Calcium-Permeable Ion Channels in Pain Signaling

The detection and processing of painful stimuli in afferent sensory neurons is critically dependent on a wide range of different types of voltage- and ligand-gated ion channels, including sodium, calcium, and TRP channels, to name a few. The functions of these channels include the detection of mechanical and chemical insults, the generation of action potentials and regulation of neuronal firing patterns, the initiation of neurotransmitter release at dorsal horn synapses, and the ensuing activation of spinal cord neurons that project to pain centers in the brain. Long-term changes in ion channel expression and function are thought to contribute to chronic pain states. Many of the channels involved in the afferent pain pathway are permeable to calcium ions, suggesting a role in cell signaling beyond the mere generation of electrical activity. In this article, we provide a broad overview of different calcium-permeable ion channels in the afferent pain pathway and their role in pain pathophysiology.

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Extracellular vesicles (exosomes and ectosomes) play key roles in the pathology of brain diseases

Molecular Biomedicine ◽

10.1186/s43556-021-00040-5 ◽

2021 ◽

Vol 2 (1) ◽

Author(s):

Jacopo Meldolesi

Keyword(s):

Multiple Sclerosis ◽

Extracellular Vesicles ◽

Brain Diseases ◽

Target Cells ◽

Surface Binding ◽

Cells Of Origin ◽

Relapsing Remitting ◽

And Function ◽

The Brain

AbstractLast century, neurons and glial cells were mostly believed to play distinct functions, relevant for the brain. Progressively, however, it became clear that neurons, astrocytes and microglia co-operate intensely with each other by release/binding of signaling factors, direct surface binding and generation/release of extracellular vesicles, the exosomes and ectosomes, called together vesicles in this abstract. The present review is focused on these vesicles, fundamental in various brain diseases. Their properties are extraordinary. The specificity of their membrane governs their fusion with distinct target cells, variable depending on the state and specificity of their cells of origin and target. Result of vesicle fusion is the discharge of their cargos into the cytoplasm of target cells. Cargos are composed of critical molecules, from proteins (various nature and function) to nucleotides (especially miRNAs), playing critical roles in immune and neurodegenerative diseases. Among immune diseases is multiple sclerosis, affected by extensive dysregulation of co-trafficking neural and glial vesicles, with distinct miRNAs inducing severe or reducing effects. The vesicle-dependent differences between progressive and relapsing-remitting forms of the disease are relevant for clinical developments. In Alzheimer’s disease the vesicles can affect the brain by changing their generation and inducing co-release of effective proteins, such Aβ and tau, from neurons and astrocytes. Specific miRNAs can delay the long-term development of the disease. Upon their traffic through the blood-brainbarrier, vesicles of various origin reach fluids where they are essential for the identification of biomarkers, important for diagnostic and therapeutic innovations, critical for the future of many brain patients.

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A Memória de Longo Prazo e a Análise Sobre sua Função no Processo de Aprendizagem

Revista de Ensino Educação e Ciências Humanas ◽

10.17921/2447-8733.2018v19n1p66-72 ◽

2018 ◽

Vol 19 (1) ◽

pp. 66

Author(s):

Lia Almeida Mapurunga ◽

Elcyana Bezerra Elcyana Bezerra Carvalho

Keyword(s):

