Brain-Body Interactions in the Maintenance of Homeostasis: An Honorary Issue in Memory of Prof. Claude Bernard

A topical collection in Cells (ISSN 2073-4409). This collection belongs to the section "Cells of the Nervous System".

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Editors

Département Adaptations du Vivant, Centre National de la Recherche Scientifique UMR 7221, Muséum National d'Histoire Naturelle, Paris, France
Interests: developmental biology; morphogenesis; craniofacial development; reproduction; osteogenesis; brain development; neuronal differentiation; aging (or ageing...); human evolution
Molecular Physiology and Adaption, Department Adaptation of Life, Centre National de la Recherche Scientifique, Muséum National d'Histoire Naturelle, UMR 7221 Paris, France
Interests: thyroid hormone; glucocorticoids; molecular endocrinology; comparative endocrinology; metamorphosis; adaptation; environmental challenges; gene regulation; epigenome; stress; endocrine disruption

Topical Collection Information

Dear Colleagues,

At the end of his life, Prof. Claude Bernard, while at the Muséum National d’Histoire Naturelle in Paris, was the first to have a clear intuition of the importance of the brain/body interplay in maintaining homeostasis and adaptation to environmental challenges.

Indeed, the survival of an organism depends on its capacity to reach energy homeostasis equilibrating calorie consumption with motivation for feeding. In humans, disruption of this regulation engenders life-threatening conditions ranging from anorexia nervosa to obesity and, in general, the conditions associated with metabolic syndrome (MetS).

The Central Nervous System (CNS) maintains energy homeostasis regulating both feeding behaviors and different forms of energy expenditure (adaptive thermogenesis, physical activity and basal metabolic rate). In addition, the CNS coordinates the activity of peripheral tissues to ensure the conversion, storage and utilization of ingested nutrients, an integrated process referred as to “nutrient partitioning”. 

This honorary issue, in memory of Prof. Claude Bernard, collects a series of essays addressing the various aspects of brain/body/environment interactions for the maintenance of homeostasis, exploring how these regulations impact the different life stages of an organism ranging from development to aging. Furthermore, the impact of environmental factors such as climate change and endocrine disruption will be addressed.

Dr. Giovanni Levi
Dr. Laurent M. Sachs
Collection Editors

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Keywords

  • homeostasis
  • metabolism
  • central nervous system
  • endocrine disruption

Published Papers (7 papers)

