Publications by authors named "Naime Majidi Zolbanin"

14 Publications

  • Page 1 of 1

Immunopharmacological perspective on zinc in SARS-CoV-2 infection.

Int Immunopharmacol 2021 Apr 1;96:107630. Epub 2021 Apr 1.

Solid Tumor Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran. Electronic address:

The novel SARS-CoV-2 which was first reported in China is the cause of infection known as COVID-19. In comparison with other coronaviruses such as SARS-CoV and MERS, the mortality rate of SARS-CoV-2 is lower but the transmissibility is higher. Immune dysregulation is the most common feature of the immunopathogenesis of COVID-19 that leads to hyperinflammation. Micronutrients such as zinc are essential for normal immune function. According to the assessment of WHO, approximately one-third of the world's society suffer from zinc deficiency. Low plasma levels of zinc are associated with abnormal immune system functions such as impaired chemotaxis of polymorphonuclear cells (PMNs) and phagocytosis, dysregulated intracellular killing, overexpression of the inflammatory cytokines, lymphopenia, decreased antibody production, and sensitivity to microbes especially viral respiratory infections. Zinc exerts numerous direct and indirect effects against a wide variety of viral species particularly RNA viruses. The use of zinc and a combination of zinc-pyrithione at low concentrations impede SARS-CoV replication in vitro. Accordingly, zinc can inhibit the elongation step of RNA transcription. Furthermore, zinc might improve antiviral immunity by up-regulation of IFNα through JAK/STAT1 signaling pathway in leukocytes. On the other hand, zinc supplementation might ameliorate tissue damage caused by mechanical ventilation in critical COVID-19 patients. Finally, zinc might be used in combination with antiviral medications for the management of COVID-19 patients. In the current review article, we review and discuss the immunobiological roles and antiviral properties as well as the therapeutic application of zinc in SARS-CoV-2 and related coronaviruses infections.
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http://dx.doi.org/10.1016/j.intimp.2021.107630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015651PMC
April 2021

Simultaneous inhibition of CD73 and IL-6 molecules by siRNA-loaded nanoparticles prevents the growth and spread of cancer.

Nanomedicine 2021 Mar 24;34:102384. Epub 2021 Mar 24.

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:

High concentrations of adenosine and interleukin (IL)-6 in the tumor microenvironment have been identified as one of the leading causes of cancer growth. Thus, we decided to inhibit the growth of cancer cells by inhibiting the production of adenosine and IL-6 in the tumor environment at the same time. For this purpose, we used chitosan-lactate-PEG-TAT (CLP-TAT) nanoparticles (NPs) loaded with siRNA molecules against CD73, an adenosine-producing enzyme, and IL-6. Proper physicochemical properties of the produced NPs led to high cell uptake and suppression of target molecules. Administration of these NPs to tumor-bearing mice (4T1 and CT26 models) greatly reduced the size of the tumor and increased the survival of the mice, which was accompanied by an increase in anti-tumor T lymphocyte responses. These findings suggest that combination therapy using siRNA-loaded CLP-TAT NPs against CD73 and IL-6 molecules could be an effective treatment strategy against cancer that needs further study.
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http://dx.doi.org/10.1016/j.nano.2021.102384DOI Listing
March 2021

Anticancer potential of metformin: focusing on gastrointestinal cancers.

Cancer Chemother Pharmacol 2021 May 20;87(5):587-598. Epub 2021 Mar 20.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Urmia University of Medical Sciences, PO Box: 5715799313, Urmia, Iran.

Gastrointestinal cancers are one of the most common types of cancer that have high annual mortality; therefore, identification and introduction of safe drugs in the control and prevention of these cancers are of particular importance. Metformin, a lipophilic biguanide, is the most commonly prescribed agent for type 2 diabetes management. In addition to its great effects on lowering the blood glucose concentrations, the anti-cancer properties of this drug have been reported in many types of cancers such as gastrointestinal cancers. Hence the effects of this agent as a safe drug on the reduction of gastrointestinal cancer risk and suppression of these types of cancers have been studied in different clinical trials. Furthermore, the proposed mechanisms of metformin in preventing the growth of these cancers have been investigated in several studies. In this review, we discuss recent advances in elucidating the molecular mechanisms that are relevant for metformin use in gastrointestinal cancer treatment.
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http://dx.doi.org/10.1007/s00280-021-04256-8DOI Listing
May 2021

Exosomes for mRNA delivery: a novel biotherapeutic strategy with hurdles and hope.

BMC Biotechnol 2021 Mar 10;21(1):20. Epub 2021 Mar 10.

