scholarly journals Epigenetic-mediated N-methyl-D-aspartate receptor changes in the brain of isolated reared rats

Epigenomics ◽  
2020 ◽  
Vol 12 (22) ◽  
pp. 1983-1997 ◽  
Author(s):  
Camila Marcelino Loureiro ◽  
Helene Aparecida Fachim ◽  
Fabiana Corsi-Zuelli ◽  
Rosana Shuhama ◽  
Sâmia Joca ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Prefrontal Cortex ◽  
Wistar Rats ◽  
Isolation Rearing ◽  
Rt Pcr ◽  
Brain Areas ◽  
Receptor Mrna ◽  
Aspartate Receptor ◽  
Male Wistar Rats ◽  
The Brain

Aim: We investigated: Grin1, Grin2a, Grin2b DNA methylation; NR1 and NR2 mRNA/protein in the prefrontal cortex (PFC); and hippocampus of male Wistar rats exposed to isolation rearing. Materials & methods: Animals were kept isolated or grouped (n = 10/group) from weaning for 10 weeks. Tissues were dissected for RNA/DNA extraction and N-methyl-D-aspartate receptor subunits were analyzed using quantitative reverse transcription (RT)-PCR, ELISA and pyrosequencing. Results: Isolated-reared animals had: decreased mRNA in PFC for all markers, increased NR1 protein in hippocampus and hypermethylation of Grin1 in PFC and Grin2b in hippocampus, compared with grouped rats. Associations between mRNA/protein and DNA methylation were found for both brain areas. Conclusion: This study indicates that epigenetic DNA methylation may underlie N-methyl-D-aspartate receptor mRNA/protein expression alterations caused by isolation rearing.

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

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.

Cannabidiol Has a Unique Effect on Global Brain Activity: A Pharmacological, Functional MRI Study in Awake Mice 

2021 ◽  
Author(s):  
Aymen Sadaka ◽  
Ana Ozuna ◽  
Richard Ortiz ◽  
Praveen Kulkarni ◽  
Clare Johnson ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Brain Activity ◽  
Stress Disorders ◽  
Functional Coupling ◽  
Specific Information ◽  
Imaging Data ◽  
Post Traumatic Stress ◽  
Brain Areas ◽  
Dose Dependent ◽  
The Brain

Abstract Background: The phytocannabinoid cannabidiol (CBD) is a potential treatment for post-traumatic stress disorders. How does CBD interact with the brain to alter behavior? We hypothesized that CBD would produce a dose-dependent reduction in brain activity and functional coupling in neural circuitry associated with fear and defense. Methods: During the scanning session awake mice were given vehicle or CBD (3, 10, or 30 mg/kg I.P.) and imaged for 10 min post treatment. Mice were also treated with the 10 mg/kg dose of CBD and imaged one hr later for resting state BOLD functional connectivity (rsFC). Imaging data were registered to a 3D MRI mouse atlas providing site-specific information on 138 different brain areas. Blood samples were collected for CBD measurements.Results: CBD produced a dose-dependent polarization of activation along the rostral-caudal axis of the brain. The olfactory bulb and prefrontal cortex showed an increase in positive BOLD whereas the brainstem and cerebellum showed a decrease in BOLD signal. This negative BOLD affected many areas connected to the ascending reticular activating system (ARAS). The ARAS was decoupled to much of the brain but was hyperconnected to the olfactory system and prefrontal cortex. The pattern of ARAS connectivity closely overlapped with brain areas showing high levels N-acyl-phosphatidylethanolamines-specific phospholipase D (NAPE-PLD) messenger RNA.Conclusion: The CBD-induced decrease in ARAS activity is consistent with an emerging literature suggesting that CBD reduces autonomic arousal under conditions of emotional and physical stress. The putative target and mechanism of action is NAPE-PLD the enzyme responsible for the biosynthesis of lipid signaling molecules like anandamide.

