Connexins in neurons and glia: targets for intervention in disease and injury

Moore, Keith; O’Brien, John

doi:10.4103/1673-5374.160092

Cited by 24 publications

(14 citation statements)

References 63 publications

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“…Thus, a reduction of trigeminal proprioceptive signals may lead to reduced levels of neurotrophic factors for LC neurons, favoring the development of their dysfunction. Such a dysfunction may also extend to the glia, due to the large electrical coupling between Me5-LC cells and local astrocytes (Alvarez-Maubecin et al, 2000 ; Moore and O’Brien, 2015 ) and to the spread of local injury to the adjacent coupled elements, via gap junctions (bystander killing, see Moore and O’Brien, 2015 ).…”

Section: Trigeminal Visceral and Vestibular Influences On Brain Funcmentioning

confidence: 99%

Trigeminal, Visceral and Vestibular Inputs May Improve Cognitive Functions by Acting through the Locus Coeruleus and the Ascending Reticular Activating System: A New Hypothesis

et al. 2018

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It is known that sensory signals sustain the background discharge of the ascending reticular activating system (ARAS) which includes the noradrenergic locus coeruleus (LC) neurons and controls the level of attention and alertness. Moreover, LC neurons influence brain metabolic activity, gene expression and brain inflammatory processes. As a consequence of the sensory control of ARAS/LC, stimulation of a sensory channel may potential influence neuronal activity and trophic state all over the brain, supporting cognitive functions and exerting a neuroprotective action. On the other hand, an imbalance of the same input on the two sides may lead to an asymmetric hemispheric excitability, leading to an impairment in cognitive functions. Among the inputs that may drive LC neurons and ARAS, those arising from the trigeminal region, from visceral organs and, possibly, from the vestibular system seem to be particularly relevant in regulating their activity. The trigeminal, visceral and vestibular control of ARAS/LC activity may explain why these input signals: (1) affect sensorimotor and cognitive functions which are not directly related to their specific informational content; and (2) are effective in relieving the symptoms of some brain pathologies, thus prompting peripheral activation of these input systems as a complementary approach for the treatment of cognitive impairments and neurodegenerative disorders.

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Section: Trigeminal Visceral and Vestibular Influences On Brain Funcmentioning

confidence: 99%

Trigeminal, Visceral and Vestibular Inputs May Improve Cognitive Functions by Acting through the Locus Coeruleus and the Ascending Reticular Activating System: A New Hypothesis

et al. 2018

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“…In the last two decades it has become increasingly clear that glial cells have more functions and are more dynamic than previously expected. Astrocytes, in particular, constitute with neurons a highly integrated complex in which each astrocyte contacts many neurons, and many astrocytes are coupled to each other through astroglial intercellular networks based on gap junction channels (GJ) [ 48 , 49 , 50 ], formed by connexins (C × 43 and C × 30) [ 51 , 52 , 53 ]. Importantly, astroglial networks are involved in several control functions, such as ionic homeostasis and control of cell volume; they seem to finely tune neuronal circuits, by delivering to neurons energy metabolites in neuronal activity-dependent manner [ 49 ], as also suggested by their distribution and proximity to excitatory synapses [ 54 ].…”

Section: Glial Cell—neurons Lactate Shuttle and Brain Energy Metabmentioning

confidence: 99%

Lactate as a Metabolite and a Regulator in the Central Nervous System

Proia

Liegro

Schiera

et al. 2016

IJMS

201

151

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More than two hundred years after its discovery, lactate still remains an intriguing molecule. Considered for a long time as a waste product of metabolism and the culprit behind muscular fatigue, it was then recognized as an important fuel for many cells. In particular, in the nervous system, it has been proposed that lactate, released by astrocytes in response to neuronal activation, is taken up by neurons, oxidized to pyruvate and used for synthesizing acetyl-CoA to be used for the tricarboxylic acid cycle. More recently, in addition to this metabolic role, the discovery of a specific receptor prompted a reconsideration of its role, and lactate is now seen as a sort of hormone, even involved in processes as complex as memory formation and neuroprotection. As a matter of fact, exercise offers many benefits for our organisms, and seems to delay brain aging and neurodegeneration. Now, exercise induces the production and release of lactate into the blood which can reach the liver, the heart, and also the brain. Can lactate be a beneficial molecule produced during exercise, and offer neuroprotection? In this review, we summarize what we have known on lactate, discussing the roles that have been attributed to this molecule over time.