Cognitive Psychology ◽

Learning Strategies ◽

Long Term Memory ◽

Term Memory ◽

Positive Effects ◽

Bibliographical Survey ◽

And Function ◽

The Relationship ◽

The Brain

A neurociência é uma ciência natural que estuda a função e a estrutura, que compõem o cérebro. A educação, embora tenha outra natureza, tem tido muitos benefícios com as contribuições que a neurociência tem para oferecer. Como o cérebro aprende e por que aprende traz para o ensino o objetivo e a função de criar condições (entre estratégias, recursos e adequação do meio), para que ocorra a aprendizagem. E, para que essa ocorra, é necessário que as funções mentais superiores, como a memória, estejam envolvidas. O objetivo deste estudo consiste em fazer uma revisão de literatura para conhecer a função da memória de longo prazo na aprendizagem, analisar os mecanismos neurobiológicos, que ocorrem durante esse processo e algumas estratégias de aprendizagem, que se utilizam da memória como recurso. Para isso, foi realizado no período de agosto a outubro de 2016, um levantamento bibliográfico nas bases de dados Scielo, Capes, Bireme e Google Acadêmico, buscando artigos científicos, que poderiam trazer alguma contribuição na construção dessa pesquisa. Foram selecionados, preferencialmente, os que continham enfoque na relação entre aprendizagem e memória, tanto na perspectiva da neurociência, quanto da psicologia cognitiva, trazendo argumentos que pudessem comprovar o entendimento das estratégias de aprendizagem, a partir da memória de longo prazo. Também foram selecionados livros que apresentavam apoio às temáticas discorridas para esse trabalho, possibilitando essa relação. Os resultados apontam que estratégias de aprendizagens, que utilizam a memória, produzem efeitos positivos para a retenção de longo prazo.Palavras-chave: Aprendizagem. Neurociências. Estratégias de Aprendizagem.AbstractNeuroscience is a natural science that studies the function and structure that forms the brain. Although education has another nature, it has had many benefits from the contributions that neuroscience has to offer. How the brain learns and why it learns brings to teaching the intent and function to create conditions (among strategies, resources and suitability to the environment) so that learning can happen. And, for it to occur, it is necessary that higher mental functions, such as memory, beinvolved. The purpose of this study is to do a literature review to get to know the function of long-term memory on the learning process, to analyze the neurobiological mechanisms that happen during that process, and some learning strategies that use memory as a resource. Therefore a bibliographical survey was conducted at the databases Scielo, Capes, Bireme and Academic Google, from August to October 2016, searching for scientific articles that could contribute somehow on the construction of this research. The articles that used the neuroscience perspective or the cognitive psychology to focus on the relationship between learning and memory were chosen, preferentially those whose arguments could prove the learning strategies understanding about he long-term memory. Books supporting the themes discussed for this work were also selected, creating, therefore, a relationship. The results show that learning strategies that use memory have positive effects for long-term retention.Keywords: Learning. Neuroscience. Learning Strategies.

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Modern aspects of neuropathogenesis and neurological manifestations of COVID-19

INTERNATIONAL NEUROLOGICAL JOURNAL ◽

10.22141/2224-0713.17.2.2021.229887 ◽

2021 ◽

Vol 17 (2) ◽

pp. 6-15

Author(s):

L.A. Dziak ◽

O.S. Tsurkalenko ◽

K.V. Chekha ◽

V.M. Suk

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Psychiatric Symptoms ◽

Clinical Manifestations ◽

The Body ◽

Altered Level ◽

Wide Range ◽

The Central Nervous System ◽

The Brain

Coronavirus infection is a systemic pathology resulting in impairment of the nervous system. The involvement of the central nervous system in COVID-19 is diverse by clinical manifestations and main mechanisms. The mechanisms of interrelations between SARS-CoV-2 and the nervous system include a direct virus-induced lesion of the central nervous system, inflammatory-mediated impairment, thrombus burden, and impairment caused by hypoxia and homeostasis. Due to the multi-factor mechanisms (viral, immune, hypoxic, hypercoagulation), the SARS-CoV-2 infection can cause a wide range of neurological disorders involving both the central and peripheral nervous system and end organs. Dizziness, headache, altered level of consciousness, acute cerebrovascular diseases, hypogeusia, hyposmia, peripheral neuropathies, sleep disorders, delirium, neuralgia, myalgia are the most common signs. The structural and functional changes in various organs and systems and many neurological symptoms are determined to persist after COVID-19. Regardless of the numerous clinical reports about the neurological and psychiatric symptoms of COVID-19 as before it is difficult to determine if they are associated with the direct or indirect impact of viral infection or they are secondary to hypoxia, sepsis, cytokine reaction, and multiple organ failure. Penetrated the brain, COVID-19 can impact the other organs and systems and the body in general. Given the mechanisms of impairment, the survivors after COVID-19 with the infection penetrated the brain are more susceptible to more serious diseases such as Parkinson’s disease, cognitive decline, multiple sclerosis, and other autoimmune diseases. Given the multi-factor pathogenesis of COVID-19 resulting in long-term persistence of the clinical symptoms due to impaired neuroplasticity and neurogenesis followed by cholinergic deficiency, the usage of Neuroxon® 1000 mg a day with twice-day dosing for 30 days. Also, a long-term follow-up and control over the COVID-19 patients are recommended for the prophylaxis, timely determination, and correction of long-term complications.

