Loss of glia-neuronal interactions and age-dependent cell death in aDrosophilamodel of adult neurodegeneration DOI Creative Commons
Unmila P. Jhuti, Edward M. Blumenthal

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

Published: May 20, 2024

Abstract While glial dysfunction has been implicated in the development of multiple neurodegenerative diseases, role cell morphology neurodegeneration is underexplored. In fruit fly Drosophila melanogaster , mutants gene drop-dead ( drd ) exhibit adult and extremely short lifespans. The one class glia, cortex glia (CG), abnormal mutants. controls, CGs form a continuous network that wraps around all neuronal bodies, but mutants, individual are stunted CG disrupted. These phenotypes present on first day adulthood. Apoptosis central mechanism death mutants; widespread observed adulthood increases with age primarily neuronal. Apoptotic cells found both within outside remaining network, significant variation distribution among brains. degree breakdown young adults could explain why mutant flies die week unique model provides new insight into interaction between bodies.

Language: Английский

New epilepsy therapies in development DOI
Pavel Klein, Rafal M. Kaminski, Matthias J. Koepp

et al.

Nature Reviews Drug Discovery, Journal Year: 2024, Volume and Issue: 23(9), P. 682 - 708

Published: July 22, 2024

Language: Английский

Citations

34
Astrocytes as a target for therapeutic strategies in epilepsy: current insights DOI Creative Commons
Nihan Çarçak, Filiz Onat, Evgenia Sitnikova

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2023, Volume and Issue: 16

Published: July 31, 2023

Astrocytes are specialized non-neuronal glial cells of the central nervous system, contributing to neuronal excitability and synaptic transmission (gliotransmission). play a key roles in epileptogenesis seizure generation. Epilepsy, as chronic disorder characterized by hyperexcitation hypersynchronization, is accompanied substantial disturbances impairment astrocytic functions signaling. Anti-seizure drugs that provide symptomatic control seizures primarily target neural activity. In epileptic patients with inadequate available anti-seizure drugs, novel therapeutic candidates needed. These should treat epilepsy anti-epileptogenic disease-modifying effects. Evidence from human animal studies shows astrocytes have value for developing new drugs. this review, we present hyperexcitability activity following an etiology-based approach. We analyze role both development (epileptogenesis) generation (ictogenesis). Several promising strategies attempted modify astroglial treating being developed: (1) selective targeting glia-related molecular mechanisms glutamate transport; (2) modulation tonic GABA release astrocytes; (3) gliotransmission; (4) Kir4.1-BDNF system; (5) Na+/K+/ATPase activity; (6) DNA hypo- or hypermethylation candidate genes (7) gap junction regulators; (8) adenosine kinase (the major adenosine-metabolizing enzyme); (9) microglia-astrocyte communication inflammatory pathways. Novel now been developed, such astroglia-targeted gene therapy broad spectrum genetic constructs cells.

Language: Английский

Citations

30
Mechanisms of glutamate metabolic function and dysfunction in vascular dementia DOI Creative Commons
Jiawen Wang, Yingmei Zhang, Ning Tian

et al.

Neuroprotection/Neuroprotection (Chichester, England. Print), Journal Year: 2024, Volume and Issue: 2(1), P. 33 - 48

Published: Feb. 27, 2024

Abstract As the global population ages, research on pathogenesis and treatment options for older patients with dementia has become increasingly important. Vascular (VaD), second most frequent type of dementia, is characterized by vascular impairment caused inadequate blood supply to brain. VaD a complex neurological disorder involving multiple cells signaling pathways, its prevention pose clinical challenges significant behavioral implications. Glutamate, abundant amino acid in brain, plays critical role as an excitatory neurotransmitter, impacting cognitive function, learning, memory. Abnormal glutamate metabolism been closely linked reduced flow brain can lead excessive accumulation, resulting neuronal death. This article highlights connection between metabolism, aiming identify better methods preventing treating via regulating metabolism.

Language: Английский

Citations

4
Glial Cell Crosstalk in Parkinson's Disease: Mechanisms, Implications, and Therapeutic Strategies DOI Creative Commons

Ning Wang,

Xiao Xiao,

Zi-jiang Chen

et al.

