scholarly journals Cholinergic Signaling, Neural Excitability, and Epilepsy

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2258
Author(s):  
Yu Wang ◽  
Bei Tan ◽  
Yi Wang ◽  
Zhong Chen
Keyword(s):  
Cholinergic Neurons ◽  
Epileptic Seizures ◽  
Brain Disorder ◽  
Neural Excitability ◽  
Cholinergic Signaling ◽  
The Central Nervous System ◽  
Muscarinic And Nicotinic Receptors ◽  
Cumulative Evidence ◽  
Precise Role

Epilepsy is a common brain disorder characterized by recurrent epileptic seizures with neuronal hyperexcitability. Apart from the classical imbalance between excitatory glutamatergic transmission and inhibitory γ-aminobutyric acidergic transmission, cumulative evidence suggest that cholinergic signaling is crucially involved in the modulation of neural excitability and epilepsy. In this review, we briefly describe the distribution of cholinergic neurons, muscarinic, and nicotinic receptors in the central nervous system and their relationship with neural excitability. Then, we summarize the findings from experimental and clinical research on the role of cholinergic signaling in epilepsy. Furthermore, we provide some perspectives on future investigation to reveal the precise role of the cholinergic system in epilepsy.

scholarly journals Central Histaminergic Signaling, Neural Excitability and Epilepsy

2020 ◽  
Author(s):  
Lin Yang ◽  
Yi Wang ◽  
Zhong Chen
Keyword(s):  
Epileptic Seizures ◽  
Histamine Receptor ◽  
Traditional Theory ◽  
Receptor Ligands ◽  
Brain Histamine ◽  
Neural Excitability ◽  
Current Medication ◽  
The Central Nervous System ◽  
Epilepsy Models

Epilepsy is a common neurological disorder characterized by repeated and spontaneous epileptic seizures, which is not well controlled by current medication. Traditional theory supports that epilepsy results from the imbalance of excitatory glutamate neurons and inhibitory GABAergic neurons. Recently, shreds of evidence from available clinical and preclinical researches suggest that histamine in the central nervous system plays an important role in the modulation of neural excitability and pathogenesis of epilepsy. Many histamine receptor ligands show positive response in animal epilepsy models, among which the H3R antagonist pitolisant even has shown a good anti-epileptic effect in clinical trials. New insights are focusing on the potential action of histamine receptors to control and treat epilepsy. This review summarizes the findings from animal and clinical researches on the role of brain histamine and histamine receptor in epilepsy. Importantly, we further provide perspectives on some possible research directions for future studies.

scholarly journals Optogenetic studies of nicotinic contributions to cholinergic signaling in the central nervous system

2014 ◽  
Vol 25 (6) ◽  
Author(s):  
Li Jiang ◽  
Gretchen Y. López-Hernández ◽  
James Lederman ◽  
David A. Talmage ◽  
Lorna W. Role
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
New Technology ◽  
Cholinergic Neurons ◽  
Difficult Problem ◽  
Receptor Subtypes ◽  
Cholinergic Signaling ◽  
The Central Nervous System ◽  
The Many

AbstractMolecular manipulations and targeted pharmacological studies provide a compelling picture of which nicotinic receptor subtypes are where in the central nervous system (CNS) and what happens if one activates or deletes them. However, understanding the physiological contribution of nicotinic receptors to endogenous acetylcholine (ACh) signaling in the CNS has proven a more difficult problem to solve. In this review, we provide a synopsis of the literature on the use of optogenetic approaches to control the excitability of cholinergic neurons and to examine the role of CNS nicotinic ACh receptors (nAChRs). As is often the case, this relatively new technology has answered some questions and raised others. Overall, we believe that optogenetic manipulation of cholinergic excitability in combination with some rigorous pharmacology will ultimately advance our understanding of the many functions of nAChRs in the brain.

scholarly journals Alteration of Mesopontine Cholinergic Function by the Lack of KCNQ4 Subunit

2021 ◽  
Vol 15 ◽  
Author(s):  
T. Bayasgalan ◽  
S. Stupniki ◽  
A. Kovács ◽  
A. Csemer ◽  
P. Szentesi ◽  
...  
Keyword(s):  
Expression Patterns ◽  
Cholinergic Neurons ◽  
Pedunculopontine Nucleus ◽  
M Current ◽  
Behavioral Studies ◽  
Cholinergic Signaling ◽  
Light Darkness ◽  
Reticular Activating System ◽  
The Central Nervous System

