Transcriptional and cell type profiles of cortical brain regions showing ultradian cortisol rhythm dependent responses to emotional face stimulation

Philippe C Habets; Konstantinos Kalafatakis; Oleh Dzyubachyk; Steven J A van der Werff; Arlin Keo; Jamini Thakrar; Ahmed Mahfouz; Alberto M Pereira; Georgina M Russell; Stafford L Lightman; Onno C Meijer

doi:10.1016/j.ynstr.2023.100514

Transcriptional and cell type profiles of cortical brain regions showing ultradian cortisol rhythm dependent responses to emotional face stimulation

Philippe C Habets^*, Konstantinos Kalafatakis, Oleh Dzyubachyk, Steven J A van der Werff, Arlin Keo, Jamini Thakrar, Ahmed Mahfouz, Alberto M Pereira^*, Georgina M Russell, Stafford L Lightman, Onno C Meijer

^*Corresponding author for this work

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Abstract

The characteristic endogenous circadian rhythm of plasma glucocorticoid concentrations is made up from an underlying ultradian pulsatile secretory pattern. Recent evidence has indicated that this ultradian cortisol pulsatility is crucial for normal emotional response in man. In this study, we investigate the anatomical transcriptional and cell type signature of brain regions sensitive to a loss of ultradian rhythmicity in the context of emotional processing. We combine human cell type and transcriptomic atlas data of high spatial resolution with functional magnetic resonance imaging (fMRI) data. We show that the loss of cortisol ultradian rhythm alters emotional processing response in cortical brain areas that are characterized by transcriptional and cellular profiles of GABAergic function. We find that two previously identified key components of rapid non-genomic GC signaling - the ANXA1 gene and retrograde endocannabinoid signaling - show most significant differential expression (q = 3.99e-10) and enrichment (fold enrichment = 5.56, q = 9.09e-4). Our results further indicate that specific cell types, including a specific NPY-expressing GABAergic neuronal cell type, and specific G protein signaling cascades underly the cerebral effects of a loss of ultradian cortisol rhythm. Our results provide a biological mechanistic underpinning of our fMRI findings, indicating specific cell types and cascades as a target for manipulation in future experimental studies.

Original language	English
Article number	100514
Journal	Neurobiology of Stress
Volume	22
Early online date	4 Jan 2023
DOIs	https://doi.org/10.1016/j.ynstr.2023.100514
Publication status	Published - 22 Jan 2023

Bibliographical note

Funding Information:
Philippe Habets would like to express his gratitude to Aurina Arnatkevičiūtė for her support and guidance in the field of fMRI transcriptomics, the availability of the MATLAB pipeline for AHBA data, and to the highly insightful and useful work on combining AHBA and imaging data she and others of the Fornito lab have published. Konstantinos Kalafatakis would like to express his gratitude to Bodossaki Foundation (https://www.bodossaki.gr/en/) for supporting the research on modelling biomedical data, especially related to glucocorticoid biorhythmicity. The fMRI data was obtained from studies funded by the Medical Research Council and the Wellcome Trust to Stafford Lightman.

Funding Information:
Philippe Habets would like to express his gratitude to Aurina Arnatkevičiūtė for her support and guidance in the field of fMRI transcriptomics, the availability of the MATLAB pipeline for AHBA data, and to the highly insightful and useful work on combining AHBA and imaging data she and others of the Fornito lab have published. Konstantinos Kalafatakis would like to express his gratitude to Bodossaki Foundation ( https://www.bodossaki.gr/en/ ) for supporting the research on modelling biomedical data, especially related to glucocorticoid biorhythmicity. The fMRI data was obtained from studies funded by the Medical Research Council and the Wellcome Trust to Stafford Lightman.

