Involvement of the brain serotonergic system in the locomotor stimulant effects of chlorpheniramine in Wistar rats: implication of postsynaptic 5-HT1A receptors

Polychlorinated biphenyls (PCBs) are a ubiquitous class of environmental pollutants with toxic and hepatocellular effects, including accumulation of fat, proliferated smooth endoplasmic recticulum (SER), and concentric membrane arrays (CMAs) (1-3). The CMAs appear to be a membrane storage and degeneration organelle composed of a large number of concentric membrane layers usually surrounding one or more lipid droplets often with internalized membrane fragments (3). The present study documents liver alteration after a short term single dose exposure to PCBs with high chlorine content, and correlates them with reported animal weights and central nervous system (CNS) measures. In the brain PCB congeners were concentrated in particular regions (4) while catecholamine concentrations were decreased (4-6). Urinary levels of homovanillic acid a dopamine metabolite were evaluated (7).Wistar rats were gavaged with corn oil (6 controls), or with a 1:1 mixture of Aroclor 1254 and 1260 in corn oil at 500 or 1000 mg total PCB/kg (6 at each level).

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The role of tryptophan in hepatic encephalopathy

Acta Neuropsychiatrica ◽

10.1017/s0924270800033810 ◽

1993 ◽

Vol 5 (4) ◽

pp. 71-75

Author(s):

C. Aaldijk ◽

W.W. Van Den Broek ◽

R.C. Van Der Mast

Keyword(s):

Hepatic Encephalopathy ◽

Clinical Picture ◽

Serotonergic System ◽

Pathogenetic Mechanisms ◽

Research Findings ◽

Glutamine Synthesis ◽

The Brain ◽

Tryptophan Uptake

SummaryIn this review the most important hypotheses for the occurrence of the clinical picture of hepatic encephalopathy are discussed. As possible pathogenetic mechanisms are raised: dysfunction of the serotonergic system due to an increased tryptophan uptake in the brain, an elevated intracerebral ammoniac concentration and glutamine synthesis, and a heightened intracerebral GABA-activity.The dysregulation of the serotonergic system as a consequence of the increased intracerebral tryptophan uptake is described as one of the most important pathogenetic mechanisms. The elevated intracerebral ammoniac concentration and the elevated intracerebral glutamine synthesis play in this a facilitating role. The similarity in symptomatology of the clinical picture of HE and the serotonergic syndrome support this hypothesis. Due to contradictory research findings the role of the GABA-ergic system and the occurrence of HE remains unclear.

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Modafinil Effects on Behavior and Oxidative Damage Parameters in Brain of Wistar Rats

Behavioural Neurology ◽

10.1155/2014/917246 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 5

Author(s):

Felipe Ornell ◽

Samira S. Valvassori ◽

Amanda V. Steckert ◽

Pedro F. Deroza ◽

Wilson R. Resende ◽

...

Keyword(s):

Oxidative Damage ◽

Open Field ◽

Wistar Rats ◽

Thiobarbituric Acid ◽

Protein Carbonyl ◽

Behavioral Changes ◽

Protein Damage ◽

Behavioral Parameters ◽

Carbonyl Formation ◽

The Brain

The effects of modafinil (MD) on behavioral and oxidative damage to protein and lipid in the brain of rats were evaluated. Wistar rats were given a single administration by gavage of water or MD (75, 150, or 300 mg/kg). Behavioral parameters were evaluated in open-field apparatus 1, 2, and 3 h after drug administration. Thiobarbituric acid reactive substances (TBARS) and protein carbonyl formation were measured in the brain. MD increased locomotor activity at the highest dose 1 and 3 h after administration. MD administration at the dose of 300 mg/kg increased visits to the center of open-field 1 h after administration; however, 3 h after administration, all administered doses of MD increased visits to the open-field center. MD 300 mg/kg increased lipid damage in the amygdala, hippocampus, and striatum. Besides, MD increased protein damage in the prefrontal cortex, amygdala, and hippocampus; however, this effect varies depending on the dose administered. In contrast, the administration of MD 75 and 300 mg/kg decreased the protein damage in the striatum. This study demonstrated that the MD administration induces behavioral changes, which was depending on the dose used. In addition, the effects of MD on oxidative damage parameters seemed to be in specific brain region and doses.

