scholarly journals Changes in Glutamate/NMDA Receptor Subunit 1 Expression in Rat Brain after Acute and Subacute Exposure to Methamphetamine

2009 ◽  
Vol 2009 ◽  
pp. 1-4 ◽  
Author(s):  
Walailuk Kerdsan ◽  
Samur Thanoi ◽  
Sutisa Nudmamud-Thanoi
Keyword(s):  
Nmda Receptor ◽  
Frontal Cortex ◽  
Behavioral Sensitization ◽  
Hippocampal Formation ◽  
Receptor Expression ◽  
Receptor Subunit ◽  
Sprague Dawley ◽  
Acute Group ◽  
And Control ◽  
Subacute Exposure

Methamphetamine (METH) is a psychostimulant drug of abuse that produces long-term behavioral changes including behavioral sensitization, tolerance, and dependence. METH has been reported to induce neurotoxic effects in several areas of the brain via the dopaminergic system. Changes of dopamine function can induce malfunction of the glutamatergic system. Therefore, the aim of the present study was to examine the effects of METH administration on the expression of glutamate N-methyl-D-aspartate receptor subunit 1 (NMDAR1) in frontal cortex, striatum, and hippocampal formation after acute and subacute exposure to METH by western blotting. Male Sprague-Dawley rats were injected intraperitoneally with a single dose of 8 mg/kg METH, 4 mg/kg/day METH for 14 days and saline in acute, subacute, and control groups, respectively. A significant increase in NMDAR1 immunoreactive protein was found in frontal cortex in the subacute group (P=.036) but not in the acute group (P=.580). Moreover, a significant increase in NMDAR1 was also observed in striatum in both acute (P=.025) and subacute groups (P=.023). However, no significant differences in NMDAR1 in hippocampal formation were observed in either acute or subacute group. The results suggest that an upregulation of NMDA receptor expression may be a consequence of glutamatergic dysfunction induced by METH.

FC29-03 - Effects of chronic oral treatment with aripiprazole on expression of nmda receptor subunits and binding sites in rat brain

2011 ◽  
Vol 26 (S2) ◽  
pp. 1979-1979
Author(s):  
M. Zink ◽  
N. Segnitz ◽  
T. Ferbert ◽  
A. Schmitt ◽  
P. Gass ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Negative Symptoms ◽  
Oral Treatment ◽  
Antipsychotic Agents ◽  
Brain Regions ◽  
Relative Increase ◽  
Receptor Expression ◽  
Sprague Dawley ◽  
Adult Type ◽  
Mk 801

IntroductionThe glutamatergic theory of schizophrenia proposes a dysfunction of ionotropic N-Methyl-D-aspartate (NMDA)-receptors (NR). Several therapeutic strategies address NR function and effects of antipsychotic agents on NR expression have been described.ObjectivesThe partial dopaminergic and serotonergic agonist aripiprazole (APZ) was able to counteract behavioural effects of NR antagonists, but effects of APZ on NR expression have not been investigated.AimsTo evaluate effects of APZ on NR mRNA and protein expressionMethodsWe treated Sprague-Dawley rats for 4 weeks or 4 months with APZ in daily oral doses of 10 and 40 mg per kg body weight. Expression of the NR subunits NR1, NR2A, NR2B, NR2C and NR2D was assessed by semiquantitative radioactive in situ-hybridization, and in parallel receptor binding using 3H-MK-801 receptor autoradiography.ResultsIncreased expression levels of NR1 (4 weeks), NR2A (4 weeks), NR2C (4 weeks and 4 months) and NR2D (4 months) were observed in several hippocampal and cortical brain regions. The parallel reduced expression of NR2B mRNAs (4 months) resulted in a relative increase of the NR2A/NR2B ratio. Marked differences between specific brain regions, the doses and time points of assessment became obvious. On the receptor level, increased MK-801-binding was found after 4 weeks in the 40 mg-group and after 4 months in the 10 mg-group.ConclusionsThe effects of APZ converge in enhanced NMDA-receptor expression and a shift of subunit-composition towards adult-type receptors. Our results confirm regulatory connections between dopaminergic, serotonergic and glutamatergic neurotransmission with relevance for cognitive and negative symptoms of schizophrenia.

scholarly journals Extended access self-administration of methamphetamine is associated with age- and sex-dependent differences in drug taking behavior and recognition memory deficits in rats

2019 ◽  
Author(s):  
Sara R. Westbrook ◽  
Megan R. Dwyer ◽  
Laura R. Cortes ◽  
Joshua M. Gulley
Keyword(s):  
Nmda Receptor ◽  
Drug Use ◽  
Expression Profiles ◽  
D1 Receptor ◽  
Receptor Expression ◽  
Cognitive Test ◽  
Adult Onset ◽  
Sprague Dawley ◽  
Self Administration ◽  
Long Access

