Thyroid hormone remodels cortex to coordinate body-wide metabolism and exploration.

Autor:	Hochbaum DR; Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA; Society of Fellows, Harvard University, Cambridge, MA 02138, USA., Hulshof L; Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA., Urke A; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA., Wang W; Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA., Dubinsky AC; Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA., Farnsworth HC; Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA., Hakim R; Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA., Lin S; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA., Kleinberg G; Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA., Robertson K; Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA., Park C; Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA., Solberg A; Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA., Yang Y; Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA., Baynard C; Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA., Nadaf NM; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Beron CC; Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA., Girasole AE; Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA., Chantranupong L; Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA., Cortopassi MD; Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA., Prouty S; Department of Neurobiology, University of Massachusetts Chan Medical School, Worcester, MA 01655, USA., Geistlinger L; Center for Computational Biomedicine, Harvard Medical School, Boston, MA 02215, USA., Banks AS; Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA., Scanlan TS; Department of Chemical Physiology & Biochemistry, Oregon Health & Science University, Portland, OR 97239, USA., Datta SR; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA., Greenberg ME; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA., Boulting GL; Department of Neurobiology, University of Massachusetts Chan Medical School, Worcester, MA 01655, USA., Macosko EZ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Psychiatry, Massachusetts General Hospital, Boston, MA 02114, USA., Sabatini BL; Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: bernardo_sabatini@hms.harvard.edu.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2024 Oct 03; Vol. 187 (20), pp. 5679-5697.e23. Date of Electronic Publication: 2024 Aug 22.
DOI:	10.1016/j.cell.2024.07.041
Abstrakt:	Animals adapt to environmental conditions by modifying the function of their internal organs, including the brain. To be adaptive, alterations in behavior must be coordinated with the functional state of organs throughout the body. Here, we find that thyroid hormone-a regulator of metabolism in many peripheral organs-directly activates cell-type-specific transcriptional programs in the frontal cortex of adult male mice. These programs are enriched for axon-guidance genes in glutamatergic projection neurons, synaptic regulatory genes in both astrocytes and neurons, and pro-myelination factors in oligodendrocytes, suggesting widespread plasticity of cortical circuits. Indeed, whole-cell electrophysiology revealed that thyroid hormone alters excitatory and inhibitory synaptic transmission, an effect that requires thyroid hormone-induced gene regulatory programs in presynaptic neurons. Furthermore, thyroid hormone action in the frontal cortex regulates innate exploratory behaviors and causally promotes exploratory decision-making. Thus, thyroid hormone acts directly on the cerebral cortex in males to coordinate exploratory behaviors with whole-body metabolic state. Competing Interests: Declaration of interests T.S.S. is an advisor and founder of Autobahn Therapeutics and is an inventor on several patents related to sobetirome and its derivatives. T.S.S. provided the sobetirome used in this study but was not involved in the study design, performing the work described, or in the analysis and presentation of the results. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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