Anxiety-related behavior in hyperhomocysteinemia induced by methionine nutritional overload in rats: role of the brain oxidative stress

2016 ◽  
Vol 94 (10) ◽  
pp. 1074-1082 ◽  
Author(s):  
Dragan Hrncic ◽  
Jelena Mikić ◽  
Aleksandra Rasic-Markovic ◽  
Milica Velimirović ◽  
Tihomir Stojković ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Open Field ◽  
Wistar Rats ◽  
Brain Regions ◽  
Oxidative Status ◽  
Standard Diet ◽  
Male Wistar Rats ◽  
Brain Oxidative Stress ◽  
The Brain

The aim of this study was to examine the effects of a methionine-enriched diet on anxiety-related behavior in rats and to determine the role of the brain oxidative status in these alterations. Adult male Wistar rats were fed from the 30th to 60th postnatal day with standard or methionine-enriched diet (double content comparing with standard diet: 7.7 g/kg). Rats were tested in open field and light–dark tests and afterwards oxidative status in the different brain regions were determined. Hyperhomocysteinemia induced by methionine-enriched diet in this study decreased the number of rearings, as well as the time that these animals spent in the center of the open field, but increased index of thigmotaxy. Oxidative status was selectively altered in the examined regions. Lipid peroxidation was significantly increased in the cortex and nc. caudatus of rats developing hyperhomocysteinemia, but unaltered in the hippocampus and thalamus. Based on the results of this research, it could be concluded that hyperhomocysteinemia induced by methionine nutritional overload increased anxiety-related behavior in rats. These proanxiogenic effects could be, at least in part, a consequence of oxidative stress in the rat brain.

Differential oxidative stress and DNA damage in rat brain regions and blood following chronic arsenic exposure

2008 ◽  
Vol 24 (4) ◽  
pp. 247-256 ◽  
Author(s):  
D Mishra ◽  
SJS Flora
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Drinking Water ◽  
Wistar Rats ◽  
Arsenic Exposure ◽  
Brain Regions ◽  
Single Strand ◽  
Male Wistar Rats ◽  
Chronic Arsenic Exposure ◽  
The Brain

Chronic arsenic poisoning caused by contaminated drinking water is a wide spread and worldwide problem particularly in India and Bangladesh. One of the possible mechanisms suggested for arsenic toxicity is the generation of reactive oxygen species (ROS). The present study was planned 1) to evaluate if chronic exposure to arsenic leads to oxidative stress in blood and brain – parts of male Wistar rats and 2) to evaluate which brain region of the exposed animals was more sensitive to oxidative injury. Male Wistar rats were exposed to arsenic (50 ppm sodium arsenite in drinking water) for 10 months. The brain was dissected into five major parts, pons medulla, corpus striatum, cortex, hippocampus, and cerebellum. A number of biochemical variables indicative of oxidative stress were studied in blood and different brain regions. Single-strand DNA damage using comet assay was also assessed in lymphocytes. We observed a significant increase in blood and brain ROS levels accompanied by the depletion of GSH/GSSG ratio and glucose-6-phosphate dehydrogenase (G6PD) activity in different brain regions of arsenic-exposed rats. Chronic arsenic exposure also caused significant single-strand DNA damage in lymphocytes as depicted by comet with a tail in arsenic-exposed cells compared with the control cells. On the basis of results, we concluded that the cortex region of the brain was more sensitive to oxidative injury compared with the other regions studied. The present study, thus, leads us to suggest that arsenic induces differential oxidative stress in brain regions with cortex followed by hippocampus and causes single-strand DNA damage in lymphocytes.

scholarly journals Riboceine Regimen Attenuates Ethanol-induced Neuronal Damage in the Cerebellum of Adult Male Wistar Rats

2021 ◽  
Vol 15 (4) ◽  
pp. 249-256
Author(s):  
Taiwo Adekemi Abayomi ◽  
◽  
Olorunfemi Samuel Tokunbo ◽  
Moyinoluwa Ajayi ◽  
Olawale Ayobami Abayomi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Wistar Rats ◽  
Neuronal Damage ◽  
Motor Impairment ◽  
Stress Profile ◽  
Stress Markers ◽  
Ethanol Toxicity ◽  
Male Wistar Rats ◽  
Cerebellar Astrocytes ◽  
The Brain

