scholarly journals Homeostasis Imbalance of Microglia and Astrocytes Leads to Alteration in the Metabolites of the Kynurenine Pathway in LPS-Induced Depressive-Like Mice

2020 ◽  
Vol 21 (4) ◽  
pp. 1460 ◽  
Author(s):  
Xue Tao ◽  
Mingzhu Yan ◽  
Lisha Wang ◽  
Yunfeng Zhou ◽  
Zhi Wang ◽  
...  

In the pathology-oriented study of depression, inflammation hypothesis has received increasing attention for recent years. To mimic the depressive state caused by inflammation, rodents injected intraperitoneally with lipopolysaccharide (LPS) are usually used to stimulate an immune response. However, the dose of LPS that causes depressive-like behavior varies widely across many literatures. Previous study has uncovered the non-linearity in the dose-effect relationship for the depressive-like behavior induced by LPS administration, while the reason for this is still unclear. The present study aims to investigate the underlying mechanisms of this non-linear dose-dependent relationship. Four groups of mice were injected intraperitoneally with different doses of LPS (0, 0.32, 0.8, and 2 mg/kg). The tail suspension test was conducted to evaluate the depressive-like behavior within 23–25 h after the LPS administration. The neuroplasticity was assessed by the levels of related proteins, TrkB and PSD-95, and by the quantification of neurons using Nissl staining. The levels of the two metabolites of the kynurenine (KYN) pathway, 3-hydroxykynurenine (3-HK) and kynurenic acid (KYNA), in the brain were analyzed by LC-MS/MS. Activation of microglia and astrocytes in the brain were also determined by immunohistochemistry and western blotting, respectively. The results showed that, compared with the control group, the mice in the 0.8 mg/kg LPS-treated group exhibited a remarkable increase of immobility time in the tail suspension test. The neuroplasticity of mice in the 0.8 mg/kg LPS-treated group was also significantly reduced. The neurotoxic metabolite, 3-HK, was accumulated significantly in the hippocampus of the 0.8 mg/kg LPS-treated mice. Surprisingly, the 2 mg/kg LPS-treated mice did not exhibit a remarkable change of 3-HK but expressed increased KYNA significantly, which is neuroprotective. Furthermore, the activation of microglia and astrocytes, which were recognized as the primary source of 3-HK and KYNA, respectively, corresponded to the content of these two metabolites of the KYN pathway in each group. Consequently, it was speculated that the homeostasis of different glial cells could lead to a non-linear dose-dependent behavior by regulating the KYN pathway in the LPS-induced depressive-like mice.

2021 ◽  
Author(s):  
Minghui Tang ◽  
Yong Ai ◽  
Siyang Zhu ◽  
Ni Song ◽  
Xian Xu ◽  
...  

Abstract Citrus reticulata, has been used for various diseases such as cough. According to previous studies, the essential oil of C. reticulata (CREOs) have been shown to be effectively alleviate depression-like behaviors in mice. This study is aimed to investigate the antidepressant-like effect of CREOs in the rapid reserpine-induced depression model mice as well as its possible mechanisms. The experiment was conducted in six groups, each with four mice. The essential oil group and the control group were administered by sniffing (1h/d), while the reserpine group and fluoxetine group by intraperitoneal injection. Body weight, forced swimming test (FST) and tail suspension test (TST) were used to assess depressive behavior. The compositions and contents of CREOs were analyzed by GC-MS. The results indicated that reserpine could reduce the weight of mice and prolong the immobility time of FST and TST. Moreover, the level of 5HT-1A, GR and Nissl bodies in the brain tissue were significantly reduced, while the level of BDNF was increased in reserpine-treated mice. The administration of CREOs could effectively inhibit the weight loss and the prolongation of immobility time caused by reserpine. In addition, the treatment of CREOs has also been shown to reverse the changes in Nissl body, 5-HT, GR and BDNF levels. Limonene was the main active component of CREOs and might be related to the reduction of BDNF. By up-regulating the level of BDNF, CREOs could regulate the hyperexcitability of the HPA axis, thereby increasing the level of neurotransmitters and restoring neurons.


