scholarly journals Mechanisms of spreading depolarization in vertebrate and insect central nervous systems

2016 ◽  
Vol 116 (3) ◽  
pp. 1117-1127 ◽  
Author(s):  
Kristin E. Spong ◽  
R. David Andrew ◽  
R. Meldrum Robertson
Keyword(s):  
Locusta Migratoria ◽  
Model Systems ◽  
Control Mechanisms ◽  
Cellular Mechanisms ◽  
Nervous Systems ◽  
Spreading Depolarization ◽  
Metathoracic Ganglion ◽  
Evolutionarily Conserved ◽  
Central Nervous Systems ◽  
The Central Nervous System

Spreading depolarization (SD) is generated in the central nervous systems of both vertebrates and invertebrates. SD manifests as a propagating wave of electrical depression caused by a massive redistribution of ions. Mammalian SD underlies a continuum of human pathologies from migraine to stroke damage, whereas insect SD is associated with environmental stress-induced neural shutdown. The general cellular mechanisms underlying SD seem to be evolutionarily conserved throughout the animal kingdom. In particular, SD in the central nervous system of Locusta migratoria and Drosophila melanogaster has all the hallmarks of mammalian SD. Locust SD is easily induced and monitored within the metathoracic ganglion (MTG) and can be modulated both pharmacologically and by preconditioning treatments. The finding that the fly brain supports repetitive waves of SD is relatively recent but noteworthy, since it provides a genetically tractable model system. Due to the human suffering caused by SD manifestations, elucidating control mechanisms that could ultimately attenuate brain susceptibility is essential. Here we review mechanisms of SD focusing on the similarities between mammalian and insect systems. Additionally we discuss advantages of using invertebrate model systems and propose insect SD as a valuable model for providing new insights to mammalian SD.

scholarly journals A Functional Role for Neutralizing Antibodies in Borna Disease: Influence on Virus Tropism outside the Central Nervous System

1998 ◽  
Vol 72 (11) ◽  
pp. 8884-8892 ◽  
Author(s):  
L. Stitz ◽  
K. Nöske ◽  
O. Planz ◽  
E. Furrer ◽  
W. I. Lipkin ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Rna Virus ◽  
Passive Immunization ◽  
Cns Infection ◽  
Nervous Systems ◽  
Humoral Immune ◽  
Central Nervous Systems ◽  
The Central Nervous System ◽  
And Behavior ◽  
Borna Disease

ABSTRACT Borna disease virus (BDV) is a negative-strand RNA virus that infects the central nervous systems (CNS) of warm-blooded animals and causes disturbances of movement and behavior. The basis for neurotropism remains poorly understood; however, the observation that the distribution of infectious virus in immunocompetent rats is different from that in immunoincompetent rats indicates a role for the immune system in BDV tropism: whereas in immunocompetent rats virus is restricted to the central, peripheral, and autonomic nervous systems, immunoincompetent rats also have virus in nonneural tissues. In an effort to examine the influence of the humoral immune response on BDV pathogenesis, we examined the effects of passive immunization with neutralizing antiserum in immunoincompetent rats. Serum transfer into immunoincompetent rats did not prevent persistent CNS infection but did result in restriction of virus to neural tissues. These results indicate that neutralizing antibodies may play a role in preventing generalized infection with BDV.

scholarly journals Neural shutdown under stress: an evolutionary perspective on spreading depolarization

2020 ◽  
Vol 123 (3) ◽  
pp. 885-895 ◽  
Author(s):  
R. Meldrum Robertson ◽  
Ken D. Dawson-Scully ◽  
R. David Andrew
Keyword(s):  
Systems Approach ◽  
Cellular Membrane ◽  
Membrane Potentials ◽  
Model Systems ◽  
Neural Function ◽  
Nervous Systems ◽  
Spreading Depolarization ◽  
Rapid Information Processing ◽  
Electrical Signaling ◽  
Open Question

Neural function depends on maintaining cellular membrane potentials as the basis for electrical signaling. Yet, in mammals and insects, neuronal and glial membrane potentials can reversibly depolarize to zero, shutting down neural function by the process of spreading depolarization (SD) that collapses the ion gradients across membranes. SD is not evident in all metazoan taxa with centralized nervous systems. We consider the occurrence and similarities of SD in different animals and suggest that it is an emergent property of nervous systems that have evolved to control complex behaviors requiring energetically expensive, rapid information processing in a tightly regulated extracellular environment. Whether SD is beneficial or not in mammals remains an open question. However, in insects, it is associated with the response to harsh environments and may provide an energetic advantage that improves the chances of survival. The remarkable similarity of SD in diverse taxa supports a model systems approach to understanding the mechanistic underpinning of human neuropathology associated with migraine, stroke, and traumatic brain injury.

