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Special Issue "Effects of Hormones on the Nervous System and Behavior"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (31 May 2021).

Special Issue Editor

Assoc. Prof. Hirotaka Sakamoto
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Guest Editor
Laboratory of Neuroendocrinology, Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University, 130-17 Kashino, Ushimado, Setouchi, Okayama 701-4303, Japan
Interests: neuroendocrinology; neuropeptides; sex steroids; central nervous system; autonomic nervous system; socio-sexual behaviors; sexual dimorphism in the brain; spinal cord; hypothalamus

Special Issue Information

Dear Colleagues,

Instinct behaviors are inherent in most animals. These control mechanisms are formed and maintained by complicated neural circuits. The neurohypophysial hormones (neuropeptides) oxytocin and vasopressin control a series of behaviors, including territorial behavior, courtship behavior, pair bonding, reproductive behavior, and nurturing behavior, in addition to the peripheral functions; e.g., antidiuretic and reproductive functions. Steroid hormones, such as sex steroids and corticosteroids, also regulate various social behaviors, including sexual, aggressive, and parental behaviors, food intake, stress responses, mood regulation, and social anxiety, and modulate the somatosensory system and inflammation. Considering how these behaviors at the organismal level are regulated, ‘hormonal regulations’ appear to play an important role in these behaviors in addition to the neural activation. However, we do not fully understand how and when ‘hormones’ act on the nervous system and regulate these behaviors.

This Special Issue aims to collect state-of-the-art primary research studies and review articles from international experts and diverse leading groups in the field to update our current understanding of neuroendocrinological mechanisms underlying courtship–reproductive behavior, pair bonding, nurturing, biological rhythms, feardaunn, anxiety, escape, food intake, the somatosensory system, stress response/coping, and any other social behaviors. Suitable studies that use both vertebrates and invertebrates are welcome.

Assoc. Prof. Hirotaka Sakamoto
Guest Editor

Manuscript Submission Information

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Keywords

  • Neuroendocrinology;
  • neuropeptides;
  • steroid hormones;
  • central nervous system;
  • autonomic nervous system;
  • behavior;
  • sexual behavior;
  • social behavior;
  • stress responses;
  • mood disorder.

Published Papers (11 papers)

