Neuroglobin over Expressing Mice: Expression Pattern and Effect on Brain Ischemic Infarct Size

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2013 Oct 8

PMID 24098534

Citations 21

Authors

Zindy Raida

Christian Ansgar Hundahl

Jens R Nyengaard

Anders Hay-Schmidt

Affiliations

Soon will be listed here.

Abstract

Background: Stroke is a major cause of death and severe disability, but effective treatments are limited. Neuroglobin, a neuronal heme-globin, has been advocated as a novel pharmacological target in combating stroke and neurodegenerative disorders based on cytoprotective properties. Using thoroughly validated antibodies and oligos, we give a detailed brain anatomical characterization of transgenic mice over expressing Neuroglobin. Moreover, using permanent middle artery occlusion the effect of elevated levels of Neuroglobin on ischemic damage was studied. Lastly, the impact of mouse strain genetic background on ischemic damage was investigated.

Principal Findings: A four to five fold increase in Neuroglobin mRNA and protein expression was seen in the brain of transgenic mice. A β-actin promoter was used to drive Neuroglobin over expression, but immunohistochemistry and in situ hybridization showed over expression to be confined to primarily the cortex, hippocampus, cerebellum, and only in neurons. The level and expression pattern of endogenous Neuroglobin was unaffected by insertion of the over expressing Ngb transgene. Neuroglobin over expression resulted in a significant reduction in infarct volume 24 hours after ischemia. Immunohistochemistry showed no selective sparing of Neuroglobin expressing cells in the ischemic core or penumbra. A significant difference in infarct volume was found between mice of the same strain, but from different colonies.

Significance: In contrast to some previous reports, Neuroglobin over expression is not global but confined to a few well-defined brain regions, and only in neurons. This study confirms previous reports showing a correlation between reduced infarct volume and elevated Neuroglobin levels, but underlines the need to study the likely contribution from compensatory mechanisms to the phenotype following a genetic perturbation. We also stress, that care should be taken when comparing results where different mouse strains and colonies have been used due to large genetic background contribution to the observed phenotype.

Citing Articles

Expression of Acidic Fibrillar Protein and Neuroglobin in Thrombolytic Patients in Ischemic Stroke.

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Intravitreal Neuroglobin Mitigates Primate Experimental Glaucomatous Structural Damage in Association with Reduced Optic Nerve Microglial and Complement 3-Astrocyte Activation.

Chan A, Tun S, Lynn M, Ho C, Tun T, Girard M Biomolecules. 2023; 13(6).

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New Strategies for Stroke Therapy: Nanoencapsulated Neuroglobin.

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Neuroglobin deficiency increases seizure susceptibility but does not affect basal behavior in mice.

Gotzsche C, Woldbye D, Hundahl C, Hay-Schmidt A J Neurosci Res. 2022; 100(10):1921-1932.

PMID: 35822521 PMC: 9544565. DOI: 10.1002/jnr.25105.

Probing the Role of Murine Neuroglobin CDloop-D-Helix Unit in CO Ligand Binding and Structural Dynamics.

Exertier C, Sebastiani F, Freda I, Gugole E, Cerutti G, Parisi G ACS Chem Biol. 2022; 17(8):2099-2108.

PMID: 35797699 PMC: 9396615. DOI: 10.1021/acschembio.2c00172.

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