scholarly journals Decrease of ARC protein expression in the striatum after tone fear conditioning

2021 ◽  
Vol 29 ◽  
pp. 1-22
Author(s):  
Bruno Antonio ◽  
Kil Sun Lee ◽  
Liz Paola Domingues ◽  
Dimitri Daldegan-Bueno ◽  
Tatiana Lima Ferreira ◽  
...  
Keyword(s):  
Fear Conditioning ◽  
Neural Plasticity ◽  
Dorsal Striatum ◽  
Treated Group ◽  
Nmda Receptor Antagonist ◽  
Glutamatergic Transmission ◽  
Protein Levels ◽  
Fos Protein ◽  
Dorsal Hippocampal ◽  
Striatal System

Introduction. The involvement of the striatal system in S-R learning is usually based on neural plasticity related to immediate early-genes (IEGs). Previous studies also have shown that the dorsal striatum plays a role in tone fear conditioning (TFC). Objectives. Given that IEg expression in dorsal striatum supports S-R learning we analyzed early molecular consolidation events in the striatum by measuring the protein levels of the EGR1, C-Fos, and Arc in the striatum 30 and 90 minutes after the TFC training. Additionally, to minimize a dorsal hippocampal possible interference, glutamatergic transmission was disrupted during fear conditioning training using the NMDA receptor antagonist AP5 injection into hippocampus. Method. Wistar rats received AP5 or saline injection in the hippocampus five minutes before undergoing tone fear conditioning (tone and foot-shock pairings) or tone only. Results. Animals that received tone and footshock pairings presented a decrease in ARC protein 30 minutes after training when compared to the tone groups. AP5 treated group exposed to tone only condition presented a decrease in EGR protein 90 minutes after training when compared to the saline and tone. No differences were observed in FOS protein levels. Conclusions. Our results suggest that it is possible that some interaction between striatum and hippocampus in processing tone experience and that reduced levels of ARC could be related to the associative features of this pavlovian task.

scholarly journals Time-Dependent Expression of Arc and Zif268 after Acquisition of Fear Conditioning

2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Mary E. Lonergan ◽  
Georgette M. Gafford ◽  
Timothy J. Jarome ◽  
Fred J. Helmstetter
Keyword(s):  
Fear Conditioning ◽  
Neural Plasticity ◽  
Memory Consolidation ◽  
Dorsal Hippocampus ◽  
Expression Profiles ◽  
Time Dependent ◽  
Early Gene ◽  
Temporal Expression ◽  
Protein Levels ◽  
Minute Post

Memory consolidation requires transcription and translation of new protein. Arc, an effector immediate early gene, and zif268, a regulatory transcription factor, have been implicated in synaptic plasticity underlying learning and memory. This study explored the temporal expression profiles of these proteins in the rat hippocampus following fear conditioning. We observed a time-dependent increase of Arc protein in the dorsal hippocampus 30-to-90-minute post training, returning to basal levels at 4 h. Zif268 protein levels, however, gradually increased at 30-minute post training before peaking in expression at 60 minute. The timing of hippocampal Arc and zif268 expression coincides with the critical period for protein synthesis-dependent memory consolidation following fear conditioning. However, the expression of Arc protein appears to be driven by context exploration, whereas, zif268 expression may be more specifically related to associative learning. These findings suggest that altered Arc and zif268 expression are related to neural plasticity during the formation of fear memory.

scholarly journals Amelioration of caffeine-induced seizures by modulators of sigma, N-methyl-d-Aspartate and ryanodine receptors in mice

2017 ◽  
Vol 04 (02) ◽  
pp. 144-149
Author(s):  
Mojtaba Keshavarz ◽  
Seyyed Hoseini ◽  
Samad Akbarzadeh
Keyword(s):  
Receptor Antagonist ◽  
Synergistic Effects ◽  
Ryanodine Receptors ◽  
Treated Group ◽  
Nmda Receptor Antagonist ◽  
Clonic Seizure ◽  
Positive Control ◽  
Control Group ◽  
Gamma Aminobutyric Acid ◽  
Clonic Seizures

