INVESTIGADORES
BELLINI Maria Jose
artículos
Título:
Sex differences in the inflammatory response of primary astrocytes to lipopolysaccharide
Autor/es:
SANTOS-GALINDO M; ACAZ-FONSECA E; BELLINI MJ; GARCIA-SEGURA LM
Revista:
Biology of sex differences
Editorial:
BioMed Central
Referencias:
Lugar: Londres; Año: 2011 p. 2 - 7
ISSN:
2042-6410
Resumen:
Abstract
Background: Numerous neurological and psychiatric disorders show sex differences in incidence, age of onset,
symptomatology or outcome. Astrocytes, one of the glial cell types of the brain, show sex differences in number,
differentiation and function. Since astrocytes are involved in the response of neural tissue to injury and
inflammation, these cells may participate in the generation of sex differences in the response of the brain to
pathological insults. To explore this hypothesis, we have examined whether male and female astrocytes show a
different response to an inflammatory challenge and whether perinatal testosterone influences this response.
Methods: Cortical astrocyte cultures were prepared from postnatal day 1 (one day after birth) male or female CD1
mice pups. In addition, cortical astrocyte cultures were also prepared from female pups that were injected at birth
with 100 μg of testosterone propionate or vehicle. Cultures were treated for 5 hours with medium containing
lipopolysaccharide (LPS) or with control medium. The mRNA levels of IL6, interferon-inducible protein 10 (IP10),
TNFa, IL1b, Toll-like receptor 4 (TLR4), steroidogenic acute regulatory protein and translocator protein were
assessed by quantitative real-time polymerase chain reaction. Statistical significance was assessed by unpaired t-test
or by one-way analysis of variance followed by the Tukey post hoc test.
Results: The mRNA levels of IL6, TNFa and IL1b after LPS treatment were significantly higher in astrocytes derived
from male or androgenized females compared to astrocytes derived from control or vehicle-injected females. In
contrast, IP10 mRNA levels after LPS treatment were higher in astrocytes derived from control or vehicle-injected
females than in those obtained from males or androgenized females. The different response of male and female
astrocytes to LPS was due neither to differences in the basal expression of the inflammatory molecules nor to
differences in the expression of the LPS receptor TLR4. In contrast, the different inflammatory response was
associated with increased mRNA levels of translocator protein, a key steroidogenic regulator, in female astrocytes
that were treated with LPS.
Conclusions: Male and female cortical astrocytes respond differentially to an inflammatory challenge and this may
be predetermined by perinatal testosterone exposure.