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© 2023 The Authors

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Habets, P. C., Kalafatakis, K., Dzyubachyk, O., van der Werff, S. J. A., Keo, A., Thakrar, J., Mahfouz, A., Pereira, A. M., Russell, G. M., Lightman, S. L., & Meijer, O. C. (2023). Transcriptional and cell type profiles of cortical brain regions showing ultradian cortisol rhythm dependent responses to emotional face stimulation. Neurobiology of Stress, 22, Article 100514. https://doi.org/10.1016/j.ynstr.2023.100514

@article{add898848c7d493c93cce5b359b55836,

title = "Transcriptional and cell type profiles of cortical brain regions showing ultradian cortisol rhythm dependent responses to emotional face stimulation",

abstract = "The characteristic endogenous circadian rhythm of plasma glucocorticoid concentrations is made up from an underlying ultradian pulsatile secretory pattern. Recent evidence has indicated that this ultradian cortisol pulsatility is crucial for normal emotional response in man. In this study, we investigate the anatomical transcriptional and cell type signature of brain regions sensitive to a loss of ultradian rhythmicity in the context of emotional processing. We combine human cell type and transcriptomic atlas data of high spatial resolution with functional magnetic resonance imaging (fMRI) data. We show that the loss of cortisol ultradian rhythm alters emotional processing response in cortical brain areas that are characterized by transcriptional and cellular profiles of GABAergic function. We find that two previously identified key components of rapid non-genomic GC signaling - the ANXA1 gene and retrograde endocannabinoid signaling - show most significant differential expression (q = 3.99e-10) and enrichment (fold enrichment = 5.56, q = 9.09e-4). Our results further indicate that specific cell types, including a specific NPY-expressing GABAergic neuronal cell type, and specific G protein signaling cascades underly the cerebral effects of a loss of ultradian cortisol rhythm. Our results provide a biological mechanistic underpinning of our fMRI findings, indicating specific cell types and cascades as a target for manipulation in future experimental studies.",

author = "Habets, {Philippe C} and Konstantinos Kalafatakis and Oleh Dzyubachyk and {van der Werff}, {Steven J A} and Arlin Keo and Jamini Thakrar and Ahmed Mahfouz and Pereira, {Alberto M} and Russell, {Georgina M} and Lightman, {Stafford L} and Meijer, {Onno C}",

note = "Funding Information: Philippe Habets would like to express his gratitude to Aurina Arnatkevi{\v c}iūtė for her support and guidance in the field of fMRI transcriptomics, the availability of the MATLAB pipeline for AHBA data, and to the highly insightful and useful work on combining AHBA and imaging data she and others of the Fornito lab have published. Konstantinos Kalafatakis would like to express his gratitude to Bodossaki Foundation (https://www.bodossaki.gr/en/) for supporting the research on modelling biomedical data, especially related to glucocorticoid biorhythmicity. The fMRI data was obtained from studies funded by the Medical Research Council and the Wellcome Trust to Stafford Lightman. Funding Information: Philippe Habets would like to express his gratitude to Aurina Arnatkevi{\v c}iūtė for her support and guidance in the field of fMRI transcriptomics, the availability of the MATLAB pipeline for AHBA data, and to the highly insightful and useful work on combining AHBA and imaging data she and others of the Fornito lab have published. Konstantinos Kalafatakis would like to express his gratitude to Bodossaki Foundation ( https://www.bodossaki.gr/en/ ) for supporting the research on modelling biomedical data, especially related to glucocorticoid biorhythmicity. The fMRI data was obtained from studies funded by the Medical Research Council and the Wellcome Trust to Stafford Lightman. Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

month = jan,

day = "22",

doi = "10.1016/j.ynstr.2023.100514",

language = "English",

volume = "22",

journal = "Neurobiology of Stress",

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Habets, PC, Kalafatakis, K, Dzyubachyk, O, van der Werff, SJA, Keo, A, Thakrar, J, Mahfouz, A, Pereira, AM, Russell, GM , Lightman, SL & Meijer, OC 2023, 'Transcriptional and cell type profiles of cortical brain regions showing ultradian cortisol rhythm dependent responses to emotional face stimulation', Neurobiology of Stress, vol. 22, 100514. https://doi.org/10.1016/j.ynstr.2023.100514

TY - JOUR

T1 - Transcriptional and cell type profiles of cortical brain regions showing ultradian cortisol rhythm dependent responses to emotional face stimulation