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Research

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Article
In Vivo Electrophysiology of Peptidergic Neurons in Deep Layers of the Lumbar Spinal Cord after Optogenetic Stimulation of Hypothalamic Paraventricular Oxytocin Neurons in Rats
Int. J. Mol. Sci. 2021, 22(7), 3400; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22073400 - 26 Mar 2021
Viewed by 622
Abstract
The spinal ejaculation generator (SEG) is located in the central gray (lamina X) of the rat lumbar spinal cord and plays a pivotal role in the ejaculatory reflex. We recently reported that SEG neurons express the oxytocin receptor and are activated by oxytocin [...] Read more.
The spinal ejaculation generator (SEG) is located in the central gray (lamina X) of the rat lumbar spinal cord and plays a pivotal role in the ejaculatory reflex. We recently reported that SEG neurons express the oxytocin receptor and are activated by oxytocin projections from the paraventricular nucleus of hypothalamus (PVH). However, it is unknown whether the SEG responds to oxytocin in vivo. In this study, we analyzed the characteristics of the brain–spinal cord neural circuit that controls male sexual function using a newly developed in vivo electrophysiological technique. Optogenetic stimulation of the PVH of rats expressing channel rhodopsin under the oxytocin receptor promoter increased the spontaneous firing of most lamina X SEG neurons. This is the first demonstration of the in vivo electrical response from the deeper (lamina X) neurons in the spinal cord. Furthermore, we succeeded in the in vivo whole-cell recordings of lamina X neurons. In vivo whole-cell recordings may reveal the features of lamina X SEG neurons, including differences in neurotransmitters and response to stimulation. Taken together, these results suggest that in vivo electrophysiological stimulation can elucidate the neurophysiological response of a variety of spinal neurons during male sexual behavior. Full article
(This article belongs to the Special Issue Effects of Hormones on the Nervous System and Behavior)
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Article
Tumor Necrosis Factor α and Interleukin-1β Acutely Inhibit AgRP Neurons in the Arcuate Nucleus of the Hypothalamus
Int. J. Mol. Sci. 2020, 21(23), 8928; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21238928 - 25 Nov 2020
Viewed by 555
Abstract
Obesity-associated low-grade inflammation favors weight gain, whereas systemic infection frequently leads to anorexia. Thus, inflammatory signals can either induce positive or negative energy balance. In this study, we used whole-cell patch-clamp to investigate the acute effects of three important proinflammatory cytokines, tumor necrosis [...] Read more.
Obesity-associated low-grade inflammation favors weight gain, whereas systemic infection frequently leads to anorexia. Thus, inflammatory signals can either induce positive or negative energy balance. In this study, we used whole-cell patch-clamp to investigate the acute effects of three important proinflammatory cytokines, tumor necrosis factor α (TNF-α), interleukin-6, and interleukin-1β (IL-1β) on the membrane excitability of agouti-related peptide (AgRP)- or proopiomelanocortin (POMC)-producing neurons. We found that both TNF-α and IL-1β acutely inhibited the activity of 35–42% of AgRP-producing neurons, whereas very few POMC neurons were depolarized by TNF-α. Interleukin-6 induced no acute changes in the activity of AgRP or POMC neurons. Our findings indicate that the effect of TNF-α and IL-1β, especially on the activity of AgRP-producing neurons, may contribute to inflammation-induced anorexia observed during acute inflammatory conditions. Full article
(This article belongs to the Special Issue Effects of Hormones on the Nervous System and Behavior)
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Article
Effects of Chronic Intracerebroventricular Infusion of RFamide-Related Peptide-3 on Energy Metabolism in Male Mice
Int. J. Mol. Sci. 2020, 21(22), 8606; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21228606 - 15 Nov 2020
Cited by 1 | Viewed by 663
Abstract
RFamide-related peptide-3 (RFRP-3), the mammalian ortholog of avian gonadotropin-inhibitory hormone (GnIH), plays a crucial role in reproduction. In the present study, we explored the other functions of RFRP-3 by investigating the effects of chronic intracerebroventricular infusion of RFRP-3 (6 nmol/day) for 13 days [...] Read more.
RFamide-related peptide-3 (RFRP-3), the mammalian ortholog of avian gonadotropin-inhibitory hormone (GnIH), plays a crucial role in reproduction. In the present study, we explored the other functions of RFRP-3 by investigating the effects of chronic intracerebroventricular infusion of RFRP-3 (6 nmol/day) for 13 days on energy homeostasis in lean male C57BL/6J mice. The infusion of RFRP-3 increased cumulative food intake and body mass. In addition, the masses of brown adipose tissue (BAT) and the liver were increased by the administration of RFRP-3, although the mass of white adipose tissue was unchanged. On the other hand, RFRP-3 decreased O2 consumption, CO2 production, energy expenditure, and core body temperature during a short time period in the dark phase. These results suggest that the increase in food intake and the decrease in energy expenditure contributed to the gain of body mass, including the masses of BAT and the liver. The present study shows that RFRP-3 regulates not only reproductive function, but also energy metabolism, in mice. Full article
