Mutations in the transcriptional regulator MeCP2 severely impact key cellular and molecular signatures of human astrocytes during maturation DOI Creative Commons
Jialin Sun,

Sivan Osenberg,

Austin Irwin

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(1), P. 111942 - 111942

Published: Jan. 1, 2023

Mutations in the MECP2 gene underlie a spectrum of neurodevelopmental disorders, most commonly Rett syndrome (RTT). We ask whether mutations interfere with human astrocyte developmental maturation, thereby affecting their ability to support neurons. Using human-based models, we show that RTT-causing greatly impact key role astrocytes regulating overall brain bioenergetics and these metabolic aberrations are likely mediated by dysfunctional mitochondria. During post-natal rely on neurons induce complex stellate morphology transcriptional changes. While cause cell-intrinsic landscape, surprisingly, they do not affect neuron-induced expression. Notably, however, unable develop mature due cell- non-cell-autonomous caused mutations. Thus, critically cellular molecular features and, hence, interact structural functional maturation

Language: Английский

Mitochondrial biogenesis in developing astrocytes regulates astrocyte maturation and synapse formation DOI Creative Commons
Tamara Zehnder, Francesco Petrelli, Jennifer Romanos

et al.

Cell Reports, Journal Year: 2021, Volume and Issue: 35(2), P. 108952 - 108952

Published: April 1, 2021

The mechanisms controlling the post-natal maturation of astrocytes play a crucial role in ensuring correct synaptogenesis. We show that mitochondrial biogenesis developing is necessary for coordinating astrocyte and astrocytic depends on transient upregulation metabolic regulator peroxisome proliferator-activated receptor gamma (PPARγ) co-activator 1α (PGC-1α), which controlled by metabotropic glutamate 5 (mGluR5). At tissue level, loss or downregulation PGC-1α sustains proliferation, dampens morphogenesis, impairs formation function neighboring synapses, whereas its genetic re-expression sufficient to restore mitochondria compartment astroglial synaptic defects. Our findings developmental enhancement critical mechanism supporting synaptogenesis, thus suggesting may be therapeutic target case neurodevelopmental psychiatric disorders characterized impaired

Language: Английский

Citations

88
Adaptive responses to neurodegenerative stress in glaucoma DOI
David J. Calkins

Progress in Retinal and Eye Research, Journal Year: 2021, Volume and Issue: 84, P. 100953 - 100953

Published: Feb. 25, 2021

Language: Английский

Citations

76
Microglia and astrocyte involvement in neurodegeneration and brain cancer DOI Creative Commons
Arthur A. Vandenbark, Halina Offner,

Szymon Matejuk

et al.

Journal of Neuroinflammation, Journal Year: 2021, Volume and Issue: 18(1)

Published: Dec. 1, 2021

The brain is unique and the most complex organ of body, containing neurons several types glial cells different origins properties that protect ensure normal structure function. Neurological disorders are result a failure nervous system multifaceted cellular networks. Although great progress has been made in understanding glia involvement neuropathology, therapeutic outcomes still not satisfactory. Here, we discuss recent perspectives on role microglia astrocytes neurological disorders, including two common neurodegenerative conditions, Alzheimer disease progranulin-related frontotemporal lobar dementia, as well astrocytoma tumors. We emphasize key factors astrocytic biology such highly heterogeneic nature strongly dependent environment, genetic predispose to certain pathologies senescence inevitably changes CNS landscape. Our diverse contributions diseases can lead advances their functional recovery after malfunction.

Language: Английский

Citations

64
How expensive is the astrocyte? DOI
L. Felipe Barros

Journal of Cerebral Blood Flow & Metabolism, Journal Year: 2022, Volume and Issue: 42(5), P. 738 - 745

Published: Jan. 26, 2022

The energy cost of information processing is thought to be chiefly neuronal, with a minor fraction attributed glial cells. However, there compelling evidence that astrocytes capture synaptic K + using their Na /K ATPase, and not solely through Kir4.1 channels as was once thought. When this active buffering taken into account, the rises by >200%. Gram-per-gram, turn out expensive neurons. This conclusion supported 3D reconstruction neuropil showing similar mitochondrial densities in neurons astrocytes, cell-specific transcriptomics proteomics, rates tricarboxylic acid cycle. Possible consequences for reactive astrogliosis brain disease are discussed.

Language: Английский

Citations

39
Mutations in the transcriptional regulator MeCP2 severely impact key cellular and molecular signatures of human astrocytes during maturation DOI Creative Commons
Jialin Sun,

Sivan Osenberg,

Austin Irwin

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(1), P. 111942 - 111942

Published: Jan. 1, 2023

Mutations in the MECP2 gene underlie a spectrum of neurodevelopmental disorders, most commonly Rett syndrome (RTT). We ask whether mutations interfere with human astrocyte developmental maturation, thereby affecting their ability to support neurons. Using human-based models, we show that RTT-causing greatly impact key role astrocytes regulating overall brain bioenergetics and these metabolic aberrations are likely mediated by dysfunctional mitochondria. During post-natal rely on neurons induce complex stellate morphology transcriptional changes. While cause cell-intrinsic landscape, surprisingly, they do not affect neuron-induced expression. Notably, however, unable develop mature due cell- non-cell-autonomous caused mutations. Thus, critically cellular molecular features and, hence, interact structural functional maturation

Language: Английский

Citations

32