Abstract
Overexpression of suppressor of cytokine signalling 2 (SOCS2) has been shown to promote hippocampal neurogenesis in vivo and promote neurite outgrowth of neurons in vitro. In the adult mouse brain, SOCS2 is most highly expressed in the hippocampal CA3 region and at lower levels in the dentate gyrus, an expression pattern that suggests a role in adult neurogenesis. Herein we examine generation of neuroblasts and their maturation into more mature neurons in SOCS2 null (SOCS2KO) mice. EdU was administered for 7 days to label proliferative neural precursor cells. The number of EdU-labelled doublecortin+ neuroblasts and NeuN+ mature neurons they generated was examined at day 8 and day 35, respectively. While no effect of SOCS2 deletion was observed in neuroblast generation, it reduced the numbers of EdU-labelled mature newborn neurons at 35 days. As SOCS2 regulates neurite outgrowth and dentate granule neurons project to the CA3 region, alterations in dendritic arborisation or spine formation may have correlated with the decreased numbers of EdU-labelled newborn neurons. SOCS2KO mice were crossed with Nes-CreERT2/mTmG mice, in which membrane eGFP is inducibly expressed in neural precursor cells and their progeny, and the dendrite and dendritic spine morphology of newborn neurons were examined at 35 days. SOCS2 deletion had no effect on total dendrite length, number of dendritic segments, number of branch points or total dendritic spine density but increased the number of mature “mushroom” spines. Our results suggest that endogenous SOCS2 regulates numbers of EdU-labelled mature newborn adult hippocampal neurons, possibly by mediating their survival and that this may be via a mechanism regulating dendritic spine maturation.
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Acknowledgments
We thank Dr Clare Faux, University of Melbourne, for performing SOCS2 in situ hybridisations and Dr R. Kageyama, Kyoto University and Dr T. Merson, Florey Institute of Neuroscience and Mental Health for provision of the Nestin-CreERT2 mice. We thank Stem Cells Australia for additional support. Grant sponsor: National Health and Medical Research Council of Australia; Project Grant 1045125 and Fellowship (to AMT) 628344; Stem Cells Australia.
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Basrai, H.S., Turbic, A., Christie, K.J. et al. Suppressor of Cytokine Signalling 2 (SOCS2) Regulates Numbers of Mature Newborn Adult Hippocampal Neurons and Their Dendritic Spine Maturation. Cell Mol Neurobiol 37, 899–909 (2017). https://doi.org/10.1007/s10571-016-0427-3
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DOI: https://doi.org/10.1007/s10571-016-0427-3