Buffon Viviane Aline, Filho Jurandir M Ribas, Malafaia Osvaldo, Tassinari Isadora D, Roesler Rafael, Isolan Gustavo R
Graduate Program in Principles of Surgery, Mackenzie Evangelical University, Curitiba 80730-000, Brazil.
Laboratory of Neurobiology and Metabolism (NeuroMet), Department of Physiology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre 90035-003, Brazil.
Brain Sci. 2025 Jul 11;15(7):746. doi: 10.3390/brainsci15070746.
Medulloblastoma (MB) is the most common malignant brain tumor in children and typically arises in the cerebellum, likely due to disruptions in neuronal precursor development. The primary inhibitory neurotransmitter in the central nervous system (CNS), γ-aminobutyric acid (GABA), exerts its effects through GABA, GABA, and GABA receptors. GABA receptor activity regulates the development and function of cerebellar neurons, including glutamatergic cerebellar granule cells (CGCs). Beyond the nervous system, GABA is also a common metabolite in non-neuronal cell types. An increasing body of evidence indicates that GABA can influence cell proliferation, differentiation, and migration in several types of adult solid tumors, including brain cancers. GABA and GABA receptor agonists can impair the viability and survival of MB cells, primarily acting on GABA receptors containing the α5 subunit. A marked expression of the gene encoding the α5 subunit is found across all MB tumor molecular subgroups, particularly Group 3 MB, which has a poor prognosis. Importantly, high levels of the γ-aminobutyric acid type A receptor subunit α5 ) gene are associated with shorter patient overall survival in Group 3 and Group 4 MB. In contrast, high γ-aminobutyric acid type A receptor subunit β1 () gene expression is related to longer survival in all MB subgroups. The GABAergic system may, therefore, regulate MB cell function and tumor progression and influence patient prognosis, and is worthy of further investigation as a biomarker and therapeutic target in MB.
髓母细胞瘤（MB）是儿童中最常见的恶性脑肿瘤，通常起源于小脑，这可能是由于神经元前体发育受到破坏所致。中枢神经系统（CNS）中的主要抑制性神经递质γ-氨基丁酸（GABA）通过GABA、GABA和GABA受体发挥作用。GABA受体活性调节小脑神经元的发育和功能，包括谷氨酸能小脑颗粒细胞（CGC）。除神经系统外，GABA也是非神经元细胞类型中的常见代谢物。越来越多的证据表明，GABA可以影响几种类型的成人实体肿瘤（包括脑癌）中的细胞增殖、分化和迁移。GABA和GABA受体激动剂可以损害MB细胞的活力和存活，主要作用于含有α5亚基的GABA受体。在所有MB肿瘤分子亚组中，特别是预后较差的3组MB中，发现编码α5亚基的基因有明显表达。重要的是，在3组和4组MB中，高水平的γ-氨基丁酸A型受体亚基α5（）基因与患者较短的总生存期相关。相比之下，高γ-氨基丁酸A型受体亚基β1（）基因表达与所有MB亚组中较长的生存期相关。因此，GABA能系统可能调节MB细胞功能和肿瘤进展，并影响患者预后，作为MB中的生物标志物和治疗靶点值得进一步研究。