AbstractIndividuals who begin drug use during early adolescence experience more adverse consequences compared to those initiating later, especially if they are female. The mechanisms for these age and gender differences remain obscure, but studies in rodents suggest that psychostimulants may disrupt the normal ontogeny of dopamine and glutamate systems in the prefrontal cortex (PFC). Here, we studied Sprague-Dawley rats of both sexes who began methamphetamine (METH, i.v.) self-administration (SA) in adolescence (postnatal [P] day 41) or adulthood (P91). Rats received seven daily 2-h SA sessions with METH or saccharin as the reinforcer, followed by 14 daily long access (LgA; 6 h) sessions. After 7 and 14 days of abstinence, novel object (OR) or object-in-place (OiP) recognition was assessed. PFC and nucleus accumbens were collected 7 days after the final cognitive test and NMDA receptor subunits and dopamine D1 receptor expression was measured. We found that during LgA sessions, adolescent-onset rats escalated METH intake more rapidly than adult-onset rats, with adolescent-onset females earning the most infusions. Adolescent-onset rats exhibited modest deficits in OiP compared to adult-onset rats, but there was no sex difference in this effect and no groups differed in OR. We found no group differences in D1 and NMDA receptor expression, suggesting no long-lasting alteration of ontogenetic expression profiles. Our findings suggest that adolescent-onset drug use is more likely to lead to compulsive-like patterns of drug-taking and subsequent dysfunction of PFC-dependent cognition.

Hypoxia upregulates lung microvascular neurokinin-1 receptor expression

2006 ◽  
Vol 291 (1) ◽  
pp. L102-L110 ◽  
Author(s):  
Eric D. Zee ◽  
Stacey Schomberg ◽  
Todd C. Carpenter
Keyword(s):  
Substance P ◽  
Pulmonary Edema ◽  
Receptor Expression ◽  
Receptor Protein ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Edema Formation ◽  
Moderate Hypoxia ◽  
Neurokinin 1 ◽  
Subacute Exposure

Subacute exposure to moderate hypoxia can promote pulmonary edema formation. The tachykinins, a family of proinflammatory neuropeptides, have been implicated in the pathogenesis of pulmonary edema in some settings, including the pulmonary vascular leak associated with exposure to hypoxia. The effects of hypoxia on tachykinin receptor and peptide expression in the lung, however, remain poorly understood. We hypothesized that subacute exposure to moderate hypoxia increases lung neurokinin-1 (NK-1) receptor expression as well as lung substance P levels. We tested this hypothesis by exposing weanling Sprague-Dawley rats to hypobaric hypoxia (barometric pressure 0.5 atm) for 0, 24, 48, or 72 h. Hypoxia led to time-dependent increases in lung NK-1 receptor mRNA expression and lung NK-1 receptor protein levels at 48 and 72 h of exposure ( P < 0.05). Immunohistochemistry and in situ NK-1 receptor labeling with substance P-conjugated fluorescent nanocrystals demonstrated that hypoxia increased NK-1 expression primarily in the pulmonary microvasculature and in alveolar macrophages. Hypoxia also led to increases in lung substance P levels by 48 and 72 h ( P < 0.05) but led to a decrease in preprotachykinin mRNA levels ( P < 0.05). We conclude that subacute exposure to moderate hypoxia upregulates lung NK-1 receptor expression and lung substance P peptide levels primarily in the lung microvasculature. We speculate that this effect may contribute to the formation of pulmonary edema in the setting of regional or environmental hypoxia.

scholarly journals Differential Effects of Insufflated, Subcutaneous, and Intravenous Growth Hormone on Bone Growth, Cognitive Function, and NMDA Receptor Subunit Expression

Endocrinology ◽  
2010 ◽  
Vol 151 (9) ◽  
pp. 4418-4427 ◽  
Author(s):  
Sung Won Park ◽  
Sooyoung Shin ◽  
Chi Hwa Kim ◽  
Ah-ra Ko ◽  
Min Jung Kwak ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Nmda Receptor ◽  
Bone Growth ◽  
Inflammatory Responses ◽  
Escape Latency ◽  
Growth Promotion ◽  
Receptor Expression ◽  
Learning Ability ◽  
Sprague Dawley ◽  
Subunit Expression

