Publications by authors named "Fatemeh Goshadrou"

20 Publications

  • Page 1 of 1

Rabies virus matrix protein targets host actin cytoskeleton: a protein-protein interaction analysis.

Pathog Dis 2021 Jan;79(1)

Biotechnology Research Center, Pasteur Institute of Iran, Tehran, 1316943551, Iran.

Multifunctional matrix protein (M) of rabies virus (RABV) plays essential roles in the pathogenesis of rabies infection. Identification of M protein interacting partners in target hosts could help to elucidate the biological pathways and molecular mechanisms involved in the pathogenesis of this virus. In this study, two-dimensional Far-western blotting (2D-Far-WB) technique was applied to find possible matrix protein partners in the rat brainstem. Recombinant RABV M was expressed in Pichia pastoris and was partially purified. Subsequently, 2D-Far-WB-determined six rat brainstem proteins interacted with recombinant M proteins that were identified by mass spectrometry. Functional annotation by gene ontology analysis determined these proteins were involved in the regulation of synaptic transmission processes, metabolic process and cell morphogenesis-cytoskeleton organization. The interaction of viral M protein with selected host proteins in mouse Neuro-2a cells infected with RABV was verified by super-resolution confocal microscopy. Molecular docking simulations also demonstrated the formation of RABV M complexes. However, further confirmation with co-immunoprecipitation was only successful for M-actin cytoplasmic 1 interaction. Our study revealed actin cytoplasmic 1 as a binding partner of M protein, which might have important role(s) in rabies pathogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/femspd/ftaa075DOI Listing
January 2021

Nucleus basalis of Meynert modulates signal processing in rat layer 5 somatosensory cortex but leads to memory impairment and tactile discrimination deficits following lesion.

Behav Brain Res 2020 05 16;386:112608. Epub 2020 Mar 16.

Department of Physiology, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Biochemistry, Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran. Electronic address:

In rodents, exploring through continuous whisking is a process resulted from sensorimotor networking among different layers of somatosensory cortex (SC) such as layer 5 (L5) or barrel field, and regions like the nucleus basalis of Meynert (NBM). NBM is densely packed with cholinergic fibers and its dysfunction leads to diminished acetylcholine release within SC, tactile deficits and Alzheimer's disease (AD)-like memory impairment. Using extracellular single-unit recording, we investigated mechanisms underlying changes in response characteristics of L5b neurons to single or paired deflection of selected principle and adjacent whiskers (PW and AW), following NBM electrical stimulation in normal rats or ibotenic acid-induced NBM lesion leading to potential tactile deficiency and memory loss during passive avoidance learning (PAL) in AD-like neuropathology. Our results indicated that NBM electrical stimulation decreased ON and OFF response magnitude in nearly half of the units upon vibrissal deflection. The larger the response was evoked to whisker deflection before NBM stimulation, the smaller it gets after stimulation. Neuronal spontaneous activity was not changed with NBM stimulation or lesion. Leading to more sublinear response summation and decreased condition-test ratio, NBM lesion decreased ON response magnitude and facilitation, increased AW surround inhibition in paired whisker deflection, increased excitatory and decreased inhibitory receptive fields, weakened information processing during whisking, and resulted in AD-like declined PAL performance. These findings provide further understandings to develop translational approaches in precision therapeutics to target highly specific regions such as NBM or SC, and pathways like cholinergic system involved in tactile and memory deficits in AD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbr.2020.112608DOI Listing
May 2020

A Metabolomic Study to Identify Potential Tissue Biomarkers for Indomethacin-Induced Gastric Ulcer in Rats.

Avicenna J Med Biotechnol 2019 Oct-Dec;11(4):299-307

Department of Basic Sciences, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Gastric Ulcer (GU) is the most prevalent gastrointestinal disorder induced by various factors and Non-Steroid Anti-Inflammatory Drugs (NSAIDs) as one of the most common reasons. Due to the absence of appropriate molecular markers for GU, the aim of this study was to utilize a metabolomics approach in order to find potential metabolite markers for the disease.

