INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2019
·Vol. 20
·期 17
·4282
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IF 4.183
Yunfeng Zhou,Xue Tao,Zhi Wang,Li Feng,Lisha Wang,Xinmin Liu,Ruile Pan,Yonghong Liao,Qi Chang
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.Keywords:olfactory bulbectomy;depression;hippocampus;metabonomics;autophagy
研究领域:
神经科学
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药理学
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行为科学
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产品关联
DOI
PubMed
高影响因子
Cell and Bioscience
·
2023
·Vol. 13
·期 1
·1-20
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IF 7.5
Liu Xing-Yang,Wang Ke,Deng Xian-Hua,Wei Yi-Hua,Guo Rui,Liu Sui-Feng,Zhu Yi-Fan,Zhong Jia-Jun,Zheng Jing-Yuan,Wang Meng-Dan,Ye Qiu-Hong,He Jian-Quan,Guo Kai-Hang,Zhu Jun-Rong,Huang Shu-Qiong,Chen Ze-Xu,Lv Chong-Shan,Wen Lei
Background Olfactory dysfunction is among the earliest non-motor symptoms of Parkinson’s disease (PD). As the foremost pathological hallmark, α-synuclein initiates the pathology in the olfactory pathway at the early stage of PD, particularly in the olfactory epithelium (OE) and olfactory bulb (OB). However, the local neural microcircuit mechanisms underlying olfactory dysfunction between OE and OB in early PD remain unknown.Results We observed that odor detection and discrimination were impaired in 6-month-old SNCA-A53T mice, while their motor ability remained unaffected. It was confirmed that α-synuclein increased and accumulated in OB but not in OE. Notably, the hyperactivity of mitral/tufted cells and the excitation/inhibition imbalance in OB were found in 6-month-old SNCA-A53T mice, which was attributed to the impaired GABAergic transmission and aberrant expression of GABA transporter 1 and vesicular GABA transporter in OB. We further showed that tiagabine, a potent and selective GABA reuptake inhibitor, could reverse the impaired olfactory function and GABAergic signaling in OB of SNCA-A53T mice.Conclusion sTaken together, our findings demonstrate potential synaptic mechanisms of local neural microcircuit underlying olfactory dysfunction at the early stage of PD. These results highlight the critical role of aberrant GABAergic signaling of OB in early diagnosis and provide a potential therapeutic strategy for early-stage PD.
研究领域:
神经科学
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药理学
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疾病模型
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Jingbin Chen,Yali Liu,Yonggui Song,Huihui Liang,Genhua Zhu,Bike Zhang,Liangliang Liao,Jian Luo,Ming Yang,Dan Su
Ethnopharmacological relevance Citri Reticulata Pericarpium Viride (also known Qing-Pi or QP) is a plant in the Rutaceae family, QP is a traditional Qi-regulating medicine in Chinese medicine that is compatible with other Chinese medicine components and has extensive clinical practice in treating anxiety and depression. Reports on the pharmacological effects of QP have demonstrated its neuroprotective effects and antioxidant capacities. Numerous pharmacological benefits of QP are attributed to its antioxidant abilities. Anxiety disorders are a broadly defined category of mental illnesses. Oxidative stress and an imbalance in the antioxidant defense system are typical pathological features of these disorders. Aim of the study The aim of this study was to evaluate the effects of QP essential oil on anxiety using animal models and investigate the underlying neurobiological mechanisms. Materials and methods This study aimed to develop an animal model of anxiety using chronic restraint stress and investigate the effects of inhalation of Citri Reticulata Pericarpium Viride essential oil on anxiety-like behavior, olfactory function, and olfactory bulb neurogenesis in mice with anxiety. Results The results showed that long-term chronic restraint stimulation caused a decrease in olfactory function, significant anxiety-like behavior, and a notable reduction in the number of neurons in the olfactory bulb. However, inhalation of Citri Reticulata Pericarpium Viride essential oil reversed these effects, improving the olfactory function, neuro-stimulating effect, alleviating anxiety-like behavior, and regulating theta (4-12Hz) oscillation in the hippocampus DG area. These effects were associated with changes in the expression levels of glutamate receptor NMDAR and NeuN in olfactory bulb. Conclusions The study revealed that mice with anxiety induced by chronic restraint stress exhibited significant olfactory dysfunction, providing strong evidence for the causal relationship between anxiety disorders and olfactory dysfunction. Moreover, QP essential oil has the potential to be developed as a therapeutic drug for anxiety disorders, in addition to its role as a complementary anxiolytic.