2022

16 pages, 3743 KiB  
Article
Dlx5/6 Expression Levels in Mouse GABAergic Neurons Regulate Adult Parvalbumin Neuronal Density and Anxiety/Compulsive Behaviours
by Rym Aouci, Mey El Soudany, Zakaria Maakoul, Anastasia Fontaine, Hiroki Kurihara, Giovanni Levi and Nicolas Narboux-Nême
Cells 2022, 11(11), 1739; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11111739 - 25 May 2022
Viewed by 2742
Abstract
Neuronal circuits integrating Parvalbumin-positive GABAergic inhibitory interneurons (PV) are essential for normal brain function and are often altered in psychiatric conditions. During development, Dlx5 and Dlx6 (Dlx5/6) genes are involved in the differentiation of PV-interneurons. In the adult, Dlx5/6 continue to [...] Read more.
Neuronal circuits integrating Parvalbumin-positive GABAergic inhibitory interneurons (PV) are essential for normal brain function and are often altered in psychiatric conditions. During development, Dlx5 and Dlx6 (Dlx5/6) genes are involved in the differentiation of PV-interneurons. In the adult, Dlx5/6 continue to be expressed at low levels in most telencephalic GABAergic neurons, but their importance in determining the number and distribution of adult PV-interneurons is unknown. Previously, we have shown that targeted deletion of Dlx5/6 in mouse GABAergic neurons (Dlx5/6VgatCre mice) results in altered behavioural and metabolic profiles. Here we evaluate the consequences of targeted Dlx5/6 gene dosage alterations in adult GABAergic neurons. We compare the effects on normal brain of homozygous and heterozygous (Dlx5/6VgatCre and Dlx5/6VgatCre/+ mice) Dlx5/6 deletions to those of Dlx5 targeted overexpression (GABAergicDlx5/+ mice). We find a linear correlation between Dlx5/6 allelic dosage and the density of PV-positive neurons in the adult prelimbic cortex and in the hippocampus. In parallel, we observe that Dlx5/6 expression levels in GABAergic neurons are also linearly associated with the intensity of anxiety and compulsivity-like behaviours. Our findings reinforce the notion that regulation of Dlx5/6 expression is involved in individual cognitive variability and, possibly, in the genesis of certain neuropsychiatric conditions. Full article
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6 pages, 26031 KiB  
Editorial
Claude Bernard, the Founder of Modern Medicine
by René Habert
Cells 2022, 11(10), 1702; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11101702 - 20 May 2022
Cited by 1 | Viewed by 2727
Abstract
Claude Bernard is the first and one of the very few French scientists to have been honored with a national funeral [...] Full article
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23 pages, 1766 KiB  
Review
Thyroid and Corticosteroid Signaling in Amphibian Metamorphosis
by Bidisha Paul, Zachary R. Sterner, Daniel R. Buchholz, Yun-Bo Shi and Laurent M. Sachs
Cells 2022, 11(10), 1595; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11101595 - 10 May 2022
Cited by 11 | Viewed by 3512
Abstract
In multicellular organisms, development is based in part on the integration of communication systems. Two neuroendocrine axes, the hypothalamic–pituitary–thyroid and the hypothalamic–pituitary–adrenal/interrenal axes, are central players in orchestrating body morphogenesis. In all vertebrates, the hypothalamic–pituitary–thyroid axis controls thyroid hormone production and release, whereas [...] Read more.
In multicellular organisms, development is based in part on the integration of communication systems. Two neuroendocrine axes, the hypothalamic–pituitary–thyroid and the hypothalamic–pituitary–adrenal/interrenal axes, are central players in orchestrating body morphogenesis. In all vertebrates, the hypothalamic–pituitary–thyroid axis controls thyroid hormone production and release, whereas the hypothalamic–pituitary–adrenal/interrenal axis regulates the production and release of corticosteroids. One of the most salient effects of thyroid hormones and corticosteroids in post-embryonic developmental processes is their critical role in metamorphosis in anuran amphibians. Metamorphosis involves modifications to the morphological and biochemical characteristics of all larval tissues to enable the transition from one life stage to the next life stage that coincides with an ecological niche switch. This transition in amphibians is an example of a widespread phenomenon among vertebrates, where thyroid hormones and corticosteroids coordinate a post-embryonic developmental transition. The review addresses the functions and interactions of thyroid hormone and corticosteroid signaling in amphibian development (metamorphosis) as well as the developmental roles of these two pathways in vertebrate evolution. Full article
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26 pages, 1922 KiB  
Review
Schwann Cells in Digestive System Disorders
by Karina Goluba, Liga Kunrade, Una Riekstina and Vadims Parfejevs
Cells 2022, 11(5), 832; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11050832 - 28 Feb 2022
Cited by 4 | Viewed by 4398
Abstract
Proper functioning of the digestive system is ensured by coordinated action of the central and peripheral nervous systems (PNS). Peripheral innervation of the digestive system can be viewed as intrinsic and extrinsic. The intrinsic portion is mainly composed of the neurons and glia [...] Read more.
Proper functioning of the digestive system is ensured by coordinated action of the central and peripheral nervous systems (PNS). Peripheral innervation of the digestive system can be viewed as intrinsic and extrinsic. The intrinsic portion is mainly composed of the neurons and glia of the enteric nervous system (ENS), while the extrinsic part is formed by sympathetic, parasympathetic, and sensory branches of the PNS. Glial cells are a crucial component of digestive tract innervation, and a great deal of research evidence highlights the important status of ENS glia in health and disease. In this review, we shift the focus a bit and discuss the functions of Schwann cells (SCs), the glial cells of the extrinsic innervation of the digestive system. For more context, we also provide information on the basic findings regarding the function of innervation in disorders of the digestive organs. We find diverse SC roles described particularly in the mouth, the pancreas, and the intestine. We note that most of the scientific evidence concerns the involvement of SCs in cancer progression and pain, but some research identifies stem cell functions and potential for regenerative medicine. Full article
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20 pages, 6815 KiB  
Article
Analysis of the Glucose-Dependent Transcriptome in Murine Hypothalamic Cells
by Leonhard Webert, Dennis Faro, Sarah Zeitlmayr, Thomas Gudermann and Andreas Breit
Cells 2022, 11(4), 639; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11040639 - 11 Feb 2022
Cited by 2 | Viewed by 1971