Methods: Stomach tissue samples from indomethacin-treated rats and normal controls were used to perform a 1H-NMR metabolomics study. The altered metabolites were identified using random forest multivariate analysis.

Results: ROC curves showed that the random forest model had a good predictive performance with AUC of 1 for the test and 0.708 for the training sets. Seventeen differentially expressed metabolites were found between GU and normal tissue sample. These metabolites included trimethylamine, betaine, carnitine, methionine, acetylcho line, choline, N,N-Dimethylglycine, cis-aconitate, tryptophan, spermidine, acetylcarnitine, creatinine, pantothenate, taurine, isoleucine, glucose and kynurenine.

Conclusion: The results of the study demonstrated that metabolomics approach could serve as a viable method to find potential markers for GU. Surely, further studies are needed for the validation of the results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925398PMC
January 2020

Therapeutic effects of hydro-alcoholic extract of Achillea wilhelmsii C. Koch on indomethacin-induced gastric ulcer in rats: a proteomic and metabolomic approach.

BMC Complement Altern Med 2019 Aug 7;19(1):205. Epub 2019 Aug 7.

Department of Basic Sciences, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Gastric ulcer is one of the most prevalent diseases worldwide. In Iranian folk medicine, Achillea wilhelmsii (AW) is used as a treatment for gastric ulcer. Previous reports also mentioned Antiulcerogenic properties for this herbal plant. This study investigated the therapeutic effects of Achillea wilhelmsii C. Koch extract on indomethacin-induced gastric lesion in rats, from both proteomic and metabolomic perspectives.

Methods: The rats were divided into 4 groups. Gastric ulceration was induced by a single dose of indomethacin (45 mg/kg) by oral gavage. An amount of 800 mg/kg of AW extract was administered orally. Serum and tissue samples were collected for further investigations. The metabolomic study was performed by H-NMR CPMG spectrometry. Proteomic analysis was also executed by using two dimensional gel electrophoresis (2DE) followed by liquid chromatography coupled to tandem mass spectrometry (LC-ESI/MS/MS). Real time PCR was used to confirm some of the genes.

Results: The macroscopic and microscopic investigations confirmed the effectiveness of the AW extract. There was a panel of metabolites which showed alteration during gastric lesion development. The levels of some of these metabolite reversed nearly to their control values after the administration of AW extract. There were also changes in the levels of some proteins including Alb, Fabp5, Hspb1, Tagln, Lgals7, Csta and Myl9 which were reversed after AW administration.

Conclusions: Our findings suggested that Achillea wilhelmsii C. Koch extract could be a potential therapy to be used for indomethacin-induced gastric lesion treatment in the future. However, further investigations are needed to confirm the results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12906-019-2623-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6686504PMC
August 2019

Effect of ghrelin on serum metabolites in Alzheimer's disease model rats; a metabolomics studies based on 1H-NMR technique.

Iran J Basic Med Sci 2018 Dec;21(12):1245-1254

Department of Basic Medical Sciences, Neyshabur University of Medical Sciences, Neyshabur, Iran.

Objectives: Alzheimer's disease (AD) is dysfunction of the central nervous system and as a neurodegenerative disease. The objective of this work is to investigate metabolic profiling in the serum of animal models of AD compared to healthy controls and then to peruse the role of ghrelin as a therapeutic approach for the AD.

Materials And Methods: Nuclear magnetic resonance (NMR) technique was used for identification of metabolites that are differentially expressed in the serum of a rat model of the AD with or without ghrelin treatment. Using multivariate statistical analysis, models were built and indicated.

Results: There were significant differences and high predictive power between AD and ghrelin-treated groups. The area under curve (AUC) of receiver operating characteristic (ROC) curve and Q were 0.870 and 0.759, respectively. A biomarker panel consisting of 14 metabolites was identified to discriminate the AD from the control group. Another panel of 12 serum metabolites was used to differentiate AD models from treated models.