The objective of this study was to characterize the effect of inhalable growth hormone (GH) delivered by an insufflator to the lungs of hypophysectomized Sprague Dawley rats. In the first cohort, the safety and efficacy of the insufflated GH were evaluated. Three experimental groups (n = 7 per group) were treated with GH for 15 d: One group received sc injection of GH daily at 200 μg/kg (SC200). Two other groups received GH by insufflation daily: 200 μg/kg (INS 200) and 600 μg/kg (INS 600). In the second set of experiments, GH was administered in three routes [SC200, INS200, intravenous (IV200)] (n=10) for 5 d, and escape latency and N-methyl D-aspartate (NMDA) receptor expression were evaluated. In the first cohort, INS200 showed similar bioactivity as SC200 in growth promotion, tibial growth, as well as escape latency on the 12th day of treatment. Insufflated GH was well tolerated without significant inflammatory responses. In the second cohort, expression of the NMDA receptor 1 and 2B in hippocampus measured after 3 or 6 d of daily treatments were significantly higher in INS200 as compared to IV200, consistent with the improvement of the escape latency. In summary, the inhalable form of GH delivered by intratracheal insufflation was safe, and its bioactivity was comparable to sc injection both in promotion of growth and acquisition of learning ability. If applied properly to human, inhalable GH would be effective for growth promotion and possibly for several disorders caused by underexpression of NMDA receptors.

Tanshinone IIA attenuates elastase-induced AAA in rats via inhibition of MyD88-dependent TLR-4 signaling

VASA ◽  
2014 ◽  
Vol 43 (1) ◽  
pp. 39-46 ◽  
Author(s):  
Tao Shang ◽  
Feng Ran ◽  
Qian Qiao ◽  
Zhao Liu ◽  
Chang-Jian Liu
Keyword(s):  
Nuclear Factor Κb ◽  
Tanshinone Iia ◽  
Myeloid Differentiation ◽  
Aortic Tissue ◽  
Toll Like Receptor ◽  
Sprague Dawley ◽  
Toll Like Receptor 4 ◽  
Tissue Samples ◽  
Myeloid Differentiation Factor ◽  
And Control

Background: The purpose of this study was to determine whether myeloid differentiation factor88-dependent Toll-Like Receptor-4 (TLR-4) signaling contributed to the inhibition of abdominal aortic aneurysm (AAA) by Tanshinone IIA (Tan IIA). Materials and methods: Male Sprague-Dawley rats (n = 12 / group) were randomly distributed into three groups: Tan IIA, control, and sham. The rats from Tan IIA and control groups under-went intra-aortic elastase perfusion to induce AAAs, and those in the sham group were perfused with saline. Only the Tan IIA group received Tan IIA (2 mg / rat / d). Aortic tissue samples were harvested at 24 d after perfusion and evaluated using reverse transcriptase-polymerase chain reaction, Western blot, immunohistochemistry and immunofluorescence. Results: The over-expression of Toll-Like Receptor-4 (TLR-4), Myeloid Differentiation factor 88 (MyD88), Phosphorylated Nuclear Factor κB (pNF-κB) and Phosphorylated IκBα (pIκBα) induced by elastase perfusion were significantly decreased by Tan IIA treatment. Conclusions: Tan IIA attenuates elastase-induced AAA in rats possibly via the inhibition of MyD88-dependent TLR-4 signaling, which may be one potential explanation of why Tan IIA inhibits AAA development through multiple effects.

Electroacupuncture ameliorates CUMS-induced depression-like behavior: involvement of the glutamatergic system and apoptosis in rats

2020 ◽  
Vol 23 ◽  
Author(s):  
Qin Guo ◽  
Xian-Ming Lin ◽  
Zhong Di ◽  
Quan-Ai Zhang ◽  
Shuo Jiang
Keyword(s):  
Nmda Receptor ◽  
Caspase 3 ◽  
B Cell Lymphoma ◽  
Sucrose Preference ◽  
Expression Level ◽  
Receptor Subunit ◽  
Glutamatergic System ◽  
Ionotropic Receptor ◽  
Nmda Receptor Subunit ◽  
Expression Levels