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IMMUNOHISTOCHEMICAL STUDIES OF BLOOD BRAIN BARRIER AFTER ADMINISTRATION OF ABHRAK BHASM IN WISTAR RATS

10.36106/ijsr/6505925 ◽

2021 ◽

pp. 13-19

Author(s):

Amita Singh ◽

Raj Kumar ◽

S. K. Kannaujia ◽

Manikrishna Manikrishna ◽

N. P. Singh

Keyword(s):

Blood Brain Barrier ◽

Wistar Rats ◽

Brain Parenchyma ◽

Brain Barrier ◽

Major Constituent ◽

Control Group ◽

Blood Brain ◽

Biological Studies ◽

Immunohistochemical Studies ◽

The Brain

Abhrak bhasma (AB) is a type of bhasma prepared from repeated incineration of mineral mica with decoctions of about 72 herbs. The particle size of Abhrak bhasm has been shown to be in the range of 29-88 nanometers and Fe, Ca, Si, Mg and K are found to be as major constituent. Many drugs developed to treat Central Nervous System (CNS) disorders are unable to reach the brain parenchyma in therapeutically relevant concentrations. The blood brain barrier protects brain parenchyma from the uctuation of plasma composition, from pathogenic agents and maintains homeostasis of the brain parenchyma by restricting non-specic ux of ions, peptides, proteins and even cells into and out the brain. Immunohistochemistry is being widely employed as a tool for biological studies. This study is conducted to examine the change in the continuity of Blood brain barrier by using immunohistochemistry, once Abhrak bhasm drug is given in experimental animal and also to examine the histology of organs. In this study a total of 30 adult albino Wistar rats of approximately 4 months age (approx. 150-200 gms) of either sex selected randomly to see the effect of Abhrak bhasm, an ayurvedic drug on Wistar rats. The rats were weighed, marked and divided into 5 groups each consisting of six animals. In normal control group (Group E), no drug was administered and in rest of the four treated groups (Group-A,B,C,D), Abhrak bhasm @ 36 mg/kg B.wt. was administered orally once in each rat. Brain, liver, kidneys,spleen and blood samples were collected in 10% formalin solution after euthanizing the rats at 0.5,2,6 & 12 hours of Abhrak bhasma drug intervention. The alterations in any of the biochemical parameters are within the tolerable limits of liver and kidney since the dose of abhrak bhasm did not affect liver and kidneys. In the present study, the increase in ALP level may be the result of alterations in metabolisms that occurred without any signicant alteration in histology of liver. After applying the immunohistochemistry with the research markers GFAP, CD 34, S 100, GLUT-1 and RECA-1 on the rats in groups A,B,C and D, there was no change in the intensity of immunohistochemistry, with respect to control. While on applying the Occludin, the intensity of immunohistochemistry was reduced in all the treatment groups as compared to the control group. On the basis of ndings of present study it can be concluded that the therapeutic dose of Abhrak bhasma causes changes at the level of tight junctions present in blood brain barrier in rats which is shown by immunohistochemistry with occludin research marker. There is no toxic effect of drug on different organs of rats as no signicant changes in histology of organs are seen. More studies need to be done to check the permeability of blood brain barrier for Abhrak bhasma drug, like calculating its concentration in brain tissues and other vital organs of rat.

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Expression of NMDA receptor and microRNA-219 in rats submitted to cerebral ischemia associated with alcoholism

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20160188 ◽

2017 ◽

Vol 75 (1) ◽

pp. 30-35 ◽

Cited By ~ 1

Author(s):

Cristiane Iozzi Silva ◽

Paulo Cézar Novais ◽

Andressa Romualdo Rodrigues ◽

Camila A.M. Carvalho ◽

Benedicto Oscar Colli ◽

...

