scholarly journals Yi-Gan San Restores Behavioral Alterations and a Decrease of Brain Glutathione Level in a Mouse Model of Schizophrenia

2009 ◽  
Vol 1 ◽  
pp. JCNSD.S2255 ◽  
Author(s):  
Manabu Makinodan ◽  
Takahira Yamauchi ◽  
Kouko Tatsumi ◽  
Hiroaki Okuda ◽  
Yoshinobu Noriyama ◽  
...  

The traditional Chinese herbal medicine yi-gan san has been used to cure neuropsychological disorders. Schizophrenia can be one of the target diseases of yi-gan san. We aimed at evaluating the possible use of yi-gan san in improving the schizophrenic symptoms of an animal model. Yi-gan san or distilled water was administered to mice born from pregnant mice injected with polyinosinic-polycytidilic acid or phosphate buffered saline. The former is a model of schizophrenia based on the epidemiological data that maternal infection leads to psychotic disorders including schizophrenia in the offspring. Prepulse inhibition and sensitivity to methamphetamine in open field tests were analyzed and the total glutathione content of whole brains was measured. Yi-gan san reversed the decrease in prepulse inhibition, hypersensitivity to methamphetamine and cognitive deficits found in the model mice to the level of control mice. Total glutathione content in whole brains was reduced in the model mice but was restored to normal levels by yi-gan san treatment. These results suggest that yi-gan san may have ameliorating effects on the pathological symptoms of schizophrenia.

2013 ◽  
Vol 7 ◽  
pp. JEN.S12979 ◽  
Author(s):  
Shilpa D. Kadam ◽  
Beth M. French ◽  
S-T. Kim ◽  
Christy M. Morris-Berry ◽  
Andrew W. Zimmerman ◽  
...  

Auto antibodies found in the mothers of children with autistic disorder (MCAD) when passively transferred to pregnant mice cause behavioral alterations in juvenile and adult offspring. The goal of this study was to identify whether intraperitoneal injection of MCAD-IgG during gestation affected postnatal cell proliferation and survival in P7 offspring. Pooled MCAD-IgG or IgG from mothers of unaffected children (MUC) or phosphate-buffered saline was injected daily into C57BL/J6 pregnant dams (gestational days E13–E18). MCAD-IgG exposure significantly increased cell proliferation in the subventricular and subgranular zones. In contrast, BrdU-labeled cells on P1 and surviving until P7 (P1-generated cells) showed reduced cell densities in layers 2–4 of frontal and parietal cortices of MCAD mice compared to those in MUC and PBS-injected mice. In conclusion, significant increases in cell proliferation at P7 and reduced densities of P1-generated cells distinguish in utero exposure to MCAD compared to MUC and PBS.


2020 ◽  
Vol 6 (2) ◽  
pp. eaaw6284 ◽  
Author(s):  
J. Barbeito-Andrés ◽  
P. Pezzuto ◽  
L. M. Higa ◽  
A. A. Dias ◽  
J. M. Vasconcelos ◽  
...  

Zika virus (ZIKV) infection during pregnancy is associated with a spectrum of developmental impairments known as congenital Zika syndrome (CZS). The prevalence of this syndrome varies across ZIKV endemic regions, suggesting that its occurrence could depend on cofactors. Here, we evaluate the relevance of protein malnutrition for the emergence of CZS. Epidemiological data from the ZIKV outbreak in the Americas suggest a relationship between undernutrition and cases of microcephaly. To experimentally examine this relationship, we use immunocompetent pregnant mice, which were subjected to protein malnutrition and infected with a Brazilian ZIKV strain. We found that the combination of protein restriction and ZIKV infection leads to severe alterations of placental structure and embryonic body growth, with offspring displaying a reduction in neurogenesis and postnatal brain size. RNA-seq analysis reveals gene expression deregulation required for brain development in infected low-protein progeny. These results suggest that maternal protein malnutrition increases susceptibility to CZS.