Background: Converging evidence indicates that glutamatergic system and glia are directly implicated in the pathophysiology of depression. Clinical studies indicate that electroacupuncture (EA) has antidepressant-like effect with low side effects for depression. However, the underlying antidepressant mechanism of acupuncture remains obscure. Methods: Chronic unpredictable mild stress (CUMS)-induced depressive rats were used to induce depressive-like behavior, and evaluated by the weight change, open field test, sucrose preference test, and novelty suppressed feeding test. EA, NMDA receptor subunit 2A antagonist (NR2A RA) or NMDA receptor subunit 2B antagonist (NR2B RA) was used for comparison. High performance liquid chromatography (HPLC) was performed to detect the content of hippocampal glutamate, while western blot for the hippocampal protein expression levels of calcium/calmodulin-dependent protein kinase II (CaMKII), Bax, caspase 3 and B-cell lymphoma-2 (Bcl-2). The distribution of glutamate ionotropic receptor NMDA type subunit 2A (NR2A), neuronal nuclear protein (NeuN), glutamate ionotropic receptor NMDA type subunit 2B (NR2B) and glial fibrillary acidic protein (GFAP) were detected by immunofluorescence. Results: Significant depression behavior (reduced body weight and sucrose preference, increased feeding and immobility time) was produced in CUMS-induced depressive rats, which was reversed significantly by EA. EA decreased hippocampal glutamate level. EA led to a significant decrease in expression levels of Bax, caspase 3 and CaMKⅡ accompanied by increased Bcl-2 expression level. Furthermore, EA significantly increased NR2A expression level as well as decreased NR2B expression level in hippocampus. Conclusion: EA ameliorated depression-like behavior in CUMS rats, which might be mediated, at least in part, by regulating the glutamate, NMDA receptors and apoptosis in the hippocampus.

EFFECT OF EXPERIMENTALLY INDUCED THYROIDITIS ON BIOSYNTHESIS OF THYROXINE IN RATS

1969 ◽  
Vol 62 (1) ◽  
pp. 11-20 ◽  
Author(s):  
Colum A. Gorman ◽  
James W. Anderson ◽  
Eunice V. Flock ◽  
Charles A. Owen ◽  
Khalil G. Wakim
Keyword(s):  
Intravenous Administration ◽  
Hashimoto's Thyroiditis ◽  
Sprague Dawley ◽  
Thyroid Extract ◽  
Histologic Appearance ◽  
Gland Weight ◽  
Sprague Dawley Rats ◽  
Thyroid Glands ◽  
And Control ◽  
Experimentally Induced

ABSTRACT Thyroiditis was induced in Sprague-Dawley rats by repeated immunization with thyroid extract and Freund's adjuvant. Immunized and control animals were killed at intervals up to 6 hours after intravenous administration of 131I as iodide at 5, 8 and 10 weeks after the first injection. Radioiodinated compounds in the thyroid glands were identified chromatographically. Evidence of moderate thyroiditis was present (histologic appearance, gland weight, and protein-bound iodine-butanol-extractable iodine difference) but the rate of incorporation of radioiodide into thyroxine, the percentage of radioactivity in the gland as iodide, and the MIT/DIT ratio were not significantly different in immunized and control animals. The MIT/DIT ratio was found to vary with time after 131I administration in both immunized and control animals. These studies did not uncover a defect in organification of iodide in experimental thyroiditis similar to that described by others in humans with Hashimoto's thyroiditis.

scholarly journals The Neuronal Actions of Leptin and the Implications for Treating Alzheimer’s Disease

2021 ◽  
Vol 14 (1) ◽  
pp. 52
Author(s):  
Kirsty Hamilton ◽  
Jenni Harvey
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Energy Homeostasis ◽  
Leptin Receptor ◽  
Hippocampal Formation ◽  
Synaptic Function ◽  
Receptor Expression ◽  
Neuroprotective Actions ◽  
Novel Target ◽  
Leptin System

It is widely accepted that the endocrine hormone leptin controls food intake and energy homeostasis via activation of leptin receptors expressed on hypothalamic arcuate neurons. The hippocampal formation also displays raised levels of leptin receptor expression and accumulating evidence indicates that leptin has a significant impact on hippocampal synaptic function. Thus, cellular and behavioural studies support a cognitive enhancing role for leptin as excitatory synaptic transmission, synaptic plasticity and glutamate receptor trafficking at hippocampal Schaffer collateral (SC)-CA1 synapses are regulated by leptin, and treatment with leptin enhances performance in hippocampus-dependent memory tasks. Recent studies indicate that hippocampal temporoammonic (TA)-CA1 synapses are also a key target for leptin. The ability of leptin to regulate TA-CA1 synapses has important functional consequences as TA-CA1 synapses are implicated in spatial and episodic memory processes. Moreover, degeneration is initiated in the TA pathway at very early stages of Alzheimer’s disease, and recent clinical evidence has revealed links between plasma leptin levels and the incidence of Alzheimer’s disease (AD). Additionally, accumulating evidence indicates that leptin has neuroprotective actions in various AD models, whereas dysfunctions in the leptin system accelerate AD pathogenesis. Here, we review the data implicating the leptin system as a potential novel target for AD, and the evidence that boosting the hippocampal actions of leptin may be beneficial.

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