AbstractObjectives The aim of this study was to evaluate the antiepileptic effects of opipramol, a sigma receptor agonist, diazepam, ketamine, an N-methyl-d-Aspartate (NMDA) receptor antagonist, and dantrolene, a ryanodine receptor antagonist, against caffeine-induced seizures in mice.Methods We used caffeine (1000 mg/kg) intraperitoneally for inducing clonic and tonic-clonic seizures in male albino Swiss strain of mice. We used opipramol in three different doses (10, 20 and 50 mg/kg), ketamine (50 mg/kg), dantrolene (40 mg/kg), opipramol (20 mg/kg) plus ketamine (50 mg/kg), opipramol (20 mg/kg) plus dantrolene (40 mg/kg), diazepam (5 mg/kg as a positive control) and the vehicle 30 min before injecting caffeine. We recorded the onset of clonic, tonic-clonic seizures and the time of death of animals after using caffeine.Results Animals treated with opipramol at a dose of 50 mg/kg or diazepam had a higher onset of clonic seizure compared with the vehicle-treated group. Dantrolene alone or with opipramol (20 mg/kg) increased the latency of clonic seizure compared with the control group. Opipramol (20 and 50 mg/kg), diazepam, ketamine alone or with opipramol, and dantrolene plus opipramol increased the latency of tonic-clonic seizures in mice. All the treatments except opipramol (10 mg/kg) and dantrolene alone increased the latency of death of animals.Conclusion Opipramol attenuated seizures produced by high doses of caffeine. Moreover, the activation of sigma receptors and inhibition of ryanodine receptors may produce synergistic effects against caffeine-induced seizures. Our study may imply that different mechanisms such as inhibition of gamma-aminobutyric acid-A receptors, activation of NMDA and ryanodine receptors may contribute to the caffeine-induced seizures.

scholarly journals Short-Term Feeding of Fibre-Enriched Biscuits: Protective Effect against Hepatotoxicity in Diabetic Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Ochuko L. Erukainure ◽  
Osaretin A. T. Ebuehi ◽  
Folasade O. Adeboyejo ◽  
Olufunmilola O. Oladunmoye ◽  
Muhammad Aliyu ◽  
...  
Keyword(s):  
Protective Effect ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hepatic Function ◽  
Treated Group ◽  
Albumin Level ◽  
Diabetic Rats ◽  
Protein Levels ◽  
Significant Difference ◽  
Alloxan Monohydrate

The effects of fibre-enriched biscuit on biomarkers associated with hepatotoxicity in diabetic rats were investigated. Diabetes was induced by single intraperitoneal injection of alloxan monohydrate. Treatment lasted for 14 days after which the rats were sacrificed by cervical dislocation. Blood serum was analyzed to determine hepatic function enzymes. The liver was also analyzed to determine hepatic lipid profile and antioxidant enzymes. Induction of diabetes led to elevated levels of ALP, AST, and ALT. These were, however, significantly (p<0.05) reduced in the fibre-enriched biscuit fed (treated) group. There was no significant difference in the serum bilirubin and total protein levels of the studied groups. Reduced albumin level was observed in the diabetic group; this was further lowered on feeding with fibre-enriched biscuits. Induction of diabetes led to increased hepatic level of cholesterol, triglyceride (TG), low density lipoprotein (LDL), and lipid peroxidation and decreased activities of glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) and HDL level. These were significantly (p<0.05) reversed on feeding with fibre-enriched biscuit. This study portrays the protective effect of fibre-enriched biscuit on increased oxidative stress and hyperlipidemia in hepatic tissues of alloxan-induced diabetic rats.

scholarly journals Nucleus reuniens is required for encoding and retrieving precise, hippocampal-dependent contextual fear memories in rats

2018 ◽  
Author(s):  
Karthik R. Ramanathan ◽  
Reed L. Ressler ◽  
Jingji Jin ◽  
Stephen Maren
Keyword(s):  
Prefrontal Cortex ◽  
Spatial Memory ◽  
Fear Conditioning ◽  
Medial Prefrontal Cortex ◽  
Thalamic Nucleus ◽  
Nmda Receptor Antagonist ◽  
Pavlovian Fear Conditioning ◽  
Contextual Memory ◽  
Nucleus Reuniens ◽  
Contextual Fear

