CREM, PRM I and II gene expression in Wistar rats testes treated with antipsychotic drugs: Chlorpromazine, Rauwolfia vomitoria and co-administration of reserpine, zinc and ascorbic acid

AbstractObjectivesThe prolonged uses of fourth-generation antipsychotics have been implicated in inducing extrapyramidal syndromes characterized by the motor deficit. This was attributed to the loss of dopamine-2 receptor (D2R) signaling. However, ascorbic acid (SVCT2R stimulation) in the brain is proposed to modulate D2R activity. We, therefore, investigated the beneficial roles of ascorbic acid in improving the extrapyramidal symptoms seen in D2R loss.MethodsTwenty adult male Wistar rats of average weight 200 g were distributed randomly into four groups. The control (NS) received normal saline for 28 days, Untreated D2R inhibition group (−D2R) received normal saline for seven days and then subsequently received chlorpromazine for 21 days, D2R inhibition group treated with ascorbic acid (−D2R+SVCT2R) received chlorpromazine for 21 days and was subsequently treated with ascorbate for seven days while the withdrawal group (WG) received chlorpromazine for 21 days and subsequently received normal saline for seven days. Motor deficits were assessed using a rotarod and cylinder test. The corpus striatum was harvested, processed, and stained using H&E and Nissl stains. Cellular density was analyzed using Image J software 1.8.0.ResultsMotor deficit was observed in −D2R animals administered chlorpromazine with less improvement in WG compared to control (p<0.05) in both rotarod and cylinder test. Ascorbic acid (SVCT2R stimulation) significantly (p<0.001) improved the latency of fall and climbing attempts observed in −D2R animals. The density of basophilic trigoid bodies was significantly (p<0.001) restored in −D2R+SVCT2R group, suggesting recovery of neural activity in the corpus striatum. Moreover, the hallmarks of neuronal degeneration were less expressed in the ascorbic acid treatment groups.ConclusionsAscorbic acid putatively ameliorates extrapyramidal symptoms observed in D2R blockage by chlorpromazine in Wistar rats.

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Interaction of clozapine with metformin in a schizophrenia rat model

Scientific Reports ◽

10.1038/s41598-021-96478-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

G. Horvath ◽

G. Kis ◽

G. Kekesi ◽

A. Büki ◽

L. G. Adlan ◽

...

Keyword(s):

Gene Expression ◽

Cognitive Function ◽

Negative Symptoms ◽

Antipsychotic Drugs ◽

D1 Receptor ◽

Antidiabetic Drug ◽

Beneficial Effects ◽

Adjuvant Therapies ◽

Behavioral Parameters ◽

The Brain

AbstractThe low efficacy of antipsychotic drugs (e.g., clozapine) for negative symptoms and cognitive impairment has led to the introduction of adjuvant therapies. Because previous data suggest the procognitive potential of the antidiabetic drug metformin, this study aimed to assess the effects of chronic clozapine and metformin oral administration (alone and in combination) on locomotor and exploratory activities and cognitive function in a reward-based test in control and a schizophrenia-like animal model (Wisket rats). As impaired dopamine D1 receptor (D1R) function might play a role in the cognitive dysfunctions observed in patients with schizophrenia, the second goal of this study was to determine the brain-region-specific D1R-mediated signaling, ligand binding, and mRNA expression. None of the treatments affected the behavior of the control animals significantly; however, the combination treatment enhanced D1R binding and activation in the cerebral cortex. The Wisket rats exhibited impaired motivation, attention, and cognitive function, as well as a lower level of cortical D1R binding, signaling, and gene expression. Clozapine caused further deterioration of the behavioral parameters, without a significant effect on the D1R system. Metformin blunted the clozapine-induced impairments, and, similarly to that observed in the control animals, increased the functional activity of D1R. This study highlights the beneficial effects of metformin (at the behavioral and cellular levels) in blunting clozapine-induced adverse effects.

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Determination of the L-ascorbic acid requirements in Wistar osteogenic disorder Shionogi rats for prolonged carcinogenesis experiments

Laboratory Animals ◽

10.1258/002367796780739826 ◽

1996 ◽

Vol 30 (4) ◽

pp. 337-346 ◽

Cited By ~ 10

Author(s):

S. W. Y. Chan ◽

P. C. Reade

Keyword(s):

