scholarly journals The Role of Phospholipase C in GABAergic Inhibition and Its Relevance to Epilepsy

2021 ◽  
Vol 22 (6) ◽  
pp. 3149
Author(s):  
Hye Yun Kim ◽  
Pann-Ghill Suh ◽  
Jae-Ick Kim
Keyword(s):  
Phospholipase C ◽  
Intracellular Signaling ◽  
Neuronal Development ◽  
Gabaergic Inhibition ◽  
Inhibitory Neurotransmitter ◽  
Intracellular Signaling Pathway ◽  
Key Enzyme ◽  
The Central Nervous System ◽  
Neuronal Functions ◽  
The Brain

Epilepsy is characterized by recurrent seizures due to abnormal hyperexcitation of neurons. Recent studies have suggested that the imbalance of excitation and inhibition (E/I) in the central nervous system is closely implicated in the etiology of epilepsy. In the brain, GABA is a major inhibitory neurotransmitter and plays a pivotal role in maintaining E/I balance. As such, altered GABAergic inhibition can lead to severe E/I imbalance, consequently resulting in excessive and hypersynchronous neuronal activity as in epilepsy. Phospholipase C (PLC) is a key enzyme in the intracellular signaling pathway and regulates various neuronal functions including neuronal development, synaptic transmission, and plasticity in the brain. Accumulating evidence suggests that neuronal PLC is critically involved in multiple aspects of GABAergic functions. Therefore, a better understanding of mechanisms by which neuronal PLC regulates GABAergic inhibition is necessary for revealing an unrecognized linkage between PLC and epilepsy and developing more effective treatments for epilepsy. Here we review the function of PLC in GABAergic inhibition in the brain and discuss a pathophysiological relationship between PLC and epilepsy.

Krešimir Krnjević (1927–2021) and GABAergic inhibition: a lifetime dedication

2021 ◽  
pp. 1-4
Author(s):  
Yehezkel Ben-Ari ◽  
Enrico Cherubini ◽  
Massimo Avoli
Keyword(s):  
Canadian Journal ◽  
Chief Editor ◽  
Aminobutyric Acid ◽  
Gabaergic Inhibition ◽  
Inhibitory Neurotransmitter ◽  
Neuroscience Research ◽  
Personal Interactions ◽  
The Brain ◽  
Made In

After over seven decades of neuroscience research, it is now well established that γ-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the brain. In this paper dedicated to Krešimir Krnjević (1927–2021), a pioneer and leader in neuroscience, we briefly highlight the fundamental contributions he made in identifying GABA as an inhibitory neurotransmitter in the brain and our personal interactions with him. Of note, between 1972 and 1978 Dr. Krnjević was a highly reputed Chief Editor of the Canadian Journal of Physiology and Pharmacology.

scholarly journals An Updated Review on Pharmaceutical Properties of Gamma-Aminobutyric Acid

Molecules ◽  
2019 ◽  
Vol 24 (15) ◽  
pp. 2678 ◽  
Author(s):  
Dai-Hung Ngo ◽  
Thanh Sang Vo
Keyword(s):  
Neuronal Development ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Peripheral Tissues ◽  
Inhibitory Neurotransmitter ◽  
Anti Cancer ◽  
The Central Nervous System ◽  
Potential Alternative ◽  
Pharmaceutical Properties ◽  
Anti Inflammation

Gamma-aminobutyric acid (Gaba) is a non-proteinogenic amino acid that is widely present in microorganisms, plants, and vertebrates. So far, Gaba is well known as a main inhibitory neurotransmitter in the central nervous system. Its physiological roles are related to the modulation of synaptic transmission, the promotion of neuronal development and relaxation, and the prevention of sleeplessness and depression. Besides, various pharmaceutical properties of Gaba on non-neuronal peripheral tissues and organs were also reported due to anti-hypertension, anti-diabetes, anti-cancer, antioxidant, anti-inflammation, anti-microbial, anti-allergy, hepato-protection, reno-protection, and intestinal protection. Therefore, Gaba may be considered as potential alternative therapeutics for prevention and treatment of various diseases. Accordingly, this updated review was mainly focused to describe the pharmaceutical properties of Gaba as well as emphasize its important role regarding human health.

scholarly journals Chemokines and chemokine receptors in the brain: implication in neuroendocrine regulation

