scholarly journals Ionic Imbalances and Coupling in Synchronization of Responses in Neurons

J ◽  
2019 ◽  
Vol 2 (1) ◽  
pp. 17-40
Author(s):  
Seyed-Ali Sadegh-Zadeh ◽  
Chandrasekhar Kambhampati ◽  
Darryl Davis

Most neurodegenerative diseases (NDD) are a result of changes in the chemical composition of neurons. For example, Alzheimer’s disease (AD) is the product of Aβ peptide deposition which results in changes in the ion concentration. These changes in ion concentration affect the responses of the neuron to stimuli and often result in inducing excessive excitation or inhibition. This paper investigates the dynamics of a single neuron as ion changes occur. These changes are incorporated using the Nernst equation. Within the central and peripheral nervous system, signals and hence rhythms, are propagated through the coupling of the neurons. It was found that under certain conditions the coupling strength between two neurons could mitigate changes in ion concentration. By defining the state of perfect synchrony, it was shown that the effect of ion imbalance in coupled neurons was reduced while in uncoupled neurons these changes had a more significant impact on the neuronal behavior.

Author(s):  
Patrizia Polverino de Laureto ◽  
Luana Palazzi ◽  
Laura Acquasaliente

Several therapeutic approaches have been suggested so far for the treatment of neurodegenerative diseases, but to date, there are no approved therapies. The available ones are only symptomatic; they are employed to mitigate the disease manifestations and to improve the patient life quality. These diseases are characterized by the accumulation and aggregation of misfolded proteins in the nervous system, with different specific hallmarks. The onset mechanisms are not completely elucidated. Some promising approaches are focused on the inhibition of the amyloid aggregation of the proteins involved in the etiopathology of the disease, such as Aβ peptide, Tau, and α-synuclein, or on the increase of their clearance in order to avoid their aberrant accumulation. Here, we summarize traditional and new therapeutic approaches proposed for Alzheimer’s and Parkinson’s diseases and the recent technologies for brain delivery.


2020 ◽  
Vol 27 (34) ◽  
pp. 5790-5828 ◽  
Author(s):  
Ze Wang ◽  
Chunyang He ◽  
Jing-Shan Shi

Neurodegenerative diseases are a heterogeneous group of disorders characterized by the progressive degeneration of the structure and function of the central nervous system or peripheral nervous system. Alzheimer's Disease (AD), Parkinson's Disease (PD) and Spinal Cord Injury (SCI) are the common neurodegenerative diseases, which typically occur in people over the age of 60. With the rapid development of an aged society, over 60 million people worldwide are suffering from these uncurable diseases. Therefore, the search for new drugs and therapeutic methods has become an increasingly important research topic. Natural products especially those from the Traditional Chinese Medicines (TCMs), are the most important sources of drugs, and have received extensive interest among pharmacist. In this review, in order to facilitate further chemical modification of those useful natural products by pharmacists, we will bring together recent studies in single natural compound from TCMs with neuroprotective effect.


2016 ◽  
Vol 2016 ◽  
pp. 1-20 ◽  
Author(s):  
Maulilio John Kipanyula ◽  
Wahabu Hamisi Kimaro ◽  
Paul F. Seke Etet

The ongoing epidemics of metabolic diseases and increase in the older population have increased the incidences of neurodegenerative diseases. Evidence from murine and cell line models has implicated calcineurin-nuclear factor of activated T-lymphocytes (NFAT) signaling pathway, a Ca2+/calmodulin-dependent major proinflammatory pathway, in the pathogenesis of these diseases. Neurotoxins such as amyloid-β, tau protein, andα-synuclein trigger abnormal calcineurin/NFAT signaling activities. Additionally increased activities of endogenous regulators of calcineurin like plasma membrane Ca2+-ATPase (PMCA) and regulator of calcineurin 1 (RCAN1) also cause neuronal and glial loss and related functional alterations, in neurodegenerative diseases, psychotic disorders, epilepsy, and traumatic brain and spinal cord injuries. Treatment with calcineurin/NFAT inhibitors induces some degree of neuroprotection and decreased reactive gliosis in the central and peripheral nervous system. In this paper, we summarize and discuss the current understanding of the roles of calcineurin/NFAT signaling in physiology and pathologies of the adult and developing nervous system, with an emphasis on recent reports and cutting-edge findings. Calcineurin/NFAT signaling is known for its critical roles in the developing and adult nervous system. Its role in physiological and pathological processes is still controversial. However, available data suggest that its beneficial and detrimental effects are context-dependent. In view of recent reports calcineurin/NFAT signaling is likely to serve as a potential therapeutic target for neurodegenerative diseases and conditions. This review further highlights the need to characterize better all factors determining the outcome of calcineurin/NFAT signaling in diseases and the downstream targets mediating the beneficial and detrimental effects.


1988 ◽  
Vol 66 (5) ◽  
pp. 637-642 ◽  
Author(s):  
Timothy J. Blaxter ◽  
Peter L. Carlen

The dendrites of granule cells in hippocampal slices responded to γ-aminobutyric acid (GABA) with a depolarization. The response was blocked by picrotoxin in a noncompetitive manner. Reductions in the extracellular chloride ion concentration changed the reversal potential of the response by an amount predicted from the Nernst equation for chloride ion. Chloride-dependent hyperpolarizing responses were sometimes also found in the cell body of the granule cells. Since the reversal potential followed that predicted from the Nernst equation for chloride, we conclude that the response was mediated by chloride ions alone with no contribution from other ions. This has not previously been shown for the depolarizing response to GABA in central neurons.


