scholarly journals Subchronic Arsenic Exposure Induces Anxiety-Like Behaviors in Normal Mice and Enhances Depression-Like Behaviors in the Chemically Induced Mouse Model of Depression

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Chia-Yu Chang ◽  
How-Ran Guo ◽  
Wan-Chen Tsai ◽  
Kai-Lin Yang ◽  
Li-Chuan Lin ◽  
...  
Keyword(s):  
Drinking Water ◽  
Prefrontal Cortex ◽  
Mouse Model ◽  
Arsenic Exposure ◽  
Tail Suspension Test ◽  
Behavioral Disturbances ◽  
Chemically Induced ◽  
Contaminated Drinking Water ◽  
Swimming Test ◽  
Underlying Mechanisms

Accumulating evidence implicates that subchronic arsenic exposure causes cerebral neurodegeneration leading to behavioral disturbances relevant to psychiatric disorders. However, there is still little information regarding the influence of subchronic exposure to arsenic-contaminated drinking water on mood disorders and its underlying mechanisms in the cerebral prefrontal cortex. The aim of this study is to assess the effects of subchronic arsenic exposure (10 mg/LAs2O3 in drinking water) on the anxiety- and depression-like behaviors in normal mice and in the chemically induced mouse model of depression by reserpine pretreatment. Our findings demonstrated that 4 weeks of arsenic exposure enhance anxiety-like behaviors on elevated plus maze (EPM) and open field test (OFT) in normal mice, and 8 weeks of arsenic exposure augment depression-like behaviors on tail suspension test (TST) and forced swimming test (FST) in the reserpine pretreated mice. In summary, in this present study, we demonstrated that subchronic arsenic exposure induces only the anxiety-like behaviors in normal mice and enhances the depression-like behaviors in the reserpine induced mouse model of depression, in which the cerebral prefrontal cortex BDNF-TrkB signaling pathway is involved. We also found that eight weeks of subchronic arsenic exposure are needed to enhance the depression-like behaviors in the mouse model of depression. These findings imply that arsenic could be an enhancer of depressive symptoms for those patients who already had the attribute of depression.

Nitric oxide mediates the antidepressant-like effect of modafinil in mouse forced swimming and tail suspension tests

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Hossein Omidi-Ardali ◽  
Abolfazl Ghasemi Badi ◽  
Elham Saghaei ◽  
Hossein Amini-Khoei
Keyword(s):  
Nitric Oxide ◽  
Effective Dose ◽  
Animal Studies ◽  
Tail Suspension Test ◽  
Forced Swimming ◽  
Antidepressant Effect ◽  
Tail Suspension ◽  
Immobility Time ◽  
Swimming Test ◽  
Underlying Mechanisms

AbstractObjectivesPrevious studies have suggested antidepressant properties for modafinil; however, the underlying mechanisms mediating the antidepressant effect of modafinil have not been well recognized in clinical and animal studies. Nitric oxide (NO) is involved in the pathophysiology of depression. We attempted to investigate the possible role of NO in the antidepressant-like effect of modafinil in mouse forced swimming test (FST) and tail suspension test (TST).MethodsThe antidepressant-like effect of modafinil (25, 50 and 75 mg/kg), alone and in combination with l-arginine, l-arg, (100 mg/kg) and NG-l-arginine methyl ester, l-NAME (5 mg/kg), was evaluated using FST and TST. Following behavioral tests, the hippocampi were dissected out to measure nitrite levels.ResultsFindings suggested that administration of modafinil at doses of 50 and 75 mg/kg significantly reduced immobility time in the FST and TST. Furthermore, administration of l-arg and l-NAME increased and decreased, respectively, the immobility time in the FST and TST. We showed that co-administration of a sub-effective dose of modafinil (25 mg/kg) plus l-NAME potentiated the antidepressant-like effect of the sub-effective dose of modafinil. In addition, co-treatment of an effective dose of modafinil (75 mg/kg) with l-arg attenuated the antidepressant-like effect of the effective dose of modafinil. We showed that the antidepressant-like effect of modafinil is associated with decreased nitrite levels in the hippocampus.ConclusionsOur findings for the first time support that the modulation of NO, partially at least, is involved in the antidepressant-like effect of modafinil in mouse FST and TST.