Solid Tumor Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Shafa St, Ershad Blvd, P.O. BoX: 1138, Urmia, 57147, Iran.

Over the past decade, therapeutic messenger RNAs (mRNAs) have emerged as a highly promising new class of drugs for protein replacement therapies. Due to the recent developments, the incorporation of modified nucleotides in synthetic mRNAs can lead to maximizing protein expression and reducing adverse immunogenicity. Despite these stunning improvements, mRNA therapy is limited by the need for the development of safe and efficient carriers to protect the mRNA integrity for in vivo applications. Recently, leading candidates for in vivo drug delivery vehicles are cell-derived exosomes, which have fewer immunogenic responses. In the current study, the key hurdles facing mRNA-based therapeutics, with an emphasis on recent strategies to overcoming its immunogenicity and instability, were highlighted. Then the immunogenicity and toxicity of exosomes derived from various cell sources were mentioned in detail. Finally, an overview of the recent strategies in using exosomes for mRNA delivery in the treatment of multiple diseases was stated.
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http://dx.doi.org/10.1186/s12896-021-00683-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7945253PMC
March 2021

The role of regulatory T cells in the pathogenesis and treatment of prostate cancer.

Life Sci 2021 Jan 26:119132. Epub 2021 Jan 26.

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:

Despite developments in the treatment of various cancers, prostate cancer is one of the deadliest diseases known to men. Systemic therapies such as androgen deprivation, chemotherapy, and radiation therapy have not been very successful in treating this disease. Numerous studies have shown that there is a direct relationship between cancer progression and inhibition of anti-tumor immune responses that can lead to progression of various malignancies, including prostate cancer. Interestingly, CD4CD25FoxP3 regulatory T cells significantly accumulate and increase in draining lymph nodes and PBMCs of patients with prostate cancer and other solid tumors. In vivo and in vitro studies have shown that Tregs can suppress anti-tumor responses, which is directly related to the increased risk of cancer recurrence. Tregs are essential for preserving self-tolerance and inhibiting extra immune responses harmful to the host. Since the tumor-related antigens are mainly self-antigens, Tregs could play a major role in tumor progression. Accordingly, it has discovered that prostate cancer patients with higher Tregs have poor prognosis and low survival rates. However, anti-tumor responses can be reinforced by suppression of Tregs with using monoclonal antibodies against CD25 and CTLA-4. Therefore, depleting Tregs or suppressing their functions could be one of the effective ways for prostate cancer immunotherapy. The purpose of this review is to investigate the role of Treg cells in the progression of prostate cancer and to evaluate effective strategies for the treatment of prostate cancer by regulating Treg cells.
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http://dx.doi.org/10.1016/j.lfs.2021.119132DOI Listing
January 2021

The versatile role of exosomes in human retroviral infections: from immunopathogenesis to clinical application.

Cell Biosci 2021 Jan 15;11(1):19. Epub 2021 Jan 15.

Solid Tumor Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Shafa St, Ershad Blvd., P.O. Box: 1138, 57147, Urmia, Iran.

Eukaryotic cells produce extracellular vesicles (EVs) mediating intercellular communication. These vesicles encompass many bio-molecules such as proteins, nucleic acids, and lipids that are transported between cells and regulate pathophysiological actions in the recipient cell. Exosomes originate from multivesicular bodies inside cells and microvesicles shed from the plasma membrane and participate in various pathological conditions. Retroviruses such as Human Immunodeficiency Virus -type 1 (HIV-1) and Human T-cell leukemia virus (HTLV)-1 engage exosomes for spreading and infection. Exosomes from virus-infected cells transfer viral components such as miRNAs and proteins that promote infection and inflammation. Additionally, these exosomes deliver virus receptors to target cells that make them susceptible to virus entry. HIV-1 infected cells release exosomes that contribute to the pathogenesis including neurological disorders and malignancy. Exosomes can also potentially carry out as a modern approach for the development of HIV-1 and HTLV-1 vaccines. Furthermore, as exosomes are present in most biological fluids, they hold the supreme capacity for clinical usage in the early diagnosis and prognosis of viral infection and associated diseases. Our current knowledge of exosomes' role from virus-infected cells may provide an avenue for efficient retroviruses associated with disease prevention. However, the exact mechanism involved in retroviruses infection/ inflammation remains elusive and related exosomes research will shed light on the mechanisms of pathogenesis.
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http://dx.doi.org/10.1186/s13578-021-00537-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810184PMC
January 2021

Mesenchymal stem cell derived-exosomes: a modern approach in translational medicine.

J Transl Med 2020 11 27;18(1):449. Epub 2020 Nov 27.

