scholarly journals CCL2/CCR2 system in neuroepithelial radial glia progenitor cells: Involvement in stimulatory, sexually dimorphic effects of maternal ethanol on embryonic development of hypothalamic peptide neurons

2020 ◽  
Author(s):  
Guo-Qing Chang ◽  
Olga Karatayev ◽  
Devi Sai Sri Kavya Boo ◽  
Sarah F. Leibowitz
Keyword(s):  
Progenitor Cells ◽  
Animal Studies ◽  
Radial Glia ◽  
Drinking Behavior ◽  
Primary Source ◽  
Ethanol Exposure ◽  
Ethanol Administration ◽  
Sexually Dimorphic ◽  
Pregnant Rats ◽  
Ccr2 Antagonist

Abstract Background: Clinical and animal studies show that alcohol consumption during pregnancy produces lasting behavioral disturbances in offspring, including increased alcohol drinking, which are linked to inflammation in the brain and disturbances in neurochemical systems that promote these behaviors. These include the neuropeptide, melanin-concentrating hormone (MCH), which is mostly expressed in the lateral hypothalamus (LH). Maternal ethanol administration at low-to-moderate doses, while stimulating MCH neurons without affecting apoptosis or gliogenesis, increases in LH the density of neurons expressing the inflammatory chemokine C-C motif ligand 2 (CCL2) and its receptor CCR2 and their colocalization with MCH. These neural effects associated with behavioral changes are reproduced by maternal CCL2 administration, reversed by a CCR2 antagonist, and consistently stronger in females than males. The present study investigates in the embryo the developmental origins of this CCL2/CCR2-mediated stimulatory effect of maternal ethanol exposure on MCH neurons.Methods: Pregnant rats from embryonic day 10 (E10) to E15 during peak neurogenesis were orally administered ethanol at a moderate dose (2 g/kg/day) or peripherally injected with CCL2 or CCR2 antagonist to test this neuroimmune system’s role in ethanol’s actions. Using real-time quantitative PCR, immunofluorescence histochemistry, in situ hybridization, and confocal microscopy, we examined in embryos at E19 the CCL2/CCR2 system and MCH neurons in relation to radial glia progenitor cells in the hypothalamic neuroepithelium where neurons are born and radial glia processes projecting laterally through the medial hypothalamus that provide scaffolds for neuronal migration into LH. Results: We demonstrate that maternal ethanol increases radial glia cell density and their processes while stimulating the CCL2/CCR2 system and these effects are mimicked by maternal administration of CCL2 and blocked by a CCR2 antagonist. While stimulating CCL2 colocalization with radial glia and neurons but not microglia, ethanol increases MCH neuronal number near radial glia cells and making contact along their processes projecting into LH. Further tests identify the CCL2/CCR2 system in NEP as a primary source of ethanol’s sexually dimorphic actions.Conclusions: These findings provide new evidence for how an inflammatory chemokine pathway functions within neuroprogenitor cells to mediate ethanol’s long-lasting, stimulatory effects on peptide neurons linked to adolescent drinking behavior.

scholarly journals CCL2/CCR2 system in neuroepithelial radial glia progenitor cells: Involvement in stimulatory, sexually dimorphic effects of maternal ethanol on embryonic development of hypothalamic peptide neurons

2019 ◽  
Author(s):  
Guo-Qing Chang ◽  
Olga Karatayev ◽  
Devi Sai Sri Kavya Boo ◽  
Sarah F. Leibowitz
Keyword(s):  
Progenitor Cells ◽  
Animal Studies ◽  
Radial Glia ◽  
Drinking Behavior ◽  
Primary Source ◽  
Ethanol Exposure ◽  
Ethanol Administration ◽  
Sexually Dimorphic ◽  
Pregnant Rats ◽  
Ccr2 Antagonist

