Urinary metabolic disturbance in the olfactory bulbectomized rats and the modulatory effects of fluoxetine

Zhou, Yunfeng; Feng, Linyin; Liu, Xinmin; Xue, Tao; Wang, Lisha; Zhang, Meng-Di; Wang, Zhi; Chen, Shanguang; Chang, Qi

doi:10.1016/j.lfs.2019.116751

Cited by 15 publications

(9 citation statements)

References 58 publications

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“…FLX induced an antidepressant-like effect in OBX rats since the immobility time was statistically significant reduced vs the OBX-saline group (Fisher’s LSD post hoc: P < .05) as previously described ( Zhou et al, 2019 ) ( Figure 2A ).…”

Section: Resultssupporting

confidence: 81%

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Galanin (1-15) Enhances the Behavioral Effects of Fluoxetine in the Olfactory Bulbectomy Rat, Suggesting a New Augmentation Strategy in Depression

Flores-Burgess

Millón

Gago

et al. 2021

International Journal of Neuropsychopharmacology

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Background Selective serotonergic reuptake inhibitors, including fluoxetine (FLX), are the most commonly used for the treatment of major depression. However, they are only effective for remission in 30% of patients. Recently we observed that Galanin (1-15) [GAL(1-15)] enhanced the antidepressant effects of FLX in naïve animals suggesting a new augmentation strategy in depression. Methods We have analyzed in an animal model of depression, the olfactory bulbectomy (OBX) rats the effect of GAL(1–15) on FLX-mediated responses in the forced swimming test (FST) and in sucrose preference test (SPT) and the involvement of GALR2 with its antagonist M871. We have also studied the corticosterone levels in OBX after the coadministration of GAL(1-15) with FLX. Moreover, we studied whether the effects of GAL(1–15) on FLX actions were mediated via 5-HT1AR analyzing the binding characteristics, mRNA levels and the functionality of 5-HT1AR in the dorsal hippocampus. Results GAL(1-15) enhances the antidepressant-like effects induced by FLX in OBX animals in the FST and in the SPT. The involvement of the GALR2 was demonstrated with M871. Importantly, the mechanism underlying the GAL(1-15)/FLX interactions in the OBX animals involves the 5-HT1AR in the hippocampus at the plasma membrane (increase of affinity and density of 5HT1AR in the DG) and transcriptional (increase of 5HT1AR mRNA levels in DG and CA1) levels. Besides, the coadministration of GAL(1-15) and FLX also reduced OBX-increased corticosterone levels Conclusions The results open up the possibility to use GAL(1-15) in combination with FLX as a novel strategy for the treatment of depression.

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Section: Resultssupporting

confidence: 81%

“…On the other hand, in the SPT that detects an anhedonia-like condition, which is a core feature of major depression and characteristic of the OBX model ( Millón et al, 2019 ; Zhou et al, 2019 ), we observed increased anhedonia ( Zhu et al, 2020 ).…”

Section: Discussioncontrasting

confidence: 52%

Galanin (1-15) Enhances the Behavioral Effects of Fluoxetine in the Olfactory Bulbectomy Rat, Suggesting a New Augmentation Strategy in Depression

Flores-Burgess

Millón

Gago

et al. 2021

International Journal of Neuropsychopharmacology

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“…The disorganized pathways correlated to these endogenous biomarkers included amino acid metabolism, fatty acid metabolism, purine metabolism, and energy metabolism. Similar metabolic changes were also found in the urine of OBX rats in our previous research, in which 26 altered metabolites were regarded as urine biomarkers for the OBX model and 15 of them were normalized by fluoxetine treatment [7]. These results indicated that fluoxetine partly alleviated the turbulent metabolic pathways not only in the urine, but also in the hippocampus of OBX rats.…”

Section: Discussionsupporting

confidence: 80%

“…Recently developed metabonomics technology has become a powerful approach in the exploration of pathological processes, the identification of potential biomarkers, and the explanation of biochemical pathways in diverse complex diseases [2], including depression and AD. The urinary metabolic profile in OBX rats has been investigated by the metabonomics approach in our recent report [7]. Hippocampus is a critical brain region in the regulation of memory and mood, and hippocampus metabolic profiles have been explored in various depression-related and AD-related animal models by using the metabonomics strategy.…”

Section: Introductionmentioning

confidence: 99%

Hippocampus Metabolic Disturbance and Autophagy Deficiency in Olfactory Bulbectomized Rats and the Modulatory Effect of Fluoxetine