(This article belongs to the Special Issue Effects of Hormones on the Nervous System and Behavior)
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Article
Recovery of BDNF and CB1R in the Prefrontal Cortex Underlying Improvement of Working Memory in Prenatal DEHP-Exposed Male Rats after Aerobic Exercise
Int. J. Mol. Sci. 2020, 21(11), 3867; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21113867 - 29 May 2020
Cited by 1 | Viewed by 866
Abstract
Early-life exposure to di-(2-ethylhexyl)-phthalate (DEHP) has been suggested to relate to hyperactivity, lack of attention, and working memory deficits in school-age children. Brain-derived neurotrophic factor (BDNF) and endocannabinoids are induced by aerobic exercises to provide beneficial effects on brain functions. This study investigated [...] Read more.
Early-life exposure to di-(2-ethylhexyl)-phthalate (DEHP) has been suggested to relate to hyperactivity, lack of attention, and working memory deficits in school-age children. Brain-derived neurotrophic factor (BDNF) and endocannabinoids are induced by aerobic exercises to provide beneficial effects on brain functions. This study investigated the mechanisms underlying working memory impairment and the protective role of exercise in prenatal DEHP-exposed male rats. Sprague Dawley dams were fed with vehicle or DEHP during gestation. The male offspring were trained to exercise on a treadmill for 5 weeks, which was followed by an assessment of their working memory with a T-maze delayed non-match-to-sample task. The expressions of BDNF, dopamine D1 receptor (D1R), cannabinoid receptor 1 (CB1R), and fatty acid amide hydrolase (FAAH) in the prefrontal cortex were detected by Western blot. The results showed that DEHP-exposed rats exhibited working memory impairments without significant alterations in locomotor activities. The reduced expressions of prefrontal BDNF and CB1R were obtained in the DEHP-exposed rats, while D1R and FAAH were barely affected. Importantly, aerobic exercise during childhood-adolescence prevented the impairment of working memory in the DEHP-exposed rats by recovering the BDNF and CB1R expressions in the prefrontal cortex. These findings suggest that exercise may provide beneficial effects in ameliorating the impairment of working memory in the prenatal DEHP-exposed male rats at late adolescence. Full article
(This article belongs to the Special Issue Effects of Hormones on the Nervous System and Behavior)
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Article
Myocyte Enhancer Factor 2A (MEF2A) Defines Oxytocin-Induced Morphological Effects and Regulates Mitochondrial Function in Neurons
Int. J. Mol. Sci. 2020, 21(6), 2200; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21062200 - 23 Mar 2020
Cited by 4 | Viewed by 1118
Abstract
The neuropeptide oxytocin (OT) is a well-described modulator of socio-emotional traits, such as anxiety, stress, social behavior, and pair bonding. However, when dysregulated, it is associated with adverse psychiatric traits, such as various aspects of autism spectrum disorder (ASD). In this study, we [...] Read more.
The neuropeptide oxytocin (OT) is a well-described modulator of socio-emotional traits, such as anxiety, stress, social behavior, and pair bonding. However, when dysregulated, it is associated with adverse psychiatric traits, such as various aspects of autism spectrum disorder (ASD). In this study, we identify the transcription factor myocyte enhancer factor 2A (MEF2A) as the common link between OT and cellular changes symptomatic for ASD, encompassing neuronal morphology, connectivity, and mitochondrial function. We provide evidence for MEF2A as the decisive factor defining the cellular response to OT: while OT induces neurite retraction in MEF2A expressing neurons, OT causes neurite outgrowth in absence of MEF2A. A CRISPR-Cas-mediated knockout of MEF2A and retransfection of an active version or permanently inactive mutant, respectively, validated our findings. We also identified the phosphatase calcineurin as the main upstream regulator of OT-induced MEF2A signaling. Further, MEF2A signaling dampens mitochondrial functioning in neurons, as MEF2A knockout cells show increased maximal cellular respiration, spare respiratory capacity, and total cellular ATP. In summary, we reveal a central role for OT-induced MEF2A activity as major regulator of cellular morphology as well as neuronal connectivity and mitochondrial functioning, with broad implications for a potential treatment of disorders based on morphological alterations or mitochondrial dysfunction. Full article
(This article belongs to the Special Issue Effects of Hormones on the Nervous System and Behavior)
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Review