Author(s):  
Chiranjeevi Bonda ◽  
Sudhir Pawar ◽  
Jaisen Lokhande

Background: The aim of the study was to evaluate the antidepressant effect of opioid analgesic tramadol using forced swim test and tail suspension test models.Methods: The antidepressant effect was assessed by recording the immobility time in Forced swim test (FST) and Tail suspension test (TST). The mice were randomly divided into five groups. Mice belonging to group I was given normal saline (0.1ml/kg) which acted as control. Group II received imipramine (15mg/kg) considered as the standard drug tramadol was given in graded dose (10, 20 and 40 mg/kg) to mice of groups III, IV, V respectively. All drugs were administered intraperitoneally for seven successive days; test was done on 7th day.Results: Tramadol and Imipramine showed antidepressant activity when compared to control. There is dose dependent increase in antidepressant activity of tramadol. The antidepressant activity of imipramine was significantly (P<0.05) more than tramadol at dose 10 and 20 mg/kg but antidepressant activity with tramadol 40mg/kg was comparable to imipramine treated mice.Conclusions: The results of this study indicated the presence of antidepressant activity of tramadol at 40mg/kg.


Dose-Response ◽  
2019 ◽  
Vol 17 (4) ◽  
pp. 155932581989126 ◽  
Author(s):  
Hafiz Muhammad Asif ◽  
Abdul Hayee ◽  
Muhammad Rahil Aslam ◽  
Khalil Ahmad ◽  
Abdul Sattar Hashmi

The present work was carried out to assess the Onosma bracteatum anxiolytic and antidepressant properties. Swiss albino mice (male) were fed orally with hydroalcoholic extract at different doses 50, 100, and 200 mg 1 hour prior to test with the standard diazepam and fluoxetine. Anxiolytic and antidepressant activities were evaluated by using open field, elevated plus maze, force swimming, and tail suspension test. Results of open field test showed an increase in number of line crossing as well as number of rearing in dosage-dependent design. Although results of elevated plus maze test evidently showed antianxiety effect of O bracteatum by increasing the time spent in open arms along with decreasing the time spent in closed arms in dosage-dependent way. For the evaluation of antidepressant effect, O bracteatum diminished the immobility time and expanded mobility time in forced swim model in dosage-dependent way. Likewise, O bracteatum expanded time span of mobility along with diminished immobility time in tail suspension method in dosage-dependent way. Outcome demonstrated that plant at the dose of 200 mg/kg body weight showed significant potential which was similar to that standard diazepam and fluoxetine. Hence, O bracteatum may be used as potent natural psychotherapeutic agent against the mental disorders.


2016 ◽  
Vol 11 (3) ◽  
pp. 634
Author(s):  
Sumeet Gupta ◽  
Priyanaka Kashyap ◽  
Mohammed Asad ◽  
Ipshita Chattopadhyaya ◽  
Randhir Dahiya

<p class="Abstract">The present study assesses the protective effect of <em>Nyctanthes arbor-tristis</em> (<em>Nyctaginaceae</em>) extracts and in combination with fluoxetine on stress-induced depression in mice. Leaves were extracted using different solvents (petroleum ether, chloroform and hydroethanol) and administered orally for 14 days. These extracts showed significant improvement in the mobility percentage but among these, hydroethanol extract showed better protective effect from day 1 to 14 in both forced swimming and tail suspension test model. Hydroethanol (100 mg/kg) and chloroform (100 mg/kg) extracts with fluoxetine showed synergistic effect when compared with fluoxetine treated group (10 mg/kg) alone at day 7 and 14. Among monoamine levels only hydroethanol extract (400 mg/kg) restored the 5-HT level near to level of fluoxetine-treated group. Hydroethanol extracts with two higher doses showed significant decrease in glucose and triglycerides levels. Clinically, it may useful as anti-depressant drug.          </p><p><strong>Video Clip:</strong></p><p><a href="https://youtube.com/v/EYRuTWpPDqk">Tail suspension test:</a> 5 min 57 sec </p>