Background: Although ethanol exerts its neurotoxic effect on the brain through inflammatory and oxidative processes, the effect of Riboceine on the brain following ethanol neurotoxicity is yet to be elucidated. Therefore, this study was designed to evaluate the effects of riboceine on the cellular, behavioral, and molecular impairments induced by ethanol toxicity in rats. Methods: A total of 24 male Wistar rats weighing between 160-170 grams were used for the study, and were divided into four groups of six rats each. After completion of the administration of ethanol and riboceine, and testing for motor impairment, the rats were sacrificed. The cerebellum was excised and processed for oxidative stress analyses, based on oxidative stress markers and histological examinations. The immunohistochemical expression of astrocytes in the cerebellum was examined, using Glial Fibrillary Acidic Protein (GFAP) stain. Results: This study demonstrated that ethanol-induced neurotoxicity in the cerebellum, characterized by increased oxidative stress profile, astrocyte activation, and neuronal death in the cerebellum, especially the Purkinje layer. Necrosis, significant decrease in Superoxide Dismutase (SOD), Catalase (CAT) and Gluathione (GSH) activities (P<0.05) as well as astrogliosis was associated with ethanol treatment. However, riboceine was observed to significantly increase the cerebellar SOD, CAT and GSH activities with significantly reduced Malondialdehyde (MDA) levels (P<0.05). It also attenuated the histomorphological alteration of the cerebellum and reduced the cerebellar astrocytes activation following ethanol-induced neurotoxicity, thus leading to the attenuation of motor impairment. Conclusion: Riboceine attenuated motor impairment caused by chronic ethanol-induced neurotoxicity, suggestive of its anti-oxidative and anti-inflammatory properties.

scholarly journals Effect of Electronic Cigarette on Brain Prefrontal Cortex of Male Wistar Rats

2020 ◽  
Vol 6 (3) ◽  
pp. 98-102
Author(s):  
Centaury Noor Kuncorowati ◽  
◽  
Sofia Mawaddatul Urfah ◽  
Devanico Yuangga Duta Maulana ◽  
Mochamad Bahrudin ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Wistar Rats ◽  
Electronic Cigarette ◽  
Male Wistar Rats

Imaging Imagination: Brain Scanning of the Imagined Future

2007 ◽  
Author(s):  
MORTEN L. KRINGELBACH ◽  
JOHN G. GEAKE
Keyword(s):  
Prefrontal Cortex ◽  
Real World ◽  
Orbitofrontal Cortex ◽  
Counterfactual Thinking ◽  
Brain Areas ◽  
Functional Roles ◽  
Selection Processes ◽  
Dorsolateral Prefrontal ◽  
Interacting Networks ◽  
The Brain

Imagination is believed to be made-up of two components. The first one suggests that acts of imagination engage similar networks in the brain to those used for motor and sensory processing during interactions with the real world. The second component purports that the selection processes used in the subcomponents of imagination such as mindedness, anticipation, and counterfactual thinking rely on the subcortical and cortical networks of the brain which consist of components such as the cerebellum, orbitofrontal cortex, dorsolateral prefrontal cortex, and cingulate cortex. This chapter reviews the emerging literature on neuroimaging of various components of imagination. Imaging and other neuroscientific techniques offer various possibilities in the architecture of the imaginative mind. It shows how the neural bases of the imaginative activities are organized. Imaginative processes are distributed activities which recruit several brain areas and networks. These complex relations within and between these various networks are illustrated by the Dynamic Workspace Hypothesis. However it is expected that the precise functional roles of these interacting networks can be accurately defined through the advent of brain scanning and neuroimaging, particularly through the technical breakthroughs imagined in a Coda.

Identification and Distribution of β-Phenylethylamine in the Rat

1973 ◽  
Vol 51 (7) ◽  
pp. 995-1002 ◽  
Author(s):  
D. A. Durden ◽  
S. R. Philips ◽  
Alan A. Boulton
Keyword(s):  
Wistar Rats ◽  
Internal Standard ◽  
Ion Exchange Chromatography ◽  
Exchange Chromatography ◽  
Mass Spectrometric ◽  
Ion Current ◽  
Mammalian Tissues ◽  
Male Wistar Rats ◽  
Dansyl Derivatives ◽  
The Brain

A procedure for the quantitative evaluation of some amines present in mammalian tissues has been developed. It includes isolation of the amines by ion exchange chromatography followed by conversion to dansyl derivatives, chromatographic separation, and quantitation by the mass spectrometric integrated ion current technique. The use of an isotopically labelled internal standard improves the precision and sensitivity of the analysis.The concentrations of β-phenylethylamine in some tissues of male Wistar rats were (ng/g); brain 1.8 ± 0.4, heart 5.7 ± 3.1, kidney 20.5 ± 2.2, liver 2.0 ± 0.7, lung 4.0 ± 1.4, and spleen 4.7 ± 2.7. In the brain the hypothalamus contained 25.3 ± 5.0, the cerebellum 3.4 ± 0.5, the stem 2.2 ± 0.9, the caudate nucleus 8.0 ± 0.3, and the 'rest' 1.1 ± 0.2 ng/g, respectively.

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