The pedunculopontine nucleus (PPN), a structure known as a cholinergic member of the reticular activating system (RAS), is source and target of cholinergic neuromodulation and contributes to the regulation of the sleep–wakefulness cycle. The M-current is a voltage-gated potassium current modulated mainly by cholinergic signaling. KCNQ subunits ensemble into ion channels responsible for the M-current. In the central nervous system, KCNQ4 expression is restricted to certain brainstem structures such as the RAS nuclei. Here, we investigated the presence and functional significance of KCNQ4 in the PPN by behavioral studies and the gene and protein expressions and slice electrophysiology using a mouse model lacking KCNQ4 expression. We found that this mouse has alterations in the adaptation to changes in light–darkness cycles, representing the potential role of KCNQ4 in the regulation of the sleep–wakefulness cycle. As cholinergic neurons from the PPN participate in the regulation of this cycle, we investigated whether the cholinergic PPN might also possess functional KCNQ4 subunits. Although the M-current is an electrophysiological hallmark of cholinergic neurons, only a subpopulation of them had KCNQ4-dependent M-current. Interestingly, the absence of the KCNQ4 subunit altered the expression patterns of the other KCNQ subunits in the PPN. We also determined that, in wild-type animals, the cholinergic inputs of the PPN modulated the M-current, and these in turn can modulate the level of synchronization between neighboring PPN neurons. Taken together, the KCNQ4 subunit is present in a subpopulation of PPN cholinergic neurons, and it may contribute to the regulation of the sleep–wakefulness cycle.

scholarly journals Social Isolation: How Can the Effects on the Cholinergic System Be Isolated?

2021 ◽  
Vol 12 ◽  
Author(s):  
Jaromir Myslivecek
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Social Isolation ◽  
Cholinergic System ◽  
System Response ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Cholinergic Signaling ◽  
The Central Nervous System

Social species form organizations that support individuals because the consequent social behaviors help these organisms survive. The isolation of these individuals may be a stressor. We reviewed the potential mechanisms of the effects of social isolation on cholinergic signaling and vice versa how changes in cholinergic signaling affect changes due to social isolation.There are two important problems regarding this topic. First, isolation schemes differ in their duration (1–165 days) and initiation (immediately after birth to adulthood). Second, there is an important problem that is generally not considered when studying the role of the cholinergic system in neurobehavioral correlates: muscarinic and nicotinic receptor subtypes do not differ sufficiently in their affinity for orthosteric site agonists and antagonists. Some potential cholinesterase inhibitors also affect other targets, such as receptors or other neurotransmitter systems. Therefore, the role of the cholinergic system in social isolation should be carefully considered, and multiple receptor systems may be involved in the central nervous system response, although some subtypes are involved in specific functions. To determine the role of a specific receptor subtype, the presence of a specific subtype in the central nervous system should be determined using search in knockout studies with the careful application of specific agonists/antagonists.

Migraine and the Hypothalamus

Cephalalgia ◽  
2009 ◽  
Vol 29 (8) ◽  
pp. 809-817 ◽  
Author(s):  
KB Alstadhaug
Keyword(s):  
Nervous System ◽  
Joint Effect ◽  
Emission Tomography ◽  
Minor Role ◽  
Brain Disorder ◽  
Positron Emission ◽  
Pet Scanning ◽  
The Central Nervous System ◽  
Hypothalamic Activation

Migraine is a complex brain disorder where several neuronal pathways and neurotransmitters are involved in the pathophysiology. To search for a specific anatomical or physiological defect in migraine may be futile, but the hypothalamus, with its widespread connections with other parts of the central nervous system and its paramount control of the hypophysis and the autonomic nervous system, is a suspected locus in quo. Several lines of evidence support involvement of this small brain structure in migraine. However, whether it plays a major or minor role is unclear. The most convincing support for a pivotal role so far is the activation of the hypothalamus shown by positron emission tomography (PET) scanning during spontaneous migraine attacks. A well-known theory is that the joint effect of several triggers may cause temporary hypothalamic dysfunction, resulting in a migraine attack. If PET scanning had consistently confirmed hypothalamic activation prior to migraine headache, this hypothesis would have been supported. However, such evidence has not been provided, and the role of the hypothalamus in migraine remains puzzling. This review summarizes and discusses some of the clues.

Gut microbiome-mediated epigenetic regulation of brain disorder and application of machine learning for multi-omics data analysis

Genome ◽  
2020 ◽  
pp. 1-17
Author(s):  
Harpreet Kaur ◽  
Yuvraj Singh ◽  
Surjeet Singh ◽  
Raja B. Singh
Keyword(s):  
Machine Learning ◽  
Nervous System ◽  
Gut Microbiota ◽  
Epigenetic Regulation ◽  
Omics Data ◽  
Brain Disorder ◽  
Deacetylase Inhibitor ◽  
The Central Nervous System ◽  
Host Metabolism

The gut–brain axis (GBA) is a biochemical link that connects the central nervous system (CNS) and enteric nervous system (ENS). Clinical and experimental evidence suggests gut microbiota as a key regulator of the GBA. Microbes living in the gut not only interact locally with intestinal cells and the ENS but have also been found to modulate the CNS through neuroendocrine and metabolic pathways. Studies have also explored the involvement of gut microbiota dysbiosis in depression, anxiety, autism, stroke, and pathophysiology of other neurodegenerative diseases. Recent reports suggest that microbe-derived metabolites can influence host metabolism by acting as epigenetic regulators. Butyrate, an intestinal bacterial metabolite, is a known histone deacetylase inhibitor that has shown to improve learning and memory in animal models. Due to high disease variability amongst the population, a multi-omics approach that utilizes artificial intelligence and machine learning to analyze and integrate omics data is necessary to better understand the role of the GBA in pathogenesis of neurological disorders, to generate predictive models, and to develop precise and personalized therapeutics. This review examines our current understanding of epigenetic regulation of the GBA and proposes a framework to integrate multi-omics data for prediction, prevention, and development of precision health approaches to treat brain disorders.