Conclusion: Both panels had good agreements with clinical diagnosis. Analysis of the results displayed that ghrelin improved memory and cognitive abilities. Affected pathways by ghrelin included oxidative stress, and osteoporosis pathways and vascular risk factors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.22038/ijbms.2018.30596.7373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312673PMC
December 2018

Three-way interaction model with switching mechanism as an effective strategy for tracing functionally-related genes.

Expert Rev Proteomics 2019 02 24;16(2):161-169. Epub 2018 Dec 24.

a Department of Basic Sciences, Faculty of Paramedical Sciences , Shahid Beheshti University of Medical Sciences , Tehran , Iran.

: Identification of functionally-related genes is an important step in understanding biological systems. The most popular strategy to infer functional dependence is to study pairwise correlations between gene expression levels. However, certain functionally-related genes may have a low expression correlation due to their nonlinear interactions. The use of a three-way interaction (3WI) model with switching mechanism (SM) is a relatively new strategy to trace functionally-related genes. The 3WI model traces the dynamic and nonlinear nature of the co-expression relationship of two genes by introducing their link to the expression level of a third gene. : In this paper, we reviewed a variety of existing methods for tracing the 3WIs. Furthermore, we provide a comprehensive review of the previous biological studies based on 3WI models. : Comparison of features of these methods indicates that the modified liquid association algorithm has the best efficiency for tracing 3WI between others. The limited number of biological studies based on the 3WI suggests that high computational demand of the available algorithms is a major challenge to apply this approach for analyzing high-throughput omics data.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14789450.2019.1559734DOI Listing
February 2019

Chronic ghrelin administration restores hippocampal long-term potentiation and ameliorates memory impairment in rat model of Alzheimer's disease.

Hippocampus 2018 10 5;28(10):724-734. Epub 2018 Sep 5.

Department of Physiology, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Alzheimer's disease (AD), as a common age-related dementia, is a progressive manifestation of cognitive decline following synaptic failure resulted majorly by senile plaques composed of deposits of amyloid beta (Aβ). Ghrelin is a multifunctional peptide hormone with receptors present in various brain tissues including hippocampus and has been associated with neuroprotection, neuromodulation, and memory processing. Here, we investigated the neuroprotective and therapeutic effects of intracerebroventricular (icv) ghrelin infusion for 2 weeks on passive avoidance learning (PAL), memory retention, and synaptic plasticity in the hippocampal dentate gyrus (DG) and CA1 of both normal rats and Aβ1-42-induced neurotoxicity in AD model. Male Wistar rats were evaluated for their passive memory performance using a shuttle box while some groups had already received Aβ1-42 and/or chronic ghrelin. Using field potential recording, the induction of short- and long-term potentiation (STP and LTP) was studied in DG granule cells along with the LTP changes in CA1 pyramidal neurons through stimulation of the medial perforant path (mPP) and Schaffer collaterals (SCs), respectively. Our results demonstrated that chronic ghrelin treatment not only improved memory processing and retrieval in normal rats during the PAL task, but also promoted memory retention and alleviated memory loss by amelioration of Aβ1-42-induced synaptic plasticity impairment in AD subjects through augmentation of field excitatory postsynaptic potential (fEPSP) slope that led to LTP restitution in both the mPP-DG and the CA3-CA1 synapses. Meanwhile, STP was not significantly changed, meaning that although ghrelin enhanced postsynaptic excitability in DG, it did not change presynaptic transmitter release significantly. This suggests the involvement of postsynaptic mechanisms in long-term ghrelin-enhanced memory. In conclusion, it can be inferred that chronic ghrelin administration has an auspicious therapeutic value for impaired cognitive performance and memory deficits in AD-like neuropathology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hipo.23002DOI Listing
October 2018

Valproic acid inhibits the protective effects of stromal cells against chemotherapy in breast cancer: Insights from proteomics and systems biology.