AbstractThe nucleus reuniens (RE) is a ventral midline thalamic nucleus that interconnects the medial prefrontal cortex (mPFC) and hippocampus (HPC). Considerable data indicate that HPC-mPFC circuits are involved in contextual and spatial memory; however, it is not clear whether the RE mediates the acquisition or retrieval of these memories. To examine this question, we inactivated the RE with muscimol before either the acquisition or retrieval of Pavlovian fear conditioning in rats; freezing served as the index of fear. We found that RE inactivation before conditioning impaired the acquisition of contextual freezing, whereas inactivation of the RE prior to retrieval testing increased the generalization of freezing to a novel context; inactivation of the RE did not affect either the acquisition or expression of auditory fear conditioning. Interestingly, contextual conditioning impairments were absent when retrieval testing was also conducted after RE inactivation. Contextual memories acquired under RE inactivation were hippocampal-independent, insofar as contextual freezing in rats conditioned under RE inactivation was insensitive to intra-hippocampal infusions of the NMDA receptor antagonist, D,L-amino-5-phosophonovaleric acid (APV). Together, these data reveal that the RE supports hippocampal-dependent encoding of precise contextual memories that allow discrimination of dangerous from safe contexts. When the RE is inactive, however, alternate neural systems acquire an impoverished contextual memory that is only expressed when the RE is offline.SIGNIFICANCE STATEMENTThe midline thalamic nucleus reuniens (RE) coordinates communication between the hippocampus and medial prefrontal cortex, brain areas critical for contextual and spatial memory. Here we show that temporary pharmacological inactivation of RE impairs the acquisition and precision of contextual fear memories after Pavlovian fear conditioning in rats. However, inactivating the RE prior to retrieval testing restored contextual memory in rats conditioned after RE inactivation. Critically, we show that imprecise contextual memories acquired under RE inactivation are learned independently of the hippocampus. These data reveal that the RE is required for hippocampal-dependent encoding of precise contextual memories to support the discrimination of safe and dangerous contexts.

Abstract P112: Estradiol Induces Physiological Hypertrophic Growth in the Healthy Mouse Heart

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Georgios Kararigas ◽  
Ba Tiep Nguyen ◽  
Hubertus Jarry ◽  
Vera Regitz-Zagrosek
Keyword(s):  
Weight Ratio ◽  
Treated Group ◽  
Left Ventricular ◽  
Heart Weight ◽  
Cardiomyocyte Hypertrophy ◽  
Mouse Heart ◽  
Cross Sectional ◽  
Hypertrophic Growth ◽  
Protein Levels ◽  
Cycle Regulation

Estradiol-17beta (E2) has been shown to exert anti-hypertrophic actions by either attenuating or blunting the development of left ventricular hypertrophy. However, the vast majority of these studies have been performed in stressed or diseased hearts. Consequently, very little is known about the actions of E2 in the stress- and disease-free heart. The aim of our study was to identify and characterize structurally and molecularly the role of E2 in the healthy heart. Female C57Bl/6J mice were ovariectomized at the age of two months. Mice were randomly assigned into groups feeding on either an E2-containing (n = 19) or soy-free (Ctrl; n = 19) diet for three months. Following this, all mice were sacrificed and hearts were collected for weight measurement. Left ventricles were analyzed structurally by immunohistochemistry and molecularly by genome-wide expression profiling. E2 led to an increase in the heart weight (11%; P < 0.001) and the heart-to-body weight ratio (32%; P < 0.001) compared to Ctrl mice. Cardiomyocyte cross-sectional area revealed cardiomyocyte hypertrophy in E2 (n = 6) compared to Ctrl (n = 5) mice (32%; P = 0.004). Analysis of the left ventricular transcriptome identified 1059 probe sets (adjusted P ≤ 0.05) differentially expressed between E2 (n = 5) and Ctrl (n = 5). Hypergeometric testing for Gene Ontology showed most genes to be associated with cell cycle, regulation of growth, cell and tissue development. Pathway analysis revealed 140 pathways (adjusted P = 0.05) modulated between the two groups, such as the DNA replication and Wnt signaling pathways. Next, we tested the hypothesis that this hypertrophic effect of E2 is of the physiological type. To this extent, we identified that angiogenesis was increased with cardiac growth as determined by the microarray analysis and VEGF-A protein levels assessed by Western blotting. Furthermore, the embryonic gene program was not activated and no fibrosis was observed in the E2-treated group. In conclusion, our study is the first to demonstrate pro-hypertrophic actions of E2 in the healthy heart through the modulation of growth-related genes and pathways. Due to that we have characterized the hypertrophic effect of E2 as physiological, we expect this effect to be beneficial for the heart.