2007 ◽  
Vol 38 (3) ◽  
pp. 355-363 ◽  
Author(s):  
Céline Callewaere ◽  
Ghazal Banisadr ◽  
William Rostène ◽  
Stéphane Mélik Parsadaniantz
Keyword(s):  
Chemokine Receptors ◽  
Cell Types ◽  
Normal Brain ◽  
Ability To Act ◽  
The Central Nervous System ◽  
Neuronal Functions ◽  
The Brain ◽  
Neuroendocrine Functions

Chemokines are small secreted proteins that chemoattract and activate immune and non-immune cells both in vivo and in vitro. In addition to their well-established role in the immune system, several recent reports have suggested that chemokines and their receptors may also play a role in the central nervous system (CNS). The best known central action is their ability to act as immunoinflammatory mediators. Indeed, these proteins regulate leukocyte infiltration in the brain during inflammatory and infectious diseases. However, we and others recently demonstrated that they are expressed not only in neuroinflammatory conditions, but also constitutively by different cell types including neurons in the normal brain, suggesting that they may act as modulators of neuronal functions. The goal of this review is to highlight the role of chemokines in the control of neuroendocrine functions. First, we will focus on the expression of chemokines and their receptors in the CNS, with the main spotlight on the neuronal expression in the hypothalamo–pituitary system. Secondly, we will discuss the role – we can now suspect – of chemokines and their receptors in the regulation of neuroendocrine functions. In conclusion, we propose that chemokines can be added to the well-described neuroendocrine regulatory mechanisms, providing an additional fine modulatory tuning system in physiological conditions.

scholarly journals Impact of estrogens and estrogen receptor-α in brain lipid metabolism

2018 ◽  
Vol 315 (1) ◽  
pp. E7-E14 ◽  
Author(s):  
Eugenia Morselli ◽  
Roberta de Souza Santos ◽  
Su Gao ◽  
Yenniffer Ávalos ◽  
Alfredo Criollo ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Intracellular Signaling ◽  
Fatty Acid Content ◽  
Estrogen Receptor Α ◽  
Signaling Cascades ◽  
Brain Lipid ◽  
Adipose Tissues ◽  
The Central Nervous System ◽  
The Brain

Estrogens and their receptors play key roles in regulating body weight, energy expenditure, and metabolic homeostasis. It is known that lack of estrogens promotes increased food intake and induces the expansion of adipose tissues, for which much is known. An area of estrogenic research that has received less attention is the role of estrogens and their receptors in influencing intermediary lipid metabolism in organs such as the brain. In this review, we highlight the actions of estrogens and their receptors in regulating their impact on modulating fatty acid content, utilization, and oxidation through their direct impact on intracellular signaling cascades within the central nervous system.

Exposure to 835 MHz radiofrequency electromagnetic field induces autophagy in hippocampus but not in brain stem of mice

2017 ◽  
Vol 34 (1) ◽  
pp. 23-35 ◽  
Author(s):  
Ju Hwan Kim ◽  
Da-Hyeon Yu ◽  
Hyo-Jeong Kim ◽  
Yang Hoon Huh ◽  
Seong-Wan Cho ◽  
...  
Keyword(s):  
Brain Stem ◽  
Mobile Phones ◽  
Hippocampal Neurons ◽  
Brain Regions ◽  
Pcr Analysis ◽  
Limited Information ◽  
The Central Nervous System ◽  
Neuronal Functions ◽  
Adaptation Processes ◽  
The Brain

The exploding popularity of mobile phones and their close proximity to the brain when in use has raised public concern regarding possible adverse effects from exposure to radiofrequency electromagnetic fields (RF-EMF) on the central nervous system. Numerous studies have suggested that RF-EMF emitted by mobile phones can influence neuronal functions in the brain. Currently, there is still very limited information on what biological mechanisms influence neuronal cells of the brain. In the present study, we explored whether autophagy is triggered in the hippocampus or brain stem after RF-EMF exposure. C57BL/6 mice were exposed to 835 MHz RF-EMF with specific absorption rates (SAR) of 4.0 W/kg for 12 weeks; afterward, the hippocampus and brain stem of mice were dissected and analyzed. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis demonstrated that several autophagic genes, which play key roles in autophagy regulation, were significantly upregulated only in the hippocampus and not in the brain stem. Expression levels of LC3B-II protein and p62, crucial autophagic regulatory proteins, were significantly changed only in the hippocampus. In parallel, transmission electron microscopy (TEM) revealed an increase in the number of autophagosomes and autolysosomes in the hippocampal neurons of RF-EMF-exposed mice. The present study revealed that autophagy was induced in the hippocampus, not in the brain stem, in 835 MHz RF-EMF with an SAR of 4.0 W/kg for 12 weeks. These results could suggest that among the various adaptation processes to the RF-EMF exposure environment, autophagic degradation is one possible mechanism in specific brain regions.

