Conduction block and glial injury induced in developing central white matter by glycine, GABA, noradrenalin, or nicotine, studied in isolated neonatal rat optic nerve

Constantinou, Stavros; Fern, Robert

doi:10.1002/glia.20839

Cited by 19 publications

(20 citation statements)

References 66 publications

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“…Conduction velocity along myelinated axons has been shown to depend also on neuron-glia interactions (123,190,526,570). Importantly, depolarization of a single oligodendrocyte was found to increase the action potential conduction velocity of the axons it myelinates by ϳ10% (570).…”

Section: Modulation Of Conduction Velocitymentioning

confidence: 98%

Axon Physiology

Debanne

Campanac

Bialowas

et al. 2011

Physiological Reviews

557

492

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Axons are generally considered as reliable transmission cables in which stable propagation occurs once an action potential is generated. Axon dysfunction occupies a central position in many inherited and acquired neurological disorders that affect both peripheral and central neurons. Recent findings suggest that the functional and computational repertoire of the axon is much richer than traditionally thought. Beyond classical axonal propagation, intrinsic voltage-gated ionic currents together with the geometrical properties of the axon determine several complex operations that not only control signal processing in brain circuits but also neuronal timing and synaptic efficacy. Recent evidence for the implication of these forms of axonal computation in the short-term dynamics of neuronal communication is discussed. Finally, we review how neuronal activity regulates both axon morphology and axonal function on a long-term time scale during development and adulthood.

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Section: Modulation Of Conduction Velocitymentioning

confidence: 98%

Axon Physiology

Debanne

Campanac

Bialowas

et al. 2011

Physiological Reviews

557

492

View full text Add to dashboard Cite

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“…For example, the effects of GABA-A receptor activation are associated with elevated extracellular [K 1 ] that may originate from glia, but experimentally elevating [K 1 ] does not duplicate the effects of GABA upon excitability leading to the conclusion that receptor expression is axonal (Sakatani et al, 1994). In general, it may be assumed that the effects of neurotransmitters on glial Ca 21 and membrane properties appear to be mediated largely by glial expression of neurotransmitter receptors (Butt and Jennings, 1994;Hamilton et al, 2008), whereas effects upon axonal excitability appear to be mediated largely by axolemma expression, rather than (Constantinou and Fern, 2009;Sakatani et al, 1991Sakatani et al, , 1992Sun and Chiu, 1999) (Sun and Chiu, 1999) Increase ischemia-tolerance RON (Fern et al, 1994(Fern et al, , 1995 Glycine Reduced axon excitability nRON (Constantinou and Fern, 2009 glial responses that subsequently modify excitability (Nikolaeva et al, 2009;Sun and Chiu, 1999;Zhang et al, 2004).…”

Section: Multiple Neurotransmitters Are Present In Wmmentioning

confidence: 99%

“…Dopamine and noradrenaline can evoke physiological responses in rat spinal cord WM via D1 or a1/a2/b adrenoreceptors respectively, and there is some evidence for low levels of D1 receptor expression in human WM (Sovago et al, 2005;Venugopalan et al, 2006). Catecholamines can influence ischemic injury in adult WM and are toxic to developing WM (Constantinou and Fern, 2009;Nikolaeva et al, 2009); the role of neurotransmitters in WM pathology is covered in a companion review in this volume. …”