Arsenic exposure with reference to neurological impairment: an overview

2019 ◽  
Vol 34 (4) ◽  
pp. 403-414
Author(s):  
Anupama Sharma ◽  
Sunil Kumar
Keyword(s):  
Nervous System ◽  
Drinking Water ◽  
Memory Impairment ◽  
Environmental Problem ◽  
Arsenic Exposure ◽  
Neurological Impairment ◽  
The World ◽  
Contaminated Drinking Water ◽  
Existing Data ◽  
As Toxicity

Abstract Arsenic (As) toxicity has become a public health and environmental problem, which is a serious issue in certain parts of the world. Many people are exposed to As through contaminated drinking water, food and soil, through occupation, etc. Chronic As exposure is linked to various hostile health effects including skin problems, cancer, diabetes, cardiovascular disease, reproductive and developmental and neurological problems in exposed subjects. Experimental existing data indicate that chronic As exposure affects the nervous system by impairing the nerve and brain tissues of the exposed animals, and clinical studies indicate that As exposure leads to both central nervous system and peripheral nervous system impairments and also causes depression, memory impairment and difficulty in problem solving, affects body coordination, etc. Various prenatal and postnatal studies with respect to As exposure also suggest that developing offspring and young children are susceptible to As exposure. The only solution to this serious health problem is to stop occupational As exposure and provide As free drinking water to the affected population.

scholarly journals Celastrol alleviates comorbid obesity and depression by directly binding amygdala hnRNPA1 in a mouse model

2020 ◽  
Author(s):  
Chunyan Zhu ◽  
Jun Yang ◽  
Yongping Zhu ◽  
Jiahao Li ◽  
Hongyu Chi ◽  
...  
Keyword(s):  
Mouse Model ◽  
Binding Assay ◽  
Tail Suspension Test ◽  
Competitive Binding ◽  
Mediating Effect ◽  
Mice Model ◽  
Chemical Proteomics ◽  
Competitive Binding Assay ◽  
Target Molecules ◽  
Swimming Test

Background and Purpose: Obesity and depression are highly comorbid and far from effective treating. Celastrol was reported useful for obesity, but its role in the obesity-depression comorbidity remains unknown. This study aims to investigate the efficacy and associated mechanism of celastrol in this comorbidity. Experimental Approach: A comorbidity mice model of obesity and depression were constructed. Bodyweight, adipose tissue rate, blood glucose, and blood lipids were used to assess obesity. Forced swimming test and tail suspension test were investigated to evaluate depression. In microglial cells, direct targets of celastrol were screened and determined by chemical proteomics, pull-down experiment, and competitive binding assay. In the mice model, the target gene’s mediating effect was investigated by stereotactic injection of AAV9 virus. The expression level of target molecules was detected by immunofluorescence. Key Results: Celastrol relieved the comorbid symptoms, inhibited the mal-activated Neuropeptide Y, and activated the mal-inhibited 5-HT neurons in the amygdala. The efficacy was associated with the inhibition of the mal-activated microglia. Chemical proteomics, pull-down experiment, and competitive binding assay results indicated celastrol’s directly binding hnRNPA1. In the animal model, downregulation of hnRNPA1 in the amygdala relived symptoms and NPY and 5-HT neurons’ changes. Meanwhile, overexpression of hnRNPA1 aggravated the comorbidity and antagonized the effect of celastrol. Conclusion and Implications: Celastrol alleviated comorbid obesity and depression in a mouse model by directly binding hnRNPA1 in the amygdala. Celastrol may become a potential drug, and hnRNPA1 in the amygdala could be a useful target to combat the comorbidity.

scholarly journals Tetragonia tetragonioides Relieves Depressive-Like Behavior through the Restoration of Glial Loss in the Prefrontal Cortex

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Yujin Choi ◽  
Yunna Kim ◽  
Hwa-Young Lee ◽  
Seung-Hun Cho
Keyword(s):  
Prefrontal Cortex ◽  
Preference Test ◽  
Tail Suspension Test ◽  
Antidepressant Effect ◽  
Antidepressant Agent ◽  
Immobility Time ◽  
Swimming Test ◽  
Asian Pacific ◽  
Sucrose Preference Test ◽  
Tetragonia Tetragonioides

Tetragonia tetragonioides, which is a halophyte and grows widely in Asian-Pacific regions, has been used for the treatment of digestive disorders in traditional oriental medicine. This study examined the potential antidepressant effect of Tetragonia tetragonioides in an astroglial degeneration model of depression, which was established based on the postmortem study of depressive patients’ brain presenting diminished astrocytes in the prefrontal cortex. C57BL/6 male mice were exposed to glial ablation in the prefrontal cortex by the administration of the gliotoxin, L-alpha-aminoadipic acid (L-AAA) to induce depression. Tetragonia tetragonioides at doses of 100 mg/kg and 300 mg/kg, imipramine at a dose of 15 mg/kg, and distilled water were orally administrated to mice for 18 days. Behavioral tests including the open field test (OFT), sucrose preference test (SPT), forced swimming test (FST), and tail suspension test (TST) were carried out after 2 days of L-AAA injection. The expression levels of GFAP and NeuN in the prefrontal cortex were determined by immunohistochemistry. Mice subjected to glial ablation in the prefrontal cortex displayed decreased sucrose consumption in SPT and increased immobility time in FST and TST. Treatment with imipramine and Tetragonia tetragonioides remarkably ameliorated the behavioral despair induced by L-AAA. In addition, immunohistochemistry analysis showed that treatment with Tetragonia tetragonioides significantly restored the glial loss as indicated by the elevated GFAP expression level. These findings suggest that Tetragonia tetragonioides exerts an antidepressant effect through the restoration of glial loss under conditions of depression and can be a candidate for an antidepressant agent.