scholarly journals Spreading depolarization in the brain of Drosophila is induced by inhibition of the Na+/K+-ATPase and mitigated by a decrease in activity of protein kinase G

2016 ◽  
Vol 116 (3) ◽  
pp. 1152-1160 ◽  
Author(s):  
Kristin E. Spong ◽  
Esteban C. Rodríguez ◽  
R. Meldrum Robertson
Keyword(s):  
Protein Kinase ◽  
Brain Activity ◽  
Molecular Genetic ◽  
Protein Kinase G ◽  
Extracellular Potassium ◽  
Control Mechanisms ◽  
Wild Type ◽  
Cellular Mechanisms ◽  
Spreading Depolarization ◽  
The Brain

Spreading depolarization (SD) is characterized by a massive redistribution of ions accompanied by an arrest in electrical activity that slowly propagates through neural tissue. It has been implicated in numerous human pathologies, including migraine, stroke, and traumatic brain injury, and thus the elucidation of control mechanisms underlying the phenomenon could have many health benefits. Here, we demonstrate the occurrence of SD in the brain of Drosophila melanogaster, providing a model system, whereby cellular mechanisms can be dissected using molecular genetic approaches. Propagating waves of SD were reliably induced by disrupting the extracellular potassium concentration ([K+]o), either directly or by inhibition of the Na+/K+-ATPase with ouabain. The disturbance was monitored by recording the characteristic surges in [K+]o using K+-sensitive microelectrodes or by monitoring brain activity by measuring direct current potential. With the use of wild-type flies, we show that young adults are more resistant to SD compared with older adults, evidenced by shorter bouts of SD activity and attenuated [K+]o disturbances. Furthermore, we show that the susceptibility to SD differs between wild-type flies and w1118 mutants, demonstrating that our ouabain model is influenced by genetic strain. Lastly, flies with low levels of protein kinase G (PKG) had increased latencies to onset of both ouabain-induced SD and anoxic depolarization compared with flies with higher levels. Our findings implicate the PKG pathway as a modulator of SD in the fly brain, and given the conserved nature of the signaling pathway, it could likely play a similar role during SD in the mammalian central nervous system.

scholarly journals Chill coma in the locust, Locusta migratoria, is initiated by spreading depolarization in the central nervous system

2017 ◽  
Author(s):  
R. Meldrum Robertson ◽  
Kristin E. Spong ◽  
Phinyaphat Srithiphaphirom
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Locusta Migratoria ◽  
Neural Function ◽  
Geographic Ranges ◽  
Spreading Depolarization ◽  
Chill Coma ◽  
The Central Nervous System ◽  
Species Specific

AbstractThe ability of chill-sensitive insects to function at low temperatures limits their geographic ranges. They have species-specific temperatures below which movements become uncoordinated prior to entering a reversible state of neuromuscular paralysis. In spite of decades of research, which in recent years has focused on muscle function, the role of neural mechanisms in detemining chill coma is unknown. Spreading depolarization (SD) is a phenomenon that causes a shutdown of neural function in the integrating centres of the central nervous system. We investigated the role of SD in the process of entering chill coma in the locust, Locusta migratoria. We used thermolimit respirometry and electromyography in whole animals and extracellular and intracellular recording techniques in semi-intact preparations to characterize neural events during chilling. We show that chill-induced SD in the central nervous system is the mechanism underlying the critical thermal minimum for coordinated movement in locusts. This finding will be important for understanding how insects adapt and acclimate to changing environmental temperatures.

Commitment of abdominal neuroblasts in Drosophila to a male or female fate is dependent on genes of the sex-determining hierarchy

Development ◽  
1992 ◽  
Vol 114 (3) ◽  
pp. 625-642 ◽  
Author(s):  
B.J. Taylor ◽  
J.W. Truman
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Larval Instar ◽  
Genetic Regulation ◽  
S Phase ◽  
Male And Female ◽  
Nervous Systems ◽  
Neuronal Stem Cells ◽  
Central Nervous Systems ◽  
The Central Nervous System

Adult specific neurons in the central nervous system of holometabolous insects are generated by the postembryonic divisions of neuronal stem cells (neuroblasts). In the ventral nervous system of Drosophila melanogaster, sex-specific divisions by a set of abdominal neuroblasts occur during larval and early pupal stages. Animals mutant for several sex-determining genes were analyzed to determine the genetic regulation of neuroblast commitment to the male or female pattern of division and the time during development when these decisions are made. We have found that the choice of the sexual pathway taken by sex-specific neuroblasts depends on the expression of one of these genes, doublesex (dsx). In the absence of any functional dxs+ products, the sex-specific neuroblasts fail to undergo any postembryonic divisions in male or female larval nervous systems. From the analysis of intersexes generated by dominant alleles of dsx, it has been concluded that the same neuroblasts provide the sex-specific neuroblasts in both male and female central nervous systems. The time when neuroblasts become committed to generate their sex-specific divisions were identified by shifting tra-2ts flies between the male- and female-specifying temperatures at various times during larval development. Neuroblasts become determined to adopt a male or female state at the end of the first larval instar, a time when abdominal neuroblasts enter their first postembryonic S-phase.

