Front cover:
A central problem in neurotoxicology is detecting the unpredictable damage to specific cells in select brain regions. However, the accompanying astrogliosis, indicated by increased expression of glial fibrillary acidic protein (GFAP), can mark the areas of the brain that are damaged by toxicant exposure. Unfortunately, there are not many biomarkers of astrogliosis. Aldehyde dehydrogenase 1 family member L1 bacterial artificial chromosome, translating ribosome affinity purification (ALDH1L1 bacTRAP) transgenic mice provide the opportunity to selectively measure transcriptional changes in astrocytes in response to exposures or conditions, in vivo. In this study, we evaluated the use of ALDH1L1 bacTRAP mice in neurotoxicology research and used these transgenic mice to identify novel biomarkers of toxicant‐induced astrogliosis that are useful across different neurotoxic exposures. Our analyses identified TIMP1 and miR‐147 as potential markers of astrogliosis that were validated using both MPTP and trimethyl tin (TMT) exposures. Overall, we demonstrated that the ALDH1L1 bacTRAP transgenic mice provide a useful, in vivo tool for the discovery of astrogliosis biomarkers and the genes identified here, as well as those that may be identified in the future, may serve as targets for intervention in treating or preventing neurotoxic damage.
Image content: The image shows that native ALDH1L1 protein (green) colocalizes with GFAP‐positive astrocytes (red) in the hippocampus of adult male Long‐Evans rats 72 hours after exposure to TMT (8 mg/kg, i.p.), confirming that ALDH1L1‐driven bacTRAP transgene expression is astrocyte‐specific and unaffected by neurotoxicant exposure.
Read the full article ‘Astrocyte‐specific transcriptome analysis using the ALDH1L1 bacTRAP mouse reveals novel biomarkers of astrogliosis in response to neurotoxicity’ by L. T. Michalovicz, K. A. Kelly, S. Vashishtha, R. Ben‐Hamo, S. Efroni, J. V. Miller, A. R. Locker, K. Sullivan, G. Broderick, D. B. Miller, J. P. O’Callaghan (J. Neurochem. 2019, vol. 150 (4), pp. 420–440) on doi: 10.1111/jnc.14800