Solid Tumor Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Shafa St, Ershad Blvd, P.O. BoX: 1138, 57147, Urmia, Iran.

Mesenchymal stem cells (MSCs) have captured great attention in regenerative medicine for over a few decades by virtue of their differentiation capacity, potent immunomodulatory properties, and their ability to be favorably cultured and manipulated. Recent investigations implied that the pleiotropic effects of MSCs is not associated to their ability of differentiation, but rather is mediated by the secretion of soluble paracrine factors. Exosomes, nanoscale extracellular vesicles, are one of these paracrine mediators. Exosomes transfer functional cargos like miRNA and mRNA molecules, peptides, proteins, cytokines and lipids from MSCs to the recipient cells. Exosomes participate in intercellular communication events and contribute to the healing of injured or diseased tissues and organs. Studies reported that exosomes alone are responsible for the therapeutic effects of MSCs in numerous experimental models. Therefore, MSC-derived exosomes can be manipulated and applied to establish a novel cell-free therapeutic approach for treatment of a variety of diseases including heart, kidney, liver, immune and neurological diseases, and cutaneous wound healing. In comparison with their donor cells, MSC-derived exosomes offer more stable entities and diminished safety risks regarding the administration of live cells, e.g. microvasculature occlusion risk. This review discusses the exosome isolation methods invented and utilized in the clinical setting thus far and presents a summary of current information on MSC exosomes in translational medicine.
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http://dx.doi.org/10.1186/s12967-020-02622-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691969PMC
November 2020

Targeted Co-Delivery of Docetaxel and cMET siRNA for Treatment of Mucin1 Overexpressing Breast Cancer Cells.

Adv Pharm Bull 2018 Aug 29;8(3):383-393. Epub 2018 Aug 29.

Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Targeted treatment of breast cancer through combination of chemotherapeutic agents and siRNA had been drawing much attention in recent researches. This study was carried out to evaluate mucin1 aptamer-conjugated chitosan nanoparticles containing docetaxel and cMET siRNA on SKBR3 cells. Nano-drugs were characterized by transmission electron microscope, Zetasizer and loading efficiency calculation. siRNA entrapment onto nanoparticles, stability of siRNA-loaded nanoparticles and conjugation of mucin1 aptamer to nanoparticles were evaluated via separate electrophoresis. Cellular uptake of the targeted nanoparticles was evaluated through GFP-plasmid expression in mucin1+ SKBR3 vs. mucin1- CHO cells. Protein expression, cell viability and gene expression were assessed by Western Blotting, MTT assay, and Quantitative Real Time-PCR, respectively. Characterization of nano-drugs represented the ideal size (110.5± 3.9 nm), zeta potential (11.6± 0.8 mV), and loading efficiency of 90.7% and 88.3% for siRNA and docetaxel, respectively. Different gel electrophoresis affirmed the conjugation of aptamers to nanoparticles and entrapment of siRNA onto nanoparticles. Increased cellular uptake of aptamer-conjugated nanoparticles was confirmed by GFP expression. cMET gene silencing was confirmed by Western Blotting. The significant (p ≤0.0001) impact of combination targeted therapy vs. control on cell viability was shown. Results of Quantitative Real Time-PCR represented a remarkably decreased (p ≤0.0001) expression of the studied genes involving in tumorigenicity, metastasis, invasion, and angiogenesis (STAT3, IL8, MMP2, MMP9, and VEGF) by targeted combination treatment vs. control. The mucin1 aptamer-conjugated chitosan nanoparticles, containing docetaxel and cMET siRNA, is suggested for treatment of mucin1 metastatic breast cancer cells. However, further studies should be conducted on animal models.
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http://dx.doi.org/10.15171/apb.2018.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156474PMC
August 2018

Anti-Mucin1 Aptamer-Conjugated Chitosan Nanoparticles for Targeted Co-Delivery of Docetaxel and IGF-1R siRNA to SKBR3 Metastatic Breast Cancer Cells

Iran Biomed J 2019 01 25;23(1):21-33. Epub 2018 Jul 25.

Immunology Research Center, Division of Inflammation and Inflammatory Diseases, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Targeted co-delivery of siRNA and a chemotherapeutic drug is an attractive approach to cancer drug design and treatment. This study was carried out to design an anti-Mucin1 aptamer (Apt)-conjugated chitosan nanoparticle (NP) for targeted co-delivery of insulin-like growth factor receptor 1 (IGF-1R) Silencer siRNA and docetaxel (DTX) to SKBR3 cells.

Methods: Characterization of nano-drugs, cellular uptake of NPs, cell viability, and gene expression studies were evaluated based on metastatic breast cancer cells.