AU - Habets, Philippe C

AU - Kalafatakis, Konstantinos

AU - Dzyubachyk, Oleh

AU - van der Werff, Steven J A

AU - Keo, Arlin

AU - Thakrar, Jamini

AU - Mahfouz, Ahmed

AU - Pereira, Alberto M

AU - Russell, Georgina M

AU - Lightman, Stafford L

AU - Meijer, Onno C

N1 - Funding Information: Philippe Habets would like to express his gratitude to Aurina Arnatkevičiūtė for her support and guidance in the field of fMRI transcriptomics, the availability of the MATLAB pipeline for AHBA data, and to the highly insightful and useful work on combining AHBA and imaging data she and others of the Fornito lab have published. Konstantinos Kalafatakis would like to express his gratitude to Bodossaki Foundation (https://www.bodossaki.gr/en/) for supporting the research on modelling biomedical data, especially related to glucocorticoid biorhythmicity. The fMRI data was obtained from studies funded by the Medical Research Council and the Wellcome Trust to Stafford Lightman. Funding Information: Philippe Habets would like to express his gratitude to Aurina Arnatkevičiūtė for her support and guidance in the field of fMRI transcriptomics, the availability of the MATLAB pipeline for AHBA data, and to the highly insightful and useful work on combining AHBA and imaging data she and others of the Fornito lab have published. Konstantinos Kalafatakis would like to express his gratitude to Bodossaki Foundation ( https://www.bodossaki.gr/en/ ) for supporting the research on modelling biomedical data, especially related to glucocorticoid biorhythmicity. The fMRI data was obtained from studies funded by the Medical Research Council and the Wellcome Trust to Stafford Lightman. Publisher Copyright: © 2023 The Authors

PY - 2023/1/22

Y1 - 2023/1/22

N2 - The characteristic endogenous circadian rhythm of plasma glucocorticoid concentrations is made up from an underlying ultradian pulsatile secretory pattern. Recent evidence has indicated that this ultradian cortisol pulsatility is crucial for normal emotional response in man. In this study, we investigate the anatomical transcriptional and cell type signature of brain regions sensitive to a loss of ultradian rhythmicity in the context of emotional processing. We combine human cell type and transcriptomic atlas data of high spatial resolution with functional magnetic resonance imaging (fMRI) data. We show that the loss of cortisol ultradian rhythm alters emotional processing response in cortical brain areas that are characterized by transcriptional and cellular profiles of GABAergic function. We find that two previously identified key components of rapid non-genomic GC signaling - the ANXA1 gene and retrograde endocannabinoid signaling - show most significant differential expression (q = 3.99e-10) and enrichment (fold enrichment = 5.56, q = 9.09e-4). Our results further indicate that specific cell types, including a specific NPY-expressing GABAergic neuronal cell type, and specific G protein signaling cascades underly the cerebral effects of a loss of ultradian cortisol rhythm. Our results provide a biological mechanistic underpinning of our fMRI findings, indicating specific cell types and cascades as a target for manipulation in future experimental studies.

AB - The characteristic endogenous circadian rhythm of plasma glucocorticoid concentrations is made up from an underlying ultradian pulsatile secretory pattern. Recent evidence has indicated that this ultradian cortisol pulsatility is crucial for normal emotional response in man. In this study, we investigate the anatomical transcriptional and cell type signature of brain regions sensitive to a loss of ultradian rhythmicity in the context of emotional processing. We combine human cell type and transcriptomic atlas data of high spatial resolution with functional magnetic resonance imaging (fMRI) data. We show that the loss of cortisol ultradian rhythm alters emotional processing response in cortical brain areas that are characterized by transcriptional and cellular profiles of GABAergic function. We find that two previously identified key components of rapid non-genomic GC signaling - the ANXA1 gene and retrograde endocannabinoid signaling - show most significant differential expression (q = 3.99e-10) and enrichment (fold enrichment = 5.56, q = 9.09e-4). Our results further indicate that specific cell types, including a specific NPY-expressing GABAergic neuronal cell type, and specific G protein signaling cascades underly the cerebral effects of a loss of ultradian cortisol rhythm. Our results provide a biological mechanistic underpinning of our fMRI findings, indicating specific cell types and cascades as a target for manipulation in future experimental studies.

U2 - 10.1016/j.ynstr.2023.100514

DO - 10.1016/j.ynstr.2023.100514

M3 - Article (Academic Journal)

C2 - 36660181

SN - 2352-2895

VL - 22

JO - Neurobiology of Stress

JF - Neurobiology of Stress

M1 - 100514

ER -

Transcriptional and cell type profiles of cortical brain regions showing ultradian cortisol rhythm dependent responses to emotional face stimulation

Abstract

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