New roles for astrocytes: Redefining the functional architecture of the brain

Ransom, Bruce R.; Goldman, Steven A.

doi:10.1016/j.tins.2003.08.008

Cited by 1,138 publications

(828 citation statements)

References 58 publications

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“…First, the ratio of glia to neurons in the human cortex is ∼1.65:1. In rodents however, this ratio is close to 0.3:1 (Nedergaard et al, 2003; Sherwood et al, 2006). The human brain appears to exhibit classes of GFAP‐positive cells that are different from cells found in the rodent brain.…”

Section: Human Brain Astrocytesmentioning

confidence: 90%

Morphological plasticity of astroglia: Understanding synaptic microenvironment

Heller

Rusakov

2015

Glia

130

137

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Memory formation in the brain is thought to rely on the remodeling of synaptic connections which eventually results in neural network rewiring. This remodeling is likely to involve ultrathin astroglial protrusions which often occur in the immediate vicinity of excitatory synapses. The phenomenology, cellular mechanisms, and causal relationships of such astroglial restructuring remain, however, poorly understood. This is in large part because monitoring and probing of the underpinning molecular machinery on the scale of nanoscopic astroglial compartments remains a challenge. Here we briefly summarize the current knowledge regarding the cellular organisation of astroglia in the synaptic microenvironment and discuss molecular mechanisms potentially involved in use‐dependent astroglial morphogenesis. We also discuss recent observations concerning morphological astroglial plasticity, the respective monitoring methods, and some of the newly emerging techniques that might help with conceptual advances in the area. GLIA 2015;63:2133–2151

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Section: Human Brain Astrocytesmentioning

confidence: 90%

Morphological plasticity of astroglia: Understanding synaptic microenvironment

Heller

Rusakov

2015

Glia

130

137

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“…The astrocytes also send processes to the neighboring blood vessels, and in this way they form a neurovascular unit. 22 …”

Section: Structural Functionmentioning

confidence: 99%

Astrocytes in Alzheimer's Disease

et al. 2010

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Summary:The circuitry of the human brain is formed by neuronal networks embedded into astroglial syncytia. The astrocytes perform numerous functions, providing for the overall brain homeostasis, assisting in neurogenesis, determining the micro-architecture of the grey matter, and defending the brain through evolutionary conserved astrogliosis programs.Astroglial cells are engaged in neurological diseases by determining the progression and outcome of neuropathological process. Astrocytes are specifically involved in various neurodegenerative diseases, including Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, and various forms of dementia. Recent evidence suggest that early stages of neurodegenerative processes are associated with atrophy of astroglia, which causes disruptions in synaptic connectivity, disbalance in neurotransmitter homeostasis, and neuronal death through increased excitotoxicity. At the later stages, astrocytes become activated and contribute to the neuroinflammatory component of neurodegeneration.

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“…402 In astrocytes, where a key function for gap junctions is calcium wave signaling, Cx43 is the major connexin. 403 In neurons, Cx36 and Cx45 play an important role and provide electrical coupling between neurons in cortex and hippocampus. 404 In oligodendrocytes, Cx32 and Cx47 provide nutrients to the myelin sheaths.…”

Section: Gap Junctions (Connexins)mentioning

confidence: 99%

Molecular Targets for Antiepileptic Drug Development

2007

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Summary:This review considers how recent advances in the physiology of ion channels and other potential molecular targets, in conjunction with new information on the genetics of idiopathic epilepsies, can be applied to the search for improved antiepileptic drugs (AEDs). Marketed AEDs predominantly target voltage-gated cation channels (the ␣ subunits of voltagegated Na ϩ channels and also T-type voltage-gated Ca 2ϩ channels) or influence GABA-mediated inhibition. Recently, ␣2-␦ voltage-gated Ca 2ϩ channel subunits and the SV2A synaptic vesicle protein have been recognized as likely targets. Genetic studies of familial idiopathic epilepsies have identified numerous genes associated with diverse epilepsy syndromes, including genes encoding Na ϩ channels and GABA A receptors, which are known AED targets. A strategy based on genes associated with epilepsy in animal models and humans suggests other potential AED targets, including various voltage-gated Ca 2ϩ channel subunits and auxiliary proteins, A-or M-type voltage-gated K ϩ channels, and ionotropic glutamate receptors. Recent progress in ion channel research brought about by molecular cloning of the channel subunit proteins and studies in epilepsy models suggest additional targets, including G-protein-coupled receptors, such as GABA B and metabotropic glutamate receptors; hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channel subunits, responsible for hyperpolarization-activated current I h ; connexins, which make up gap junctions; and neurotransmitter transporters, particularly plasma membrane and vesicular transporters for GABA and glutamate. New information from the structural characterization of ion channels, along with better understanding of ion channel function, may allow for more selective targeting. For example, Na ϩ channels underlying persistent Na ϩ currents or GABA A receptor isoforms responsible for tonic (extrasynaptic) currents represent attractive targets. The growing understanding of the pathophysiology of epilepsy and the structural and functional characterization of the molecular targets provide many opportunities to create improved epilepsy therapies.

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New roles for astrocytes: Redefining the functional architecture of the brain

Cited by 1,138 publications

References 58 publications

Morphological plasticity of astroglia: Understanding synaptic microenvironment

Morphological plasticity of astroglia: Understanding synaptic microenvironment

Astrocytes in Alzheimer's Disease

Molecular Targets for Antiepileptic Drug Development

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