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Review
Neural and Hormonal Basis of Opposite-Sex Preference by Chemosensory Signals
Int. J. Mol. Sci. 2021, 22(15), 8311; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22158311 (registering DOI) - 02 Aug 2021
Viewed by 161
Abstract
In mammalian reproduction, sexually active males seek female conspecifics, while estrous females try to approach males. This sex-specific response tendency is called sexual preference. In small rodents, sexual preference cues are mainly chemosensory signals, including pheromones. In this article, we review the physiological [...] Read more.
In mammalian reproduction, sexually active males seek female conspecifics, while estrous females try to approach males. This sex-specific response tendency is called sexual preference. In small rodents, sexual preference cues are mainly chemosensory signals, including pheromones. In this article, we review the physiological mechanisms involved in sexual preference for opposite-sex chemosensory signals in well-studied laboratory rodents, mice, rats, and hamsters of both sexes, especially an overview of peripheral sensory receptors, and hormonal and central regulation. In the hormonal regulation section, we discuss potential rodent brain bisexuality, as it includes neural substrates controlling both masculine and feminine sexual preferences, i.e., masculine preference for female odors and the opposite. In the central regulation section, we show the substantial circuit regulating sexual preference and also the influence of sexual experience that innate attractants activate in the brain reward system to establish the learned attractant. Finally, we review the regulation of sexual preference by neuropeptides, oxytocin, vasopressin, and kisspeptin. Through this review, we clarified the contradictions and deficiencies in our current knowledge on the neuroendocrine regulation of sexual preference and sought to present problems requiring further study. Full article
(This article belongs to the Special Issue Effects of Hormones on the Nervous System and Behavior)
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Review
The Role of Neuropeptide Y in the Nucleus Accumbens
Int. J. Mol. Sci. 2021, 22(14), 7287; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22147287 - 07 Jul 2021
Viewed by 397
Abstract
Neuropeptide Y (NPY), an abundant peptide in the central nervous system, is expressed in neurons of various regions throughout the brain. The physiological and behavioral effects of NPY are mainly mediated through Y1, Y2, and Y5 receptor subtypes, which are expressed in regions [...] Read more.
Neuropeptide Y (NPY), an abundant peptide in the central nervous system, is expressed in neurons of various regions throughout the brain. The physiological and behavioral effects of NPY are mainly mediated through Y1, Y2, and Y5 receptor subtypes, which are expressed in regions regulating food intake, fear and anxiety, learning and memory, depression, and posttraumatic stress. In particular, the nucleus accumbens (NAc) has one of the highest NPY concentrations in the brain. In this review, we summarize the role of NPY in the NAc. NPY is expressed principally in medium-sized aspiny neurons, and numerous NPY immunoreactive fibers are observed in the NAc. Alterations in NPY expression under certain conditions through intra-NAc injections of NPY or receptor agonists/antagonists revealed NPY to be involved in the characteristic functions of the NAc, such as alcohol intake and drug addiction. In addition, control of mesolimbic dopaminergic release via NPY receptors may take part in these functions. NPY in the NAc also participates in fat intake and emotional behavior. Accumbal NPY neurons and fibers may exert physiological and pathophysiological actions partly through neuroendocrine mechanisms and the autonomic nervous system. Full article
(This article belongs to the Special Issue Effects of Hormones on the Nervous System and Behavior)
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Review
Neural Contributions of the Hypothalamus to Parental Behaviour
Int. J. Mol. Sci. 2021, 22(13), 6998; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22136998 - 29 Jun 2021
Viewed by 408
Abstract
Parental behaviour is a comprehensive set of neural responses to social cues. The neural circuits that govern parental behaviour reside in several putative nuclei in the brain. Melanin concentrating hormone (MCH), a neuromodulator that integrates physiological functions, has been confirmed to be involved [...] Read more.
Parental behaviour is a comprehensive set of neural responses to social cues. The neural circuits that govern parental behaviour reside in several putative nuclei in the brain. Melanin concentrating hormone (MCH), a neuromodulator that integrates physiological functions, has been confirmed to be involved in parental behaviour, particularly in crouching behaviour during nursing. Abolishing MCH neurons in innate MCH knockout males promotes infanticide in virgin male mice. To understand the mechanism and function of neural networks underlying parental care and aggression against pups, it is essential to understand the basic organisation and function of the involved nuclei. This review presents newly discovered aspects of neural circuits within the hypothalamus that regulate parental behaviours. Full article
(This article belongs to the Special Issue Effects of Hormones on the Nervous System and Behavior)
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Review
Neurosteroids and Focal Epileptic Disorders
Int. J. Mol. Sci. 2020, 21(24), 9391; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21249391 - 10 Dec 2020
Cited by 4 | Viewed by 529
Abstract