Molecules ◽  
2019 ◽  
Vol 24 (24) ◽  
pp. 4569 ◽  
Author(s):  
Ariyawan Tantipongpiradet ◽  
Orawan Monthakantirat ◽  
Onchuma Vipatpakpaiboon ◽  
Charinya Khampukdee ◽  
Kaoru Umehara ◽  
...  

Daily treatment of ovariectomized (OVX) ICR mice with puerarin, a glycosyl isoflavone isolated from the root bark of Pueraria candollei var. mirifica, and 17β-estradiol attenuated ovariectomy-induced depression-like behavior, as indicated by a decrease in immobility times in the tail suspension test (TST) and the forced swimming test (FST), an increase in the uterine weight and volume, a decrease in serum corticosterone levels, and dose-dependently normalized the downregulated transcription of the brain-derived neurotrophic factor (BDNF) and estrogen receptor (Erβ and Erα) mRNAs. Like 17β-estradiol, puerarin also inhibited ovariectomy-induced suppression of neurogenesis in the dentate gyrus of the hippocampus (increased the number of doublecortin (DCX)-immunosuppressive cells). These results suggest that puerarin exerts antidepressant-like effects in OVX animals, possibly by attenuating the OVX-induced hyperactivation of the HPA axis and/or normalizing the downregulated transcription of BDNF and ER mRNA in the brain.


1992 ◽  
Vol 7 (5) ◽  
pp. 235-238
Author(s):  
E De Castro-e-Silva ◽  
MF Peres ◽  
P Brito ◽  
C Cobas ◽  
A Saraiva ◽  
...  

SummaryChronically stressed adult male Balb C mice were submitted to the tail suspension test. Chronic immobilization stress (6 h/d for 14 consecutive days) induced a significant reduction in immobility time when compared to non-stressed controls. Pretreatment with LY 53857, a serotonin 5HT2 antagonist, and IPS 339, a selective beta-2 adrenoceptor blocker, reversed immobility time to the levels of non-stressed controls. Chronic administration of corticosterone (100 mg/kg for 7 d) did not modify immobility time as compared to saline treated controls. It is suggested that both serotonergic and adrenergic pathways in the brain may participate in the stress-induced changes occurring in the tail suspension test response and that corticosterone does not appear to play a role in this process.


Author(s):  
Silvio Leite Monteiro da Silva ◽  
Maria Martha Bernardi ◽  
Leoni Villano Bonamin

Background: Depression is a hot topic for research including for the homeopathy community. Laboratory models for human diseases offer the possibility to evaluate depression-like behavior in mice by the tail suspension test (TST), such as the challenge of mothers with induced inflammation by lipopolysaccharide (LPS) during gestation. Moreover, it is known that gender influences depression prevalence and treatment evolution as well in a homeopathic approach. Aims: Verify if the treatment of LPS-challenged pregnant mice with homeopathic Zincum metallicum would change the depression-like behavior of the offspring according to the gender. Methodology: the procedures with animals were previously approved according to local and international law (CEUA-UNIP protocol 156-13). Pregnant randomized BALB/c mice were treated in blind with Zincum metallicum 200c, 30c, 5c and Lactose 5c as control. The treatment lasted 31 days: 21 days from the mating day to the delivery plus ten days of lactating. At the 9.5 days of pregnancy, mothers were challenged or not with 100 microgram/Kg of LPS IP. The pups were separated by sex and mother treatment. The tail suspension test was performed to all pups after they grow up to adulthood (2 months old). Results: The treatment influenced the TST according to gender, but not according to mother’s LPS exposition. Female mice born from mothers treated with 200c potency showed reduction in the immobility time in relation to the control (p-value


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