Animal Model ◽

Ascorbic Acid ◽

Drinking Water ◽

Normal Level ◽

Physical Condition ◽

Wistar Rats ◽

Clinical Signs ◽

Supplement Group ◽

Palatal Mucosa

Wistar Shionogi rats of the ( od/od) substrain with the osteogenic disorder are unable to synthesize L-ascorbic acid ( L-AA) and appear to be an appropriate animal model for studying the effect of L-AA in carcinogenesis. To determine the minimal L-AA requirements of these animals for prolonged survival in a satisfactory physical condition during experimentation, four concentrations of L-AA (0.33 g/l, 0.67 g/l, 1.67 g/l and 3.33 g/l) were administered via drinking water to four groups of animals ( n=2). Their water intake per cage was recorded three times weekly and the plasma L-AA levels were determined at the start, after 2, 4, 8 and 12 weeks and at the termination of the experiment. To simulate the procedures to be undertaken in oral mucosal carcinogenesis experiments, the animals were gently restrained and a designated amount of sterile NaCl was applied to the palatal mucosa three times a week for 26 weeks. The L-AA supplement group with the lowest concentration (0.33 g/l L-AA) achieved mean plasma levels of 7 ± 1.38 μM, approximately one-eighth that of the normal level (mean plasma L-AA level in outbred Wistar rats was found to be 58 ± 3 μM) whilst those in the higher supplement group (3.33 g/l L-AA) achieved a mean of 18 ± 1.25 μM. All of the animals employed in the present study survived for 26 weeks and showed no clinical signs of L-AA deficiency during this period.

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Contrasting Roles of Ang II and ACEA in the Regulation of IL10 and IL1β Gene Expression in Primary SHR Astroglial Cultures

Molecules ◽

10.3390/molecules26103012 ◽

2021 ◽

Vol 26 (10) ◽

pp. 3012

Author(s):

Dhanush Haspula ◽

Michelle A. Clark

Keyword(s):

Gene Expression ◽

Wistar Rats ◽

Gene Signature ◽

Brain Regions ◽

Inhibitory Effect ◽

Ang Ii ◽

Cannabinoid Type 1 Receptor ◽

Il10 Gene ◽

Cerebellar Astrocytes

Angiotensin (Ang) II is well-known to have potent pro-oxidant and pro-inflammatory effects in the brain. Extensive crosstalk between the primary Ang II receptor, Ang type 1 receptor (AT1R), and the cannabinoid type 1 receptor (CB1R) has been demonstrated by various groups in the last decade. Since activation of glial CB1R has been demonstrated to play a key role in the resolution of inflammatory states, we investigated the role of Ang II (100 nM) and/or ACEA (10 nM), a potent CB1R-specific agonist in the regulation of inflammatory markers in astrocytes from spontaneously hypertensive rats (SHR) and Wistar rats. Astrocytes were cultured from brainstems and cerebellums of SHR and Wistar rats and assayed for IL1β and IL10 gene expression and secreted fraction, in treated and non-treated cells, by employing qPCR and ELISA, respectively. mRNA expression of both IL10 and IL1β were significantly elevated in untreated brainstem and cerebellar astrocytes isolated from SHR when compared to Wistar astrocytes. No changes were observed in the secreted fraction. While ACEA-treatment resulted in a significant increase in IL10 gene expression in Wistar brainstem astrocytes (Log2FC ≥ 1, p < 0.05), its effect in SHR brainstem astrocytes was diminished. Ang II treatment resulted in a strong inhibitory effect on IL10 gene expression in astrocytes from both brain regions of SHR and Wistar rats (Log2FC ≤ −1, p < 0.05), and an increase in IL1β gene expression in brainstem astrocytes from both strains (Log2FC ≥ 1, p < 0.05). Co-treatment of Ang II and ACEA resulted in neutralization of Ang II-mediated effect in Wistar brainstem and cerebellar astrocytes, but not SHR astrocytes. Neither Ang II nor ACEA resulted in any significant changes in IL10 or IL1β secreted proteins. These data suggest that Ang II and ACEA have opposing roles in the regulation of inflammatory gene signature in astrocytes isolated from SHR and Wistar rats. This however does not translate into changes in their secreted fractions.

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Histomorphological effect of ascorbic acid on mercury chloride-induced changes on the cerebellum of adult wistar rats

Journal of Morphological Sciences ◽

10.4322/jms.063713 ◽

2014 ◽

Vol 31 (04) ◽

pp. 219-224 ◽

Cited By ~ 2

Author(s):

A. Ibegbu ◽

A. Animoku Abdulrazaq ◽

Ayuba Micheal ◽

Brosu Daniel ◽

A. Adamu Sadeeq ◽

...