Results: The results of this study showed that NPs had spherical and smooth morphology with 110-118 nm in size and had positive zeta potential (12-14 mV). siRNA and DTX were considerably loaded into NPs. The appropriate conjugation of the Apt to the NPs was affirmed by gel electrophoresis. The Apt-conjugated NPs were observed to enhance the cellular uptake of NPs into the SKBR3 cells. Although the combination treatment significantly decreased the cell viability of SKBR3 cells, the augmentative effect was observed when Apt was conjugated to NPs. Furthermore, Apt-conjugated NPs dramatically reduced the genetic expression of IGF-1R, signal transducers and activators of transcription 3 (STAT3), matrix metalloproteinases (MMP9), and vascular growth factor (VEGF).

Conclusion: The targeted NPs may augment the targeting of pathways involved in tumorigenesis and metastasis of breast cancer. Therefore, more animal model experiments are needed to further clarify the efficacy and safety of this functionalized nanodrug.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305820PMC
January 2019

A study on drug delivery tracing with radiolabeled mesoporous hydroxyapatite nanoparticles conjugated with 2DG/DOX for breast tumor cells.

Nucl Med Rev Cent East Eur 2018 10;21(1):32-36. Epub 2018 Jan 10.

Background: Mesoporous nanoparticles have a great potential in targeted therapy approaches due to their ideal properties for encapsulation of various drugs, proteins and also biologically active molecules.

Material And Methods: We used mesoporous hydroxyapatite (HA) nanoparticles as a drug carrier and developed radiolabeled mesoporous HA containing of 2-deoxy-D-glucose (2DG) and Doxorubicin (DOX) with technetium-99m (99mTc) for imaging in in vitro and in vivo studies.

Results: 2DG and DOX in presence of mesoporous HA nanoparticles more reduced the fraction of viable cells in the MDA-MB-231, MCF-7 human and MC4-L2 Balb/c mice breast cancer cells. The radiochemical purity of the nano-2DG-DOX complex with 99mTc was calculated to 96.8%. The results of cellular uptake showed a 44.77% increase in uptake of the [99mTc]-nano-2DG-DOX compared to the complex without nanoparticles (p < 0.001).

Conclusion: Radioisotopic imaging demonstrated a high biochemical stability for [99mTc]-nano-2DG-DOX complex. The results demonstrated that [99mTc]-nano-2DG-DOX, may be used as an attractive candidate in cancer imaging and treatment managing.
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http://dx.doi.org/10.5603/NMR.a2018.0008DOI Listing
September 2018

Selenium effect on oxidative stress factors in septic rats.

Adv Pharm Bull 2014 7;4(3):289-93. Epub 2014 Feb 7.

Student Research Committee, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.

Purpose: Severe oxidative stress is an important event that occurs in patients with sepsis. The body has extensive and multiple defense mechanisms against the reactive oxygen species (ROS) produced during inflammation and sepsis. One of these mechanisms includes a group of enzymes that utilize selenium as their cofactor. The purpose of this study is investigating of Selenium effect on oxidative stress factors in animal model of sepsis.

Methods: Sepsis was induced by caecal ligation and puncture (CLP) method. 30 Male Wistar rats were divided into following groups: sham group; CLP group; 100 μg/kg Selenium- treated CLP group. 12 hours after inducing sepsis animals were killed and lungs were removed. One of the lungs was frozen in liquid nitrogen and kept at -70°C for enzymatic activity analysis and the other was kept in formalin 10% until tissue section preparation performed for histopathological studies.

Results: The Myeloperoxidase (MPO) activity was decreased in Selenium- treated CLP group. Inflammation score of lung tissue was lowered in Selenium- treated CLP group, but it wasn't statically significant. Level of glutathione peroxidase (GPx) was higher in CLP and Selenium- treated CLP groups.

Conclusion: It seems that Selenium has protective effect on lung inflammation during acute lung injury. Also it may improve some stress oxidative profile during CLP model of sepsis.
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http://dx.doi.org/10.5681/apb.2014.042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3992966PMC
April 2014

Testosterone replacement attenuates haloperidol-induced catalepsy in male rats.

Adv Pharm Bull 2014 7;4(3):237-41. Epub 2014 Feb 7.

Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Purpose: Parkinson's disease (PD) is a progressive neurodegenerative disease. Recent studies have indicated a higher prevalence of PD in male gender. Furthermore testosterone deficiency is more common among male parkinsonians in compare to healthy men. This study was aimed to investigate the effect of testosterone on catalepsy, in male rats.

