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The Role of Neurons in Human Health and Disease

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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 July 2022) | Viewed by 30401

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Dr. Yasemin M. Akay

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Department of Biomedical Engineering, University of Houston, Houston, TX 77204-5060, USA
Interests: coronary artery disease; stent; noninvasive monitoring; nonlinear dynamics analysis; approximate entropy; 3D co-culture; glioblastoma; astrocytes; tumor microenvironment; PEGDA; addiction; cancer research; data science in medicine
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Dear Colleagues,

The brain is the central regulator of the organism, responsible for maintaining its homeostasis. Neurons are the most critical components of the central and peripheral nervous systems. The immune system protects us from all possible threats that could endanger the well-being of a human body. A strong immune system or a weakened one could make all the differences between the healthy and diseased conditions of a human body.The nervous and the immune systems are both crucial for the survival of the human beings. Nervous system affects the activity of the immune system due to its unique anatomical structure and function.The brain can directly regulate the function of the most physiological systems. Neuronal regulation promotes the improvement of the conditions under which the immune system works by synchronizing its activity with other physiological functions. Brain has the ability to perceive and evaluate the threats before they physically affect the organism. This predictive capacity also helps the immune system prepare in advance for a possible danger and could induce a more effective and faster response.One of the most prominent differences between the nervous and the immune systems is their speed of reaction. The nervous system can react within milliseconds, whereas immunological responses often require from several minutes up to weeks to develop. Although the slower immune reaction is sufficing most of the times, a faster response may be more helpful in some cases. In this Special Issue we focus mainly how the brain and nervous system affect immunity, specifically peripheral immunity and play an essential role in the human health and disease.

Dr. Yasemin M. Akay
Guest Editor

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Keywords

brain
nervous system
neurons
immune system
human health and disease

Published Papers (10 papers)

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Editorial

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3 pages, 181 KiB

Open AccessEditorial

The Role of Neurons in Human Health and Disease

by Yasemin M. Akay

Int. J. Mol. Sci. 2023, 24(8), 7107; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24087107 - 12 Apr 2023

Viewed by 728

Abstract

Neurons are the functional units of the nervous system [...] Full article

(This article belongs to the Special Issue The Role of Neurons in Human Health and Disease)

Research

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19 pages, 4662 KiB

Open AccessArticle

Development of the Periventricular Nucleus as a Brain Center, Containing Dopaminergic Neurons and Neurons Expressing Individual Enzymes of Dopamine Synthesis

by Tatiana Pronina, Ekaterina Pavlova, Liliya Dil’mukhametova and Michael Ugrumov

Int. J. Mol. Sci. 2022, 23(23), 14682; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232314682 - 24 Nov 2022

Cited by 4 | Viewed by 1177

Abstract

We have recently shown that the periventricular nucleus (PeVN) of adult rats is a “mixed dopaminergic (DAergic) center” containing three thousand neurons: DAergic neurons and those expressing one of the dopamine (DA)-synthesizing enzymes. This study aims to evaluate the development of the PeVN as a mixed DAergic center in rats in the perinatal period, critical for brain morphogenesis. During this period, the PeVN contains DAergic neurons and monoenzymatic neurons expressing individual enzymes of DA synthesis: tyrosine hydroxylase (TH) or aromatic L-amino acid decarboxylase (AADC). In the perinatal period, the total number of such neurons triples, mainly due to monoenzymatic neurons; the content of L-DOPA, the end product of monoenzymatic TH neurons, doubles; and the content of DA, the end product of monoenzymatic AADC neurons and DAergic neurons, increases sixfold. Confocal microscopy has shown that, in the PeVN, all types of neurons and their processes are in close relationships, which suggests their mutual regulation by L-DOPA and DA. In addition, monoenzymatic and DAergic fibers are close to the third cerebral ventricle, located in the subependymal zone, between ependymal cells and in the supraependymal zone. These observations suggest that these fibers deliver L-DOPA and DA to the cerebrospinal fluid, participating in the neuroendocrine regulation of the brain. Full article

(This article belongs to the Special Issue The Role of Neurons in Human Health and Disease)