scholarly journals Quantitative Structure-Activity Relationship Model to Predict Antioxidant Effects of the Peptide Fraction Extracted from a Co-Culture System of Chlorella pyrenoidosa and Yarrowia lipolytica

Marine Drugs ◽  
2019 ◽  
Vol 17 (11) ◽  
pp. 633
Author(s):  
Huifan Liu ◽  
Sufen Li ◽  
Yuming Zhong ◽  
Jianliang Liu ◽  
Hui Liu ◽  
...  
Keyword(s):  
Yarrowia Lipolytica ◽  
Chlorella Pyrenoidosa ◽  
Treated Group ◽  
Quantitative Structure Activity Relationship ◽  
Control Group ◽  
Related Factor ◽  
Protective Effects ◽  
Protein Levels ◽  
Antioxidant Agents ◽  
Relationship Model

In this study, the antioxidant components in co-culture of Chlorella pyrenoidosa and Yarrowia lipolytica (3:1 ratio) were confirmed as trypsin-hydrolyzed peptides (EHPs). The EHPs were composed of 836 different peptides with molecular weights ranging from 639 to 3531 Da and were mainly composed of hydrophobic amino acids (48.1%). These peptides showed remarkable protective effects against oxidative stress in HepG2, which may be attributed to their structures. Furthermore, the mRNA and protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) were significantly lower in the peptide-treated group than in the control group, suggesting that the antioxidant enzyme-coding genes were not activated. The EC50 value of three peptides in the EHPs were in the order of AGYSPIGFVR (0.04 ± 0.002 mg/mL) > VLDELTLAR (0.09 ± 0.001 mg/mL) > LFDPVYLFDQG (0.41 ± 0.03 mg/mL); these results agreed with the prediction of the model (R2 > 0.9, Q2 > 0.5). Thus, EHPs show potential as potent new antioxidant agents.

scholarly journals A Novel NMDA Receptor Antagonist Protects against Cognitive Decline Presented by Senescent Mice

Pharmaceutics ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 284 ◽  
Author(s):  
Júlia Companys-Alemany ◽  
Andreea L. Turcu ◽  
Aina Bellver-Sanchis ◽  
Maria I Loza ◽  
José M. Brea ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Late Onset ◽  
B Cell Lymphoma ◽  
Nmda Receptor Antagonist ◽  
Mice Model ◽  
Object Recognition Test ◽  
Protein Levels ◽  
Preclinical Treatment

Alzheimer’s disease (AD) is the leading cause of dementia. Non-competitive N-Methyl-D-aspartate (NMDA) receptor antagonist memantine improved cognition and molecular alterations after preclinical treatment. Nevertheless, clinical results are discouraging. In vivo efficacy of the RL-208, a new NMDA receptor blocker described recently, with favourable pharmacokinetic properties was evaluated in Senescence accelerated mice prone 8 (SAMP8), a mice model of late-onset AD (LOAD). Oral administration of RL-208 improved cognitive performance assessed by using the three chamber test (TCT), novel object recognition test (NORT), and object location test (OLT). Consistent with behavioural results, RL-208 treated-mice groups significantly changed NMDAR2B phosphorylation state levels but not NMDAR2A. Calpain-1 and Caspase-3 activity was reduced, whereas B-cell lymphoma-2 (BCL-2) levels increased, indicating reduced apoptosis in RL-208 treated SAMP8. Superoxide Dismutase 1 (SOD1) and Glutathione Peroxidase 1 (GPX1), as well as a reduction of hydrogen peroxide (H2O2), was also determined in RL-208 mice. RL-208 treatment induced an increase in mature brain-derived neurotrophic factor (mBDNF), prevented Tropomyosin-related kinase B full-length (TrkB-FL) cleavage, increased protein levels of Synaptophysin (SYN) and Postsynaptic density protein 95 (PSD95). In whole, these results point out to an improvement in synaptic plasticity. Remarkably, RL-208 also decreased the protein levels of Cyclin-Dependent Kinase 5 (CDK5), as well as p25/p35 ratio, indicating a reduction in kinase activity of CDK5/p25 complex. Consequently, lower levels of hyperphosphorylated Tau (p-Tau) were found. In sum, these results demonstrate the neuroprotectant role of RL-208 through NMDAR blockade.