ET-1 induces cortical spreading depression via activation of the ETA receptor/phospholipase C pathway in vivo

2004 ◽  
Vol 286 (4) ◽  
pp. H1339-H1346 ◽  
Author(s):  
Jörg Kleeberg ◽  
Gabor C. Petzold ◽  
Sebastian Major ◽  
Ulrich Dirnagl ◽  
Jens P. Dreier
Keyword(s):  
Receptor Antagonist ◽  
Phospholipase C ◽  
Intracellular Signaling ◽  
Neuronal Excitability ◽  
Calcium Waves ◽  
Direct Stimulation ◽  
Intracellular Signaling Pathway ◽  
Receptor Profile

Recently, it has been shown that brain topical superfusion of endothelin (ET)-1 at concentrations around 100 nM induces repetitive cortical spreading depressions (CSDs) in vivo. It has remained unclear whether this effect of ET-1 is related to a primary neuronal/astroglial effect, such as an increase in neuronal excitability or induction of interastroglial calcium waves, or a penumbra-like condition after vasoconstriction. In vitro, ET-1 regulates interastroglial communication via combined activation of ETA and ETB receptors, whereas it induces vasoconstriction via single activation of ETA receptors. We have determined the ET receptor profile and intracellular signaling pathway of ET-1-induced CSDs in vivo. In contrast to the ETB receptor antagonist BQ-788 and concentration dependently, the ETA receptor antagonist BQ-123 completely blocked the occurrence of ET-1-induced CSDs. The ETB receptor antagonist did not increase the efficacy of the ETA receptor antagonist. Direct stimulation of ETB receptors with the selective ETB agonist BQ-3020 did not trigger CSDs. The phospholipase C (PLC) antagonist U-73122 inhibited CSD occurrence in contrast to the protein kinase C inhibitor Gö-6983. Our findings indicate that ET-1 induces CSDs through ETA receptor and PLC activation. We conclude that the induction of interastroglial calcium waves is unlikely the primary cause of ET-1-induced CSDs. On the basis of the receptor profile, likely primary targets of ET-1 mediating CSD are either neurons or vascular smooth muscle cells.

scholarly journals Fyn Tyrosine Kinase as Harmonizing Factor in Neuronal Functions and Dysfunctions

2020 ◽  
Vol 21 (12) ◽  
pp. 4444 ◽  
Author(s):  
Carmela Matrone ◽  
Federica Petrillo ◽  
Rosarita Nasso ◽  
Gabriella Ferretti
Keyword(s):  
Tyrosine Kinase ◽  
Signaling Pathways ◽  
Common Factor ◽  
Original Description ◽  
Therapeutic Interventions ◽  
Molecular Signaling ◽  
The Central Nervous System ◽  
Neurological Conditions ◽  
Neuronal Functions ◽  
The Brain

Fyn is a non-receptor or cytoplasmatic tyrosine kinase (TK) belonging to the Src family kinases (SFKs) involved in multiple transduction pathways in the central nervous system (CNS) including synaptic transmission, myelination, axon guidance, and oligodendrocyte formation. Almost one hundred years after the original description of Fyn, this protein continues to attract extreme interest because of its multiplicity of actions in the molecular signaling pathways underlying neurodevelopmental as well as neuropathologic events. This review highlights and summarizes the most relevant recent findings pertinent to the role that Fyn exerts in the brain, emphasizing aspects related to neurodevelopment and synaptic plasticity. Fyn is a common factor in healthy and diseased brains that targets different proteins and shapes different transduction signals according to the neurological conditions. We will primarily focus on Fyn-mediated signaling pathways involved in neuronal differentiation and plasticity that have been subjected to considerable attention lately, opening the fascinating scenario to target Fyn TK for the development of potential therapeutic interventions for the treatment of CNS injuries and certain neurodegenerative disorders like Alzheimer’s disease.