Abstract
Glucose provides vital energy for cells and contributes to gene expression. The hypothalamus is key for metabolic homeostasis, but effects of glucose on hypothalamic gene expression have not yet been investigated in detail. Thus, herein, we monitored the glucose-dependent transcriptome in murine hypothalamic [...] Read more.
Glucose provides vital energy for cells and contributes to gene expression. The hypothalamus is key for metabolic homeostasis, but effects of glucose on hypothalamic gene expression have not yet been investigated in detail. Thus, herein, we monitored the glucose-dependent transcriptome in murine hypothalamic mHypoA-2/10 cells by total RNA-seq analysis. A total of 831 genes were up- and 1390 genes were downregulated by at least 50%. Key genes involved in the cholesterol biosynthesis pathway were upregulated, and total cellular cholesterol levels were significantly increased by glucose. Analysis of single genes involved in fundamental cellular signaling processes also suggested a significant impact of glucose. Thus, we chose ≈100 genes involved in signaling and validated the effects of glucose on mRNA levels by qRT-PCR. We identified Gnai13, Adyc6, Irs1, Igfr1, Hras, and Elk3 as new glucose-dependent genes. In line with this, cAMP measurements revealed enhanced noradrenalin-induced cAMP levels, and reporter gene assays elevated activity of the insulin-like growth factor at higher glucose levels. Key data of our studies were confirmed in a second hypothalamic cell line. Thus, our findings link extra cellular glucose levels with hypothalamic lipid synthesis and pivotal intracellular signaling processes, which might be of particular interest in situations of continuously increased glucose levels. Full article
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36 pages, 7267 KiB  
Review
Physiological Function during Exercise and Environmental Stress in Humans—An Integrative View of Body Systems and Homeostasis
by Gavin Travers, Pascale Kippelen, Steven J. Trangmar and José González-Alonso
Cells 2022, 11(3), 383; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11030383 - 24 Jan 2022
Cited by 16 | Viewed by 16518
Abstract
Claude Bernard’s milieu intérieur (internal environment) and the associated concept of homeostasis are fundamental to the understanding of the physiological responses to exercise and environmental stress. Maintenance of cellular homeostasis is thought to happen during exercise through the precise matching of cellular energetic [...] Read more.
Claude Bernard’s milieu intérieur (internal environment) and the associated concept of homeostasis are fundamental to the understanding of the physiological responses to exercise and environmental stress. Maintenance of cellular homeostasis is thought to happen during exercise through the precise matching of cellular energetic demand and supply, and the production and clearance of metabolic by-products. The mind-boggling number of molecular and cellular pathways and the host of tissues and organ systems involved in the processes sustaining locomotion, however, necessitate an integrative examination of the body’s physiological systems. This integrative approach can be used to identify whether function and cellular homeostasis are maintained or compromised during exercise. In this review, we discuss the responses of the human brain, the lungs, the heart, and the skeletal muscles to the varying physiological demands of exercise and environmental stress. Multiple alterations in physiological function and differential homeostatic adjustments occur when people undertake strenuous exercise with and without thermal stress. These adjustments can include: hyperthermia; hyperventilation; cardiovascular strain with restrictions in brain, muscle, skin and visceral organs blood flow; greater reliance on muscle glycogen and cellular metabolism; alterations in neural activity; and, in some conditions, compromised muscle metabolism and aerobic capacity. Oxygen supply to the human brain is also blunted during intense exercise, but global cerebral metabolism and central neural drive are preserved or enhanced. In contrast to the strain seen during severe exercise and environmental stress, a steady state is maintained when humans exercise at intensities and in environmental conditions that require a small fraction of the functional capacity. The impact of exercise and environmental stress upon whole-body functions and homeostasis therefore depends on the functional needs and differs across organ systems. Full article
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11 pages, 1454 KiB  
Article
LEAP-2 Counteracts Ghrelin-Induced Food Intake in a Nutrient, Growth Hormone and Age Independent Manner
by Javier Lugilde, Sabela Casado, Daniel Beiroa, Juan Cuñarro, Montserrat Garcia-Lavandeira, Clara V. Álvarez, Rubén Nogueiras, Carlos Diéguez and Sulay Tovar
Cells 2022, 11(3), 324; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11030324 - 19 Jan 2022
Cited by 15 | Viewed by 3740
Abstract
Data gleaned recently shows that ghrelin, a stomach derived peptide, and liver-expressed-antimicrobial peptide 2 (LEAP-2) play opposite roles on food intake. However, the data available with LEAP-2 in relation to in vivo studies are still very scanty and some key questions regarding the [...] Read more.
Data gleaned recently shows that ghrelin, a stomach derived peptide, and liver-expressed-antimicrobial peptide 2 (LEAP-2) play opposite roles on food intake. However, the data available with LEAP-2 in relation to in vivo studies are still very scanty and some key questions regarding the interplay among ghrelin and LEAP-2 remain to be answered. In this work, using rats and mice, we study fasting-induced food intake as well as testing the effect of diet exposure, e.g., standard diet and high fat diet, in terms of ghrelin-induced food intake. The anorexigenic effect of LEAP-2 on fasting induced food intake appears to be dependent on energy stores, being more evident in ob/ob than in wild type mice and also in animals exposed to high fat diet. On the other hand, LEAP-2 administration markedly inhibited ghrelin-induced food intake in lean, obese (ob/ob and DIO) mice, aged rats and GH-deficient dwarf rats. In contrast, the inhibitory effect on glucose levels can only be observed in some specific experimental models indicating that the mechanisms involved are likely to be quite different. Taken together from these data, LEAP-2 emerged as a potential candidate to be therapeutically useful in obesity. Full article
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: The remodeling of the aging body and its new physiology
Authors: Claudio Franceschi; Paolo Garagnani, Maria Giulia Bacalini, Cristina Giuliani and Aurelia Santoro
Affiliation: Department of Specialty, Diagnostic and Experimental Medicine (DIMES) Via S. Giacomo 12, 40126 Bologna, Italy
Abstract: \