scholarly journals Expression of the Immediate Early Gene c-fos in Basal Ganglia: Induction by Dopaminergic Drugs

1991 ◽  
Vol 18 (S3) ◽  
pp. 380-383 ◽  
Author(s):  
H.A. Robertson ◽  
M.L. Paul ◽  
R. Moratalla ◽  
A.M. Graybiel
Keyword(s):  
Dopamine Agonists ◽  
Immediate Early Gene ◽  
Early Gene ◽  
Immediate Early ◽  
Dopaminergic Drugs ◽  
Protein Levels ◽  
Selective Antagonists ◽  
Fos Protein ◽  
High Doses

ABSTRACT:Expression of the immediate early gene c-fos is increased in mammalian neurons by a number of stimuli and the usefulness of this gene as a marker of neuronal activation has been demonstrated in several systems. Directlyacting dopamine agonists of the D1-type (SKF 38393, CY 208-243) and indirectly-acting dopamine gonists (amphetamine, cocaine) all produce a rapid and transient increase in Fos protein levels in varying patterns in striatum and cerebral cortex. irectly-acting dopamine agonists only produce c-fos activation in denervated (supersensitive) striatum whereas cocaine and amphetamine activate c-fos in striatum in naive animals. Remarkably, D2 selective antagonists such as haloperidol, albeit in high doses, also activate c-fos expression. Activation of c-fos and other immediate early genes may play a part in the development of such long-term dopamine-related effects as dyskinetic movements and addiction.

255 THE ESTROGENIC EVALUATION OF PARABENS USING RAT UTERINE CALBINDIN-D9k

2010 ◽  
Vol 22 (1) ◽  
pp. 285
Author(s):  
T. T. B. Vo ◽  
E. B. Jeung
Keyword(s):  
Gene Expression ◽  
Adverse Effects ◽  
Treated Group ◽  
Environmental Chemicals ◽  
Female Rats ◽  
Protein Levels ◽  
Calbindin D9k ◽  
The Difference

In the current study, calbindin-D9k (CaBP-9k), a potent biomarker for screening estrogen-like environmental chemicals in vivo and in vitro, was adopted to examine the potential estrogen-like property of the following parabens: propyl-, isopropyl-, butyl-, and isobutyl-paraben. Immature female rats were administered for 3 days from postnatal day 14 to 16 with 17?-ethinylestradiol (EE, 1 mg/kg of body weight (BW) per day) or parabens (62.5, 250, and 1000 mg/kg of BW per day). In uterotrophic assays, significantly increased uterus weights were detected in the EE-treated group and in the groups treated with the greatest dose of isopropyl-, butyl- and isobutyl-paraben. In addition, these parabens induced uterine CaBP-9k mRNA and protein levels, whereas co-treatment of parabens and fulvestrant (Faslodex, formerly known as ICI 182, 780), a pure estrogen receptor (ER) antagonist, completely reversed the paraben-induced gene expression and increased uterine weights. To investigate the ER-mediated mechanism(s) by which parabens exert their effects, the expression level of ERα and progesterone receptor (PR) was analyzed. Exposure to EE or parabens caused a dramatic decrease in expression of both ER? mRNA and protein levels, whereas co-treatment with fulvestrant reversed these effects. These data showed the difference of CaBP-9k and ER? expression, suggesting that CaBP-9k might not express via ER? pathway. In the effect of parabens on CaBP-9k expression through PR mediation, a significantly increased expression of uterine PR gene, a well-known ER regulating gene, at both transcriptional and translational levels was indicated in the greatest dose of isopropyl- and butyl-paraben. These parabens induced PR gene expression that was completely blocked by fulvestrant. This result indicates that CaBP-9k expression might involve PR mediates in the estrogenic effect of paraben in immature rat uteri. Taken together, parabens exhibited an estrogen-like property in vivo, which might be mediated by a PR and/or ER? signaling pathway. In addition, our results expanded the current understanding of the potential adverse effects of parabens associated with their estrogen-like activities. Further investigation is needed to elucidate in greater detail the adverse effects of parabens in humans and wildlife.

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