Expression changes in ion channel and immunity genes are associated with glioma-related epilepsy in patients with diffuse gliomas

Li, Lianwang; Zhang, Chuanbao; Wang, Zheng; Guo, Yuhao; Wang, Yinyan; Fan, Xing; Jiang, Tao

doi:10.1007/s00432-022-04049-3

Cited by 5 publications

(2 citation statements)

References 39 publications

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“…A wide spectrum of possible underlying causes for GBM's ability to use neural hyperexcitation for to its own advantage and its resistance to therapy have been proposed (Jung et al, 2019;Keough & Monje, 2022;Torres & Canoll, 2019) . Recent studies provide multiple lines of evidence for the ability of GBM to promote its spread by taking advantage of the unique microenvironment in the brain that results in a complex feedback system of increased glutamate metabolism (Alcoreza et al, 2019;Buckingham et al, 2011;Sørensen et al, 2018), synaptogenesis (Venkataramani et al, 2019;Venkatesh et al, 2019;Yu et al, 2020), suppression of GABAergic inhibition (Campbell et al, 2015;Tewari et al, 2018), and alteration of other signaling pathways (Li et al, 2022;Piao et al, 2009;Venkatesh et al, 2015) . Despite these advances, many questions about GBM progression and how the reciprocal feedback mechanisms with the surrounding neural activity unfold remain unanswered.…”

Section: Discussionmentioning

confidence: 99%

Glioblastoma disrupts cortical network activity at multiple spatial and temporal scales

Meyer

Deneen

et al. 2022

Preprint

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The emergence of glioblastoma in cortical tissue is accompanied by signs of neural hyperexcitability that may manifest with symptoms ranging from mild cognitive impairment to convulsive seizures. Glioblastoma exploits the complex interplay between neurons and glia to create a microenvironment favorable for its own expansion, impeding efforts to achieve long-term clinical remission compared to other solid tumors. We employed a novel CRISPR-Cas9 in-utero electroporation system to induce two distinct GBM tumor models in immunocompetent mice in combination with prolonged EEG recording and single and 2-photon imaging of calcium and glutamate reporters to analyze dynamic changes in peritumoral cortical network activity at different spatial and temporal scales. We find a biphasic elevation in neuronal calcium activity followed by a linear but only partially overlapping accumulation of peritumoral glutamate during tumor growth indicating these processes are not entirely coordinated. The patterns are strongly influenced by tumor genetics. The global changes in excitability homeostasis alter the higher order modularity and connectivity patterns of local and remote neuronal populations and can transform inter-areal brain information processing over time.

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Section: Discussionmentioning

confidence: 99%

Glioblastoma disrupts cortical network activity at multiple spatial and temporal scales

Meyer

Deneen

et al. 2022

Preprint

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“…Therefore, this relationship could be therapeutically leveraged to improve the quality of life for patients with brain tumors. For example, LGICs have also been associated with the development of glioma-related epilepsy (GRE) in diffuse glioma patients [ 117 ]. As such, GABA A modulators have been commonly used in both general epilepsy and GRE.…”

Section: Lgics As a Clinical Targetmentioning

confidence: 99%

Ligand-Gated Ion Channels: Prognostic and Therapeutic Implications for Gliomas

Hey

Rao

Carter

et al. 2023

JPM

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Gliomas are common primary brain malignancies that remain difficult to treat due to their overall aggressiveness and heterogeneity. Although a variety of therapeutic strategies have been employed for the treatment of gliomas, there is increasing evidence that suggests ligand-gated ion channels (LGICs) can serve as a valuable biomarker and diagnostic tool in the pathogenesis of gliomas. Various LGICs, including P2X, SYT16, and PANX2, have the potential to become altered in the pathogenesis of glioma, which can disrupt the homeostatic activity of neurons, microglia, and astrocytes, further exacerbating the symptoms and progression of glioma. Consequently, LGICs, including purinoceptors, glutamate-gated receptors, and Cys-loop receptors, have been targeted in clinical trials for their potential therapeutic benefit in the diagnosis and treatment of gliomas. In this review, we discuss the role of LGICs in the pathogenesis of glioma, including genetic factors and the effect of altered LGIC activity on the biological functioning of neuronal cells. Additionally, we discuss current and emerging investigations regarding the use of LGICs as a clinical target and potential therapeutic for gliomas.

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