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Neuroadaptations and TGF-β signaling: emerging role in models of neuropsychiatric disorders

Molecular Psychiatry volume 27, pages 296–306 (2022)Cite this article

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Abstract

Neuropsychiatric diseases are manifested by maladaptive behavioral plasticity. Despite the greater understanding of the neuroplasticity underlying behavioral adaptations, pinpointing precise cellular mediators has remained elusive. This has stymied the development of pharmacological interventions to combat these disorders both at the level of progression and relapse. With increased knowledge on the putative role of the transforming growth factor (TGF- β) family of proteins in mediating diverse neuroadaptations, the influence of TGF-β signaling in regulating maladaptive cellular and behavioral plasticity underlying neuropsychiatric disorders is being increasingly elucidated. The current review is focused on what is currently known about the TGF-β signaling in the central nervous system in mediating cellular and behavioral plasticity related to neuropsychiatric manifestations.

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Fig. 1: The TGF-β family of proteins mediates brain region-specific divergent neuroadaptations involving dysregulated ubiquitin proteasomal system, abnormal chromatin remodeling, and altered transcriptional and synaptic mechanisms underlying cocaine-induced plasticity.
Fig. 2: Temporal functionality of TGF-β family of proteins across neural substrates underlying cocaine-induced plasticity.

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Acknowledgements

This work was supported by the National Institutes of Health (NIDA R01DA037257 to DMD, NIDA U01DA051947 to DMD, NIDA R21DA044486 to DMD).

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  1. Department of Pharmacology and Toxicology; Program in Neuroscience, Jacobs School of Medicine and Biomedical Sciences, The State University of New York at Buffalo, Buffalo, NY, USA

    Swarup Mitra, Craig Werner & David M Dietz

  2. National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA

    Craig Werner

  3. Department of Pharmacology and Physiology, Oklahoma State University, Center for Health Sciences, Tulsa, OK, USA

    Craig Werner

  4. Department of Psychology, The State University of New York at Buffalo, Buffalo, NY, USA

    David M Dietz

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Mitra, S., Werner, C. & Dietz, D.M. Neuroadaptations and TGF-β signaling: emerging role in models of neuropsychiatric disorders. Mol Psychiatry 27, 296–306 (2022). https://doi.org/10.1038/s41380-021-01186-y

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