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20 pages, 5477 KiB

Open AccessArticle

High-Fat Diet Consumption in Adolescence Induces Emotional Behavior Alterations and Hippocampal Neurogenesis Deficits Accompanied by Excessive Microglial Activation

by Xiuting Yao, Chenxi Yang, Conghui Wang, Hong Li, Jingyi Zhao, Xiaomin Kang, Zhuodong Liu, Lingyan Chen, Xinyu Chen, Tianshu Pu, Qinyang Li and Lijie Liu

Int. J. Mol. Sci. 2022, 23(15), 8316; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23158316 - 27 Jul 2022

Cited by 10 | Viewed by 2307

Abstract

Adolescence is a developmental epoch characterized by massive neural circuit remodeling; thus, the brain is particularly vulnerable to environmental influences during this period. Excessive high-fat diet (HFD) consumption, which is very common among adolescents, has long been recognized as a potent risk factor for multiple mood disorders, including depression and anxiety. However, the precise mechanisms underlying the influences of HFD consumption in adolescence on emotional health are far from clear. In the present study, C57BL/6 mice were fed a control diet (CD) or HFD for about 4 weeks from postnatal day (P) 28 to P60, spanning most of the adolescence period, and then subjected to behavioral assessments and histological examinations. HFD mice exhibited elevated levels of depression and anxiety, decreased hippocampal neurogenesis, and excessive microglial activation in the ventral hippocampus. Furthermore, in HFD-fed mice, microglia showed increased DCX⁺ inclusions, suggesting aberrant microglial engulfment of newborn neurons in HFD-fed adolescents. To our knowledge, this is the first observation suggesting that the negative effects of HFD consumption in adolescence on emotion and neuroplasticity may be attributed at least in part to aberrant microglial engulfment of nascent neurons, extending our understanding of the mechanism underlying HFD-related affective disorders in young people. Full article

(This article belongs to the Special Issue The Role of Neurons in Human Health and Disease)

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14 pages, 3094 KiB

Open AccessArticle

Neuroprotective Effects of VEGF in the Enteric Nervous System

by Ines Hecking, Lennart Norman Stegemann, Verena Theis, Matthias Vorgerd, Veronika Matschke, Sarah Stahlke and Carsten Theiss

Int. J. Mol. Sci. 2022, 23(12), 6756; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23126756 - 17 Jun 2022

Cited by 7 | Viewed by 2057

Abstract

Although the enteric nervous system (ENS) functions largely autonomously as part of the peripheral nervous system (PNS), it is connected to the central nervous system (CNS) via the gut–brain axis. In many neurodegenerative diseases, pathological changes occur in addition to gastrointestinal symptoms, such as alpha-synuclein aggregates in Parkinson’s disease, which are found early in the ENS. In both the CNS and PNS, vascular endothelial growth factor (VEGF) mediates neuroprotective and neuroregenerative effects. Since the ENS with its close connection to the microbiome and the immune system is discussed as the origin of neurodegenerative diseases, it is necessary to investigate the possibly positive effects of VEGF on enteric neurons. Using laser microdissection and subsequent quantitative RT-PCR as well as immunohistochemistry, for the first time we were able to detect and localize VEGF receptor expression in rat myenteric neurons of different ages. Furthermore, we demonstrate direct neuroprotective effects of VEGF in the ENS in cell cultures. Thus, our results suggest a promising approach regarding neuroprotection, as the use of VEGF (may) prevent neuronal damage in the ENS. Full article

(This article belongs to the Special Issue The Role of Neurons in Human Health and Disease)

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Review

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20 pages, 2416 KiB

Open AccessReview

Molecular Organization and Patterning of the Medulla Oblongata in Health and Disease

by Dina Diek, Marten Piet Smidt and Simone Mesman

Int. J. Mol. Sci. 2022, 23(16), 9260; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23169260 - 17 Aug 2022

Cited by 7 | Viewed by 5395

Abstract

The medulla oblongata, located in the hindbrain between the pons and the spinal cord, is an important relay center for critical sensory, proprioceptive, and motoric information. It is an evolutionarily highly conserved brain region, both structural and functional, and consists of a multitude of nuclei all involved in different aspects of basic but vital functions. Understanding the functional anatomy and developmental program of this structure can help elucidate potential role(s) of the medulla in neurological disorders. Here, we have described the early molecular patterning of the medulla during murine development, from the fundamental units that structure the very early medullary region into 5 rhombomeres (r7–r11) and 13 different longitudinal progenitor domains, to the neuronal clusters derived from these progenitors that ultimately make-up the different medullary nuclei. By doing so, we developed a schematic overview that can be used to predict the cell-fate of a progenitor group, or pinpoint the progenitor domain of origin of medullary nuclei. This schematic overview can further be used to help in the explanation of medulla-related symptoms of neurodevelopmental disorders, e.g., congenital central hypoventilation syndrome, Wold–Hirschhorn syndrome, Rett syndrome, and Pitt–Hopkins syndrome. Based on the genetic defects seen in these syndromes, we can use our model to predict which medullary nuclei might be affected, which can be used to quickly direct the research into these diseases to the likely affected nuclei. Full article