研究领域:
药理学
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神经科学
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民族药理学
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行为科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
LIFE SCIENCES
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2019
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IF 3.448
Yun-Feng Zhou,Li Feng,Xin-Min Liu,Xue Tao,Li-Sha Wang,Meng-Di Zhang,Zhi Wang,Shan-Guang Chen,Qi Chang
Aims The present study aims to investigate the impacts of olfactory bulbectomy (OBX) on urinary metabolic profile and tryptophan metabolites in prefrontal cortex (PFC) of rats, and to explore the regulation effects of fluoxetine. Main methods OBX model was developed by aspiration of olfactory bulbs. After fluoxetine treatment (10 mg/kg) for 14 days, urine samples were collected and behavior tests were applied. Tryptophan (TRP) metabolites and neurotransmitters in PFC were determined by prominence ultrafast liquid chromatography-QTRAP-mass spectrometry, and tryptophan hydroxylase 2 (TPH2) and indoleamine-2,3-dioxygenase 1 (IDO1) were evaluated by western blot. Urinary metabolites were analyzed by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry-based metabonomics strategy. Key finding OBX rats showed hyperlocomotion in open field, hyperactivity in open arm and despair status, and fluoxetine reserved these behavioral abnormalities. The levels of TRP, 5-HIAA, 5-HIAA/5-HT ratio and DA increased, while kynurenine and 5-HT decreased in PFC of OBX rats. The activities of TPH2 and IDO1were inhibited after OBX. Twenty-six altered metabolites were identified as potential biomarkers in OBX rats involved in tryptophan metabolism, gut microbiota metabolism, energy metabolism, purine metabolism, ascorbate and aldarate metabolism, and tyrosine metabolism. Among them, 15 abnormal metabolites were corrected by fluoxetine to some extent. Significance Our results revealed that urinary metabolic profile changed greatly in OBX rats, and identified biomarkers might be helpful for the diagnosis of agitated depression. The regulation effects of fluoxetine on urinary metabolic profile and tryptophan metabolites in PFC might contribute to its antidepressant action in OBX rats.
研究领域:
神经科学
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药理学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2019
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IF 3.414
Bojun Chen,Jijun Li,Yuhuan Xie,Xi Ming,Gang Li,Jinjin Wang,Meng Li,Xiaohong Li,Lei Xiong
Ethnopharmacological relevance Cang-ai volatile oil (CAVO) is a traditional Chinese medicine (TCM) inhalational preparation for the treatment of some depressive and emotive disorders. Aim of the study This research aimed to evaluate the efficiency and possible mechanism of intranasal CAVO administration on depression in chronic unpredictable mild stress (CUMS)-induced rats compared to lavender volatile oil (LVO) treatment after CUMS exposure and bilateral olfactory bulb impairment (OBI) in rats. Materials and methods Forty depressive-like model rats induced by CUMS were evaluated by the forced swim test (FST), open field test (OFT), and sucrose preference test (SPT). The model rats were divided into five groups: CUMS (n = 8), CAVOh + CUMS (n = 8), CAVOl + CUMS (n = 8), LVO + CUMS (n = 8), and OBI + CAVO + CUMS (n = 8). The CUMS-induced rats were treated for a period of 4 weeks. The other healthy rats were regarded as the control (CTR, n = 8) subjects. The levels of serotonin (5-HT) and dopamine (DA) and their respective metabolites homovanillic acid (HVA) and 5-hydroxyindol acetic acid (5-HIAA) were measured in brain tissue homogenates of CUMS-induced rats using enzyme-linked immunosorbent assay (ELISA). Results CAVO ameliorated depressive-like behaviors (p < 0.05 ). The levels of DA in the CUMS group were lower than those in the CTR and CAVOh groups (** p < 0.01 and * p < 0.05 ). The levels of HVA were lower in the CUMS group than in the CTR, LVO, OBI + CAVOh and CAVOh groups (** p < 0.01 and * p < 0.05 ) and lower in the OBI + CAVOh group than in the CAVOh group (** p < 0.01 ). The levels of 5-HT in the CUMS group were lower than those in the CTR and CAVOh groups (** p < 0.01 ). The levels of 5-HIAA were lower in the CUMS and OBI + CAVOh groups than in the CTR, LVO and CAVOh groups (** p < 0.01 ). Conclusions CAVO can improve depressive-like behaviors concomitant with the regulation of DA and 5-HT metabolism in the brains of CUMS-induced rats.
研究领域:
药理学
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神经科学
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中医
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DOI
PubMed
高影响因子
Acta Physiologica
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2023
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IF 6.3
Hanyu Fu,Jingwei Zhou,Shan Li,Ying Zhang,Zhiyun Chen,Yingying Yang,Anan Li,Dejuan Wang
Aim General anesthesia can induce cognitive deficits in both humans and rodents, correlating with pathological alterations in the hippocampus. However, whether general anesthesia affects olfactory behaviors remains controversial as clinical studies have produced inconsistent results. Therefore, we aimed to investigate how olfactory behaviors and neuronal activity are affected by isoflurane exposure in adult mice. Methods The olfactory detection test, olfactory sensitivity test, and olfactory preference/avoidance test were used to examine olfactory function. In vivo electrophysiology was performed in awake, head-fixed mice to record single-unit spiking and local field potentials in the olfactory bulb (OB). We also performed patch-clamp recordings of mitral cell activity. For morphological studies, immunofluorescence and Golgi–Cox staining were applied. Results Repeated exposure to isoflurane impaired olfactory detection in adult mice. The main olfactory epithelium, the first region exposed to anesthetics, displayed increased proliferation of basal stem cells. In the OB, a crucial hub for olfactory processing, repeated isoflurane exposure increased the odor responses of mitral/tufted cells. Furthermore, the odor-evoked high gamma response was decreased after isoflurane exposure. Whole-cell recordings further indicated that repeated isoflurane exposure increased the excitability of mitral cells, which may be due to weakened inhibitory input in isoflurane-exposed mice. In addition, elevated astrocyte activation and glutamate transporter-1 expression in the OB were observed in isoflurane-exposed mice. Conclusions Our findings indicate that repeated isoflurane exposure impairs olfactory detection by increasing neuronal activity in the OB in adult mice.
