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International Journal of Molecular... May 2023Harmful alcohol use is responsible for a group of disorders collectively named alcohol use disorders (AUDs), according to the DSM-5 classification. The damage induced by... (Review)
Review
Harmful alcohol use is responsible for a group of disorders collectively named alcohol use disorders (AUDs), according to the DSM-5 classification. The damage induced by alcohol depends on the amount, time, and consumption patterns (continuous and heavy episodic drinking). It affects individual global well-being and social and familial environments with variable impact. Alcohol addiction manifests with different degrees of organ and mental health detriment for the individual, exhibiting two main traits: compulsive drinking and negative emotional states occurring at withdrawal, frequently causing relapse episodes. Numerous individual and living conditions, including the concomitant use of other psychoactive substances, lie in the complexity of AUD. Ethanol and its metabolites directly impact the tissues and may cause local damage or alter the homeostasis of brain neurotransmission, immunity scaffolding, or cell repair biochemical pathways. Brain modulator and neurotransmitter-assembled neurocircuitries govern reward, reinforcement, social interaction, and consumption of alcohol behaviors in an intertwined manner. Experimental evidence supports the participation of neurotensin (NT) in preclinical models of alcohol addiction. For example, NT neurons in the central nucleus of the amygdala projecting to the parabrachial nucleus strengthen alcohol consumption and preference. In addition, the levels of NT in the frontal cortex were found to be lower in rats bred to prefer alcohol to water in a free alcohol-water choice compared to wild-type animals. NT receptors 1 and 2 seem to be involved in alcohol consumption and alcohol effects in several models of knockout mice. This review aims to present an updated picture of the role of NT systems in alcohol addiction and the possible use of nonpeptide ligands modulating the activity of the NT system, applied to experimental animal models of harmful drinking behavior mimicking alcohol addiction leading to health ruin in humans.
Topics: Mice; Humans; Rats; Animals; Neurotensin; Alcoholism; Reinforcement, Psychology; Reward; Receptors, Neurotensin; Alcohol Drinking; Ethanol; Animals, Wild
PubMed: 37240004
DOI: 10.3390/ijms24108656 -
CNS Neuroscience & Therapeutics Feb 2024Autonomic dysfunction with central autonomic network (CAN) damage occurs frequently after intracerebral hemorrhage (ICH) and contributes to a series of adverse outcomes.... (Review)
Review
AIMS
Autonomic dysfunction with central autonomic network (CAN) damage occurs frequently after intracerebral hemorrhage (ICH) and contributes to a series of adverse outcomes. This review aims to provide insight and convenience for future clinical practice and research on autonomic dysfunction in ICH patients.
DISCUSSION
We summarize the autonomic dysfunction in ICH from the aspects of potential mechanisms, clinical significance, assessment, and treatment strategies. The CAN structures mainly include insular cortex, anterior cingulate cortex, amygdala, hypothalamus, nucleus of the solitary tract, ventrolateral medulla, dorsal motor nucleus of the vagus, nucleus ambiguus, parabrachial nucleus, and periaqueductal gray. Autonomic dysfunction after ICH is closely associated with neurological functional outcomes, cardiac complications, blood pressure fluctuation, immunosuppression and infection, thermoregulatory dysfunction, hyperglycemia, digestive dysfunction, and urogenital disturbances. Heart rate variability, baroreflex sensitivity, skin sympathetic nerve activity, sympathetic skin response, and plasma catecholamine concentration can be used to assess the autonomic functional activities after ICH. Risk stratification of patients according to autonomic functional activities, and development of intervention approaches based on the restoration of sympathetic-parasympathetic balance, would potentially improve clinical outcomes in ICH patients.
CONCLUSION
The review systematically summarizes the evidence of autonomic dysfunction and its association with clinical outcomes in ICH patients, proposing that targeting autonomic dysfunction could be potentially investigated to improve the clinical outcomes.
Topics: Humans; Autonomic Nervous System; Sympathetic Nervous System; Autonomic Nervous System Diseases; Vagus Nerve; Cerebral Hemorrhage; Heart Rate
PubMed: 38372446
DOI: 10.1111/cns.14544 -
Current Opinion in Physiology Jun 2020Sleep-wake control is dependent upon multiple brain areas widely distributed throughout the neural axis. Historically, the monoaminergic and cholinergic neurons of the...
Sleep-wake control is dependent upon multiple brain areas widely distributed throughout the neural axis. Historically, the monoaminergic and cholinergic neurons of the ascending arousal system were the first to be discovered, and it was only relatively recently that GABAergic and glutamatergic wake- and sleep-promoting populations have been identified. Contemporary advances in molecular-genetic tools have revealed both the complexity and heterogeneity of GABAergic NREM sleep-promoting neurons as well as REM sleep-regulating populations in the brainstem such as glutamatergic neurons in the sublaterodorsal nucleus. The sleep-wake cycle progresses from periods of wakefulness to non-rapid eye movement (NREM) sleep and subsequently rapid eye movement (REM) sleep. Each vigilance stage is controlled by multiple neuronal populations, via a complex regulation that is still incompletely understood. In recent years the field has seen a proliferation in the identification and characterization of new neuronal populations involved in sleep-wake control thanks to newer, more powerful molecular genetic tools that are able to reveal neurophysiological functions via selective activation, inhibition and lesion of neuroanatomically defined sub-types of neurons that are widespread in the brain, such as GABAergic and glutamatergic neurons..