2021 ◽  
Vol 40 (4) ◽  
pp. 13-24
Author(s):  
Igor V. Litvinenko ◽  
Igor V. Krasakov

The involvement of the nervous system in the pathological process that occurs when COVID-19 is infected is becoming more and more obvious. The question of the possibility of the debut or progression of the already developed Parkinsonism syndrome in patients who have undergone COVID-19 is regularly raised. A large number of hypotheses are put forward to explain this relationship. It is assumed that a violation of iron metabolism in the brain may underlie the development and progression of neurodegenerative diseases, including after the new coronavirus infection SARS-CoV-2. The analysis of stu dies on the possible influence of iron metabolism disorders on the occurrence and mechanism of development of neurodegenerative diseases after infection with SARS-CoV-2 has been carried out. The processes of physiological maintenance of iron homeostasis, as well as the influence of physiological aging on the accumulation of iron in the central nervous system are described. The relationship between hyperferritinemia occurring in COVID-19 and ferroptosis as the basis of the neurodegenerative process in Parkinsons disease and Alzheimers disease is discussed. The main molecular mechanisms involved in ferroptosis are described. Examples of involvement of metal homeostasis disorders in the process of altering the structure of -synuclein, synthesis of -amyloid, hyperphosphorylated tau- protein are given. The causes of excessive iron accumulation in certain brain structures are discussed. The question of the possibility of using the assessment of changes in iron metabolism as a new biomarker of the progression of Parkinsons disease is analyzed. (1 figure, bibliography: 62 refs)


2021 ◽  
Vol 22 (16) ◽  
pp. 8658
Author(s):  
Azin EbrahimAmini ◽  
Shanthini Mylvaganam ◽  
Paolo Bazzigaluppi ◽  
Mohamad Khazaei ◽  
Alexander Velumian ◽  
...  

A normally functioning nervous system requires normal extracellular potassium ion concentration ([K]o). Throughout the nervous system, several processes, including those of an astrocytic nature, are involved in [K]o regulation. In this study we investigated the effect of astrocytic photostimulation on [K]o. We hypothesized that in vivo photostimulation of eNpHR-expressing astrocytes leads to a decreased [K]o. Using optogenetic and electrophysiological techniques we showed that stimulation of eNpHR-expressing astrocytes resulted in a significantly decreased resting [K]o and evoked K responses. The amplitude of the concomitant spreading depolarization-like events also decreased. Our results imply that astrocytic membrane potential modification could be a potential tool for adjusting the [K]o.


2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yang Tian ◽  
Chen Fu ◽  
Yifan Wu ◽  
Yao Lu ◽  
Xuemei Liu ◽  
...  

Exosomes are a type of extracellular vesicles secreted by almost all kinds of mammalian cells that shuttle “cargo” from one cell to another, indicative of its role in cell-to-cell transportation. Interestingly, exosomes are known to undergo alterations or serve as a pathway in multiple diseases, including neurodegenerative diseases. In the central nervous system (CNS), exosomes originating from neurons or glia cells contribute to or inhibit the progression of CNS-related diseases in special ways. In lieu of this, the current study investigated the effect of CNS cell-derived exosomes on different neurodegenerative diseases.


eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Tai-Heng Chen ◽  
Jun-An Chen

Two crucial questions in neuroscience are how neurons establish individual identity in the developing nervous system and why only specific neuron subtypes are vulnerable to neurodegenerative diseases. In the central nervous system, spinal motor neurons serve as one of the best-characterized cell types for addressing these two questions. In this review, we dissect these questions by evaluating the emerging role of regulatory microRNAs in motor neuron generation in developing embryos and their potential contributions to neurodegenerative diseases such as spinal muscular atrophy (SMA). Given recent promising results from novel microRNA-based medicines, we discuss the potential applications of microRNAs for clinical assessments of SMA disease progression and treatment.


1968 ◽  
Vol 48 (1) ◽  
pp. 25-37
Author(s):  
J. A. HASKELL ◽  
W. R. HARVEY ◽  
R. M. CLARK

1. The electrical potential across the isolated midgut of five developmental stages of the Cecropia silkworm was studied by changing the concentration of single cations in solutions bathing each side of the midgut. The stages included feeding fourth-instar insects, insects moulting from the fourth to the fifth instar, feeding fifth-instar insects, insects which had evacuated their midguts, and insects spinning cocoons. 2. Average values of the initial maximal potential exhibited by the midgut in solutions containing K, Mg, and Ca but no Na, for the stages mentioned above, were 68, 83, 90, 124, and 2 mV., respectively. 3. In all of the developmental stages studied except the ‘spinning larva’, reducing the potassium concentration from 32 to 2 mM/l. on the blood-side of the isolated gut lowers the potential, on the lumen-side of the gut raises the potential and on both sides gives an intermediate value. 4. When the potential prior to a decrease in concentration of potassium on the blood-side is over 100 mV., the Nernst slope approaches 59 mV. 5. A tenfold reduction in the concentration of magnesium or the addition of 32 mM/l. sodium to the solutions bathing the isolated gut has no systematic effect on the potential. 6. A tenfold drop in the concentration of calcium in the solutions causes changes in the potential in the opposite direction from those predicted by the Nernst equation. 7. The pH of the midgut contents rises from early fourth instar to late fifth instar. The hydrogen-ion concentration of the blood is about 1000 times more than that of midgut contents in fifth-instar insects. 8. Neither synthetic ecdysone, partially purified natural ecdysone nor juvenile hormone has an effect on the potential or current of the isolated midgut over periods as long as 30 min.


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