Increased levels of tumour necrosis factor alpha (TNFα) but not transforming growth factor-beta 1 (TGFβ1) are associated with the severity of congenital hydrocephalus in the hyh mouse

Aims Here, we tested the hypothesis that glial responses via the production of cytokines such as transforming growth factor‐beta 1 (TGFβ1) and tumour necrosis factor alpha (TNFα), which play important roles in neurodegenerative diseases, are correlated with the severity of congenital hydrocephalus i...

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Published in:Neuropathology and applied neurobiology 2014-12, Vol.40 (7), p.911-932
Main Authors: Jiménez, Antonio-Jesús, Rodríguez-Pérez, Luis-Manuel, Domínguez-Pinos, María-Dolores, Gómez-Roldán, María-Carmen, García-Bonilla, María, Ho-Plagaro, Ailec, Roales-Buján, Ruth, Jiménez, Sebastián, Roquero-Mañueco, María-Carmen, Martínez-León, María-Isabel, García-Martín, María-Luisa, Cifuentes, Manuel, Ros, Bienvenido, Arráez, Miguel-Ángel, Vitorica, Javier, Gutiérrez, Antonia, Pérez-Fígares, José-Manuel
Format: Article
Language:English
Subjects:
Animals
Astrocytes - metabolism
biomarkers
Brain - metabolism
Brain - pathology
congenital hydrocephalus
Disease Models, Animal
Fetus
Humans
Hydrocephalus - metabolism
Hydrocephalus - pathology
Male
Medical research
Mice
microglia
Microglia - metabolism
reactive astrocyte
RNA, Messenger - metabolism
Rodents
Severity of Illness Index
TGFβ1
TNFα
Transforming Growth Factor beta1 - metabolism
Tumor Necrosis Factor-alpha - metabolism
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Summary:Aims Here, we tested the hypothesis that glial responses via the production of cytokines such as transforming growth factor‐beta 1 (TGFβ1) and tumour necrosis factor alpha (TNFα), which play important roles in neurodegenerative diseases, are correlated with the severity of congenital hydrocephalus in the hyh mouse model. We also searched for evidence of this association in human cases of primary hydrocephalus. Methods Hyh mice, which exhibit either severe or compensated long‐lasting forms of hydrocephalus, were examined and compared with wild‐type mice. TGFβ1, TNFα and TNFαR1 mRNA levels were quantified using real‐time PCR. TNFα and TNFαR1 were immunolocalized in the brain tissues of hyh mice and four hydrocephalic human foetuses relative to astroglial and microglial reactions. Results The TGFβ1 mRNA levels were not significantly different between hyh mice exhibiting severe or compensated hydrocephalus and normal mice. In contrast, severely hydrocephalic mice exhibited four‐ and two‐fold increases in the mean levels of TNFα and TNFαR1, respectively, compared with normal mice. In the hyh mouse, TNFα and TNFαR1 immunoreactivity was preferentially detected in astrocytes that form a particular periventricular reaction characteristic of hydrocephalus. However, these proteins were rarely detected in microglia, which did not appear to be activated. TNFα immunoreactivity was also detected in the glial reaction in the small group of human foetuses exhibiting hydrocephalus that were examined. Conclusions In the hyh mouse model of congenital hydrocephalus, TNFα and TNFαR1 appear to be associated with the severity of the disease, probably mediating the astrocyte reaction, neurodegenerative processes and ischaemia.
ISSN:0305-1846
1365-2990
DOI:10.1111/nan.12115