Cellular senescence is associated with changes in the function and structure of neurons and glia and one consistent finding is an increase in the activation state of microglia identified by increased expression of cell surface markers and increased production of proinflammatory cytokines. In this study, we set out to investigate age-related changes in the expression of two cell surface markers of microglial activity in the cortex of young, middle-aged and aged male Wistar rats and to assess whether these changes were associated with any change in T2 relaxation time as assessed by magnetic resonance imaging (MRI). Young, middle-aged and aged animals were anaesthetized (isofluorane (4% induction, 1.5-2% maintenance) in 100% O2), positioned in a custom-built cradle and placed in 7 Tesla BioSpec animal scanner (Bruker BioSpin, Ettlingen, Germany). T2 relaxation times were obtained from high-resolution scans and at the end of the period of acquisition, animals were transcardially perfused and brain tissue was taken for preparation of cryostat sections and immunohistochemical analysis. Sections were stained for the expression of MHC II (Major Histocompatibility Complex Class II) and CD68 which are two markers of microglial activation. An age-related decrease in T2 relaxation time in the cortex was observed with a significant difference between the values in young and aged rats (p<0.05, ANOVA, n=6). An age-related increase in the expression of MHC II was observed and analysis of staining intensity in cortex identified a significant increase in sections prepared from middle aged and aged rats, compared with young rats (p<0.05, ANOVA, n=4). A significant increase in CD68 immunoreactivity was observed in sections prepared from aged, compared with young, animals (p<0.05, ANOVA, n=4). These data reveal a positive correlation between T2 relaxation time and microglial activation in the cortex of aged rats and identify that some changes in cell surface markers of microglial activation are evident in middle age.
University College Dublin (2009) Proc Physiol Soc 15, C10
Oral Communications: Evidence of an inverse correlation between T2 relaxation time and microglial activation in the cortex of aged rats
R. E. Gonzalez-Reyes1, K. Murphy1, R. Bechara1, C. Blau1, C. Kerskens1, M. Lynch1
1. Trinity College Dublin, Dublin, Ireland.
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