antidepressant-like effects in long-term OVX rats with CUMS as compared to treatment with paroxetine alone. The co-administration of paroxetine and VD3 attenuates stress-induced modifications of CS/E2 levels in the serum, as well as- proinflammatory cytokine/NF-kB/5-HT levels in the hippocampus of long-term OVX rats exposed to CUMS. Conclusion: Supplementation of VD3 (5.0 mg/kg, s.c.)to paroxetine (10.0 mg/kg, i.p.) facilitates antianhedonic- and antidepressant-like effects of paroxetine in adult long-term OVX rats exposed to CUMS.


2019 ◽  
Author(s):  
Denis Baranenko ◽  
Vera Mironova ◽  
Julia Fedotova ◽  
Annemieke Johanna Maria van den Tol

AbstractThe aim of the present study was study changes in antidepressant-like responses to Vitamin D3 (VD3) supplementation in three different doses (1.0, 2.5, and 5.0 mg/kg, s.c.) in long-term ovariectomized (OVX) rats treated with low dose of 17β-E2 (0.5 μg/rat, s.c.) during chronic unpredictable mild stress (CUMS). Sucrose preference (SPT), forced swimming (FST), and open-field (OFT) tests were administered to measure depression-like behavior. Brain-derived neurotrophic factor (BDNF), and serotonine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels in the hippocampus were measured by ELISA, western blotting analysis, and by using high performance liquid chromatography (HPLC), respectively.The findings demonstrated that VD3 (5.0 mg/kg, s.c.) in a combination with low dose of 17β-E2 increased sucrose consumption in the SPT and decreased depression-like in the FST of the long-term OVX rats exposed to CUMS. VD3 (5.0 mg/kg) resulted in significant elevated levels of hippocampal BDNF protein expression, as well as to the normalization of 5-HT and 5-HIAA levels in long-term OVX rats plus 17β-E2 compared to the OVX rats plus solvent or 17β-E2 submitted to CUMS. There were no significant effects of VD3 (1.0 and 2.5 mg/kg) treatment on both BDNF protein levels and 5-HT turnover in the hippocampus of the long-term OVX rats treated with 17β-E2 exposed to CUMS compared to the long-term OVX with CUMS rats plus solvent.In conclusion, VD3 (5.0 mg/kg, s.c.) in a combination with low dose of 17β-E2 had a synergic antianhedonic- and antidepressant-like effects in the adult female rats following long-term ovariectomy submitted to CUMS. This is the first study in long-term OVX female rats showing beneficial effects of VD3 on depression-like behavior that are depended on the presence/absence of stressful factors.


BIOCELL ◽  
2019 ◽  
Vol 43 (4) ◽  
pp. 299-311
Author(s):  
Denis BARANENKO ◽  
Julia FEDOTOVA ◽  
Annemieke Johanna Maria VAN DEN TOL

2008 ◽  
Vol 93 (7) ◽  
pp. 2693-2701 ◽  
Author(s):  
Joyce Maalouf ◽  
Mona Nabulsi ◽  
Reinhold Vieth ◽  
Samantha Kimball ◽  
Rola El-Rassi ◽  
...  

2014 ◽  
Vol 59 (3) ◽  
pp. 258-267 ◽  
Author(s):  
Min Cui ◽  
Qiang Li ◽  
Min Zhang ◽  
Ya-Juan Zhao ◽  
Fei Huang ◽  
...  

2020 ◽  
Vol 103 ◽  
pp. 101712 ◽  
Author(s):  
Amir Raoofi ◽  
Abass Aliaghaei ◽  
Mohammad-Amin Abdollahifar ◽  
Mahdi Eskandarian Boroujeni ◽  
Sara Sadat Javadinia ◽  
...  

Endocrinology ◽  
2014 ◽  
Vol 155 (6) ◽  
pp. 2178-2189 ◽  
Author(s):  
M. P. Mosti ◽  
A. K. Stunes ◽  
M. Ericsson ◽  
H. Pullisaar ◽  
J. E. Reseland ◽  
...  

Estrogen deficiency promotes bone loss and skeletal muscle dysfunction. Peroxisome proliferator-activated receptors (PPARs) have 3 subtypes (α, δ, and γ). PPARγ agonists induce bone loss, whereas PPARα agonists increase bone mass. Although PPARδ agonists are known to influence skeletal muscle metabolism, the skeletal effects are unsettled. This study investigated the musculoskeletal effects of the PPARδ agonist GW501516 in ovariectomized (OVX) rats. Female Sprague Dawley rats, 12 weeks of age, were allocated to a sham-operated group and 3 OVX groups; high-dose GW501516 (OVX-GW5), low-dose GW501516 (OVX-GW1), and a control group (OVX-CTR), respectively (n = 12 per group). Animals received GW501516 or vehicle (methylcellulose) daily for 4 months by gavage. Bone mineral density (BMD) was assessed by dual x-ray absorptiometry at the femur, spine, and whole body. Bone microarchitecture at the proximal tibia was assessed by microcomputed tomography, and dynamic histomorphometry was performed. Quadriceps muscle morphology and the relative expression of mitochondrial proteins were analyzed. Bone metabolism markers and metabolic markers were measured in plasma. After 4 months, the OVX-GW5 group displayed lower femoral BMD than OVX-CTR. Trabecular separation was higher in the GW-treated groups, compared with OVX-CTR. The OVX-GW5 group also exhibited lower cortical area fraction and a higher structure model index than OVX-CTR. These effects coincided with impaired bone formation in both GW groups. The OVX-GW5 group displayed elevated triglyceride levels and reduced adiponectin levels, whereas no effects on muscle morphology or mitochondrial gene expression appeared. In summary, the PPARδ agonist GW501516 negatively affected bone properties in OVX rats, whereas no effects were detected in skeletal muscle.


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