(This article belongs to the Special Issue The Role of Neurons in Human Health and Disease)

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15 pages, 349 KiB

Open AccessReview

The Role of Neuro-Immune Interaction in Chronic Pain Conditions; Functional Somatic Syndrome, Neurogenic Inflammation, and Peripheral Neuropathy

by Elaine Meade and Mary Garvey

Int. J. Mol. Sci. 2022, 23(15), 8574; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23158574 - 02 Aug 2022

Cited by 18 | Viewed by 3917

Abstract

Functional somatic syndromes are increasingly diagnosed in chronically ill patients presenting with an array of symptoms not attributed to physical ailments. Conditions such as chronic fatigue syndrome, fibromyalgia syndrome, or irritable bowel syndrome are common disorders that belong in this broad category. Such syndromes are characterised by the presence of one or multiple chronic symptoms including widespread musculoskeletal pain, fatigue, sleep disorders, and abdominal pain, amongst other issues. Symptoms are believed to relate to a complex interaction of biological and psychosocial factors, where a definite aetiology has not been established. Theories suggest causative pathways between the immune and nervous systems of affected individuals with several risk factors identified in patients presenting with one or more functional syndromes. Risk factors including stress and childhood trauma are now recognised as important contributors to chronic pain conditions. Emotional, physical, and sexual abuse during childhood is considered a severe stressor having a high prevalence in functional somatic syndrome suffers. Such trauma permanently alters the biological stress response of the suffers leading to neuroexcitatory and other nerve issues associated with chronic pain in adults. Traumatic and chronic stress results in epigenetic changes in stress response genes, which ultimately leads to dysregulation of the hypothalamic-pituitary axis, the autonomic nervous system, and the immune system manifesting in a broad array of symptoms. Importantly, these systems are known to be dysregulated in patients suffering from functional somatic syndrome. Functional somatic syndromes are also highly prevalent co-morbidities of psychiatric conditions, mood disorders, and anxiety. Consequently, this review aims to provide insight into the role of the nervous system and immune system in chronic pain disorders associated with the musculoskeletal system, and central and peripheral nervous systems. Full article

(This article belongs to the Special Issue The Role of Neurons in Human Health and Disease)

18 pages, 2185 KiB

Open AccessReview

Neuronal-Immune Cell Units in Allergic Inflammation in the Nose

by Vladimir Klimov, Natalia Cherevko, Andrew Klimov and Pavel Novikov

Int. J. Mol. Sci. 2022, 23(13), 6938; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23136938 - 22 Jun 2022

Cited by 6 | Viewed by 2662

Abstract

Immune cells and immune-derived molecules, endocrine glands and hormones, the nervous system and neuro molecules form the combined tridirectional neuroimmune network, which plays a significant role in the communication pathways and regulation at the level of the whole organism and local levels, in both healthy persons and patients with allergic rhinitis based on an allergic inflammatory process. This review focuses on a new research paradigm devoted to neuronal-immune cell units, which are involved in allergic inflammation in the nose and neuroimmune control of the nasal mucociliary immunologically active epithelial barrier. The categorization, cellular sources of neurotransmitters and neuropeptides, and their prevalent profiles in constituting allergen tolerance maintenance or its breakdown are discussed. Novel data on the functional structure of the nasal epithelium based on a transcriptomic technology, single-cell RNA-sequencing results, are considered in terms of neuroimmune regulation. Notably, the research of pathogenesis and therapy for atopic allergic diseases, including recently identified local forms, from the viewpoint of the tridirectional interaction of the neuroimmune network and discrete neuronal-immune cell units is at the cutting-edge. Full article

(This article belongs to the Special Issue The Role of Neurons in Human Health and Disease)