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confidence: 99%

Neurotransmitter signaling in white matter

Butt

Fern

Matute

2014

Glia

113

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White matter (WM) tracts are bundles of myelinated axons that provide for rapid communication throughout the CNS and integration in grey matter (GM). The main cells in myelinated tracts are oligodendrocytes and astrocytes, with small populations of microglia and oligodendrocyte precursor cells. The prominence of neurotransmitter signaling in WM, which largely exclude neuronal cell bodies, indicates it must have physiological functions other than neuron-to-neuron communication. A surprising aspect is the diversity of neurotransmitter signaling in WM, with evidence for glutamatergic, purinergic (ATP and adenosine), GABAergic, glycinergic, adrenergic, cholinergic, dopaminergic and serotonergic signaling, acting via a wide range of ionotropic and metabotropic receptors. Both axons and glia are potential sources of neurotransmitters and may express the respective receptors. The physiological functions of neurotransmitter signaling in WM are subject to debate, but glutamate and ATP-mediated signaling have been shown to evoke Ca 21 signals in glia and modulate axonal conduction. Experimental findings support a model of neurotransmitters being released from axons during action potential propagation acting on glial receptors to regulate the homeostatic functions of astrocytes and myelination by oligodendrocytes. Astrocytes also release neurotransmitters, which act on axonal receptors to strengthen action potential propagation, maintaining signaling along potentially long axon tracts. The co-existence of multiple neurotransmitters in WM tracts suggests they may have diverse functions that are important for information processing. Furthermore, the neurotransmitter signaling phenomena described in WM most likely apply to myelinated axons of the cerebral cortex and GM areas, where they are doubtless important for higher cognitive function. GLIA 2014;62:1762-1779 Key words: glia, axon, astrocyte, oligodendrocyte, glutamate, ATP Introduction W hite matter (WM) is defined as a tract of myelinated axons-WM appears opaque or dense due to the fatty myelin in anatomical sections and in brain scans. Notwithstanding this, myelination is not restricted to WM and is also critical to rapid communication and integration in grey matter (GM) areas, such as in axons in the cortical GM and hippocampus. Hence, many aspects of neurotransmitter signaling to be covered in this review have resonance in GM and higher cognitive function. Indeed, in the human brain WM is a prominent feature of the cerebral cortex, the seat of higher intelligence. Myelination of GM is also evident in rodents, but discrete WM tracts are not pronounced in the cerebral cortex. As a general concept, WM are simply concentrations of myelinated axons bundled together into tracts that interconnect areas of GM. The molecular physiology of myelinated axons will be very similar in WM and GM, and they will be subject to the same neurotransmitter signaling phenomena that is the subject of this review. The main cells associated with myelinated axons are the myelinating oligodendro...

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“…This review summarizes current knowledge of the molecular mechanisms of ischemic injury to WM and discusses its translational implications for the treatment of stroke (Table). [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] …”

mentioning

confidence: 99%

Protecting White Matter From Stroke Injury

Matute

Domercq

Pérez-Samartı́n

et al. 2013

Stroke

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W hite matter (WM) exclusively contains axons and their glial cell partners including astrocytes, oligodendrocytes (myelinating and nonmyelinating), and microglia. WM comprises about half of the forebrain volume of humans, a 3-to 4-fold increase over rodents, the animals most used for neuroscience research.1,2 The low relative volume of WM in rodents led to neglect of this specialized brain area in studies of stroke pathophysiology and under-appreciation of the clinical importance of WM that has slowed progress to effective therapy.3 WM axons interconnect distant regions of the central nervous system and are metabolically independent of their cell bodies with regard to energy metabolism. Hence, proper propagation of electrical signals through WM axons demands a continuous supply of energy along their entire length and focal disruption of blood supply may compromise the viability of the whole axon. Yet, WM receives disproportionally less circulation than gray matter (GM) and is highly vulnerable to reduced blood supply exemplified by the frequency of pure WM strokes called lacunes or lacunar infarcts, 4 which can accumulate, sometimes silently, and produce vascular dementia. 5Damage of WM is a major cause of functional disability in cerebrovascular disease and the majority of ischemic strokes involve both WM and GM. 2,6 Early animal studies indicate that WM can be damaged by even brief focal ischemia.7 Thus, after 30 minutes of arterial occlusion massive swelling of oligodendrocytes and astrocytes occurs, and about 3 hours later most oligodendrocytes die. These changes precede by several hours the appearance of necrotic neurons in ischemic regions. 7 Other pathological changes in ischemic WM include segmental swelling of myelinated axons and the formation of spaces or vacuoles between the myelin sheath and axolemma (Figure 1). 7,8 These observations confirm that WM is vulnerable to ischemia and that this insult damages oligodendrocytes, myelin, and axons in a manner that can proceed independently from neuronal perikaryal injury. In fact, up to 25% of ischemic strokes in humans are of the lacunar variety and are confined to WM areas such as the internal capsule. The clinical importance of WM ischemic injury increases because the most susceptible population, the elderly, constitutes a larger and larger fraction of world population. Some types of dementia may actually represent a chronic and stealthy form of ischemia exclusive to WM. Stroke, therefore, produces disability not only as a result of dysfunction of neurons and synapses, but also by primary or secondary damage to WM axons and glia. This review summarizes current knowledge of the molecular mechanisms of ischemic injury to WM and discusses its translational implications for the treatment of stroke (Table). [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] White Matter MetabolismGlucose is the primary energy source in the adult brain. Glucose transporter (GLUT) proteins on endothelial cells, glial cells, and axons are n...

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Conduction block and glial injury induced in developing central white matter by glycine, GABA, noradrenalin, or nicotine, studied in isolated neonatal rat optic nerve

Abstract: Conduction block and glial injury induced in developing central white matter by glycine, GABA, noradrenalin or nicotine, studied in isolated neonatal rat optic nerve.

Cited by 19 publications

References 66 publications

Axon Physiology

Axon Physiology

Neurotransmitter signaling in white matter

Protecting White Matter From Stroke Injury

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