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Global enhancement of cortical excitability following coactivation of large neuronal populations

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1914869117 ◽

2020 ◽

Vol 117 (33) ◽

pp. 20254-20264 ◽

Cited By ~ 1

Author(s):

Deng Zhang ◽

Xingjian Yan ◽

Liang She ◽

Yunqing Wen ◽

Mu-ming Poo

Keyword(s):

Cortical Neurons ◽

Neuronal Excitability ◽

Cortical Excitability ◽

Large Population ◽

Neuronal Firing ◽

Enhancement Effect ◽

Neuronal Populations ◽

Mouse Cortex ◽

The Brain

Correlated activation of cortical neurons often occurs in the brain and repetitive correlated neuronal firing could cause long-term modifications of synaptic efficacy and intrinsic excitability. We found that repetitive optogenetic activation of neuronal populations in the mouse cortex caused enhancement of optogenetically evoked firing of local coactivated neurons as well as distant cortical neurons in both ipsilateral and contralateral hemispheres. This global enhancement of evoked responses required coactivation of a sufficiently large population of neurons either within one cortical area or distributed in several areas. Enhancement of neuronal firing was saturable after repeated episodes of coactivation, diminished by inhibition ofN-methyl-d-aspartic acid receptors, and accompanied by elevated excitatory postsynaptic potentials, all consistent with activity-induced synaptic potentiation. Chemogenetic inhibition of neuronal activity of the thalamus decreased the enhancement effect, suggesting thalamic involvement. Thus, correlated excitation of large neuronal populations leads to global enhancement of neuronal excitability.

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Therapeutic Use of the Ketogenic Diet in Refractory Epilepsy: What We Know and What Still Needs to Be Learned

Nutrients ◽

10.3390/nu12092616 ◽

2020 ◽

Vol 12 (9) ◽

pp. 2616

Author(s):

Iwona Maria Zarnowska

Keyword(s):

Ketogenic Diet ◽

Refractory Epilepsy ◽

Epileptic Activity ◽

Clinical Settings ◽

Modified Atkins Diet ◽

Current State ◽

Wide Range ◽

Low Carbohydrate ◽

The Brain

Ketogenic diet (KD) has been used to treat epilepsy for 100 years. It is a high-fat, low-carbohydrate, and sufficient-protein-for-growth diet that mimics the metabolic changes occurring during starvation. Except for classic KD, its modified counterparts, including modified Atkins diet and low-glycemic-index treatment, have gained grounds to increase palatability and adherence. Strong evidence exists that the KD offers protection against seizures in difficult-to-treat epilepsy and possesses long-lasting anti-epileptic activity, improving long-term disease outcome. The KD can also provide symptomatic and disease-modifying activity in a wide range of neurodegenerative diseases. In an era of highly available new anti-seizure medications (ASMs), the challenge of refractory epilepsy has still not been solved. This metabolic therapy is increasingly considered due to unique mechanisms and turns out to be a powerful tool in the hands of a skillful team. Despite decades of extensive research to explain the mechanism of its efficacy, the precise mechanism of action is to date still largely unknown. The key feature of this successful diet is the fact that energy is derived largely from fat but not from carbohydrates. Consequently, fundamental change occurs regarding the method of energy production that causes alterations in numerous biochemical pathways, thus restoring energetic and metabolic homeostasis of the brain. There are barriers during the use of this special and individualized therapy in many clinical settings worldwide. The aim of this review is to revisit the current state of the art of therapeutic application of KD in refractory epilepsy.

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Alcohol Pathophysiology

Journal of Psychophysiology ◽

10.1027/0269-8803/a000035 ◽

2010 ◽

Vol 24 (4) ◽

pp. 215-230 ◽

Cited By ~ 4

Author(s):

Claude Tomberg

Keyword(s):

Neuronal Networks ◽

Molecular Data ◽

Functional Changes ◽

Wide Range ◽

Cognitive Disturbances ◽

Specific Proteins ◽

The Central Nervous System ◽

Functional Circuitry ◽

The Brain

There is no specialized alcohol addiction area in the brain; rather, alcohol acts on a wide range of excitatory and inhibitory nervous networks to modulate neurotransmitters actions by binding with and altering the function of specific proteins. With no hemato-encephalic barrier for alcohol, its actions are strongly related to the amount of intake. Heavy alcohol intake is associated with both structural and functional changes in the central nervous system with long-term neuronal adaptive changes contributing to the phenomena of tolerance and withdrawal. The effects of alcohol on the function of neuronal networks are heterogeneous. Because ethanol affects neural activity in some brain sites but is without effect in others, its actions are analyzed in terms of integrated connectivities in the functional circuitry of neuronal networks, which are of particular interest because of the cognitive interactions discussed in the manuscripts contributing to this review. Recent molecular data are reviewed as a support for the other contributions dealing with cognitive disturbances related to alcohol acute and addicted consumption.