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22 pages, 1434 KiB

Open AccessReview

Immunity, Ion Channels and Epilepsy

by Tsang-Shan Chen, Ming-Chi Lai, Huai-Ying Ingrid Huang, Sheng-Nan Wu and Chin-Wei Huang

Int. J. Mol. Sci. 2022, 23(12), 6446; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23126446 - 09 Jun 2022

Cited by 12 | Viewed by 3392

Abstract

Epilepsy is a common chronic neurological disorder in modern society. One of the major unmet challenges is that current antiseizure medications are basically not disease-modifying. Among the multifaceted etiologies of epilepsy, the role of the immune system has attracted considerable attention in recent years. It is known that both innate and adaptive immunity can be activated in response to insults to the central nervous system, leading to seizures. Moreover, the interaction between ion channels, which have a well-established role in epileptogenesis and epilepsy, and the immune system is complex and is being actively investigated. Some examples, including the interaction between ion channels and mTOR pathways, will be discussed in this paper. Furthermore, there has been substantial progress in our understanding of the pathophysiology of epilepsy associated with autoimmune encephalitis, and numerous neural-specific autoantibodies have been found and documented. Early recognition of immune-mediated epilepsy is important, especially in cases of pharmacoresistant epilepsy and in the presence of signs of autoimmune encephalitis, as early intervention with immunotherapy shows promise. Full article

(This article belongs to the Special Issue The Role of Neurons in Human Health and Disease)

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37 pages, 3251 KiB

Open AccessReview

Reactive and Senescent Astroglial Phenotypes as Hallmarks of Brain Pathologies

by Andrijana Lazic, Vanda Balint, Danijela Stanisavljevic Ninkovic, Mina Peric and Milena Stevanovic

Int. J. Mol. Sci. 2022, 23(9), 4995; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23094995 - 30 Apr 2022

Cited by 20 | Viewed by 4477

Abstract

Astrocytes, as the most abundant glial cells in the central nervous system, are tightly integrated into neural networks and participate in numerous aspects of brain physiology and pathology. They are the main homeostatic cells in the central nervous system, and the loss of astrocyte physiological functions and/or gain of pro-inflammatory functions, due to their reactivation or cellular senescence, can have profound impacts on the surrounding microenvironment with pathological outcomes. Although the importance of astrocytes is generally recognized, and both senescence and reactive astrogliosis have been extensively reviewed independently, there are only a few comparative overviews of these complex processes. In this review, we summarize the latest data regarding astrocyte reactivation and senescence, and outline similarities and differences between these phenotypes from morphological, functional, and molecular points of view. A special focus has been given to neurodegenerative diseases, where these phenotypic alternations of astrocytes are significantly implicated. We also summarize current perspectives regarding new advances in model systems based on astrocytes as well as data pointing to these glial cells as potential therapeutic targets. Full article

(This article belongs to the Special Issue The Role of Neurons in Human Health and Disease)

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13 pages, 988 KiB

Open AccessReview

Alzheimer’s Disease and Tau Self-Assembly: In the Search of the Missing Link

by Andrea González, Sandeep Kumar Singh, Macarena Churruca and Ricardo B. Maccioni

Int. J. Mol. Sci. 2022, 23(8), 4192; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23084192 - 10 Apr 2022

Cited by 8 | Viewed by 2637

Abstract

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disease characterized by progressive cognitive impairment, apathy, and neuropsychiatric disorders. Two main pathological hallmarks have been described: neurofibrillary tangles, consisting of tau oligomers (hyperphosphorylated tau) and Aβ plaques. The influence of protein kinases and phosphatases on the hyperphosphorylation of tau is already known. Hyperphosphorylated tau undergoes conformational changes that promote its self-assembly. However, the process involving these mechanisms is yet to be elucidated. In vitro recombinant tau can be aggregated by the action of polyanions, such as heparin, arachidonic acid, and more recently, the action of polyphosphates. However, how that process occurs in vivo is yet to be understood. In this review, searching the most accurate and updated literature on the matter, we focus on the precise molecular events linking tau modifications, its misfolding and the initiation of its pathological self-assembly. Among these, we can identify challenges regarding tau phosphorylation, the link between tau heteroarylations and the onset of its self-assembly, as well as the possible metabolic pathways involving natural polyphosphates, that may play a role in tau self-assembly. Full article

(This article belongs to the Special Issue The Role of Neurons in Human Health and Disease)

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