Expanding our understanding of (mal)adapted stress physiology in psychiatric disorders: achieving single-cell characterisation of steroids and neuropeptides
Steroid hormones and neurosteroids (collectively neuroactive steroids), alongside neuropeptides, are key modulators of the central nervous system. These signalling molecules integrate environmental cues into neurobiological responses by regulating gene and protein expression in a cell-type-specific...
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Elsevier
2025-07-01
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| Series: | Neurobiology of Stress |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352289525000335 |
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| author | Katrina Z. Edmond Natalie Matosin |
| author_facet | Katrina Z. Edmond Natalie Matosin |
| author_sort | Katrina Z. Edmond |
| collection | DOAJ |
| description | Steroid hormones and neurosteroids (collectively neuroactive steroids), alongside neuropeptides, are key modulators of the central nervous system. These signalling molecules integrate environmental cues into neurobiological responses by regulating gene and protein expression in a cell-type-specific manner. Specifically, neuroactive steroids and neuropeptides modulate the hypothalamic-pituitary-adrenal axis to influence excitatory/inhibitory balance in the brain and broadly impact mood, cognition, and memory. Despite their central role in brain function, these signalling systems remain historically understudied, exposing a major gap in our understanding of stress-related psychiatric disorders, and posing a valuable opportunity for therapeutic innovation. Foundational studies using histology, genetic manipulation, and bulk transcriptomic approaches, primarily in rodent models, have provided critical insights into their roles. However, these traditional methods lack the resolution to capture region- and cell-specific mechanisms, which are needed to develop precision medicine approaches. The emergence of single-cell and spatial technologies now offers unprecedented insight into the precise cellular, molecular and spatial context in which neuroactive steroid and neuropeptide signalling occurs. By moving beyond cell-type-averaged measures, these tools enable detailed mapping of transcriptional and proteomic changes across specific brain areas and cell-types, helping to identify the microenvironments in which these systems become dysregulated. This review synthesises current knowledge of neuroactive steroids and neuropeptides in stress biology and psychiatric illness and discusses how cutting-edge molecular profiling technologies are beginning to transform our ability to study, and therapeutically target, this complex and dynamic neuroendocrine network. |
| format | Article |
| id | doaj-art-427d767b9fa948e68ef4c5cb70b63461 |
| institution | Kabale University |
| issn | 2352-2895 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Stress |
| spelling | doaj-art-427d767b9fa948e68ef4c5cb70b634612025-08-20T03:31:37ZengElsevierNeurobiology of Stress2352-28952025-07-013710073910.1016/j.ynstr.2025.100739Expanding our understanding of (mal)adapted stress physiology in psychiatric disorders: achieving single-cell characterisation of steroids and neuropeptidesKatrina Z. Edmond0Natalie Matosin1School of Medical Sciences, The University of Sydney, NSW, 2050, Australia; Charles Perkins Centre, The University of Sydney, NSW, 2050, Australia; Molecular Horizons, School of Science, Faculty of Science, Medicine and Health, University of Wollongong, Northfields Ave, Wollongong, 2522, AustraliaSchool of Medical Sciences, The University of Sydney, NSW, 2050, Australia; Charles Perkins Centre, The University of Sydney, NSW, 2050, Australia; Molecular Horizons, School of Science, Faculty of Science, Medicine and Health, University of Wollongong, Northfields Ave, Wollongong, 2522, Australia; Corresponding author. School of Medical Sciences, The University of Sydney, NSW, 2050, Australia.Steroid hormones and neurosteroids (collectively neuroactive steroids), alongside neuropeptides, are key modulators of the central nervous system. These signalling molecules integrate environmental cues into neurobiological responses by regulating gene and protein expression in a cell-type-specific manner. Specifically, neuroactive steroids and neuropeptides modulate the hypothalamic-pituitary-adrenal axis to influence excitatory/inhibitory balance in the brain and broadly impact mood, cognition, and memory. Despite their central role in brain function, these signalling systems remain historically understudied, exposing a major gap in our understanding of stress-related psychiatric disorders, and posing a valuable opportunity for therapeutic innovation. Foundational studies using histology, genetic manipulation, and bulk transcriptomic approaches, primarily in rodent models, have provided critical insights into their roles. However, these traditional methods lack the resolution to capture region- and cell-specific mechanisms, which are needed to develop precision medicine approaches. The emergence of single-cell and spatial technologies now offers unprecedented insight into the precise cellular, molecular and spatial context in which neuroactive steroid and neuropeptide signalling occurs. By moving beyond cell-type-averaged measures, these tools enable detailed mapping of transcriptional and proteomic changes across specific brain areas and cell-types, helping to identify the microenvironments in which these systems become dysregulated. This review synthesises current knowledge of neuroactive steroids and neuropeptides in stress biology and psychiatric illness and discusses how cutting-edge molecular profiling technologies are beginning to transform our ability to study, and therapeutically target, this complex and dynamic neuroendocrine network.http://www.sciencedirect.com/science/article/pii/S2352289525000335Psychological stressPsychiatric disordersNeurosteroidNeuropeptideSpatial analysisSingle-cell |
| spellingShingle | Katrina Z. Edmond Natalie Matosin Expanding our understanding of (mal)adapted stress physiology in psychiatric disorders: achieving single-cell characterisation of steroids and neuropeptides Neurobiology of Stress Psychological stress Psychiatric disorders Neurosteroid Neuropeptide Spatial analysis Single-cell |
| title | Expanding our understanding of (mal)adapted stress physiology in psychiatric disorders: achieving single-cell characterisation of steroids and neuropeptides |
| title_full | Expanding our understanding of (mal)adapted stress physiology in psychiatric disorders: achieving single-cell characterisation of steroids and neuropeptides |
| title_fullStr | Expanding our understanding of (mal)adapted stress physiology in psychiatric disorders: achieving single-cell characterisation of steroids and neuropeptides |
| title_full_unstemmed | Expanding our understanding of (mal)adapted stress physiology in psychiatric disorders: achieving single-cell characterisation of steroids and neuropeptides |
| title_short | Expanding our understanding of (mal)adapted stress physiology in psychiatric disorders: achieving single-cell characterisation of steroids and neuropeptides |
| title_sort | expanding our understanding of mal adapted stress physiology in psychiatric disorders achieving single cell characterisation of steroids and neuropeptides |
| topic | Psychological stress Psychiatric disorders Neurosteroid Neuropeptide Spatial analysis Single-cell |
| url | http://www.sciencedirect.com/science/article/pii/S2352289525000335 |
| work_keys_str_mv | AT katrinazedmond expandingourunderstandingofmaladaptedstressphysiologyinpsychiatricdisordersachievingsinglecellcharacterisationofsteroidsandneuropeptides AT nataliematosin expandingourunderstandingofmaladaptedstressphysiologyinpsychiatricdisordersachievingsinglecellcharacterisationofsteroidsandneuropeptides |