Background: It is well known that alterations in astrocytes occur in Alzheimer’s disease and
reactive astrogliosis is one of the hallmarks of the disease. Recently, data has emerged that suggests that
alterations in astrocytes may also occur early in the pathogenesis of the disease.
Objective: The aim of present work was to characterize the transcriptional alterations occurring in cultured
astrocytes from 3xTg-AD mouse pups compared to control non-transgenic mice. Furthermore, we
also compared these changes to those reported by others in astrocytes from symptomatic AD mice.
Method: We conducted a whole-genome microarray study on primary cultured astrocytes from the hippocampus
of 3xTg-AD and non-transgenic mouse newborn pups. We used cross-platform normalization
and an unsupervised hierarchical clustering algorithm to compare our results with other datasets of
cultured or freshly isolated astrocytes, including those isolated from plaque-stage APPswe/PS1dE9 AD
Results: We found a set of 993 genes differentially expressed in 3xTg-AD as compared with non-Tg
astrocytes. Over-represented gene ontology terms were related to calcium, cell-cell communication,
mitochondria, transcription, nucleotide binding and phosphorylation. Of note, no genes related to inflammation
were found in cultured 3xTg-AD astrocytes. Comparison with astrocytes isolated from
plaque stage APPswe/PS1dE9 showed that 882 out of 993 genes were selectively changed in primary
3xTg-AD astrocytes while 50 genes were co-regulated and 61 were anti-regulated (regulated in the opposite
direction in the datasets).
Conclusion: Our data show that in cultured astrocytes from an AD mouse model, transcriptional
changes occur and are different from those reported in models mimicking later stages of the disease.