Title: The Effects of Endocrine Disruptors on the Central Control of Homeostasis.
Authors: Barbara Demeneix
Affiliation: UMR 7221, Physiologie Moléculaire et Adaptations, Dept AVIV, CNRS/ Muséum National d’Histoire Naturelle, 75005 Paris, France
Abstract: Endocrine disruption arises from exposure to chemicals that harm human health, the ecosystem and biodiversity. The World Health Organisation (WHO) defines endocrine disrupting chemicals (EDCs) as exogenous substances that have the capacity to alter the function(s) of the endocrine system and consequently cause adverse health effects in an intact organism, its progeny or a (sub)population. Experimental and epidemiological evidence shows EDCs to affect whole body homeostasis. Examples include the numerous non-communicable diseases that have occurred since the 1950. The incidence of these diseases has increased and range from metabolic disorders (such as obesity and diabetes type 2), infertility, endocrine cancers and neurodevelopmental disease. These pathologies are largely associated with industrialization. The problem can be seen as jeopardizing the One Health concept, increasing the propensity for zoonoses, as amply illustrated by the current COVID-19 pandemic. How EDCs affect the central control of metabolism and whole body homeostasis is illustrated by a plethora of EDCs, whether their origin is plastics, pesticides, fertilizers, food contact materials, personal care products or atmospheric pollution. It is impossible to list all the known EDCs modifying homeostasis, a few will be our focus, notably those affecting the brain and the thyroid system.

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