Microglia, a type of macrophage, which act as the immune surveillance cells in the brain, express a unique set of genes to be termed the ‘microglial sensome’. That’s according to a new paper on healthy adult and aged mice from the Massachusetts General Hospital Centre for Immunology and Inflammatory Diseases and Division of Infectious Diseases just published online in Nature Neuroscience. Microglia scan the brain environment and respond to invading pathogens, toxins and cellular debris.
This exciting study represents the first gene expression 'snapshot' of any mammalian brain cell and it intriguingly suggests that with aging, expression of genes with potentially neural-destructive products was down-regulated while the expression of neuroprotective genes, for example those involved in microbe recognition and host defence, were up-regulated. This is in contrast to previous studies suggesting that neurotoxicity increases with age. The study’s authors suggest that the divergence in results is due to previous studies not looking the cells' full expression profile. Also, studies were often done in cultured cells rather than in vivo in animals.
The research group employed a novel direct RNA sequencing technique in the study, without amplification or cDNA synthesis. Findings were by fluorescence dual in situ hybridization, unbiased proteomic analysis and quantitative PCR.
This work establishing the ‘microglial sensome’ under normal conditions opens the way for further studies on the situation under pathological conditions. Two of the genes identified in the study have been linked to increased risk of Alzheimer’s disease and it is known that microglia become more neurotoxic as Alzheimer's disease and other neurodegenerative disorders progress. The group hope to extend their work to the ‘microglial sensome’ in humans and identify how it changes in central nervous system disorders, with the eventual aim of therapeutic pharmacological manipulation.
Sources
HICKMAN, S.E.., KINGERY, N.D., OHSUMI, T.K., BOROWSKY, M.L., WANG, L.-C., MEANS, T.K. and EL KHOURY, J., 2013. The microglial sensome revealed by direct RNA sequencing. Nature Neuroscience, 2013; DOI: 10.1038/nn.3554
Massachusetts General Hospital. "Genes uniquely expressed by brain's immune cells." ScienceDaily, 14 Nov. 2013. [Accessed 15 Nov. 2013].
This exciting study represents the first gene expression 'snapshot' of any mammalian brain cell and it intriguingly suggests that with aging, expression of genes with potentially neural-destructive products was down-regulated while the expression of neuroprotective genes, for example those involved in microbe recognition and host defence, were up-regulated. This is in contrast to previous studies suggesting that neurotoxicity increases with age. The study’s authors suggest that the divergence in results is due to previous studies not looking the cells' full expression profile. Also, studies were often done in cultured cells rather than in vivo in animals.
The research group employed a novel direct RNA sequencing technique in the study, without amplification or cDNA synthesis. Findings were by fluorescence dual in situ hybridization, unbiased proteomic analysis and quantitative PCR.
This work establishing the ‘microglial sensome’ under normal conditions opens the way for further studies on the situation under pathological conditions. Two of the genes identified in the study have been linked to increased risk of Alzheimer’s disease and it is known that microglia become more neurotoxic as Alzheimer's disease and other neurodegenerative disorders progress. The group hope to extend their work to the ‘microglial sensome’ in humans and identify how it changes in central nervous system disorders, with the eventual aim of therapeutic pharmacological manipulation.
Sources
HICKMAN, S.E.., KINGERY, N.D., OHSUMI, T.K., BOROWSKY, M.L., WANG, L.-C., MEANS, T.K. and EL KHOURY, J., 2013. The microglial sensome revealed by direct RNA sequencing. Nature Neuroscience, 2013; DOI: 10.1038/nn.3554
Massachusetts General Hospital. "Genes uniquely expressed by brain's immune cells." ScienceDaily, 14 Nov. 2013. [Accessed 15 Nov. 2013].
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