Neurosteroids are a family of compounds that are synthesized in principal excitatory neurons and glial cells, and derive from the transformation of cholesterol into pregnenolone. The most studied neurosteroids—allopregnanolone and allotetrahydrodeoxycorticosterone (THDOC)—are known to modulate GABAA receptor-mediated transmission, thus playing a role [...] Read more.
Neurosteroids are a family of compounds that are synthesized in principal excitatory neurons and glial cells, and derive from the transformation of cholesterol into pregnenolone. The most studied neurosteroids—allopregnanolone and allotetrahydrodeoxycorticosterone (THDOC)—are known to modulate GABAA receptor-mediated transmission, thus playing a role in controlling neuronal network excitability. Given the role of GABAA signaling in epileptic disorders, neurosteroids have profound effects on seizure generation and play a role in the development of chronic epileptic conditions (i.e., epileptogenesis). We review here studies showing the effects induced by neurosteroids on epileptiform synchronization in in vitro brain slices, on epileptic activity in in vivo models, i.e., in animals that were made epileptic with chemoconvulsant treatment, and in epileptic patients. These studies reveal that neurosteroids can modulate ictogenesis and the occurrence of pathological network activity such as interictal spikes and high-frequency oscillations (80–500 Hz). Moreover, they can delay the onset of spontaneous seizures in animal models of mesial temporal lobe epilepsy. Overall, this evidence suggests that neurosteroids represent a new target for the treatment of focal epileptic disorders. Full article
(This article belongs to the Special Issue Effects of Hormones on the Nervous System and Behavior)
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Review
Effects of Early-Life Stress on the Brain and Behaviors: Implications of Early Maternal Separation in Rodents
Int. J. Mol. Sci. 2020, 21(19), 7212; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21197212 - 29 Sep 2020
Cited by 4 | Viewed by 973
Abstract
Early-life stress during the prenatal and postnatal periods affects the formation of neural networks that influence brain function throughout life. Previous studies have indicated that maternal separation (MS), a typical rodent model equivalent to early-life stress and, more specifically, to child abuse and/or [...] Read more.
Early-life stress during the prenatal and postnatal periods affects the formation of neural networks that influence brain function throughout life. Previous studies have indicated that maternal separation (MS), a typical rodent model equivalent to early-life stress and, more specifically, to child abuse and/or neglect in humans, can modulate the hypothalamic–pituitary–adrenal (HPA) axis, affecting subsequent neuronal function and emotional behavior. However, the neural basis of the long-lasting effects of early-life stress on brain function has not been clarified. In the present review, we describe the alterations in the HPA-axis activity—focusing on serum corticosterone (CORT)—and in the end products of the HPA axis as well as on the CORT receptor in rodents. We then introduce the brain regions activated during various patterns of MS, including repeated MS and single exposure to MS at various stages before weaning, via an investigation of c-Fos expression, which is a biological marker of neuronal activity. Furthermore, we discuss the alterations in behavior and gene expression in the brains of adult mice exposed to MS. Finally, we ask whether MS repeats itself and whether intergenerational transmission of child abuse and neglect is possible. Full article
(This article belongs to the Special Issue Effects of Hormones on the Nervous System and Behavior)
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Review
Introducing the Amphibious Mudskipper Goby as a Unique Model to Evaluate Neuro/Endocrine Regulation of Behaviors Mediated by Buccal Sensation and Corticosteroids
Int. J. Mol. Sci. 2020, 21(18), 6748; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21186748 - 14 Sep 2020
Cited by 1 | Viewed by 668
Abstract
Some fish have acquired the ability to breathe air, but these fish can no longer flush their gills effectively when out of water. Hence, they have developed characteristic means for defense against external stressors, including thirst (osmolarity/ions) and toxicity. Amphibious fish, extant air-breathing [...] Read more.
Some fish have acquired the ability to breathe air, but these fish can no longer flush their gills effectively when out of water. Hence, they have developed characteristic means for defense against external stressors, including thirst (osmolarity/ions) and toxicity. Amphibious fish, extant air-breathing fish emerged from water, may serve as models to examine physiological responses to these stressors. Some of these fish, including mudskipper gobies such as Periophthalmodon schlosseri, Boleophthalmus boddarti and our Periophthalmus modestus, display distinct adaptational behaviors to these factors compared with fully aquatic fish. In this review, we introduce the mudskipper goby as a unique model to study the behaviors and the neuro/endocrine mechanisms of behavioral responses to the stressors. Our studies have shown that a local sensation of thirst in the buccal cavity—this being induced by dipsogenic hormones—motivates these fish to move to water through a forebrain response. The corticosteroid system, which is responsive to various stressors, also stimulates migration, possibly via the receptors in the brain. We suggest that such fish are an important model to deepen insights into the stress-related neuro/endocrine-behavioral effects. Full article
(This article belongs to the Special Issue Effects of Hormones on the Nervous System and Behavior)
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