Glia as transmitter sources and sensors in health and disease

Domingues, António Miguel de Jesus; Taylor, Mark; Fern, Robert

doi:10.1016/j.neuint.2010.03.024

Cited by 43 publications

(30 citation statements)

References 86 publications

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“…In a recent study, Fern and colleagues found that mRNA for three quarters of receptor subunits from a panel of non-glutamatergic/purinergic receptors were robustly expressed in WM glial cells, with some found at higher levels than in GM structures (Domingues et al, 2010). It seems likely that such wide-scale expression in glia, together with strong evidence for functional expression in some axons, is physiological, possibly in the same manner as described for glutamate and ATP.…”

Section: Atp and Adenosine Mediate Axonal Control Of Myelinationmentioning

confidence: 95%

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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Section: Atp and Adenosine Mediate Axonal Control Of Myelinationmentioning

confidence: 95%

Neurotransmitter signaling in white matter

Butt

Fern

Matute

2014

Glia

113

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“…The potential sources of glutamate release to cerebral white matter include astrocytes, OLs, axons and cells of the choroid plexus. Mechanisms of glutamate release from axons (Kriegler and Chiu 1993; Stirling and Stys 2010) and astrocytes (Anderson and RA 2000; Bezzi et al 2004; Domingues et al 2010; Ye et al 2003) have been defined, while oligodendroglia express Na-dependent glutamate transporters and a X c − transporter, which are all potential sources of glutamate release during hypoxia-ischemia (Deng et al 2003; DeSilva et al 2009; DeSilva et al 2007; Domercq et al 1999; Fern and Moller 2000; Oka et al 1993). There is evidence for significant release of astrocytic glutamate in isolated immature rat optic nerve during in vitro modeled ischemia (Wilke et al 2004) as well as glutamate transport mechanisms in immature axons (Arranz et al 2008).…”

Section: Cellular-molecular Mechanisms Of Acute Wmimentioning

confidence: 99%

Pathophysiology of glia in perinatal white matter injury

Back

Rosenberg

2014

Glia

172

156

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Injury to the preterm brain has a particular predilection for cerebral white matter. White matter injury (WMI) is the most common cause of brain injury in preterm infants and a major cause of chronic neurological morbidity including cerebral palsy. Factors that predispose to WMI include cerebral oxygenation disturbances and maternal-fetal infection. During the acute phase of WMI, pronounced oxidative damage occurs that targets late oligodendrocyte progenitors (preOLs). The developmental predilection for WMI to occur during prematurity appears to be related to both the timing of appearance and regional distribution of susceptible preOLs that are vulnerable to a variety of chemical mediators including reactive oxygen species, glutamate, cytokines, and adenosine. During the chronic phase of WMI, the white matter displays abberant regeneration and repair responses. Early OL progenitors responds to WMI with a rapid robust proliferative response that results in a several fold regeneration of preOLs that fail to terminally differentiate along their normal developmental time course. PreOL maturation arrest appears to be related in part to inhibitory factors that derive from reactive astrocytes in chronic lesions. Recent high field MRI data support that three distinct forms of chronic WMI exist, each of which displays unique MRI and histopathological features. These findings suggest the possibility that therapies directed at myelin regeneration and repair could be initiated early after WMI and monitored over time. These new mechanisms of acute and chronic WMI provide access to a variety of new strategies to prevent or promote repair of WMI in premature infants.

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“…Astrocytes also release glutamate [69]. Loss of astrocyte glutamate homeostasis is a prerequisite for the excitotoxic cascade, a phenomenon that is becoming recognized in an increasing number of neurological disorders [70,71]. Zn 2+ may negatively modulate Ca 2+ mobilization in CA3 pyramidal cells after regional delivery of glutamate (1 mM) to the stratum lucidum, where mossy fibers exist, suggesting that Zn 2+ attenuates glutamate excitotoxicity through the action as a negative feedback factor (Fig.…”

Section: Zn 2+ Signaling In Glutamate Excitotoxicitymentioning

confidence: 99%

Zinc Signaling in the Hippocampus and Its Relation to Pathogenesis of Depression

Takeda

2010

Mol Neurobiol

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Zinc is released from glutamatergic (zincergic) neuron terminals in the brain, followed by the increase in Zn²⁺ concentration in the intracellular (cytosol) compartment as well as that in the extracellular compartment. Intracellular Zn²⁺ concentration mainly increases through calcium-permeable channels and serves as Zn²⁺ signal as well as extracellular Zn²⁺ concentration. Hippocampal Zn²⁺ signaling may participate in synaptic plasticity such as long-term potentiation and cognitive function. On the other hand, subclinical zinc deficiency is common in the old who might be more susceptible to depression. Zinc deficiency causes abnormal glucocorticoid secretion and increases depression-like behavior in animals. Neuropsychological symptoms are observed prior to the decrease in Zn²⁺ signal in the hippocampus under zinc deficiency. This paper summarizes that hippocampal Zn²⁺ signaling serves to maintain healthy brain and that glucocorticoid signaling, which is responsive to zinc homeostasis in the living body, is linked to the pathophysiology of depression.

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Glia as transmitter sources and sensors in health and disease

Cited by 43 publications

References 86 publications

Neurotransmitter signaling in white matter

Neurotransmitter signaling in white matter

Pathophysiology of glia in perinatal white matter injury

Zinc Signaling in the Hippocampus and Its Relation to Pathogenesis of Depression

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