Astrocytes and disease: a neurodevelopmental perspective

Molofsky, Anna V.; Krenick, Robert; Ullian, Erik M.; Tsai, Hui-Hsin; Deneen, Benjamin; Richardson, William D.; Barres, Ben A.; Rowitch, David H.

doi:10.1101/gad.188326.112

Cited by 601 publications

(587 citation statements)

References 155 publications

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“…However, other studies have also proposed different mechanisms to account for a contribution of astrocytes to plasticity and memory [17,18]. Additionally, recent studies also suggest that astrocytes could participate, during development, in the formation of synaptic networks by regulating synaptogenesis [19] and spine pruning [20]. Altogether, these data indicate an important functional role of astrocytes in their interactions with synapses, despite a lack of clear mechanistic insight.…”

Section: Introductionmentioning

confidence: 67%

Activity-Dependent Structural Plasticity of Perisynaptic Astrocytic Domains Promotes Excitatory Synapse Stability

et al. 2014

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SummaryBackground: Excitatory synapses in the CNS are highly dynamic structures that can show activity-dependent remodeling and stabilization in response to learning and memory. Synapses are enveloped with intricate processes of astrocytes known as perisynaptic astrocytic processes (PAPs). PAPs are motile structures displaying rapid actin-dependent movements and are characterized by Ca 2+ elevations in response to neuronal activity. Despite a debated implication in synaptic plasticity, the role of both Ca 2+ events in astrocytes and PAP morphological dynamics remain unclear. Results: In the hippocampus, we found that PAPs show extensive structural plasticity that is regulated by synaptic activity through astrocytic metabotropic glutamate receptors and intracellular calcium signaling. Synaptic activation that induces long-term potentiation caused a transient PAP motility increase leading to an enhanced astrocytic coverage of the synapse. Selective activation of calcium signals in individual PAPs using exogenous metabotropic receptor expression and two-photon uncaging reproduced these effects and enhanced spine stability. In vivo imaging in the somatosensory cortex of adult mice revealed that increased neuronal activity through whisker stimulation similarly elevates PAP movement. This in vivo PAP motility correlated with spine coverage and was predictive of spine stability. Conclusions: This study identifies a novel bidirectional interaction between synapses and astrocytes, in which synaptic activity and synaptic potentiation regulate PAP structural plasticity, which in turn determines the fate of the synapse. This mechanism may represent an important contribution of astrocytes to learning and memory processes.

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Section: Introductionmentioning

confidence: 67%

Activity-Dependent Structural Plasticity of Perisynaptic Astrocytic Domains Promotes Excitatory Synapse Stability

et al. 2014

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“…Sox9 is initially (E8.5–E18.5) expressed in all glial (precursor) cells, and is subsequently downregulated in myelinating oligodendrocytes (Stolt et al, 2003) and becomes astrocyte‐specific (Sun et al, 2017). Also NFIA is initially (E11.5) expressed in all developing glial cells, but downregulates Olig2 and becomes exclusive to astrocytes at E13.5–E16.5 (Deneen et al, 2006; Molofsky et al, 2012). In the developing neural tube of rats, neural stem cell marker nestin is expressed directly after closing of the neural tube at E11 (Lendahl, Zimmerman, & McKay, 1990), whereas GFAP expression starts later at E18 (Oudega & Marani, 1991).…”

Section: Discussionmentioning

confidence: 99%

Affected astrocytes in the spinal cord of the leukodystrophy vanishing white matter

Leferink

Breeuwsma

Bugiani

et al. 2017

Glia

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Leukodystrophies are often devastating diseases, presented with progressive clinical signs as spasticity, ataxia and cognitive decline, and lack proper treatment options. New therapy strategies for leukodystrophies mostly focus on oligodendrocyte replacement to rescue lack of myelin in the brain, even though disease pathology also often involves other glial cells and the spinal cord. In this study we investigated spinal cord pathology in a mouse model for Vanishing White Matter disease (VWM) and show that astrocytes in the white matter are severely affected. Astrocyte pathology starts postnatally in the sensory tracts, followed by changes in the astrocytic populations in the motor tracts. Studies in post‐mortem tissue of two VWM patients, a 13‐year‐old boy and a 6‐year‐old girl, confirmed astrocyte abnormalities in the spinal cord. For proper development of new treatment options for VWM and, possibly, other leukodystrophies, future studies should investigate spinal cord involvement.

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“…The fibrous type cells occur in the white matter and are thought to promote myelination of axons through interaction with oligodendrocytes (Lundgaard et al, 2014; Molofsky et al, 2012). Protoplasmic astroglia are found in the synaptic neuropil; the present review is primarily focused on this astrocyte type (Fig.…”

Section: Subtypes and Brain‐region Specificity Of Astrogliamentioning

confidence: 99%

Morphological plasticity of astroglia: Understanding synaptic microenvironment

Heller

Rusakov

2015

Glia

132

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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Astrocytes and disease: a neurodevelopmental perspective

Cited by 601 publications

References 155 publications

Activity-Dependent Structural Plasticity of Perisynaptic Astrocytic Domains Promotes Excitatory Synapse Stability

Activity-Dependent Structural Plasticity of Perisynaptic Astrocytic Domains Promotes Excitatory Synapse Stability

Affected astrocytes in the spinal cord of the leukodystrophy vanishing white matter

Morphological plasticity of astroglia: Understanding synaptic microenvironment

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