SEX DIFFERENCES IN THE RESPONSE OF PRIMARY ASTROCYTES TO AN INFLAMMATORY CHALLENGE

SANTOS-GALINDO M; ACAZ-FONSECA E; BELLINI MJ; GARCIA-SEGURA LM

Salamanca

Congreso; XIV Congreso Nacional de la Sociedad Española de Neurociencia SENC; 2011

Sociedad Española de Neurociencias

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 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 testosterone propionate or vehicle. Cultures were treated for 5 h with medium containing lipopolysaccharide or with control medium. The mRNA levels of interlerukin 6 (IL6), interferon-inducible protein 10 (IP10), tumor necrosis factor α (TNFα), interleukin 1β (IL1β), 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, TNFα and IL1β after lipopolysaccharide treatment were significantly higher in astrocytes derived from male or androgenized females that in astrocytes derived from control or vehicle injected females. In contrast, IP10 mRNA levels after lipopolysaccharide 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 lipopolysaccharide was neither due to differences in the basal expression of the inflammatory molecules nor to differences in the expression of the lipopolysaccharide 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 lipopolysaccharide. Conclusions: Male and female cortical astrocytes respond differentially to an inflammatory challenge and this may be predetermined by perinatal testosterone exposure.