2018 ◽  
Author(s):  
Hannah Jongsma ◽  
Caitlin Turner ◽  
James Bowes Kirkbride ◽  
Peter Jones

BackgroundThe last comprehensive international systematic review of the incidence of psychotic disorders was published in 2004. New epidemiological data, from different settings, now permit a broader understanding of global variation. We synthesized this literature to examine variation by demographic characteristics and study methodology.MethodsWe followed PRISMA guidelines and registered our systematic review on PROSPERO (ID: CRD42018086800). We searched PubMed, Embase, Web of Science, PsychInfo and bibliographies, and directly contacted authors, to obtain citations of original research published between 2002 and 2017 on incidence of non-organic adult-onset psychotic disorder. Quality of yield was assessed. Data were evaluated using univariable random-effects meta-analysis, and meta-regression. ResultsFrom 56,721 records, 177 met inclusion criteria. The pooled incidence of all psychotic disorders was 26.6 (95% confidence interval [CI]:22.0-31.7) per 100,000 person-years. Pooled incidence of non-affective disorders was 18.7 (95%CI:14.8-23.7) per 100,000 person-years, and 4.6 (95%CI:3.1-6.8) for affective psychotic disorders. Heterogeneity was high (I2≥99.0%). Men were at higher risk of all psychotic disorders (incidence rate ratio [IRR]: 1.44, 95%CI:1.27-1.62) and non-affective disorders (IRR:1.60, 95%CI:1.44-1.87), but not of affective psychotic disorders (IRR:0.87, 95%CI:0.75-1.00). Ethnic minorities were also at excess risk of all psychotic disorders (IRR:1.75, 95%CI:1.53-2.00), including non-affective disorders (IRR:1.71, 95%CI:1.40-2.09). Meta-regression revealed that population registers reported higher rates of non-affective disorders (IRR:9.64, 95%CI:2.72-31.82), schizophrenia (IRR:2.51, 95%CI:1.24-5.21) and bipolar disorder (IRR:4.53, 95%CI:2.41-8.51) than first contact study designs. DiscussionThere is marked variation in incidence of psychotic disorders by personal characteristics and place. Some geographical variation could be partially explained by differences in case ascertainment methods.


2019 ◽  
Vol 16 (4) ◽  
pp. 358-364 ◽  
Author(s):  
Simone H. Schelder-Marzzani ◽  
Paula Dias ◽  
Viviane Freiberger ◽  
Letícia Ventura ◽  
Bruna B. Silva ◽  
...  

Background: Studies have shown the relationship between neuroinflammation and depressive- like parameters. However, research still has not been carried out to evaluate neuroinflammation in the neonatal period and psychiatric disorders in adulthood. Objective: To verify the association between neonatal immune activation and depressive-like parameters in adulthood using an animal model. Methods: Two days old C57BL/6 animals were exposed to lipopolysaccharides (LPS) or phosphate- buffered saline (PBS). When the animals were 46 days old, they received PBS or Imipramine at 14 days. At 60 days, the consumption of sucrose; immobility time; adrenal gland and the hippocampus weight; levels of plasma corticosterone and hippocampal Brain-derived neurotrophic factor (BDNF) were evaluated. Results: It was observed that the animals exposed to LPS in the neonatal period and evaluated in adulthood decreased the consumption of sucrose and had reducted hippocampus weight. Also, the exposed animals presented an increase of immobility time, adrenal gland weight and plasma levels of corticosteroids. The use of imipramine did not only modify the decreased hippocampal weight. On the other hand, there were no alterations in the BDNF levels in the hippocampus with or without the use of imipramine. Conclusion: These results suggest that neonatal immune activation may be associated with depressive- like parameters in adulthood. It is believed that endotoxemia may trigger physiological and behavioral alterations, increasing vulnerability for the development of depression in adulthood.