Abstract Background: Clinical and animal studies show that alcohol consumption during pregnancy produces lasting behavioral disturbances in offspring, including increased alcohol drinking, which are linked to inflammation in the brain and disturbances in neurochemical systems that promote these behaviors. These include the neuropeptide, melanin-concentrating hormone (MCH), which is mostly expressed in the lateral hypothalamus (LH). Maternal ethanol administration at low-to-moderate doses, while stimulating MCH neurons without affecting apoptosis or gliogenesis, increases in LH the density of neurons expressing the inflammatory chemokine C-C motif ligand 2 (CCL2) and its receptor CCR2 and their colocalization with MCH. These neural effects associated with behavioral changes are reproduced by maternal CCL2 administration, reversed by a CCR2 antagonist, and consistently stronger in females than males. The present study investigates in the embryo the developmental origins of this CCL2/CCR2-mediated stimulatory effect of maternal ethanol exposure on MCH neurons. Methods : Pregnant rats from embryonic day 10 (E10) to E15 during peak neurogenesis were orally administered ethanol at a moderate dose (2 g/kg/day) or peripherally injected with CCL2 or CCR2 antagonist to test this neuroimmune system’s role in ethanol’s actions. Using real-time quantitative PCR, immunofluorescence histochemistry, in situ hybridization, and confocal microscopy, we examined in embryos at E19 the CCL2/CCR2 system and MCH neurons in relation to radial glia progenitor cells in the hypothalamic neuroepithelium where neurons are born and radial glia processes projecting laterally through the medial hypothalamus that provide scaffolds for neuronal migration into LH. Results: We demonstrate that maternal ethanol increases radial glia cell density and their processes while stimulating the CCL2/CCR2 system and these effects are mimicked by maternal administration of CCL2 and blocked by a CCR2 antagonist. While stimulating CCL2 colocalization with radial glia and neurons but not microglia, ethanol increases MCH neuronal number near radial glia cells and making contact along their processes projecting into LH. Further tests identify the CCL2/CCR2 system in NEP as a primary source of ethanol’s sexually dimorphic actions. Conclusions: These findings provide new evidence for how an inflammatory chemokine pathway functions within neuroprogenitor cells to mediate ethanol’s long-lasting, stimulatory effects on peptide neurons linked to adolescent drinking behavior.

scholarly journals A Review of Advances in Hematopoietic Stem Cell Mobilization and the Potential Role of Notch2 Blockade

2020 ◽  
Vol 29 ◽  
pp. 096368972094714
Author(s):  
Marwah Albakri ◽  
Hammad Tashkandi ◽  
Lan Zhou
Keyword(s):  
Stem Cell ◽  
Progenitor Cells ◽  
Hematopoietic Stem Cell ◽  
Animal Studies ◽  
Primary Source ◽  
High Yield ◽  
Ligand Interaction ◽  
Hematopoietic Stem ◽  
Cell Mobilization ◽  
Hsc Transplantation

Hematopoietic stem cell (HSC) transplantation can be a potential cure for hematological malignancies and some nonhematologic diseases. Hematopoietic stem and progenitor cells (HSPCs) collected from peripheral blood after mobilization are the primary source to provide HSC transplantation. In most of the cases, mobilization by the cytokine granulocyte colony-stimulating factor with chemotherapy, and in some settings, with the CXC chemokine receptor type 4 antagonist plerixafor, can achieve high yield of hematopoietic progenitor cells (HPCs). However, adequate mobilization is not always successful in a significant portion of donors. Research is going on to find new agents or strategies to increase HSC mobilization. Here, we briefly review the history of HSC transplantation, current mobilization regimens, some of the novel agents that are under investigation for clinical practice, and our recent findings from animal studies regarding Notch and ligand interaction as potential targets for HSPC mobilization.