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“…The current experiments first confirmed that retinal macroglia activation after EHP could modulate these synaptic alterations in retinal neurons and, next, determined that TSP2 secreted by macroglia cells in the presence of environmental stress induced during the course of EHP might regulate synaptic protein alterations by binding to its neuronal receptor α2δ-1 in primary mixed cultures. This regulatory pathway may represent attractive targets for pharmacological intervention and require the profound understanding of their distribution and role in the nervous system to develop targeted therapies for diseases and injuries[ 54 ]. Therefore, it is reasonable to expect that strategies targeting the macroglia-TSP2-α2δ-1 pathway to regulate presynaptic changes of retinal neurons after EHP may contribute to the recovery of visual function.…”

Section: Discussionmentioning

confidence: 99%

Macroglia-derived thrombospondin 2 regulates alterations of presynaptic proteins of retinal neurons following elevated hydrostatic pressure

Wang

et al. 2017

PLoS ONE

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Many studies on retinal injury and repair following elevated intraocular pressure suggest that the survival ratio of retinal neurons has been improved by various measures. However, the visual function recovery is far lower than expected. The homeostasis of retinal synapses in the visual signal pathway is the key structural basis for the delivery of visual signals. Our previous studies found that complicated changes in the synaptic structure between retinal neurons occurred much earlier than obvious degeneration of retinal ganglion cells in rat retinae. The lack of consideration of these earlier retinal synaptic changes in the rescue strategy may be partly responsible for the limited visual function recovery with the types of protective methods for retinal neurons used following elevated intraocular pressure. Thus, research on the modulatory mechanisms of the synaptic changes after elevated intraocular pressure injury may give new light to visual function rescue. In this study, we found that thrombospondin 2, an important regulator of synaptogenesis in central nervous system development, was distributed in retinal macroglia cells, and its receptor α2δ-1 was in retinal neurons. Cell cultures including mixed retinal macroglia cells/neuron cultures and retinal neuron cultures were exposed to elevated hydrostatic pressure for 2 h. The expression levels of glial fibrillary acidic protein (the marker of activated macroglia cells), thrombospondin 2, α2δ-1 and presynaptic proteins were increased following elevated hydrostatic pressure in mixed cultures, but the expression levels of postsynaptic proteins were not changed. SiRNA targeting thrombospondin 2 could decrease the upregulation of presynaptic proteins induced by the elevated hydrostatic pressure. However, in retinal neuron cultures, elevated hydrostatic pressure did not affect the expression of presynaptic or postsynaptic proteins. Rather, the retinal neuron cultures with added recombinant thrombospondin 2 protein upregulated the level of presynaptic proteins. Finally, gabapentin decreased the expression of presynaptic proteins in mixed cultures by blocking the interaction of thrombospondin 2 and α2δ-1. Taken together, these results indicate that activated macroglia cells may participate in alterations of presynaptic proteins of retinal neurons following elevated hydrostatic pressure, and macroglia-derived thrombospondin 2 may modulate these changes via binding to its neuronal receptor α2δ-1.

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Connexins in neurons and glia: targets for intervention in disease and injury

Cited by 24 publications

References 63 publications

Trigeminal, Visceral and Vestibular Inputs May Improve Cognitive Functions by Acting through the Locus Coeruleus and the Ascending Reticular Activating System: A New Hypothesis

Trigeminal, Visceral and Vestibular Inputs May Improve Cognitive Functions by Acting through the Locus Coeruleus and the Ascending Reticular Activating System: A New Hypothesis

Lactate as a Metabolite and a Regulator in the Central Nervous System

Macroglia-derived thrombospondin 2 regulates alterations of presynaptic proteins of retinal neurons following elevated hydrostatic pressure

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