scholarly journals Caffeine Components Empower the Brain Potentiality

2020 ◽  
Vol 1 (1) ◽  
pp. 16-17
Author(s):  
Seyedeh Nasim Habibzadeh
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Standard Dose ◽  
Inhibitory Neurotransmitter ◽  
Nutritional Components ◽  
Dietary Component ◽  
The Central Nervous System ◽  
The Right ◽  
High Level ◽  
The Brain

The brain requires certain fuels to function in high level. Literally, nutritional components can modulate the brain productivity. One of the right nutrition to enhance the brain power is dietary component of caffeine. Caffeine as a component of coffee, tea and chocolate is very popular. Although, depending on the dietary demands or conventional habits some people do not consume caffeine-containing substances (i.e. foods or beverage). Nonetheless, caffeine constituents maximize the brain potential via promoting the central nervous system (CNS) through blocking an inhibitory neurotransmitter (adenosine) and releasing some other specific neurotransmitters (noradrenaline, dopamine and serotonin) in brain. The chemistry of caffeine in a standard dose in fact can affect the brain intelligence.

scholarly journals Neural Functions of Matrix Metalloproteinases: Plasticity, Neurogenesis, and Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Hiromi Fujioka ◽  
Yusuke Dairyo ◽  
Kei-ichiro Yasunaga ◽  
Kazuo Emoto
Keyword(s):  
Extracellular Matrix ◽  
Nervous System ◽  
Matrix Metalloproteinases ◽  
Neuronal Development ◽  
Neuronal Circuits ◽  
Intrinsic Factors ◽  
Neuronal Disease ◽  
Brain Changes ◽  
Neuronal Functions ◽  
The Brain

The brain changes in response to experience and altered environment. To do that, the nervous system often remodels the structures of neuronal circuits. This structural plasticity of the neuronal circuits appears to be controlled not only by intrinsic factors, but also by extrinsic mechanisms including modification of the extracellular matrix. Recent studies employing a range of animal models implicate that matrix metalloproteinases regulate multiple aspects of the neuronal development and remodeling in the brain. This paper aims to summarize recent advances of our knowledge on the neuronal functions of matrix metalloproteinases and discuss how they might relate in neuronal disease.

scholarly journals Histone Glutamine Modification by Neurotransmitters: Paradigm Shift in the Epigenetics of Neuronal Gene Activation and Dopaminergic VTA Reward Pathway

2020 ◽  
Author(s):  
Samir PATRA
Keyword(s):  
Gene Expression ◽  
Neuronal Development ◽  
Tissue Transglutaminase ◽  
Gene Activation ◽  
Central Element ◽  
Dopamine Neurons ◽  
Normal Brain ◽  
Reward Pathway ◽  
Neuronal Functions ◽  
The Brain

Normal brain function means fine-tuned neuronal circuitry with optimum neurotransmitter signaling. The classical views and experimental demonstrations established neurotransmitters release-uptake through synaptic vesicles. Current research highlighted that neurotransmitters not merely influence electrical impulses; however, contribute to gene expression, now we know, by posttranslational modifications of chromatinised histones. Epigenetic modifications of chromatin, like DNA methylation, histone methylation, acetylation, ubiquitilation etc., influence gene expression during neuronal development, differentiation and functions. Protein glutamine (Q) modification by tissue transglutaminase (TGM2) controls a wide array of metabolic and signaling activities, including neuronal functions. Dopamine neurons are central element in the brain reward system that controls the learning of numerous behaviours. The ventral tegmental area (VTA) consists of dopamine, GABA, or glutamate neurons. The VTA and adjacent substantia nigra are the two major dopaminergic areas in the brain. In view of this, and to focus insight into the neuronal functions caused by TGM2 mediated histone modifications at the Q residues, either serotonylation (for example, H3K4me3Q5 to H3K4me3Q5ser) in the context of cellular differentiation and signaling, or dopaminylation (for example, H3Q5 to H3Q5dop) in the dopaminergic VTA reward pathway and the precise role of cocaine withdrawal in this scenario are summarized and discussed in this contribution.

Sign in / Sign up

Export Citation Format

Share Document