Keyword(s):

Gene Expression ◽

Cerebral Ischemia ◽

Brain Tissue ◽

Wistar Rats ◽

Molecular Mechanisms ◽

Inverse Correlation ◽

Control Group ◽

The Brain ◽

Lower Expression ◽

Control Sham

ABSTRACT Alcohol consumption aggravates injuries caused by ischemia. Many molecular mechanisms are involved in the pathophysiology of cerebral ischemia, including neurotransmitter expression, which is regulated by microRNAs. Objective: To evaluate the microRNA-219 and NMDA expression in brain tissue and blood of animals subjected to cerebral ischemia associated with alcoholism. Methods: Fifty Wistar rats were divided into groups: control, sham, ischemic, alcoholic, and ischemic plus alcoholic. The expression of microRNA-219 and NMDA were analyzed by real-time PCR. Results: When compared to the control group, the microRNA-219 in brain tissue was less expressed in the ischemic, alcoholic, and ischemic plus alcoholic groups. In the blood, this microRNA had lower expression in alcoholic and ischemic plus alcoholic groups. In the brain tissue the NMDA gene expression was greater in the ischemic, alcoholic, and ischemic plus alcoholic groups. Conclusion: A possible modulation of NMDA by microRNA-219 was observed with an inverse correlation between them.

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Photoperiodic responses of depression-like behavior, the brain serotonergic system, and peripheral metabolism in laboratory mice

Psychoneuroendocrinology ◽

10.1016/j.psyneuen.2013.10.013 ◽

2014 ◽

Vol 40 ◽

pp. 37-47 ◽

Cited By ~ 37

Author(s):

Tsuyoshi Otsuka ◽

Misato Kawai ◽

Yuki Togo ◽

Ryosei Goda ◽

Takahiro Kawase ◽

...

Keyword(s):

Serotonergic System ◽

Laboratory Mice ◽

Photoperiodic Responses ◽

The Brain ◽

Peripheral Metabolism

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Neurotrophic factors (BDNF and GDNF) and the serotonergic system of the brain

Biochemistry (Moscow) ◽

10.1134/s0006297917030099 ◽

2017 ◽

Vol 82 (3) ◽

pp. 308-317 ◽

Cited By ~ 36

Author(s):

N. K. Popova ◽

T. V. Ilchibaeva ◽

V. S. Naumenko

Keyword(s):

Neurotrophic Factors ◽

Serotonergic System ◽

The Brain

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Affective spectrum disorders and role of serotonergic system of the brain

Hospital Pharmacology - International Multidisciplinary Journal ◽

10.5937/hpimj1403168t ◽

2014 ◽

Vol 1 (3) ◽

pp. 168-173

Author(s):

Ivana Timotijevic ◽

Mirjana Todorovic ◽

Katarina Crnic ◽

Srdjan Markovic ◽

Dragana Kastratovic

Keyword(s):

Serotonergic System ◽

Spectrum Disorders ◽

The Brain

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Abstract 421: The Subfornical Organ (SFO) Mediates CSF Na+ -induced Pressor Response via Activation of AT1 Receptors

Hypertension ◽

10.1161/hyp.60.suppl_1.a421 ◽

2012 ◽

Vol 60 (suppl_1) ◽

Author(s):

Missale A Tiruneh ◽

Bing S Huang ◽

Frans H Leenen

Keyword(s):

Crucial Role ◽

Major Part ◽

Wistar Rats ◽

Pressor Response ◽

Electrolytic Lesion ◽

Induced Responses ◽

Ang Ii ◽

At1 Receptors ◽

Pressor Responses ◽

The Brain

In salt-sensitive rats on high salt or rats with icv infusion of Na + , the increase in CSF [Na + ] leads to activation of the brain renin-angiotensin-aldosterone system and thereby to sympatho-excitation and hypertension. We tested whether the SFO and AT 1 receptors in the SFO play a crucial role in mediating the Na + -induced responses. In conscious Wistar rats, intra-SFO infusion of Na + -rich aCSF increased BP in a dose-related manner, whereas mannitol with the same osmolarity had no effects. Intra-SFO infusion of the AT 1 receptor blocker candesartan (cand.,10 μg) abolished pressor responses to intra-SFO infusion of Ang II (80 ng) or Na + -rich aCSF (0.45-0.6 M NaCl), and prevented 50% of the BP increase induced by icv infusion of Na + -rich aCSF (0.3 M NaCl, 4 μl/min for 6 min). In another set of Wistar rats, electrolytic lesion of the SFO prevented 50-65% of BP increases induced by icv infusion of Na + -rich aCSF or Ang II (5 ng/min). These data suggest that the SFO neurons are Na + -sensitive and via AT 1 receptors mediate a major part of the pressor response to CSF Na + . Data=means±SE (n=5-7). *p<.05 vs vehicle or sham lesion.