J Cell Biochem 2018 11 28;119(11):9270-9283. Epub 2018 Jun 28.

Drug Design and Bioinformatics Unit, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.

Interaction between tumor and stromal cells is beginning to be decoded as a contributor to chemotherapy resistance. Here, we aim to take a system-level approach to explore a mechanism by which stromal cells induce chemoresistance in cancer cells and subsequently identify a drug that can inhibit such interaction. Using a proteomic dataset containing quantitative data on secretome of stromal cells, we performed multivariate analyses and found that bone-marrow mesenchymal stem cells (BM-MSCs) play the most protective role against chemotherapeutics. Pathway enrichment tests showed that secreted cytokines from BM-MSCs activated 4 signaling pathways including Janus kinase-signal transducer and activator of transcription, phosphatidylinositol 3-kinase-protein kinase B, and mitogen-activated protein kinase, transforming growth factor-β in cancer cells collectively leading to nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) transcription factor activation. Based on the data from integrated Library of Integrated Network-Based Cellular Signatures (iLINCs) program, we found that among different drugs, valproic acid (VA) affected the expression of 34 genes within the identified pathways that are activated by stromal cells. Our in vitro experiments confirmed that VA inhibits NF-kB activation in cancer cells. In addition, analyzing gene expression data in patients taking oral VA showed that this drug decreased expression of antioxidant enzymes culminating in increased oxidative stress in tumor cells. These results suggest that VA confines the protective role of stromal cells by inhibiting the adaptation mechanisms toward oxidative stress which is potentiated by stromal cells. Since VA is an already prescribed drug manifesting anticancer effects, this study provides a mechanistic insight for combination of VA with chemotherapy in the clinical setting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcb.27196DOI Listing
November 2018

Effects on Rat Models of Alzheimer's Disease Through the Investigation of Serum Metabolic Features Using NMR Metabolomics.

Avicenna J Med Biotechnol 2018 Apr-Jun;10(2):83-92

Department of Basic Sciences, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Alzheimer's Disease (AD) is the most prevalent cause of memory impairment in the elderly population, but the diagnosis and treatment of the disease is still challenging. Lavender aqueous extract has recently been shown to have the potential in clearing Amyloid-beta plaques from AD rat hippocampus. To elucidate the therapeutic mechanisms of lavender, serum metabolic fingerprint of Aβ-induced rat Alzheimer's models was investigated through nuclear magnetic resonance spectrometry.

Methods: For the establishment of rat Alzheimer's models, 10 of Amyloid beta 1-42 was injected to male Wistar rats. The lavender aqueous extract was injected 20 days after the establishment of the models, once daily for 20 days. Serum samples were collected and metabolite fingerprints were obtained using 500 1H-NMR spectrometry, following multivariate statistical analyses. The resulted metabolites were then subjected to pathway analysis tools to reveal metabolic pathways affected by the lavender extract treatment.

Results: Levels of 10 metabolite markers including alanine, glutamine, serine, isoleucine, valine, carnitine, isobutyrate, pantothenate, glucose and asparagine were reversed nearly to control values after treatment with lavender extract. The results revealed that the most significantly affected pathways during treatment with lavender extract belonged to carbohydrate and amino acid metabolism, including pantothenate and CoA metabolism, glyoxilate and dicarboxylate metabolism, alanine, aspartate and glutamate metabolism, cysteine and methionine metabolism.

Conclusion: As lavender extract reversed the direction of changes of some metabolites involved in AD pathogenesis, it was concluded that the extract might play a role in the disease improvement and serve as a potential therapeutic option for the treatment of AD. Moreover, the metabolites which were found in AD rats could serve as a potential marker panel for the disease; however, much further investigation and validation of the results is needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5960064PMC
June 2018

Integrated use of bioinformatic resources reveals that co-targeting of histone deacetylases, IKBK and SRC inhibits epithelial-mesenchymal transition in cancer.

Brief Bioinform 2019 03;20(2):717-731

Drug Design and Bioinformatics Unit, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.