Zhou

Xue

Wang

et al. 2019

IJMS

Self Cite

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An olfactory bulbectomy (OBX) rodent is a widely-used model for depression (especially for agitated depression). The present study aims to investigate the hippocampus metabolic profile and autophagy-related pathways in OBX rats and to explore the modulatory roles of fluoxetine. OBX rats were given a 30-day fluoxetine treatment after post-surgery rehabilitation, and then behavioral changes were evaluated. Subsequently, the hippocampus was harvested for metabonomics analysis and Western blot detection. As a result, OBX rats exhibited a significantly increased hyperemotionality score and declined spatial memory ability. Fluoxetine reduced the hyperemotional response, but failed to restore the memory deficit in OBX rats. Sixteen metabolites were identified as potential biomarkers for the OBX model including six that were rectified by fluoxetine. Disturbed pathways were involved in amino acid metabolism, fatty acid metabolism, purine metabolism, and energy metabolism. In addition, autophagy was markedly inhibited in the hippocampus of OBX rats. Fluoxetine could promote autophagy by up-regulating the expression of LC3 II, beclin1, and p-AMPK/AMPK, and down-regulating the levels of p62, p-Akt/Akt, p-mTOR/mTOR, and p-ULK1/ULK1. Our findings indicated that OBX caused marked abnormalities in hippocampus metabolites and autophagy, and fluoxetine could partly redress the metabolic disturbance and enhance autophagy to reverse the depressive-like behavior, but not the memory deficits in OBX rats.

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“…However, in our study, we noted a thought-provoking result, which was in contradiction with the theory "serotonin hypothesis". Serotonin hypothesis indicates that TRP diverts from 5-HT to synthesize Kyn, which is a well-known theory in neurogenic disease as depression [31,32]. However, in the study, when IDO increased, TRP level had no signi cant in plasma among the three groups, while the 5-HT in plasma increased, and Kyn and KynA in plasma has no statistical signi cance, suggesting that the relationship of IDO changes and 5-HT metabolism is different with the "serotonin hypothesis"after AMI.…”

Section: Abnormalities In 5-ht Pathway After Amimentioning

confidence: 99%

Involvement of intestinal hypoperfusion related with Indoleamine 2,3-peroxidase activation and 5-HT metabolism abnormality in intestinal dysfunction after acute myocardial infarction

ZHOU²,

WANG³

et al. 2020

Preprint

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Background To investigate the intestinal dysfunction after acute myocardial infarction (AMI) and discuss the underlying mechanism. Methods Rats were divided into three groups randomly, including AMI group, Sham group and Normal (N) group. An AMI model was established with ligating the left anterior descending artery (LAD) without ventilator assisted. The body surface electrocardiogram (ECG), HE staining of myocardial tissues and echocardiogram were used to evaluate whether the model was established successfully. The HE staining for ileum tissue was applied to evaluate the structure of the ileum, the intestinal propulsive rate were conducted to investigate the intestinal dysfunction, and laser speckle technique was developed in order to measure the mesenteric blood flow. immunohistochemical method was used to determined the expression of Indoleamine 2, 3-dioxygenase (IDO) in ileum, high-performance liquid chromatography was used to detected 5-hydroxytryptamine(5-HT) metabolism in rats plasma and ileum. Results After AMI in rats, the ECG shows ST segment elevation in lead Ⅱ for more than 30 minutes and pathological Q wave appeared at 4 weeks after surgery. HE staining showed at 4 weeks after AMI, the ventricular wall of the infarcted area of the rats became thin and white. Echocardiogram showed Left ventricular internal diameters of systole(LVIDs) and Left ventricular internal diameters of diastole(LVIDd) in the AMI group increased significantly, and Interventricular septal thickness at end diastole(IVSd) decreased significantly. Left ventricular ejection fraction(LVEF) and Fractional shortening(FS) values in the AMI group were significantly decreased. HE staining showed intestinal mucosa was hyperemia, edema, and it was infiltrated by a large number of neutrophils. The intestinal propulsive rate was increased in AMI group. Laser speckle technique shows the mesenteric blood flow was decreased in AMI group. Immunohistochemistry showed the expression of IDO was increased in AMI group. High-performance liquid chromatography showed the 5-HT content in the plasma was increased, and the content of 5-HT and 5-hydroxy indole acetic acid (5-HIAA) in the ileum was increased in AMI group. Conclusion Intestinal dysfunction after AMI may be achieved by decreased intestinal blood perfusion, IDO-related inflammation and the dysfunction of 5-HT metabolic pathway.

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Urinary metabolic disturbance in the olfactory bulbectomized rats and the modulatory effects of fluoxetine

Cited by 15 publications

References 58 publications

Galanin (1-15) Enhances the Behavioral Effects of Fluoxetine in the Olfactory Bulbectomy Rat, Suggesting a New Augmentation Strategy in Depression

Galanin (1-15) Enhances the Behavioral Effects of Fluoxetine in the Olfactory Bulbectomy Rat, Suggesting a New Augmentation Strategy in Depression

Hippocampus Metabolic Disturbance and Autophagy Deficiency in Olfactory Bulbectomized Rats and the Modulatory Effect of Fluoxetine

Involvement of intestinal hypoperfusion related with Indoleamine 2,3-peroxidase activation and 5-HT metabolism abnormality in intestinal dysfunction after acute myocardial infarction

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