Myelination Trajectory and Microglial Dynamics Following Repeated Sevoflurane Exposure in Developing Brain DOI Open Access
Ji Che, Yuanyuan Wu, Jing Dong

et al.

Glia, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 10, 2025

The myelination is a critical process during brain development. This study aimed to explore the impact of volatile anesthetic sevoflurane on developing and role microglial activation in this process. Neonatal C57BL/6J mice were exposed at their postnatal 6-8 days. Neurobehavioral tests used assess fine motor cognitive functions. Myelination hippocampus (HC) corpus callosum (CC), as well activation, determined by western blotting immunostaining. Lipid droplets assessed Oil-Red-O Bodipy staining. Further, primary microglia co-cultured with oligodendrocyte precursor cell (OPC) determine proliferation differentiation OPC. And inhibitor minocycline CSF1R PLX5622 administered effects myelination. results showed that repeated exposure impaired both functions induced abnormal expressions myelin-related proteins myelin basic protein (MBP) platelet-derived growth factor α receptor (PDGFR-α). accumulations lipid found HC CC after exposure. spatiotemporal response glial cells exhibited an aberrant polarization. conditioned medium from sevoflurane-treated inhibited OPC differentiation, while or alleviated sevoflurane-induced neuroinflammation hypomyelination. Therefore, negatively affected trajectory through hyperactivating brain, leading impairments, inhibition/depletion could protect against damage

Language: Английский

Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases DOI Creative Commons
Jian Sheng Loh, Wen Qi Mak, Li Tan

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Feb. 16, 2024

Abstract The human gastrointestinal tract is populated with a diverse microbial community. vast genetic and metabolic potential of the gut microbiome underpins its ubiquity in nearly every aspect biology, including health maintenance, development, aging, disease. advent new sequencing technologies culture-independent methods has allowed researchers to move beyond correlative studies toward mechanistic explorations shed light on microbiome–host interactions. Evidence unveiled bidirectional communication between central nervous system, referred as “microbiota–gut–brain axis”. microbiota–gut–brain axis represents an important regulator glial functions, making it actionable target ameliorate development progression neurodegenerative diseases. In this review, we discuss mechanisms As provides essential cues microglia, astrocytes, oligodendrocytes, examine communications microbiota these cells during healthy states Subsequently, diseases using metabolite-centric approach, while also examining role microbiota-related neurotransmitters hormones. Next, targeting intestinal barrier, blood–brain meninges, peripheral immune system counteract dysfunction neurodegeneration. Finally, conclude by assessing pre-clinical clinical evidence probiotics, prebiotics, fecal transplantation A thorough comprehension will foster effective therapeutic interventions for management

Language: Английский

Citations

283
An inducible genetic tool to track and manipulate specific microglial states reveals their plasticity and roles in remyelination DOI Creative Commons
Kia M. Barclay, Nora Abduljawad, Zuolin Cheng

et al.

Immunity, Journal Year: 2024, Volume and Issue: 57(6), P. 1394 - 1412.e8

Published: May 30, 2024

Recent single-cell RNA sequencing studies have revealed distinct microglial states in development and disease. These include proliferative-region-associated microglia (PAMs) developing white matter disease-associated (DAMs) prevalent various neurodegenerative conditions. PAMs DAMs share a similar core gene signature. However, the extent of dynamism plasticity these states, as well their functional significance, remains elusive, partly due to lack specific tools. Here, we generated an inducible Cre driver line, Clec7a-CreER

Language: Английский

Citations

22
Itaconate in host inflammation and defense DOI
Dan Ye, Pu Wang, Leilei Chen

et al.

Trends in Endocrinology and Metabolism, Journal Year: 2024, Volume and Issue: 35(7), P. 586 - 606

Published: March 5, 2024

Language: Английский

Citations

18
Microglia phagocytic mechanisms: Development informing disease DOI
Rebecca M. Beiter, Patrick W. Sheehan, Dorothy P. Schafer

et al.

Current Opinion in Neurobiology, Journal Year: 2024, Volume and Issue: 86, P. 102877 - 102877

Published: April 16, 2024

Language: Английский

Citations

14
White matter aging and its impact on brain function DOI Creative Commons
Janos Groh, Mikael Simons

Neuron, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Aging has a detrimental impact on white matter, resulting in reduced volume, compromised structural integrity of myelinated axons, and an increase matter hyperintensities. These changes are closely linked to cognitive decline neurological disabilities. The deterioration myelin its diminished ability regenerate as we age further contribute the progression neurodegenerative disorders. Understanding these is crucial for devising effective disease prevention strategies. Here, will discuss alterations that occur with aging examine cellular molecular mechanisms driving aging-related transformations. We highlight how progressive disruption may initiate self-perpetuating cycle inflammation neural damage.

Language: Английский

Citations

13
Neural circuits regulating visceral pain DOI Creative Commons
Xiaoli Chang, Haiyan Zhang, S.R. Wayne Chen

et al.