With the advent of high-throughput technologies leading to big data generation, increasing number of gene signatures are being published to predict various features of diseases such as prognosis and patient survival. However, to use these signatures for identifying therapeutic targets, use of additional bioinformatic tools is indispensible part of research. Here, we have generated a pipeline comprised of nearly 15 bioinformatic tools and enrichment statistical methods to propose and validate a drug combination strategy from already approved drugs and present our approach using published pan-cancer epithelial-mesenchymal transition (EMT) signatures as a case study. We observed that histone deacetylases were critical targets to tune expression of multiple epithelial versus mesenchymal genes. Moreover, SRC and IKBK were the principal intracellular kinases regulating multiple signaling pathways. To confirm the anti-EMT efficacy of the proposed target combination in silico, we validated expression of targets in mesenchymal versus epithelial subtypes of ovarian cancer. Additionally, we inhibited the pinpointed proteins in vitro using an invasive lung cancer cell line. We found that whereas low-dose mono-therapy failed to limit cell dispersion from collagen spheroids in a microfluidic device as a metric of EMT, the combination fully inhibited dissociation and invasion of cancer cells toward cocultured endothelial cells. Given the approval status and safety profiles of the suggested drugs, the proposed combination set can be considered in clinical trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/bib/bby030DOI Listing
March 2019

Three-way interaction model to trace the mechanisms involved in Alzheimer's disease transgenic mice.

PLoS One 2017 21;12(9):e0184697. Epub 2017 Sep 21.

Department of Basic Sciences, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Alzheimer's disease (AD) is the most common cause for dementia in human. Currently, more than 46 million people in the world suffer from AD and it is estimated that by 2050 this number increases to more than 131 million. AD is considered as a complex disease. Therefore, understanding the mechanism of AD is a universal challenge. Nowadays, a huge number of disease-related high-throughput "omics" datasets are freely available. Such datasets contain valuable information about disease-related pathways and their corresponding gene interactions. In the present work, a three-way interaction model is used as a novel approach to understand AD-related mechanisms. This model can trace the dynamic nature of co-expression relationship between two genes by introducing their link to a third gene. Apparently, such relationships cannot be traced by the classical two-way interaction model. Liquid association method was applied to capture the statistically significant triplets which are involved in three-way interaction. Subsequently, gene set enrichment analysis (GSEA) and gene regulatory network (GRN) inference were applied to analyze the biological relevance of the statistically significant triplets. The results of this study suggest that the innate immunity processes are important in AD. Specifically, our results suggest that H2-Ob as the switching gene and the gene pair {Csf1r, Milr1} form a statistically significant and biologically relevant triplet, which may play an important role in AD. We propose that the homeostasis-related link between mast cells and microglia is presumably controlled with H2-Ob expression levels as a switching gene.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0184697PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5608283PMC
October 2017

Display of B. pumilus chitinase on the surface of B. subtilis spore as a potential biopesticide.

Pestic Biochem Physiol 2017 Aug 3;140:17-23. Epub 2017 Jun 3.

Department of Industrial and Environmental Biotechnology, National Institute of Genetics Engineering and Biotechnology (NIGEB), Tehran, Iran. Electronic address:

Background: Chitinases can inhibit the growth of many fungal diseases which are a great threat for global agricultural production. Biological control of pathogens like fungi, is believed to be one of the best ways to eliminate the adverse effects of plant pathogens. To this end, we expressed and displayed a chitinase from Bacillus pumilus (ChiS) on the surface of Bacillus subtilis spores, as a biocontrol agent.

Result: ChiS enzyme from B. pumilus was expressed on the spores of B. subtilis using CotG as a carrier protein. Immunofluorescence microscopy confirmed the expression of ChiS on the surface of the spores. Enzyme activity assay showed that the surface displayed ChiS was active and was also able to inhibit the growth of Rhizoctonia solani and Trichoderma harzianum fungi. Western blot analysis also indicated that CotG-ChiS is partially processed after display. Molecular dynamics simulation showed that the stability of the heterologous protein was decreased after fusion.