PubMed: 32647777
DOI: 10.1016/j.cophys.2019.12.012 -
Progress in Neurobiology Jan 2021Hemispheric asymmetries within the brain have been identified across taxa and have been extensively studied since the early 19th century. Here, we discuss lateralization... (Review)
Review
Hemispheric asymmetries within the brain have been identified across taxa and have been extensively studied since the early 19th century. Here, we discuss lateralization of a brain structure, the amygdala, and how this lateralization is reshaping how we understand the role of the amygdala in pain processing. The amygdala is an almond-shaped, bilateral brain structure located within the limbic system. Historically, the amygdala was known to have a role in the processing of emotions and attaching emotional valence to memories and other experiences. The amygdala has been extensively studied in fear conditioning and affect but recently has been shown to have an important role in processing noxious information and impacting pain. The amygdala is composed of multiple nuclei; of special interest is the central nucleus of the amygdala (CeA). The CeA receives direct nociceptive inputs from the parabrachial nucleus (PBN) through the spino-parabrachio-amygdaloid pathway as well as more highly processed cortical and thalamic input via the lateral and basolateral amygdala. Although the amygdala is a bilateral brain region, most data investigating the amygdala's role in pain have been generated from the right CeA, which has an overwhelmingly pro-nociceptive function across pain models. The left CeA has often been characterized to have no effect on pain modulation, a dampened pro-nociceptive function, or most recently an anti-nociceptive function. This review explores the current literature on CeA lateralization and the hemispheres' respective roles in the processing and modulation of different forms of pain.
Topics: Animals; Arthralgia; Central Amygdaloid Nucleus; Functional Laterality; Humans; Neuralgia; Nociceptive Pain; Visceral Pain
PubMed: 32730859
DOI: 10.1016/j.pneurobio.2020.101891 -
Journal of Neurochemistry Jan 2021The Kölliker-Fuse nucleus (KF) is a functionally distinct component of the parabrachial complex, located in the dorsolateral pons of mammals. The KF has a major role in... (Review)
Review
The Kölliker-Fuse nucleus (KF) is a functionally distinct component of the parabrachial complex, located in the dorsolateral pons of mammals. The KF has a major role in respiration and upper airway control. A comprehensive understanding of the KF and its contributions to respiratory function and dysfunction requires an appreciation for its neurochemical characteristics. The goal of this review is to summarize the diverse neurochemical composition of the KF, focusing on the neurotransmitters, neuromodulators, and neuropeptides present. We also include a description of the receptors expressed on KF neurons and transporters involved in each system, as well as their putative roles in respiratory physiology. Finally, we provide a short section reviewing the literature regarding neurochemical changes in the KF in the context of respiratory dysfunction observed in SIDS and Rett syndrome. By over-viewing the current literature on the neurochemical composition of the KF, this review will serve to aid a wide range of topics in the future research into the neural control of respiration in health and disease.
Topics: Animals; Humans; Kolliker-Fuse Nucleus; Respiration
PubMed: 32396650
DOI: 10.1111/jnc.15041 -
Frontiers in Physiology 2014The lateral parabrachial nucleus (LPBN) is located in an anatomical position that enables it to perform a critical role in relaying signals related to the regulation of... (Review)
Review
The lateral parabrachial nucleus (LPBN) is located in an anatomical position that enables it to perform a critical role in relaying signals related to the regulation of fluid and electrolyte intake and cardiovascular function from the brainstem to the forebrain. Early neuroanatomical studies have described the topographic organization of blood pressure sensitive neurons and functional studies have demonstrated a major role for the LPBN in regulating cardiovascular function, including blood pressure, in response to hemorrhages, and hypovolemia. In addition, inactivation of the LPBN induces overdrinking of water in response to a range of dipsogenic treatments primarily, but not exclusively, those associated with endogenous centrally acting angiotensin II. Moreover, treatments that typically cause water intake stimulate salt intake under some circumstances particularly when serotonin receptors in the LPBN are blocked. This review explores the expanding body of evidence that underlies the complex neural network within the LPBN influencing salt appetite, thirst and the regulation of blood pressure. Importantly understanding the interactions among neurons in the LPBN that affect fluid balance and cardiovascular control may be critical to unraveling the mechanisms responsible for hypertension.