研究领域:
神经科学
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麻醉学
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行为科学
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DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2020
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IF 9.038
Wei Shi,Shuge Sun,Yu Han,Yu Tang,Weishang Zhou,Xueying Du,Guangxu Liu
Recently, the ubiquitous presence of microplastics (MPs) has drawn worldwide concern over its potential threat to aquatic organisms. However, the effects of MPs on the olfactory ability of fish and the subsequent odorant evoked behaviors remain elusive. In the present study, we analyzed the potential olfactory toxicity of polystyrene (PS) MPs by assessing olfactory-driven behaviors of goldfish in response to odorants. Our results showed that the olfactory-driven behavioral responses of goldfish to L -cysteine and taurocholic acid were significantly hampered by a 28-day MP exposure. Further analysis demonstrated that exposure to MPs may suppress the expression of genes encoding olfactory G protein-coupled receptors, inhibit the enzyme activities of cation transport ATPases crucial for action potential generation, alter the in vivo contents of neurotransmitters as well as metabolites involved in the transduction of electrical signals, and cause olfactory bulb injury and neurotoxicity closely related to the processing of electrical signals. In conclusion, the results obtained in the present study suggest that MPs at environmentally relevant concentrations could impair the olfactory-mediated behavioral responses of goldfish, probably through hampering odorant identification, action potential generation, olfactory neural signal transduction, and olfactory information processing.
研究领域:
环境科学
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水生毒理学
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鱼类生物学
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神经科学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2020
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IF 4.845
Fangyuan Wang,Zhuanzhuan Yang,Mengli Liu,Yaotian Tao,Zhenbao Li,Zonghao Wu,Shuangying Gui
A rotigotine (ROT)-loaded polymer micelles thermosensitive gel (ROT-PM-TSG) delivery system was engineered to enhance the solubility of the drug, prolong the residence time, and increase the concentration of the drug in the brain tissue. First, ROT-loaded polymer micelles (ROT-PM) were tailored and optimized. The average particle size, encapsulation efficiency, and drug loading of the ROT-PM were (88.62 ± 1.47) nm , (93.5 ± 0.79) %, and (19.9 ± 0.60) %. The optimal ROT-PM-TSG formulation contained 22% P407 and 2% P188 with a gelation temperature of about 32.3 °C and a pH of 5.186. In vivo , the MRT of ROT-PM and ROT-PM-TSG nasal administration was 1.43 and 1.79 times extended than that of the intravenous. In comparison with the intravenous group, the distribution of ROT in olfactory bulb, cerebrum , cerebellum and striatum was 276.6%, 170.5%, 166.5% and 184.4%, respectively. In conclusion, the ROT-PM-TSG system has proven to be a potential application prospect as a ROT nose-to-brain delivery system.
研究领域:
药剂学
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药物递送系统
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神经药理学
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产品关联
DOI
PubMed
高影响因子
WATER RESEARCH
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2023
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IF 12.8
Lin Huang,Weixia Zhang,Difei Tong,Lingzheng Lu,Weishang Zhou,Dandan Tian,Guangxu Liu,Wei Shi
Recently, increased production and consumption of disinfectants such as triclosan (TCS) and triclocarban (TCC) have led to massive pollution of the environment, which draws global concern over the potential risk to aquatic organisms. However, the olfactory toxicity of disinfectants in fish remains elusive to date. In the present study, the impact of TCS and TCC on the olfactory capacity of goldfish was assessed by neurophysiological and behavioral approaches. As shown by the reduced distribution shifts toward amino acid stimuli and hampered electro-olfactogram responses, our results demonstrated that TCS/TCC treatment would cause deterioration of the olfactory ability of goldfish. Our further analysis found that TCS/TCC exposure suppressed the expression of olfactory G protein-coupled receptors in the olfactory epithelium, restricted the transformation of odorant stimulation into electrical responses by disturbing the cAMP signaling pathway and ion transportation, and induced apoptosis and inflammation in the olfactory bulb. In conclusion, our results demonstrated that an environmentally realistic level of TCS/TCC would weaken the olfactory capacity of goldfish by constraining odorant recognition efficiency, disrupting olfactory signal generation and transduction, and disturbing olfactory information processing.
研究领域:
环境科学
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水生毒理学
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神经生物学
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鱼类生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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