Conclusion: ChiS was successfully displayed on the surface of Bacillus spores by fusion to the CotG, one of the main spore coat proteins. In-vitro experiments showed that the displayed enzyme was effective in growth inhibition of R. solani and T. harzianum fungi.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pestbp.2017.05.008DOI Listing
August 2017

Design and expression of a chimeric vaccine candidate for avian necrotic enteritis.

Protein Eng Des Sel 2017 Jan 24;30(1):39-45. Epub 2016 Nov 24.

Department of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran 1497716316, Iran

Necrotic enteritis is an economically important disease of poultry mainly caused by Clostridium perfringens The bacteria release multiple toxins of which NetB, alpha toxin and TpeL have been reported to play important roles in pathogenicity and/or severity of the disease. In this study, the sequence of clostridial toxins NetB, alpha toxin and TpeL were analyzed using bioinformatics tools to determine protein domains with high immunogenicity factor. Several chimeric trivalent proteins consisting of the immunogenic regions of the three toxins were designed and evaluated. The separate regions were fused together using rigid linkers. Based on a modeled tertiary structure, a proper combination was selected and expressed in a bacterial host (Escherichia coli) and successfully purified. The expression of the chimeric protein was further verified by western blotting. The ability of the immunized serum in recognizing each individual subunit of the chimeric protein was also examined. Circular dichroism was used to evaluate the predicted secondary structure of the chimeric protein. In vitro potency test demonstrated that the serum from a rabbit immunized with the chimeric protein is able to partially neutralize Alpha toxin, hence the construct can potentially be used as a vaccine against C. perfringens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/protein/gzw060DOI Listing
January 2017

Stress increased ghrelin secretion from pancreatic isolated islets in male rats.

Gen Physiol Biophys 2016 Jan 27;35(1):109-17. Epub 2015 Nov 27.

Department of Biology, College of Basic Sciences, Yadegar-e-Imam Khomeini (RAH) Shahre Rey Branch, Islamic Azad University, Tehran, Iran.

It has been demonstrated that plasma ghrelin is likely affected by stress, but little attention has been paid to the effect of stress on ghrelin release from pancreatic islets. This study investigates the effect of stress on ghrelin secretion from pancreatic islets in rats. Male Wistar rats were divided into control and stressed groups. The stressed group was further divided into foot-shock and psychological stress subgroups. Stress was induced by a communication box. After stress exposure, blood sampling was performed to determine the plasma levels of corticosterone, glucose, and ghrelin. Then the animals' pancreatic islets were isolated to assess their ghrelin output at 5.6, 8.3, and 16.7 mM glucose concentrations. Acute exposure to foot-shock and psychological stress both increased plasma corticosterone concentration. Moreover, plasma glucose concentration increased in the foot-shock stress group. Chronic exposure to foot-shock decreased plasma ghrelin concentration, whereas acute exposure had no significant effect. Acute and chronic exposure to foot-shock and psychological stress increased ghrelin secretion from isolated islets in the presence of different glucose concentrations. The results of the present study suggest that ghrelin secretion from isolated islets is not glucose-dependent. However, ghrelin secretion appears to be intensely responsive to both acute and chronic stress.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4149/gpb_2015037DOI Listing
January 2016

Chronic administration of ghrelin regulates plasma glucose and normalizes insulin levels following fasting hyperglycemia and hyperinsulinemia.

Gen Comp Endocrinol 2015 Dec 6;224:113-20. Epub 2015 Jul 6.