Keyword(s):

Ascorbic Acid ◽

Cerebellar Cortex ◽

Wistar Rats ◽

Oral Route ◽

Mercury Chloride ◽

Average Weight ◽

The Central Nervous System ◽

Living Organisms ◽

Induced Changes ◽

Acid Administration

Abstract Introduction. Mercury is one of the most hazardous environmental contaminants to living organisms and the central nervous system has been shown to be the main target. Objective. The present work was aimed at evaluating the effect of ascorbic acid on mercury chloride-induced changes on the cerebellar cortex of adult Wistar rats. Material and method. Thirty Wistar rats of average weight of 200g and were randomly divided into 6 groups of 5 rats each. The animals in Group 1 (control) were administered with distilled water, Groups 2 and 3 were administered with 52mg/kg and 26.25mg/kg body weight of HgCl respectively while Groups 4 and 5 were administered with 52mg/kg of HgCl and 5mg/kg of ascorbic acid and 26.25gm/kg of HgCl and 5mg/kg of ascorbic acid respectively, while Group 6 was administered with 5mg/kg of ascorbic acid. The administration was through oral route, daily for 3 weeks. Results. The result of the biochemical parameters showed a significant increase (P < 0.05) on the mean SOD and LPO values after the administration of mercury chloride and Ascorbic acid. Histological observation of the cerebellar cortex, showed normal histo-morphology in Groups 1 and 6 while, the cerebellum in Groups 2, 3, 4 and 5 showed some degenerative, necrotic and cellular changes. Conclusion. However, ascorbic acid administration has shown to ameliorate the induced degenerative changes in the cerebellum caused by mercury chloride toxicity in Wistar rats.

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Applicability of a gene expression based prediction method to SD and Wistar rats: an example of CARCINOscreen®

The Journal of Toxicological Sciences ◽

10.2131/jts.40.805 ◽

2015 ◽

Vol 40 (6) ◽

pp. 805-807 ◽

Cited By ~ 2

Author(s):

Hiroshi Matsumoto ◽

Fumiyo Saito ◽

Masahiro Takeyoshi

Keyword(s):

Gene Expression ◽

Wistar Rats ◽

Prediction Method

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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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Dietary fatty acids alter left ventricular myocardial gene expression in Wistar rats

Nutrition Research ◽

10.1016/j.nutres.2014.07.011 ◽

2014 ◽

Vol 34 (8) ◽

pp. 694-706 ◽

Cited By ~ 3

Author(s):

Kimberly M. Jeckel ◽

Gerrit J. Bouma ◽

Ann M. Hess ◽

Erin B. Petrilli ◽

Melinda A. Frye

Keyword(s):

Gene Expression ◽

Fatty Acids ◽

Wistar Rats ◽

Left Ventricular ◽

Dietary Fatty Acids ◽

Myocardial Gene Expression

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Upregulation of Kiss-1 and Gpr54 Genes Expression in Pituitary of Male Rats Following the Central Administration of Neuropeptide Y

International journal of basic science in medicine ◽

10.34172/ijbsm.2019.03 ◽

2019 ◽

Vol 4 (4) ◽

pp. 137-142

Author(s):

Vahid Azizi ◽

Shahrbanoo Oryan ◽

Homayuon Khazali ◽

Abdolkarim Hosseini

Keyword(s):

Gene Expression ◽

Pituitary Gland ◽

Neuropeptide Y ◽

Wistar Rats ◽

Third Ventricle ◽

Male Rats ◽

Control Group ◽

Central Administration ◽

Reproductive Axis ◽

Male Wistar Rats

Introduction: The neuropeptide Y (NPY) in the neural circuits of the hypothalamus has a stimulating effect on reproductive activities in mammals. Kisspeptin (KiSS1) is a quintessential neurotransmitter in the reproductive axis which directly stimulates gonadotropin-releasing hormone neurons in the hypothalamus. The distribution of KiSS1 expressing cells in the pituitary was described previously. Despite earlier reports showing the KiSS1 receptor, G-protein coupled receptor 54 (GPR54) expression in the pituitary, the potential physiological roles of kisspeptin at this gland have remained obscure. Accordingly, this study investigated the role of NPY on the relative expression of Kiss1 and Gpr54 genes in the pituitary gland in male Wistar rats. Methods: In general, 20 male Wistar rats weighing 200-250 g in 4 groups (5 in each group) received saline, NPY (2.3 nM), BIBP3226 (NPY receptor antagonist, 7.8 nM), and NPY+ BIBP3226. Then, they received the simultaneous injection of these molecules through the third ventricle of the brain. Finally, the relative mean expressions of Kiss1 and Gpr54 genes in the anterior pituitary were quantitatively analyzed by the real-time polymerase chain reaction. Results: The central injection of NPY increased the relative mean expressions of Kiss1 and Gpr54 genes in the pituitary gland compared to the control group although the injection of BIBP3226 eradicated these effects. However, the gene expression of Gpr54 in the rats receiving NPY coupled with BIBP3226 in hypophysis in comparison to the group receiving only NPY demonstrated a significant reduction (P<0.05). Conclusion: Overall, the central injection of NPY stimulated the gene expression of Kiss1 and Gpr54 in the pituitary gland.

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