2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
Jamaan S. Ajarem ◽  
Gadh Al-Basher ◽  
Ahmed A. Allam ◽  
Ayman M. Mahmoud

Nicotine exposure during pregnancy induces oxidative stress and leads to behavioral alterations in early childhood and young adulthood. The current study aimed to investigate the possible protective effects of green tea (Camellia sinensis) against perinatal nicotine-induced behavioral alterations and oxidative stress in mice newborns. Pregnant mice received 50 mg/kg C. sinensis on gestational day 1 (PD1) to postnatal day 15 (D15) and were subcutaneously injected with 0.25 mg/kg nicotine from PD12 to D15. Nicotine-exposed newborns showed significant delay in eye opening and hair appearance and declined body weight at birth and at D21. Nicotine induced neuromotor alterations in both male and female newborns evidenced by the suppressed righting, rotating, and cliff avoidance reflexes. Nicotine-exposed newborns exhibited declined memory, learning, and equilibrium capabilities, as well as marked anxiety behavior. C. sinensis significantly improved the physical development, neuromotor maturation, and behavioral performance in nicotine-exposed male and female newborns. In addition, C. sinensis prevented nicotine-induced tissue injury and lipid peroxidation and enhanced antioxidant defenses in the cerebellum and medulla oblongata of male and female newborns. In conclusion, this study shows that C. sinensis confers protective effects against perinatal nicotine-induced neurobehavioral alterations, tissue injury, and oxidative stress in mice newborns.


2020 ◽  
Vol 23 (3) ◽  
pp. 181-191
Author(s):  
Jing Sun ◽  
Jianbang Lin ◽  
Xiaolong Feng ◽  
Zhonghua Lu ◽  
Taian Liu ◽  
...  

Abstract Background Both the clinical and preclinical studies have suggested embryonic or infant exposure to ketamine, a general anesthetic, pose a great threat to the developing brain. However, it remains unclear how ketamine may contribute to the brain dysfunctions. Methods A mouse model of prenatal exposure to ketamine was generated by i.m. injection and continuous i.p. infusion of pregnant mice. Open field test and elevated plus maze test were used to analyze the behavioral alterations induced by ketamine. Immunostaining by c-Fos was used to map the neuron activity. Chemogenetic modulation of the neurons was used to rescue the abnormal neuron activity and behaviors. Results Here we show that mice prenatally exposed to ketamine displayed anxiety-like behaviors during adulthood, but not during puberty. C-Fos immunostaining identified abnormal neuronal activity in Bed Nucleus of the Stria Terminalis, the silencing of which by chemogenetics restores the anxiety-like behaviors. Conclusions Taken together, these results demonstrate a circuitry mechanism of ketamine-induced anxiety-like behaviors.


2017 ◽  
Vol 37 (5) ◽  
pp. 540-556 ◽  
Author(s):  
Nibedita Naha ◽  
DN Gandhi ◽  
AK Gautam ◽  
J Ravi Prakash

Background: Nicotine and cigarette smoking (CS) are associated with addiction behavior, drug-seeking, and abuse. However, the mechanisms that mediate this association especially, the role of brain-derived neurotrophic factor (BDNF), dopamine (DA), and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling in the cerebral cortex, are not fully known. Therefore, we hypothesized that overexpression of BDNF and DA, and suppression of Nrf2 contribute to several pathological and behavioral alterations in adult cerebral cortex. Methodology/Principal Observations: We treated Wistar rats with different doses of oral nicotine and passive CS for 4-week (short-term) and 12-week (long-term) duration, where doses closely mimic the human smoking scenario. Our result showed dose-dependent association of anxiogenic and depressive behavior, and cognitive interference with neurodegeneration and DNA damage in the cerebral cortex upon exposure to nicotine/CS as compared to the control. Further, the results are linked to upregulation of oxidative stress, overexpression of BDNF, DA, and DA marker, tyrosine hydroxylase (TH), with concomitant downregulation of ascorbate and Nrf2 expression in the exposed cerebral cortex when compared with the control. Conclusion/Significance: Overall, our data strongly suggest that the intervention of DA and BDNF, and depletion of antioxidants are important factors during nicotine/CS-induced cerebral cortex pathological changes leading to neurobehavioral impairments, which could underpin the novel therapeutic approaches targeted at tobacco smoking/nicotine’s neuropsychological disorders including cognition and drug addiction.