Department of Physiology, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Ghrelin is an endogenous ligand for the growth hormone secretagogue receptor. The majority of the previous studies have shown that the short-term ghrelin treatment induces hyperglycemia and hypoinsulinemia in healthy humans and rodents. However, the results obtained from long-term treatment with ghrelin are not clear enough. In this study, we assessed acute (1 day) and chronic (21 days) effects of intraperitoneally administered ghrelin (at different doses of 1, 10 and 20 μg/kg) during a 12-h fasting period in rats using glucose oxidase method and direct sandwich ELISA (the Enzyme-Linked Immunosorbent Assay) and then compared the effects of exogenous ghrelin on blood glucose and insulin levels on day 21 with those on day 1. The results showed that acute ghrelin administration markedly increased fasting plasma glucose at doses of 1 and 10 μg/kg as well as insulin levels at 1 μg/kg in comparison to control values. Ghrelin (at 1 μg/kg) altered plasma glucose but not insulin levels on the 21st day compared to control values. In addition, the comparison of the influence of ghrelin administration on plasma glucose and insulin levels on day 21 with those on the first day revealed that the chronic administration of ghrelin notably decreased plasma glucose and insulin levels relative to the acute ghrelin treatment. These findings indicate that hyperglycemia and hyperinsulinemia caused by the exogenous ghrelin during acute treatment are temporary and prolonged treatment with ghrelin regulates plasma glucose and restores insulin to normal levels, suggesting a possible role for ghrelin in improving insulin resistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ygcen.2015.07.001DOI Listing
December 2015

Berberine chloride improved synaptic plasticity in STZ induced diabetic rats.

Metab Brain Dis 2013 Sep 3;28(3):421-8. Epub 2013 May 3.

Department of Physiology, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran.

Previous studies indicated that diabetes affects synaptic transmission in the hippocampus, leading to impairments of synaptic plasticity and defects in learning and memory. Although berberine treatment ameliorates memory impairment and improves synaptic plasticity in streptozotocin (STZ) induced diabetic rats, it is not clear if the effects are pre- or post-synaptic or both. The aim of this study was to evaluate the effects of berberine chloride on short-term plasticity in inhibitory interneurons in the dentate gyrus of STZ-induced diabetic rats. Experimental groups included: The control, control berberine treated (100 mg/kg), diabetic and diabetic berberine treated (50,100 mg/kg/day for 12 weeks) groups. The paired pulse paradigm was used to stimulate the perforant pathway and field excitatory post-synaptic potentials (fEPSP) were recorded in dentate gyrus (DG). In comparison with control, paired pulse facilitation in the diabetic group was significantly increased (P < 0.01) and this effect prevented by chronic berberine treatment (50,100 mg/kg). However, there were no differences between responses of the control berberine 100 mg/kg treated and diabetes berberine treated (50 and 100 mg/kg) groups as compared to the control group. The present results suggest that the pre-synaptic component of synaptic plasticity in the dentate gyrus is affected under diabetic conditions and that berberine prevents this effect.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11011-013-9411-5DOI Listing
September 2013

The effect of ghrelin on MK-801 induced memory impairment in rats.

Peptides 2013 Jun 26;44:60-5. Epub 2013 Mar 26.

Physiology Department, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Accumulating evidence indicates that the brain-gut peptide ghrelin which is expressed in hippocampus improves memory and learning processes. The MK-801, a noncompetitive NMDA receptor antagonist, has also shown amnesic properties in animal model. The current study was to find out whether intracerebroventricular administration of ghrelin can prevent amnesia induced by MK-801 in rats. A week after the surgery, during which cannuals were implanted in the lateral ventricular, the animals were trained and tested in a step-through type passive avoidance task. Memory retrieval was measured by step-through latency (STL) and total time in dark compartments (TDC). In the first series of experiments, we established a dose-response relationship for ghrelin on the passive avoidance paradigm. In the second set of experiments, animals were divided to two groups. In the first group, MK-801 (0.075, 0.15 and 0.3mg/kg) was injected intraperitoneally (i.p.) immediately after the acquisition session and in the second group MK-801 (same doses) was injected (i.p.) 30 min before the retention session. Analysis of data showed that in both groups, MK-801 impaired learning and memory. In the third set of experiments, administration of ghrelin (200 ng/rat) right after the acquisition session (i.e. before MK-801 injection) improved the MK-801 induced memory impairment, but administration of ghrelin before retrieval session did not affect the MK-801 induced memory impairment. These results show an interaction between ghrelin and glutamatergic system. A novel finding in this study is that ghrelin can prevent amnesia produced by NMDA antagonist in rats when injected in post-training phase.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.peptides.2013.03.022DOI Listing
June 2013

Hippocampal synaptic plasticity restoration and anti-apoptotic effect underlie berberine improvement of learning and memory in streptozotocin-diabetic rats.

