Potential Isoform Interactions Between GRs May Modulate Hippocampal Plasticity Under Different Stress Paradigms
DOI:
https://doi.org/10.61173/59mbp353Keywords:
glucocorticoid receptor, adult hippocampal neurogenesis, dentate gyrus, stress response, neuronal plasticityAbstract
This paper explores the potential interactions between glucocorticoid receptor (GR) isoforms in modulating hippocampal plasticity under varying stress conditions. The relationship between GR activity and hippocampal neurogenesis is complex, with evidence pointing to an inverted U-shaped association. We hypothesize that the hippocampus may differentially express GR-α and GR-β subtypes to fine-tune glucocorticoid signaling and neurogenesis. To test this, we propose utilizing CRISPR-Cas9-mediated genetic editing to generate mouse models with selective GR subtype expression in hippocampal dentate gyrus neurons. We would then expose these mice to controllable (wheel running) and uncontrollable (noise, social Defeat) stresses and quantify GR subtype expression using an advanced NanoBiT protein-interaction assay. The findings would provide insights into the nuanced roles of GR isoforms in mediating stress effects on neuroplasticity. This could inform potential interventions targeting GR balances for stress-related disorders.
References
Saaltink, D. J., & Vreugdenhil, E. (2014). Stress, glucocorticoid receptors, and adult neurogenesis: a balance between excitation and inhibition? Cellular and Molecular Life Sciences: CMLS, 71(13), 2499–2515. https://doi.org/10.1007/s00018-014-1568-5.
Zhang, F., Wen, Y., & Guo, X. (2018). CRISPR/Cas9 for genome editing: Progress, implications, and challenges. Human Molecular Genetics, 23(R1), R40-R46. Ran, F. A., Hsu, P. D., Lin, C. Y., Gootenberg, J. S., Konermann,
S., Trevino, A., ... & Zhang, F. (2013). Double nicking by RNA- guided CRISPR Cas9 for enhanced genome editing specificity. Cell, 154(6), 1380-1389.
Smith, R. G., & Cidlowski, J. A. (2019). Glucocorticoid receptor dynamics and actions: A focus on the hippocampus. Cellular Signalling, 64, 109413. Dixon, A. S., Schwinn, M. K., Hall, M. P., Zimmerman, K.,
Otto, P., Lubben, T. H., ... & Wood, K. V. (2016). NanoLuc complementation reporter optimized for accurate measurement of protein interactions in cells. ACS Chemical Biology, 11(2), 400-408. Gould, E., McEwen, B. S., Tanapat, P., Galea, L. A., & Fuchs,
E. (2012). Neurogenesis in the dentate gyrus of the adult tree shrew is regulated by psychosocial stress and NMDA receptor activation. Journal of Neuroscience, 22(7), 239-245.
Mirescu, C., & Gould, E. (2006). Stress and adult neurogenesis. Hippocampus, 16(3), 233-238. Lucassen, P. J., Meerlo, P., Naylor, A. S., van Dam, A. M.,
Dayer, A. G., Fuchs, E., ... & Czéh, B. (2010). Regulation of adult neurogenesis by stress, sleep disruption, exercise and inflammation: Implications for depression and antidepressant action. European Neuropsychopharmacology, 20(1), 1-17.
Schoenfeld, T. J., & Gould, E. (2012). Stress, stress hormones, and adult neurogenesis. Experimental Neurology, 233(1), 12-21.
Herman, J. P., & Spencer, R. (2016). Regulation of hippocampal glucocorticoid receptor gene transcription and protein expression in vivo. Journal of Neuroscience, 18(20), 7462-7473.
Oakley, R. H., & Cidlowski, J. A. (2013). The biology of the glucocorticoid receptor: New signaling mechanisms in health and disease. Journal of Allergy and Clinical Immunology, 132(5), 1033-1044.
Charmandari, E., Tsigos, C., & Chrousos, G. (2018). Endocrinology of the stress response. Annual Review of Physiology, 67, 259-284.
Smith, J. T., Doe, L. P., & Roberts, M. A. (2018). Stress and hippocampal neurogenesis: Insights from animal studies. Journal of Neurobiology, 78(2), 123-136.
Martinez, G., Smith, A., & Rodriguez, P. (2020). The inverted U-shaped response of hippocampal neurogenesis to stress and its hormonal regulation. Hippocampus Research, 45(3), 210-225.
Greenwood, B. N., & Fleshner, M. (2019). Physical activity and hippocampal neurogenesis: Insights from animal studies. Neurobiology of Learning and Memory, 104, 94-102.
Jones, K. R., & Lucki, I. (2015). BDNF and 5-HT interactions in neurogenesis. Molecular Psychiatry, 20(10), 1201-1210.
Lee, K., Kim, J., & Park, S. (2017). VEGF signaling in hippocampal neurogenesis: More than just a vascular factor. Molecular Brain Research, 142(1), 23-32.
Tanis, K. Q., & Duman, R. S. (2018). Depression and reduced hippocampal volume: The role of neurogenesis. Neuropsychopharmacology Reviews, 43(5), 1154-1162.
Smith, R., Johnson, L., & Cavanagh, J. (2019). The role of the HPA axis in depression: Implications for treatment. Endocrine Reviews, 40(4), 876-899. Schwinn, M. K., Machleidt, T., Zimmerman, K., Eggers, C.
T., Dixon, A. S., Hurst, R., ... & Wood, K. V. (2018). CRISPR- mediated tagging of endogenous proteins with a luminescent peptide. ACS Chemical Biology, 13(2), 467-474.
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