Deficits in the mitochondrial energy–generating machinery cause mitochondrial disease, a group of untreatable and usually fatal disorders. Refractory epileptic events are a common neurological presentation of mitochondrial disease, including Leigh syndrome, a severe form of mitochondrial disease associated with epilepsy. However, the neuronal substrates and circuits for mitochondrial disease–induced epilepsy remain unclear. Here, using mouse models of Leigh syndrome that lack mitochondrial complex I subunit NDUFS4 in a constitutive or conditional manner, we demonstrated that mitochondrial dysfunction leads to a reduction of GABAergic neurons in the rostral external globus pallidus (GPe) and identified a specific affectation of pallidal Lhx6–expressing inhibitory neurons contributing to altered GPe excitability. Our findings revealed that viral vector–mediated Ndufs4 reexpression in the GPe effectively prevented seizures and improved survival in the models. Additionally, we highlight the subthalamic nucleus (STN) as a critical structure in the neural circuit involved in mitochondrial epilepsy, as its inhibition effectively reduces epileptic events. Thus, we have identified a role for pallido-subthalamic projections in epilepsy development in the context of mitochondrial dysfunction. Our results suggest STN inhibition as a potential therapeutic intervention for refractory epilepsy in patients with mitochondrial disease, providing promising leads in the quest to identify effective treatments.

The aryl hydrocarbon receptor (AhR) is increasingly recognized as a physiologic modulator of the immune response, a function that extends beyond its established role as a sensor for environmental xenobiotics. In a recent report published in the JCI, Cros et al. demonstrate that the AhR restrains tonic, microbiota-driven inflammatory cytokine production in monocytes. Through the combined use of murine models, human ex vivo systems, and the analysis of patient-derived data, Cros and coworkers established that the AhR limits stimulator of IFN gene–induced (STING-induced) proinflammatory signals. These findings define cell type–specific physiologic roles for the AhR in the regulation of innate immunity and underscore its potential as a therapeutic target for the treatment of inflammatory and autoimmune diseases.

El periodismo libre te necesita

Compre online A morte é um dia que vale a pena viver: E um excelente motivo para se buscar um novo olhar para a vida, de Arantes, Ana Claudia Quintana na Amazon. Frete GRÁTIS em milhares de produtos com o Amazon Prime. Encontre diversos livros escritos por Arantes, Ana Claudia Quintana com ótimos preços.

Un nuevo caso de acoso machista en Torremolinos acorrala todavía más al gobierno de Pedro Sánchez , cuya reacción al descubrirlo habría sido mu cues

Quintana Roo asigna 122 plazas definitivas en educación básica para el ciclo 2025-2026, en un proceso público y transparente con respaldo institucional.

🔁 @SergioMQuintero retweeted @dannybarrand_ May I interest you in some Jorge Quintana switch-hitting video? https://t.co/U28sWxE1VW

“Powerful technologies require equally powerful ethical guidance.” (Bostrom, N. Superintelligence: Paths, Dangers, Strategies. Oxford University Press, 2014). The ethics of using artificial intelligence depend on how we apply its capabilities—either to enhance learning or to prevent irresponsible practices that may compromise academic integrity. In this blog, I share reflections, experiences, and insights about the impact of AI […]