Mitochondria are absent from microglial processes performing surveillance, chemotaxis, and phagocytic engulfment DOI Creative Commons
Alicia N. Pietramale, Xhoela Bame, Megan Doty

et al.

Published: Oct. 18, 2024

Microglia continually surveil the brain allowing for rapid detection of tissue damage or infection. Microglial metabolism is linked to homeostasis, yet how mitochondria are subcellularly partitioned in microglia and dynamically reorganize during surveillance, injury responses, phagocytic engulfment intact not known. Here, we performed intravital imaging mitochondria, revealing that microglial processes diverge, with some containing multiple while others completely void. engage minute-to-minute surveillance typically do have mitochondria. Moreover, unlike process mitochondrial motility does change animal anesthesia. Likewise, acutely chemoattract a lesion site initially neuron undergoing programmed cell death contain Rather, delayed arrival into responding processes. Thus, there subcellular heterogeneity partitioning asymmetry between localization acute responses.

Language: Английский

Hypoxia as a medicine DOI Open Access
Robert S. Rogers, Vamsi K. Mootha

Science Translational Medicine, Journal Year: 2025, Volume and Issue: 17(782)

Published: Jan. 22, 2025

Oxygen is essential for human life, yet a growing body of preclinical research demonstrating that chronic continuous hypoxia can be beneficial in models mitochondrial disease, autoimmunity, ischemia, and aging. This revealing exciting new unexpected facets oxygen biology, but translating these findings to patients poses major challenges, because dangerous. Overcoming barriers will require integrating insights from basic science, high-altitude physiology, clinical medicine, sports technology. Here, we explore the foundations this nascent field outline path determine how safely, effectively, practically delivered patients.

Language: Английский

Citations

4
Mitochondrial respiration in microglia is essential for response to demyelinating injury but not proliferation DOI
Joshua S. Stoolman, Rogan A. Grant, Taylor A. Poor

et al.

Nature Metabolism, Journal Year: 2024, Volume and Issue: 6(8), P. 1492 - 1504

Published: July 24, 2024

Language: Английский

Citations

10
Metabolic control of microglia in health and disease DOI
Gloria Colombo, Katia Monsorno, Rosa Chiara Paolicelli

et al.

Handbook of clinical neurology, Journal Year: 2025, Volume and Issue: unknown, P. 143 - 159

Published: Jan. 1, 2025

Language: Английский

Citations

0
Serotonin Mitigates Depression in a rotenone-induced mouse Parkinson’s Disease model by Inhibiting hippocampal Neuronal Pyroptosis and Neuroinflammation DOI
Jian Wang, Hong Zhang

Behavioural Brain Research, Journal Year: 2025, Volume and Issue: unknown, P. 115620 - 115620

Published: May 1, 2025

Language: Английский

Citations

0
Microglia: roles and genetic risk in Parkinson’s disease DOI Creative Commons

A. Trainor,

Debra S. MacDonald,

Jay Penney

et al.

Frontiers in Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Nov. 1, 2024

The prevalence of neurodegenerative disorders such as Parkinson's disease are increasing world populations age. Despite this growing public health concern, the precise molecular and cellular mechanisms that culminate in neurodegeneration remain unclear. Effective treatment options for other very limited, due part to uncertain etiology. One commonality across diseases is sustained neuroinflammation, mediated large by microglia, innate immune cells brain. Initially thought simply react neuron-derived pathology, genetic functional studies recent years suggest microglia play a more active role process than previously appreciated. Here, we review evidence roles pathogenesis progression, with particular focus on microglial functions perturbed associated genes mutations.

Language: Английский

Citations

3
Complex roles for mitochondrial complexes in microglia DOI
Rosa Chiara Paolicelli, Stefano Pluchino

Nature Metabolism, Journal Year: 2024, Volume and Issue: 6(8), P. 1426 - 1428

Published: July 24, 2024

Language: Английский

Citations

2
The PHD3-FOXO3 axis modulates the interferon type I response in microglia aggravating Alzheimer's disease progression DOI
Manuel A. Sánchez-García, Nieves Lara-Ureña, Rosana March‐Díaz

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 3, 2024

Abstract Microglia respond to Alzheimer’s disease (AD) with a variety of transcriptional responses. However, the regulation specific signatures and contribution each individual response progression is only starting be characterized. We have previously shown that hypoxia via inducible factor 1 (HIF1) strong regulator Aß plaque-associated microglia (AßAM). Here, we characterize role HIF1-mediated transcription Egln3 , encoding for PHD3, in AßAM. show oligomeric treatment (oAß) vitro induces expression Hif1a microglia, which correlates activation genes involved interferon type I signature (IFNS) PHD3-dependent manner. Mechanistically, demonstrate FOXO3 an important repressor IFNS whose abundance decreases upon presence, and, correspondingly, both human single-nucleus (sn) mouse AßAM transcriptomics, DNA binding sites define IFNS. repression dependent on our results suggesting physical interaction between proteins . In vivo loss PHD3 correlate abrogation disease-associated (DAM) Transcriptional changes associate increased proximity plaques, augmented phagocytosis by reduced parenchymal levels Aß, increase small-sized plaques. deficiency also neuropathology rescued behavioural deficits AD model. Finally, microglial overexpression during development absence pathology sufficient induce alterations. Altogether, data strongly indicate PHD3-FOXO3 axis controls cell autonomous manner, contributing AD.

Language: Английский

Citations

0
Mitochondria are absent from microglial processes performing surveillance, chemotaxis, and phagocytic engulfment DOI Creative Commons
Alicia N. Pietramale, Xhoela Bame, Megan Doty

et al.

Published: Oct. 18, 2024

Microglia continually surveil the brain allowing for rapid detection of tissue damage or infection. Microglial metabolism is linked to homeostasis, yet how mitochondria are subcellularly partitioned in microglia and dynamically reorganize during surveillance, injury responses, phagocytic engulfment intact not known. Here, we performed intravital imaging mitochondria, revealing that microglial processes diverge, with some containing multiple while others completely void. engage minute-to-minute surveillance typically do have mitochondria. Moreover, unlike process mitochondrial motility does change animal anesthesia. Likewise, acutely chemoattract a lesion site initially neuron undergoing programmed cell death contain Rather, delayed arrival into responding processes. Thus, there subcellular heterogeneity partitioning asymmetry between localization acute responses.

Language: Английский

Citations

0