Theiler’s Virus Infection of Perforin-Deficient Mice

1998 ◽  
Vol 72 (5) ◽  
pp. 4515-4519 ◽  
Author(s):  
Claudia Pena Rossi ◽  
Andrés McAllister ◽  
Myriam Tanguy ◽  
David Kägi ◽  
Michel Brahic
Keyword(s):  
T Cells ◽  
Fas Ligand ◽  
Cytotoxic T Cells ◽  
Viral Rna ◽  
Theiler's Virus ◽  
Nervous Systems ◽  
Central Nervous Systems ◽  
The Central Nervous System ◽  
Infected Cells ◽  
Deficient Mice

ABSTRACT Theiler’s virus, a murine picornavirus, infects the central nervous systems of C57BL/6 mice and is cleared after approximately 10 days by a process which requires CD8+ cytotoxic T cells. We used perforin-deficient C57BL/6 mice to test the role of this protein in viral clearance. Perforin-deficient mice died from viral encephalomyelitis between days 12 and 18 postinoculation. They had high levels of viral RNA in their central nervous systems until the time of death. In contrast, viral RNA had disappeared by day 11 postinoculation in wild-type C57BL/6 mice. Cytotoxic T cells can kill infected cells by two main mechanisms: the secretion of the pore-forming protein perforin or the interaction of the Fas ligand with the apoptosis-inducing Fas molecule on the target cell. Our results demonstrate that clearance of Theiler’s virus from the central nervous system in C57BL/6 mice is perforin dependent.

scholarly journals Review of Insulin-Like Growth Factor 1 Signaling Pathway and Its Role in Protection against Brain Diseases

2017 ◽  
Vol 3 (4) ◽  
pp. 237-245
Author(s):  
Min Wei ◽  
Lun Dong ◽  
Hengzhu Zhang ◽  
Zhenfei Teng ◽  
Xiaodong Wang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Signaling Pathway ◽  
Axon Growth ◽  
Brain Diseases ◽  
Therapeutic Effects ◽  
Insulin Like Growth Factor ◽  
Cellular Interactions ◽  
Cellular Mechanisms ◽  
Central Nervous Systems ◽  
The Central Nervous System

Insulin-like growth factor 1 (IGF-1) is a pluripotent growth factor, with multiple functions in the peripheral and central nervous systems. Increasing evidence suggests that IGF-1 fine-tunes the development of the central nervous system, ensuring proper neuronal differentiation, maturation, and connectivity. It supports neuronal survival and axon growth, and acts on myelinating Schwann cells and oligodendroglia. The biological functions of IGF-1 are modulated by the IGF-1 signaling pathway. Recent studies have proposed the modulation of the members of the IGF-1/IGF-1 signaling pathway as treatment for neuropathologies. In this study, we introduce the structure of IGF-1/2 and its receptors, with the intra-cellular interactions. Further, we review the therapeutic effects of IGF-1 in different models of brain diseases, via activation of different cellular mechanisms.

scholarly journals Incorporation of 5-Bromo-2′-deoxyuridine into DNA and Proliferative Behavior of Cerebellar Neuroblasts: All That Glitters Is Not Gold

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1453
Author(s):  
Joaquín Martí-Clúa
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
System Development ◽  
Nervous System Development ◽  
Current Data ◽  
Cellular Mechanisms ◽  
Dividing Cells ◽  
The Central Nervous System ◽  
Repeated Doses ◽  
Pyrimidine Analog

The synthetic halogenated pyrimidine analog, 5-bromo-2′-deoxyuridine (BrdU), is a marker of DNA synthesis. This exogenous nucleoside has generated important insights into the cellular mechanisms of the central nervous system development in a variety of animals including insects, birds, and mammals. Despite this, the detrimental effects of the incorporation of BrdU into DNA on proliferation and viability of different types of cells has been frequently neglected. This review will summarize and present the effects of a pulse of BrdU, at doses ranging from 25 to 300 µg/g, or repeated injections. The latter, following the method of the progressively delayed labeling comprehensive procedure. The prenatal and perinatal development of the cerebellum are studied. These current data have implications for the interpretation of the results obtained by this marker as an index of the generation, migration, and settled pattern of neurons in the developing central nervous system. Caution should be exercised when interpreting the results obtained using BrdU. This is particularly important when high or repeated doses of this agent are injected. I hope that this review sheds light on the effects of this toxic maker. It may be used as a reference for toxicologists and neurobiologists given the broad use of 5-bromo-2′-deoxyuridine to label dividing cells.

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