Early proliferative response of radial glia-like progenitor cells in the dentate gyrus following focal ischemia

2005 ◽  
Vol 32 (S 4) ◽  
Author(s):  
A Kunze ◽  
S Grass ◽  
O.W Witte ◽  
G Kempermann ◽  
C Redecker
Keyword(s):  
Dentate Gyrus ◽  
Progenitor Cells ◽  
Proliferative Response ◽  
Radial Glia ◽  
Focal Ischemia

scholarly journals Long-Term Ethanol Consumption Leadsto Lung Tissue Oxidative Stress and Injury

2010 ◽  
Vol 3 (6) ◽  
pp. 414-420 ◽  
Author(s):  
Subir Kumar Das ◽  
Sukhes Mukherjee
Keyword(s):  
Oxidative Stress ◽  
Body Weight ◽  
Matrix Metalloproteinase ◽  
Lung Tissue ◽  
Ethanol Consumption ◽  
Ethanol Exposure ◽  
Lung Homogenate ◽  
Ethanol Administration ◽  
Metalloproteinase Activity

Background: Alcohol abuse is a systemic disorder. The deleterious health effects of alcohol consumption may result in irreversible organ damage. By contrast, there currently is little evidence for the toxicity of chronic alcohol use on lung tissue. Hence, in this study we investigated long-term effects of ethanol in the lung.Results: Though body weight of rats increased significantly with duration of exposure compared to its initial weight, there was no significant change in relative weight (g/100 g body weight) of lung due to ethanol exposure. The levels of thiobarbituric acid reactive substances (TBARS), nitrite, protein carbonyl, oxidized glutathione (GSS G), redox ratio (GSS G/ GSH ) and GST activity elevated; while reduced glutathione (GSH ) level and activities of glutathione reductase (GR), glutathione peroxidase (GPx), catalase, superoxide dismutase (SOD) and Na+K+ATPase reduced significantly with duration of ethanol exposure in the lung homogenate compared to the control group. Total matrix metalloproteinase activity elevated in the lung homogenate with time of ethanol consumption. Histopathologic examination also demonstrated that severity of lung injury enhanced with duration of ethanol exposure.Methods: 16–18 week-old male albino Wistar strain rats weighing 200–220 g were fed with ethanol (1.6 g/kg body weight/day) up to 36 weeks. At the end of the experimental period, blood samples were collected from reteroorbital plexus to determine blood alcohol concentration and the animals were sacrificed. Various oxidative stress-related biochemical parameters, total matrix metalloproteinase activity and histopathologic examinations of the lung tissues were performed.Conclusions: Results of this study indicate that long-term ethanol administration aggravates systemic and local oxidative stress, which may be associated with lung tissue injury.

Final Report on the Safety Assessment of HC Blue No. 1

1994 ◽  
Vol 13 (5) ◽  
pp. 344-360
Keyword(s):  
Animal Studies ◽  
Current Data ◽  
Female Rats ◽  
Male Rats ◽  
Final Report ◽  
Positive Trend ◽  
Hair Dyes ◽  
Pregnant Rats ◽  
Hepatocellular Carcinomas ◽  
Dose Dependent

The aromatic amine HC Blue No. 1 is a hair colorant intended exclusively for use in hair dyes. While this colorant had previously been used in concentrations up to 1.6%, current information indicates it is not presently used in any hair dyes. Animal studies indicate this ingredient is absorbed slowly through the skin. Short-term and subchronic animal toxicity studies show a dose-dependent reduction in weight gain. HC Blue No. 1 was mutagenic in some, but not all, test systems, and was associated with fetal bone malformations when given orally to pregnant rats at levels that were maternally toxic. In a National Toxicology Program feeding study, dosed male rats had a positive trend in incidence of hepatic neoplastic nodules, but not in hepatic carcinomas; dosed female rats showed a positive trend in the incidence of alveolar/bronchiolar neoplasms; and mice of both sexes showed an increase in hepatocellular carcinomas. Although it is recognized that further dermal carcinogenicity data would help clarify the different findings in the current data, such information is not expected, and it is concluded on the basis of the data that are available in this report that HC Blue No. 1 is unsafe for use in cosmetic formulations (hair dyes).

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