Methods: The study carried out on male Wistar rats. To induce catalepsy, haloperidol (1 mg/kg, i.p) as D2 antagonist was administered before testing animals via Bar test. Animals were gonadectomized to investigate testosterone elimination effect on catalepsy, and also the androgen receptor blocker, flutamide, and the aromatase inhibitor, letrozole, were administered in certain groups of animals. The bar test method was used to evaluate haloperidol-induced catalepsy.

Results: Haloperidol 1 mg/kg, i.p, was able to induce catalepsy. Gonadectomy worsened the catalepsy and subchronic testosterone replacement could restore this effect to the level of normal animals. While low dose of flutamide administration represented an improvement in cataleptic symptoms, higher doses worsened catalepsy. Letrozole(4mg/kg,sc) administered animals represented nearly the same cataleptic symptoms as the control group.

Conclusion: Testosterone deficiency increases catalepsy and testosterone replacement can significantly be effective in catalepsy remission. It seems that the anticataleptic effect of testosterone is exerted through affecting on androgenic receptors.
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http://dx.doi.org/10.5681/apb.2014.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3992958PMC
April 2014

Neonatal NMDA receptor blockade alters anxiety- and depression-related behaviors in a sex-dependent manner in mice.

Neuropharmacology 2013 Oct 17;73:87-97. Epub 2013 May 17.

Department of Physiology, Faculty of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.

There is increasing evidence that N-methyl-D-aspartate (NMDA) receptor blockade in the neonatal period has a long-lasting influence on brain and behavior development and has been linked to an increased risk for neuropsychiatric disorders in later life. We sought to determine whether postnatal NMDA receptor blockade can affect normal development of body weight, corticosterone levels, anxiety- and depression-related behaviors in male and female mice in adulthood. For this purpose, male and female NMRI mice were treated with either saline or phencyclidine (PCP; 5 and 10 mg/kg, s.c.) on postnatal days (PND) 7, 9, and 11, and then subjected to different behavioral tests, including open field, elevated plus-maze, elevated zero-maze, light-dark box, tail suspension test and forced swimming test in adulthood. The results indicated that neonatal PCP treatment reduced body weight during neonatal and adulthood periods, and did not alter baseline corticosterone levels in both male and female mice. Moreover, this study obtained some experimental evidence showing the PCP at dose of 10 mg/kg increases stress-induced corticosterone levels, anxiety- and depression-related behaviors in males, while decreasing levels of anxiety without any significant effect on depression in female mice in adulthood. These data support the argument that neonatal NMDA receptor blockade can lead to behavioral abnormalities and psychiatric diseases in adulthood. Collectively, our findings suggest that neonatal exposure to PCP may have profound effects on the development of anxiety- and depression-related behaviors in a sex- and dose-dependent manner in mice.
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http://dx.doi.org/10.1016/j.neuropharm.2013.04.056DOI Listing
October 2013

Impacts of early intervention with fluoxetine following early neonatal immune activation on depression-like behaviors and body weight in mice.

Prog Neuropsychopharmacol Biol Psychiatry 2013 Jun 25;43:55-65. Epub 2012 Dec 25.

Laboratory of Immunology, Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Several reports have suggested that early neonatal immune activation adversely influences the hypothalamic-pituitary-adrenal (HPA) axis development in humans and animal models. In addition, there have been several studies indicating that early intervention with fluoxetine (FLX) can alter HPA axis development and function, and prevent occurrence of behavioral abnormalities induced by common early-life insults. The present study aims to investigate the effects of early intervention with FLX following early neonatal immune activation on depression-like behaviors and body weight in mice. Neonatal mice in their postnatal days (PNDs) 3 and 5 received either lipopolysaccharide (LPS; 50 μg/kg, s.c.) or saline treatment, then male and female mice of both neonatal intervention groups received oral administration of FLX (5 and 10 mg/kg/day) or water via regular drinking bottles during the periadolescent period (PNDs 35-65). The results showed that neonatal LPS exposure elevated depression-like behaviors accompanied by increasing corticosterone levels in adulthood and decreasing body weight during neonatal and adolescent periods. Furthermore, the periadolescent FLX treatment inhibited the depression-like behaviors induced by neonatal infection in both sexes. This study obtained some experimental evidence indicating the potential adverse impacts of the FLX on normal behavioral development in male control animals. In conclusion, our findings suggest that an early pharmacological intervention with FLX may prevent emergence of depression-like behaviors induced by neonatal immune challenge without any detrimental effect on health in a sex- and dose-dependent manner in mice.
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http://dx.doi.org/10.1016/j.pnpbp.2012.12.003DOI Listing
June 2013