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M9. RATS REARED IN SOCIAL ISOLATION INDUCES EPIGENETIC MODIFICATIONS IN THE NMDA RECEPTOR SUBUNITS

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa030.321 ◽

2020 ◽

Vol 46 (Supplement_1) ◽

pp. S136-S136

Author(s):

Camila Loureiro ◽

Fachim Helene Aparecida ◽

Corsi-Zuelli Fabiana ◽

Shuhama Rosana ◽

Joca Sâmia Regiane Lourenço ◽

...

Keyword(s):

Dna Methylation ◽

Animal Model ◽

Social Isolation ◽

Wistar Rats ◽

Cognitive Impairments ◽

Glutamatergic System ◽

Isolation Rearing ◽

Protein Levels ◽

The Brain ◽

Nmdar Subunits

Abstract Background Early-life stress is a key risk for psychiatric disorders that may produce changes in the neurodevelopment. N-methyl-d-aspartate receptor (NMDAR) have been associated with the pathophysiology of schizophrenia and evidence supports that epigenetic changes in NMDAR imply deficiencies in excitatory neurotransmission suggest its role in the neurobiology of psychoses (Uno and Coyle, 2019; Fachim et al., 2019; Gulchina et al., 2017). Aims: Although previous studies have shown abnormalities in the glutamatergic system in animal model of schizophrenia, it is not known if there are equivalent mRNA/protein alterations and DNA methylation changes in the brains of rats reared in isolation. Thus, in order to improve the knowledge of glutamatergic system role in psychosis, we investigated the NR1 and NR2 mRNA/protein and the DNA methylation levels of Grin1, Grin2a and Grin2b promoter region in the prefrontal cortex (PFC) and hippocampus (HIPPO) of male Wistar rats after isolation rearing. Furthermore, because the Parvalbumin (PV) deficit is the most consistent finding across animal models and schizophrenia itself, we also evaluated the expression of PV and other related GABAergic genes (REL and GAD1) in the brain of rats undergoing social isolation rearing as a validation of this animal model. We hypothesized that isolation rearing reduces mRNA and protein expressions of NMDAR subunits and cause DNA methylation changes. Methods Wistar rats were kept isolated or grouped (n=10/group) from weaning (21 days after birth) to 10 weeks and then exposed to the Open Field Test to assess locomotion. Afterwards the behavioural tests, the tissues were dissected for RNA/DNA extraction and NMDAR subunits were analysed using qRT-PCR, ELISA and pyrosequencing. Data were analysed by parametric tests. Results Isolated-reared animals presented: (i) decreased mRNA levels of Grin1 (p=0.011), Grin2a (p=0.039) and Grin2b (p=0.037) in the PFC followed by reduction in the GABAergic markers; (ii) increased NR1 protein levels in the HIPPO (p=0.001); (iii) hypermethylation of Grin1 at CpG5 in the PFC (p=0.047) and Grin2b CpG4 in the HIPPO when compared to grouped (p=0.024). Moreover, isolated and grouped animals presented a negative correlation between Grin1 mRNA and Grin1 methylation levels at CpG5 in the PFC (r: -0.577; p=0.010) and isolated rats presented a negative correlation between Grin2b methylation at CpG4 and NR2 protein levels in the HIPPO (r: -0.753; p=0.012). Discussion This study supports the hypothesis that the NMDAR methylation changes found in the brain tissues may underlie the NMDAR mRNA/protein expression alterations caused by the isolation period. These results highlighted the importance of the environmental influence during the development that may lead to cognitive impairments in adulthood. Moreover, we demonstrated that the social isolation rearing during 10 weeks causes long-lasting behavioral changes that may be more associated with late stages of schizophrenia. Our study contributes to the identification of the epigenetic mechanisms involved in the neuropathophysiology of schizophrenia, which can bring new pharmacotherapeutic strategies and to identify biomarkers that can improve the early interventions in schizophrenia patients. Finally, our data thus reinforce the validity of rats reared in social isolation after weaning in modelling aspects of schizophrenia, highlighting the glutamatergic and GABAergic features involved principally in the cognitive impairments related to prefrontal cortex.

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