PubMed: 25477821
DOI: 10.3389/fphys.2014.00436 -
The Journal of Physiology May 2021Arousal from sleep in response to CO is a life-preserving reflex that enhances ventilatory drive and facilitates behavioural adaptations to restore eupnoeic breathing.... (Review)
Review
Arousal from sleep in response to CO is a life-preserving reflex that enhances ventilatory drive and facilitates behavioural adaptations to restore eupnoeic breathing. Recurrent activation of the CO -arousal reflex is associated with sleep disruption in obstructive sleep apnoea. In this review we examine the role of chemoreceptors in the carotid bodies, the retrotrapezoid nucleus and serotonergic neurons in the dorsal raphe in the CO -arousal reflex. We also provide an overview of the supra-medullary structures that mediate CO -induced arousal. We propose a framework for the CO -arousal reflex in which the activity of the chemoreceptors converges in the parabrachial nucleus to trigger cortical arousal.
Topics: Arousal; Carbon Dioxide; Chemoreceptor Cells; Respiration; Sleep
PubMed: 33759184
DOI: 10.1113/JP281305 -
Brain Sciences Oct 2023Accumulated evidence has demonstrated that the gut microbiome can contribute to pain modulation through the microbiome-gut-brain axis. Various relevant microbiome... (Review)
Review
Accumulated evidence has demonstrated that the gut microbiome can contribute to pain modulation through the microbiome-gut-brain axis. Various relevant microbiome metabolites in the gut are involved in the regulation of pain signaling in the central nervous system. In this review, we summarize recent advances in gut-brain interactions by which the microbiome metabolites modulate pain, with a focus on orofacial pain, and we further discuss the role of gut-brain crosstalk in the central mechanisms of orofacial pain whereby the gut microbiome modulates orofacial pain via the vagus nerve-mediated direct pathway and the gut metabolites/molecules-mediated indirect pathway. The direct and indirect pathways both contribute to the central regulation of orofacial pain through different brain structures (such as the nucleus tractus solitarius and the parabrachial nucleus) and signaling transmission across the blood-brain barrier, respectively. Understanding the gut microbiome-regulated pain mechanisms in the brain could help us to develop non-opioid novel therapies for orofacial pain.
PubMed: 37891825
DOI: 10.3390/brainsci13101456 -
Frontiers in Public Health 2022Neuropeptide S (NPS) is a neuropeptide primarily produced within three brainstem regions including locus coeruleus, trigeminal nerve nucleus, and lateral parabrachial... (Review)
Review
Neuropeptide S (NPS) is a neuropeptide primarily produced within three brainstem regions including locus coeruleus, trigeminal nerve nucleus, and lateral parabrachial nucleus. NPS is involved in the central regulation of stress, fear, and cognitive integration. NPS is a mediator of behavior, seeking food, and the proliferation of new adipocytes in the setting of obesity. So far, current research of NPS is only limited to animal models; data regarding its functions in humans is still scarce. Animal studies showed that anxiety and appetite might be suppressed by the action of NPS. The discovery of this neuromodulator peptide is effective considering its strong anxiolytic action, which has the potential to be an interesting therapeutic option in treating neuropsychiatric disorders. In this article, we aimed to analyze the pharmaceutical properties of NPS as well as its influence on several neurophysiological aspects-modulation of behavior, association with obesity, as well as its potential application in rehabilitation and treatment of psychiatric disorders.
Topics: Animals; Anxiety; Humans; Mental Disorders; Neuropeptides; Obesity; Receptors, Neuropeptide
PubMed: 35558538
DOI: 10.3389/fpubh.2022.872430 -
Proceedings of the National Academy of... Feb 2024Neuropeptide S (NPS) was postulated to be a wake-promoting neuropeptide with unknown mechanism, and a mutation in its receptor (NPSR1) causes the short sleep duration...
Neuropeptide S (NPS) was postulated to be a wake-promoting neuropeptide with unknown mechanism, and a mutation in its receptor (NPSR1) causes the short sleep duration trait in humans. We investigated the role of different NPS nuclei in sleep/wake regulation. Loss-of-function and chemogenetic studies revealed that NPS neurons in the parabrachial nucleus (PB) are wake-promoting, whereas peri-locus coeruleus (peri-LC) NPS neurons are not important for sleep/wake modulation. Further, we found that a NPS nucleus in the central gray of the pons (CGPn) strongly promotes sleep. Fiber photometry recordings showed that NPS neurons are wake-active in the CGPn and wake/REM-sleep active in the PB and peri-LC. Blocking NPS-NPSR1 signaling or knockdown of supported the function of the NPS-NPSR1 pathway in sleep/wake regulation. Together, these results reveal that NPS and NPS neurons play dichotomous roles in sleep/wake regulation at both the molecular and circuit levels.
Topics: Humans; Sleep; Pons; Locus Coeruleus; Neurons; Neuropeptides; Receptors, G-Protein-Coupled
PubMed: 38381789
DOI: 10.1073/pnas.2320276121