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Total Shoulder Arthroplasty

The Open Orthopaedics Journal ◽

10.2174/1874325001105010106 ◽

2011 ◽

Vol 5 (1) ◽

pp. 106-114 ◽

Cited By ~ 28

Author(s):

Joaquin Sanchez-Sotelo

Keyword(s):

Shoulder Arthroplasty ◽

Soft Tissues ◽

Reverse Shoulder Arthroplasty ◽

Total Shoulder Arthroplasty ◽

Inflammatory Arthropathy ◽

Wide Range ◽

The Subject ◽

Humerus Fractures ◽

And Function

Shoulder arthroplasty has been the subject of marked advances over the last few years. Modern implants provide a wide range of options, including resurfacing of the humeral head, anatomic hemiarthroplasty, total shoulder arthroplasty, reverse shoulder arthroplasty and trauma-specific implants for fractures and nonunions. Most humeral components achieve successful long-term fixation without bone cement. Cemented all-polyethylene glenoid components remain the standard for anatomic total shoulder arthroplasty. The results of shoulder arthroplasty vary depending on the underlying diagnosis, the condition of the soft-tissues, and the type of reconstruction. Total shoulder arthroplasty seems to provide the best outcome for patients with osteoarthritis and inflammatory arthropathy. The outcome of hemiarthroplasty for proximal humerus fractures is somewhat unpredictable, though it seems to have improved with the use of fracture-specific designs, more attention to tuberosity repair, and the selective use of reverse arthroplasty, as well as a shift in indications towards internal fixation. Reverse shoulder arthroplasty has become extremely popular for patients with cuff-tear arthropathy, and its indications have been expanded to the field of revision surgery. Overall, shoulder arthroplasty is a very successful procedure with predictable pain relief and substantial improvements in motion and function.

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Transient Receptor Potential (TRP) Channels in the Brain: the Good and the Ugly

European Review ◽

10.1017/s1062798711000597 ◽

2012 ◽

Vol 20 (3) ◽

pp. 343-355 ◽

Cited By ~ 6

Author(s):

Bernd Nilius

Keyword(s):

Ion Channels ◽

Transient Receptor Potential ◽

Trp Channels ◽

Receptor Potential ◽

Sensory Function ◽

Short Paper ◽

The Novel ◽

Cellular Functions ◽

Transient Receptor ◽

The Brain

The ‘transient receptor potential’ (TRP) multigene family encodes sixspan membrane proteins that function as ion channels in mostly tetrameric structures. Members of this family are conserved from yeast, worm, fly to invertebrate, vertebrate and man. These channels have been stigmatized to function only as cell sensors occupied by sensory function. It turns out that TRP channels fulfil a plethora of cellular functions, including non-sensory functions in our brain. This short paper will highlight the advent of novel ion channels in the brain serving different functions and being significantly involved in the genesis of multiple diseases. We will certainly witness a plethora of the novel roles of this protein family in physiological and pathophysiological functions in our central nervous system.

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Nutritional and environmental effects on reproduction in small ruminants

Reproduction Fertility and Development ◽

10.1071/rd04035 ◽

2004 ◽

Vol 16 (4) ◽

pp. 491 ◽

Cited By ~ 74

Author(s):

G. B. Martin ◽

J. Rodger ◽

D. Blache

Keyword(s):

Small Ruminants ◽

Cellular Biology ◽

Cellular Processes ◽

Physiological Processes ◽

Reproductive Axis ◽

Wide Range ◽

Short And Long Term ◽

The Impact ◽

The Brain

Animals live in environments that are both complex and continually changing, so they have to respond to short- and long-term variations in a wide range of factors, such as photoperiod, nutrition and sociosexual signals. Before they were domesticated, animals developed reproductive strategies that coped with these changes and often took advantage of them. The physiological processes that implement these strategies have been modified to some extent during several millennia of controlled breeding, but most persist. Thus, many genotypes still exhibit profound responses to external inputs, such as the induction of ovulation by sociosexual signals and the doubling of litter size by a change in nutrition. The complexity in these responses is now becoming clearer. For example, with sociosexual signals, we now need to consider the stimulatory effects of males on females, of females on males and of females on females. Similarly, the impact of nutrition has been extended beyond the control of puberty and the production of gametes to include phenomena such as ‘fetal programming’, with its potentially profound effects on the life-long performance of the animals. Fortunately, our capacity to research these phenomena has been greatly enhanced by technical improvements in hormone assays, molecular and cellular biology, and real-time ultrasound. This has brought us a better understanding of several of the environmental influences on reproduction, including: the cellular processes within ovarian follicles that mediate the effect of nutrition on ovulation rate; the neuroendocrine pathways through which nutritional inputs affect the brain centres that control appetite and reproduction; and the intracerebral pathways through which sociosexual signals (olfactory and non-olfactory) stimulate the reproductive axis. Importantly, we are now beginning to realise that, as well as considering interactions between environmental inputs and genotype, we need to take into account interactions between the environmental factors themselves, just as the animals do. We still have a long way to go for a complete understanding, but we are nevertheless in a position where we can begin to use this information to develop new management systems for our animals to improve their productivity.

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