Fundamental Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
From quiescence to self-sustained activity: How astrocytes reshape neural dynamics DOI

Den Whilrex Garcia,

Sabir Jacquir

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

Published: April 1, 2025

Language: Английский

Citations

0
Astrocytes: new evidence, new models, new roles DOI
Alexey Brazhe, Andrey Yu. Verisokin, Darya V. Verveyko

et al.

Biophysical Reviews, Journal Year: 2023, Volume and Issue: 15(5), P. 1303 - 1333

Published: Oct. 1, 2023

Language: Английский

Citations

10
The Role of Glial Cells in the Pathophysiology of Epilepsy DOI Creative Commons
Filiz Onat, My Andersson, Nihan Çarçak

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(2), P. 94 - 94

Published: Jan. 10, 2025

Epilepsy is a chronic neurological disorder marked by recurrent seizures, significantly impacting individuals worldwide. Current treatments are often ineffective for third of patients and can cause severe side effects, necessitating new therapeutic approaches. Glial cells, particularly astrocytes, microglia, oligodendrocytes, emerging as crucial targets in epilepsy management. Astrocytes regulate neuronal homeostasis, excitability, synaptic plasticity, playing key roles maintaining the blood-brain barrier (BBB) mediating neuroinflammatory responses. Dysregulated astrocyte functions, such reactive astrogliosis, lead to abnormal activity seizure generation. They release gliotransmitters, cytokines, chemokines that may exacerbate or mitigate seizures. Microglia, innate immune cells CNS, contribute neuroinflammation, glutamate excitotoxicity, balance between excitatory inhibitory neurotransmission, underscoring their dual role promotion protection. Meanwhile, primarily involved myelination, also modulate axonal excitability neuron-glia network underlying pathogenesis. Understanding dynamic interactions glial with neurons provides promising avenues novel therapies. Targeting these improved control better clinical outcomes, offering hope refractory epilepsy.

Language: Английский

Citations

0
Disrupted astrocyte-neuron signaling reshapes brain activity in epilepsy and Alzheimer’s disease DOI
Mengjie Wu, Ruonan Zhang, Peng Fu

et al.

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

Published: Feb. 1, 2025

Language: Английский

Citations

0
Ultrasonic Modulation of Astrocytic and Neuronal Calcium Dynamics in Mouse Cortex DOI Open Access
Yu Yong, Hao Jiang,

C. F. Qiao

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 5, 2025

Abstract Background Astrocytes are abundant in the brain and their calcium signaling is reported to have an important effect on neuronal activity both physiological pathological conditions. Low-frequency focused ultrasound (FUS) has recently emerged as a powerful noninvasive neuromodulation approach, yet its impact astrocyte dynamics different states vivo poorly understood. Objective This study aimed elucidate effects of non-thermal FUS dynamic with cellular-resolution cell-type-specific recording identify whether influences cortical astrocytes neurons distinctive state dependent. Methods Here we combined customized 0.521MHz transducer two-photon microscopy, allowing simultaneous single-cell resoultion imaging stimulation at intensities 0.91 or 1.5 W/cm 2 examine responses somatosensory cortex awake lightly anesthetized mice. Functional clustering analysis was performed response activated inhibited subpopulations. Results In mice, significantly enhanced amplitude, frequency, temporal integral transients, while suppressing reducing proportion contrast, mice displayed blunted increased negligible modulation under FUS, suggesting that baseline suppression from anesthesia partially masks effects. Conclusions Our demonstrated elicited distinctive, state-dependent neurons, highlighting previously underappreciated targets neuromodulation. These findings will pave way for FUS-based therapies targeting astrocyte–neuron interactions conditions involving abnormal excitability. Highlights Low duty cycle low frequency induced heat Ultrasound markedly transients suppressed The cell types were reduced light anesthesia.

Language: Английский

Citations

0
Herkinorin ameliorates neuronal damage in a pentylenetetrazol-induced epilepsy rat model through altering microglial and astrocytic activation by inhibiting PARP1 and NF-κB DOI
Yun Liu,

Wenmei Zhao,

Xia Lv

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 155, P. 114588 - 114588

Published: April 10, 2025

Language: Английский

Citations

0