2020 ◽  
Author(s):  
Keltie McDonald ◽  
Tao Ding ◽  
Hannah Ker ◽  
Rebecca Dliwayo ◽  
David Osborn ◽  
...  

Background: Mental health service policymakers require evidence-based information to optimise effective care provision based on local need, but tools are unavailable. We developed and validated a population-level prediction model to forecast need for early intervention in psychosis [EIP] services in England up to 2025.Methods: We fitted six candidate Bayesian Poisson regression models, combining epidemiological data on psychosis risk, to predict new annual caseload of referrals, assessed, treated, and probable first episode psychosis [FEP] cases in EIP services, aged 16-64 years at small-area level. Models were validated against observed NHS Mental Health Services Data Set [MHSDS] data at Clinical Commissioning Group [CCG] and national levels for 2017. Projections were made up to 2025, based on small-area demographic forecasts. Outcome: In 2017, our best-fitting model predicted 8,112 (95% interval: 7,623 to 8,597) individuals with probable FEP in England, compared with 8,038 observed in the MHSDS (difference: n=+74; +0·92%), after accounting for psychosis risk by age, sex, ethnicity, small area-level deprivation, social fragmentation and regional cannabis use. In 2020, this model forecasted 9,066 new treated FEP cases (8,485 to 9,618), rising 1% annually up to 2025. For every ten treated cases, we forecasted that 23 and 21 people would be referred to and assessed by EIP services, respectively, for “suspected FEP”. Interpretation: Our methodology provides an accurate, validated toolkit to inform planners, commissioners and providers about future population need for psychosis care at different stages of the referral pathway, based on local determinants of need.Funding: Wellcome Trust, Royal Society, National Institute for Health Research


Author(s):  
Caroline A. Miller ◽  
Laura L. Bruce

The first visual cortical axons arrive in the cat superior colliculus by the time of birth. Adultlike receptive fields develop slowly over several weeks following birth. The developing cortical axons go through a sequence of changes before acquiring their adultlike morphology and function. To determine how these axons interact with neurons in the colliculus, cortico-collicular axons were labeled with biocytin (an anterograde neuronal tracer) and studied with electron microscopy.Deeply anesthetized animals received 200-500 nl injections of biocytin (Sigma; 5% in phosphate buffer) in the lateral suprasylvian visual cortical area. After a 24 hr survival time, the animals were deeply anesthetized and perfused with 0.9% phosphate buffered saline followed by fixation with a solution of 1.25% glutaraldehyde and 1.0% paraformaldehyde in 0.1M phosphate buffer. The brain was sectioned transversely on a vibratome at 50 μm. The tissue was processed immediately to visualize the biocytin.


Author(s):  
Veronika Burmeister ◽  
N. Ludvig ◽  
P.C. Jobe

Electron microscopic immunocytochemistry provides an important tool to determine the ultrastructural distribution of various molecules in both normal and pathologic tissues. However, the specific immunostaining may be obscured by artifactual immunoreaction product, misleading the investigator. Previous observations show that shortening the incubation period with the primary antibody from the generally used 12-24 hours to 1 hour substantially reduces the artifactual immunostaining. We now extend this finding by the demonstration of artifact-free ultrastructural localization of the Ca2/calmodulindependent cyclic nucleotide phosphodiesterase (CaM-dependent PDE) immunoreactivity in brain.Anesthetized rats were perfused transcardially with phosphate-buffered saline followed by a fixative containing paraformaldehyde (4%) and glutaraldehyde (0.25%) in PBS. The brains were removed, and 40μm sections were cut with a vibratome. The sections were processed for immunocytochemistry as described by Ludvig et al. Both non-immune rabbit serum and specific CaM-dependent PDE antibodies were used. In both experiments incubations were at one hour and overnight. The immunostained sections were processed for electron microscopic examination.


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