Muscone Ameliorates LPS-Induced Depressive-Like Behaviors and Inhibits Neuroinflammation in Prefrontal Cortex of Mice

2020 ◽  
Vol 48 (03) ◽  
pp. 559-577 ◽  
Author(s):  
Ming-Chao He ◽  
Zhe Shi ◽  
Meng Qin ◽  
Nan-Nan Sha ◽  
Yue Li ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Inflammatory Cytokines ◽  
Tail Suspension Test ◽  
Ang Ii ◽  
Glandular Secretion ◽  
Regulated Expression ◽  
Bv2 Microglia ◽  
The Central Nervous System ◽  
Swimming Test ◽  
Pre Treatment

Depression is partially caused by inflammation in the central nervous system. Early study demonstrated that musk, glandular secretion from male musk deer, exerted an antidepressant-like effect. The aim of this study was to investigate if muscone, a bioactive ingredient in musk, could ameliorate neuroinflammation and depressive-like behaviors as well as explore the potential action mechanism. Mice were intraperitoneally (i.p.) injected with muscone for 2 weeks prior to administration of lipopolysaccharides (LPS, 1[Formula: see text]mg/kg, i.p.). Pre-treatment with muscone reversed the LPS-induced decrease in body weight within 24[Formula: see text]h and ameliorated depressive-like behaviors shown by sucrose preference, tail suspension test, and forced swimming test. LPS-induced activation of microglial cells and elevation in expression of inflammatory cytokines including IL-1[Formula: see text], RANTES, and MCP-1 in the prefrontal cortex of mice were effectively abrogated by muscone, which significantly down-regulated expression of TLR4, MyD88, Caspase-1, NLRP3, renin, and Ang II. In addition, treatment of BV2 microglia cells with muscone markedly attenuated the LPS-induced rise in protein expression of TLR4, Ang II, and IL-1[Formula: see text]. This study revealed that muscone could ameliorate LPS-induced depressive-like behaviors by repressing neuroinflammation in the prefrontal cortex of mice caused by its suppression on microglia activation and production of inflammatory cytokines via acting on TLR4 pathway and RAS cascade.

scholarly journals Impaired D2 receptor-dependent dopaminergic transmission in prefrontal cortex of awake mouse model of Parkinson’s disease

Brain ◽  
2019 ◽  
Vol 142 (10) ◽  
pp. 3099-3115 ◽  
Author(s):  
Mingli Li ◽  
Huadong Xu ◽  
Guoqing Chen ◽  
Suhua Sun ◽  
Qinglong Wang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Prefrontal Cortex ◽  
Mouse Model ◽  
Early Onset ◽  
D2 Receptor ◽  
Motor Symptom ◽  
Dopaminergic Transmission ◽  
Brain Circuits ◽  
Underlying Mechanisms

Anxiety is a major early-onset non-motor symptom in Parkinson’s disease, but the underlying mechanisms remain largely unknown. By imaging brain circuits in an awake parkinsonian mouse model, Li, Xu et al. provide evidence that Parkinson’s disease-associated anxiety is caused by impaired postsynaptic D2 receptor-dependent dopaminergic transmission in prefrontal cortex.

Arsenic exposure and non-carcinogenic health effects

2021 ◽  
pp. 096032712110459
Author(s):  
Macario Martínez-Castillo ◽  
Eliud A García-Montalvo ◽  
Mónica G Arellano-Mendoza ◽  
Luz del C Sánchez-Peña ◽  
Luis E Soria Jasso ◽  
...  
Keyword(s):  
Drinking Water ◽  
Abdominal Pain ◽  
Urinary Tract ◽  
Health Effects ◽  
Health Problem ◽  
Molecular Mechanisms ◽  
Arsenic Exposure ◽  
Inorganic Arsenic ◽  
Severe Diarrhea ◽  
Contaminated Drinking Water

Inorganic arsenic (iAs) exposure is a serious health problem that affects more than 140 million individuals worldwide, mainly, through contaminated drinking water. Acute iAs poisoning produces several symptoms such as nausea, vomiting, abdominal pain, and severe diarrhea, whereas prolonged iAs exposure increased the risk of several malignant disorders such as lung, urinary tract, and skin tumors. Another sensitive endpoint less described of chronic iAs exposure are the non-malignant health effects in hepatic, endocrine, renal, neurological, hematological, immune, and cardiovascular systems. The present review outlines epidemiology evidence and possible molecular mechanisms associated with iAs-toxicity in several non-carcinogenic disorders.