scholarly journals Calcium Hypothesis of Gulf War Illness: Role of Calcium Ions in Neurological Morbidities in a DFP-Based Rat Model for Gulf War Illness

2020 ◽  
Vol 15 ◽  
pp. 263310552097984
Author(s):  
Kristin F Phillips ◽  
Laxmikant S Deshpande
Keyword(s):  
Experimental Models ◽  
Gulf War ◽  
Signaling Cascades ◽  
Gulf War Illness ◽  
Downstream Signaling ◽  
Cholinergic Signaling ◽  
Glutamatergic Signaling ◽  
The Central Nervous System ◽  
System Disorder

Gulf War Illness (GWI) refers to a multi-system disorder that afflicts approximately 30% of First Gulf War (GW) veterans. Amongst the symptoms exhibited, mood and memory impairment are commonly reported by GW veterans. Exposure to organophosphate (OP) compounds which target the cholinergic system is considered a leading cause for GWI symptoms. It is hypothesized that chronic OP-based war-time stimulation of cholinergic signaling led to recruitment of excitatory glutamatergic signaling and other downstream signaling cascades leading to neuronal injury, neuroinflammation, generation of reactive oxygen species, oxidative stress, and mitochondrial damage within the central nervous system. These findings have been observed in both experimental models and GWI veterans. In this context the role of calcium (Ca2+) signaling in GWI has come to the forefront. Here we present our Ca2+ hypothesis of GWI that suggests sustained neuronal Ca2+ elevations serve as a molecular trigger for pathological synaptic plasticity that has allowed for the persistence of GWI symptoms. Subsequently we discuss that therapeutic targeting of Ca2+ homeostatic mechanisms provides novel targets for effective treatment of GWI-related neurological signs in our rodent model.

scholarly journals The Dichotomous Role of Inflammation in the CNS: A Mitochondrial Point of View

Biomolecules ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1437
Author(s):  
Bianca Vezzani ◽  
Marianna Carinci ◽  
Simone Patergnani ◽  
Matteo P. Pasquin ◽  
Annunziata Guarino ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Epileptic Seizures ◽  
Point Of View ◽  
Innate Immune ◽  
Molecular Signaling ◽  
Therapeutic Approaches ◽  
Neuroinflammatory Response ◽  
The Central Nervous System

Innate immune response is one of our primary defenses against pathogens infection, although, if dysregulated, it represents the leading cause of chronic tissue inflammation. This dualism is even more present in the central nervous system, where neuroinflammation is both important for the activation of reparatory mechanisms and, at the same time, leads to the release of detrimental factors that induce neurons loss. Key players in modulating the neuroinflammatory response are mitochondria. Indeed, they are responsible for a variety of cell mechanisms that control tissue homeostasis, such as autophagy, apoptosis, energy production, and also inflammation. Accordingly, it is widely recognized that mitochondria exert a pivotal role in the development of neurodegenerative diseases, such as multiple sclerosis, Parkinson’s and Alzheimer’s diseases, as well as in acute brain damage, such in ischemic stroke and epileptic seizures. In this review, we will describe the role of mitochondria molecular signaling in regulating neuroinflammation in central nervous system (CNS) diseases, by focusing on pattern recognition receptors (PRRs) signaling, reactive oxygen species (ROS) production, and mitophagy, giving a hint on the possible therapeutic approaches targeting mitochondrial pathways involved in inflammation.

scholarly journals The Role of Astrocytes in the Cause of Alzheimer's Disease

2021 ◽  
Vol 10 (3) ◽  
Author(s):  
Nadia Priyam ◽  
Andrew Savoy
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Cholinergic Neurons ◽  
Amyloid Plaques ◽  
Nerve Growth ◽  
App Processing ◽  
Cholinergic Signaling

There are three leading hypotheses about the cause of Alzheimer’s Disease (AD): the cholinergic theory, where there is a loss of cholinergic neurons; the amyloid hypothesis, where there is an abnormal buildup of amyloid plaques; and the neurotrophic unbalance hypothesis, which states that AD-related loss of cholinergic signaling and altered amyloid precursor protein (APP) processing are due to alterations in nerve growth factor (NGF). This would ultimately mean that the loss of cholinergic neurons and a buildup of amyloid plaques are due to NGF alterations. Astrocytes are involved in the production of amyloid-beta, inflammation responses, and nerve growth. Therefore, astrocytes are an essential component of all three AD hypotheses. This paper will discuss various known and hypothesized ways that astrocytes affect the symptoms and possible causes of AD.

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