Eur J Pharmacol 2013 Jan 23;698(1-3):259-66. Epub 2012 Oct 23.

Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Chronic diabetes mellitus initiates apoptosis and negatively affects synaptic plasticity in the hippocampus with ensuing impairments of learning and memory. Berberine, an isoquinoline alkaloid, exhibits anti-diabetic, antioxidant and nootropic effects. This study was conducted to evaluate the effect of berberine on hippocampal CA1 neuronal apoptosis, synaptic plasticity and learning and memory of streptozotocin (STZ)-diabetic rats. Long-term potentiation (LTP) in perforant path-dentate gyrus synapses was recorded for assessment of synaptic plasticity and field excitatory post-synaptic potential (fEPSP) slope and population spike (PS) amplitude. PS amplitude and fEPSP significantly decreased in diabetic group versus control, and chronic berberine treatment (100mg/kg/day, p.o.) restored PS amplitude and fEPSP and ameliorated learning and memory impairment and attenuated apoptosis of pyramidal neurons in the CA1 area, as determined by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling method. In summary, chronic berberine treatment of STZ-diabetic rats significantly ameliorates learning and memory impairment and part of its beneficial effect could be attributed to improvement of synaptic dysfunction and anti-apoptotic property.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejphar.2012.10.020DOI Listing
January 2013

Attenuating the effect of Ghrelin on memory storage via bilateral reversible inactivation of the basolateral amygdale.

Behav Brain Res 2012 Jul 1;232(2):391-4. Epub 2012 Apr 1.

Department of Physiology, Paramedical Sciences Faculty, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Previous studies have shown that Ghrelin increases memory retention. They have also indicated that amygdale is involved in memory storage. The present study examined the role of basolateral amygdala (BLA) in Ghrelin-induced retention improvement, using reversible inactivation of this region with lidocaine. Rats were bilaterally implanted with cannulae at the BLA. One week later, they received intra-BLA injection of lidocaine, saline or Ghrelin with 5 min interval immediately after training. 24-72 h after training, step-through latency (STL) was measured as learning and memory index. The results showed that injection of Ghrelin into the BLA produced a significant enhancement in retention, which was attenuated by injection of lidocaine into BLA. These finding indicate that the BLA is involved in mediating the memory-modulating effect of Ghrelin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbr.2012.03.035DOI Listing
July 2012

Netrin-1 improves spatial memory and synaptic plasticity impairment following global ischemia in the rat.

Brain Res 2012 May 10;1452:185-94. Epub 2012 Mar 10.

Dept. Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Cerebral ischemia, which is the second and most common cause of mortality, affects millions of individuals worldwide. The present study was performed to investigate whether intrahippocampal administration of netrin-1 could improve spatial memory impairment in radial arm maze task and restore long-term potentiation (LTP) in 4-vessel occlusion model of global ischemia. The results showed that intrahippocampal infusion of nerin-1 24 h after ischemia (at both doses of 400 and 800 ng) significantly ameliorated spatial memory impairment and at a dose of 800 ng was capable to improve synaptic dysfunction as observed by recovery of population spike component of basal evoked potential and LTP through enhancement of excitability and normalization of paired pulse response. Taken together, the present study shows that netrin-1 dose-dependently ameliorates spatial memory impairment and improves synaptic dysfunction as observed by recovery of population spike component of basal evoked potential and LTP in rats with global ischemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.brainres.2012.03.008DOI Listing
May 2012