scholarly journals Perineuronal Nets in the Prefrontal Cortex of a Schizophrenia Mouse Model: Assessment of Neuroanatomical, Electrophysiological and Behavioral Contributions

2021 ◽  
Vol 22 (20) ◽  
pp. 11140
Author(s):  
Razia Sultana ◽  
Charles Brady Brooks ◽  
Amita Shrestha ◽  
Olalekan Michael Ogundele ◽  
Charles Chulsoo Lee
Keyword(s):  
Prefrontal Cortex ◽  
Mouse Model ◽  
Neural Activity ◽  
Medial Temporal Lobe ◽  
Neurodevelopmental Disorder ◽  
Tail Suspension Test ◽  
Enzymatic Digestion ◽  
Behavioral Pattern ◽  
Perineuronal Nets ◽  
Model Assessment

Schizophrenia is a neurodevelopmental disorder whose etiopathogenesis includes changes in cellular as well as extracellular structures. Perineuronal nets (PNNs) associated with parvalbumin-positive interneurons (PVs) in the prefrontal cortex (PFC) are dysregulated in schizophrenia. However, the postnatal development of these structures along with their associated neurons in the PFC is unexplored, as is their effects on behavior and neural activity. Therefore, in this study, we employed a DISC1 (Disruption in Schizophrenia) mutation mouse model of schizophrenia to assess these developmental changes and tested whether enzymatic digestion of PNNs in the PFC affected schizophrenia-like behaviors and neural activity. Developmentally, we found that the normal formation of PNNs, PVs, and colocalization of these two in the PFC, peaked around PND 22 (postnatal day 22). However, in DISC1, mutation animals from PND 0 to PND 60, both PNNs and PVs were significantly reduced. After enzymatic digestion of PNNs with chondroitinase in adult animals, the behavioral pattern of control animals mimicked that of DISC1 mutation animals, exhibiting reduced sociability, novelty and increased ultrasonic vocalizations, while there was very little change in other behaviors, such as working memory (Y-maze task involving medial temporal lobe) or depression-like behavior (tail-suspension test involving processing via the hypothalamic pituitary adrenal (HPA) axis). Moreover, following chondroitinase treatment, electrophysiological recordings from the PFC exhibited a reduced proportion of spontaneous, high-frequency firing neurons, and an increased proportion of irregularly firing neurons, with increased spike count and reduced inter-spike intervals in control animals. These results support the proposition that the aberrant development of PNNs and PVs affects normal neural operations in the PFC and contributes to the emergence of some of the behavioral phenotypes observed in the DISC1 mutation model of schizophrenia.

A Regional Comparative Study on Arsenic Contaminated Drinking Water in Bangladesh

2010 ◽  
Vol 40 (3) ◽  
pp. 763-777
Author(s):  
Sho SHIBATA ◽  
Yoshimi HAGIHARA ◽  
Kiyoko HAGIHARA ◽  
Akira SAKAI
Keyword(s):  
Drinking Water ◽  
Comparative Study ◽  
Contaminated Drinking Water

Dysregulation of DNA methylation during development as a potential mechanisms contributing to obsessive compulsive disorders and autism

2019 ◽  
Author(s):  
German I. Todorov ◽  
Karthikeyan Mayilvahanan ◽  
David Ashurov ◽  
Catarina Cunha
Keyword(s):  
Mouse Model ◽  
Autism Spectrum ◽  
Obsessive Compulsive ◽  
Cancer Treatments ◽  
Knock Out ◽  
Treatment Priority ◽  
Underlying Mechanisms ◽  
Knock Out Mice ◽  
Obsessive Compulsive Disorders ◽  
Compulsive Disorders

Autism Spectrum Disorder (ASD) is a pervasive developmental disorder, that is raising at a concerning rate. However, underlying mechanisms are still to be discovered. Obsessions and compulsions are the most debilitating aspect of these disorders (OCD), and they are the treatment priority for patients. SAPAP3 knock out mice present a reliable mouse model for repetitive compulsive behavior and are mechanistically closely related to the ASD mouse model Shank3 on a molecular level and AMPA receptor net effect. The phenotype of SAPAP3 knock out mice is obsessive grooming that leads to self-inflicted lesions by 4 months of age. Recent studies have accumulated evidence, that epigenetic mechanisms are important effectors in psychiatric conditions such as ASD and OCD. Methylation is the most studied mechanism, that recently lead to drug developments for more precise cancer treatments. We injected SAPAP3 mice with an epigenetic demethylation drug RG108 during pregnancy and delayed the onset of the phenotype in the offspring by 4 months. This result gives us clues about possible mechanism involved in OCD and ASD. Additionally, it shows that modulation of methylation mechanisms during development might be explored as a preventative treatment in the cases of high inherited risk of certain mental health conditions.

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