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: April 13, 2024

Abstract Visceral hypersensitivity, a common clinical manifestation of irritable bowel syndrome, may contribute to the development chronic visceral pain, which is major challenge for both patients and health providers. Neural circuits in brain encode, store, transfer pain information across regions. In this review, we focus on anterior cingulate cortex paraventricular nucleus hypothalamus highlight progress identifying neural involved pain. We also discuss several circuit mechanisms emphasize importance cross-species, multiangle approaches identification specific neurons determining that control

Language: Английский

Citations

10
Microglial cGAS–STING signaling underlies glaucoma pathogenesis DOI Creative Commons
Yutong Liu,

Ailian Wang,

Chen Chen

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(36)

Published: Aug. 27, 2024

Characterized by progressive degeneration of retinal ganglion cells (RGCs) and vision loss, glaucoma is the primary cause irreversible blindness, incurable affecting over 78 million patients. However, pathogenic mechanisms leading to glaucoma-induced RGC loss are incompletely understood. Unexpectedly, we found that cGAS-STING (2'3'-cyclic GMP-AMP-stimulator interferon genes) signaling, which surveils displaced double-stranded DNA (dsDNA) in cytosol initiates innate immune responses, was robustly activated during microglia distinct murine models. Global or microglial deletion STING markedly relieved symptoms protected while mice bearing genetic supersensitivity aggravated neuroinflammation loss. Mechanistically, dsDNA from tissue injury causing deleterious macroglia reactivity retinas cytokine-mediated microglia-macroglia interactions, progressively driving apoptotic death RGCs. Remarkably, preclinical investigations targeting signaling intraocular injection TBK1i anti-IFNAR1 antibody prevented losses RGCs vision. Therefore, unravel an essential role underlying pathogenesis suggest promising therapeutic strategies for treating this devastating disease.

Language: Английский

Citations

10
cGAS-STING targeting offers novel therapeutic opportunities in neurological diseases DOI
Hongquan Wang, Joshua S. Fleishman, Shuang Wu

et al.

Ageing Research Reviews, Journal Year: 2025, Volume and Issue: 105, P. 102691 - 102691

Published: Feb. 13, 2025

Language: Английский

Citations

2
Identifying Biomarkers for Remyelination and Recovery in Multiple Sclerosis: A Measure of Progress DOI Creative Commons
Vito A. G. Ricigliano, Silvia Marenna, Serena Borrelli

et al.

Biomedicines, Journal Year: 2025, Volume and Issue: 13(2), P. 357 - 357

Published: Feb. 4, 2025

Background: Multiple sclerosis (MS) pathology is characterized by acute and chronic inflammation, demyelination, axonal injury, neurodegeneration. After decades of research into MS-related degeneration, recent efforts have shifted toward recovery the prevention further damage. A key area focus remyelination process, where researchers are studying effects pharmacotherapy on myelin repair mechanisms. compounds being tested for their potential to foster in different clinical settings through application less or more complex techniques assess efficacy. Objective: To review current methods biomarkers track regeneration over time people with MS (PwMS), implications promyelinating drug testing. Methods: Narrative review, based a selection PubMed articles discussing measure vivo functional PwMS. Results: Non-invasive tools, such as structural Magnetic Resonance Imaging (MRI) Positron Emission Tomography (PET), implemented repair, while other like evoked potentials, MRI, digital markers allow assessment recovery. These methods, alone combination, been employed obtain precise various trials MS. Conclusions: Combining identify restoration could yield novel biomarkers, enhancing accuracy trial outcomes remyelinating therapies

Language: Английский

Citations

1
The protein kinase C modulator bryostatin-1 therapeutically targets microglia to attenuate neuroinflammation and promote remyelination DOI
Payam Gharibani, Efrat Abramson, Shruthi Shanmukha

et al.

Science Translational Medicine, Journal Year: 2025, Volume and Issue: 17(780)

Published: Jan. 8, 2025

In multiple sclerosis (MS), microglia and macrophages within the central nervous system (CNS) play an important role in determining balance among demyelination, neurodegeneration, myelin repair. Phagocytic regenerative functions of these CNS innate immune cells support remyelination, whereas chronic maladaptive inflammatory activation promotes lesion expansion disability, particularly progressive forms MS. No currently approved drugs convincingly target CNS, contributing to lack therapies aimed at promoting remyelination slowing disease progression for individuals with Here, we found that protein kinase C (PKC)–modulating drug bryostatin-1 (bryo-1), a CNS-penetrant compound established human safety profile, shifts transcriptional programs CNS-associated from proinflammatory phenotype vitro vivo. Treatment bryo-1 stimulated scavenger pathways, phagocytosis, secretion factors prevented neuroinflammatory reactive astrocytes while also neuroaxonal health oligodendrocyte differentiation. line findings, systemic treatment mice augmented after focal demyelinating injury. Our results demonstrate potential possibly wider class PKC modulators as myelin-regenerative supportive agents MS other neurologic diseases.

Language: Английский

Citations

1