Victor Bodart-Santos and al.

This study shows that in the murine model of Alzheimer's disease APPNL-G-F, the knockdown of Sepp1 (the gene encoding selenoprotein P), achieved via the intracerebral injection of a lentivirus, reduces the secretion of extracellular vesicles by plaque-associated microglial cells. The role of selenoprotein P in the biogenesis and secretion of extracellular vesicles is further confirmed in vitro in the murine BV2 microglial cell line.

Guoqiang George Sun and al.

A recent study revealed that the APOE3 Christchurch variant (APOECh) could slow the progression of Alzheimer's disease. In this study, the authors established neuron-microglia co-cultures and neuro-immune organoids using:
i) isogenic APOE3 vs APOECh microglia derived from human induced pluripotent stem cells (hiPSCs), co-cultured with ii) neurons or brain organoids carrying mutant PSEN1. The results demonstrate that APOECh microglial cells are resistant to lipid peroxidation and ferroptosis induced by amyloid β. These mechanisms enable APOECh microglial cells to maintain their phagocytic activity and promote the clearance of phosphorylated Tau.

Alexandria B. Marciante and al.

Brief episodes of acute intermittent hypoxia (AIH) induce a form of respiratory motor plasticity known as phrenic long-term facilitation (pLTF). Using a male rat model, the authors demonstrate that inhibiting the synthesis of fractalkine by phrenic motor neurons, blocking microglial fractalkine receptors (Cx3cr1), or ablating microglial cells enhances AIH-induced pLTF under moderate hypoxia but inhibits pLTF under severe hypoxia.

Chloe Lopez-Lee and al.

Alzheimer's disease (AD) and other age-related brain pathologies are associated with demyelination processes  exhibiting sex-specific differences. In this study, the authors report that, in a murine model of AD involving human APOE4 expression, the XY sex chromosomes amplify both the interferon (IFN) response and Tau-induced demyelination. The TLR7 receptor, located on X chromosome, regulates the IFN response induced by myelin damage in a sex-specific manner. Knockout of Tlr7 reduces sex differences while preventing demyelination. Similarly, in male mice, administration of a TLR7 inhibitor alleviates Tau-induced motor deficits and neurodegeneration-associated demyelination.

Rasha Barakat and al.

Using multiple "single-cell RNA-seq" datasets, the authors demonstrate that the proportion of exhausted T cells is higher in pediatric low-grade gliomas compared to pediatric or adult high-grade gliomas. In several preclinical murine models of low-grade gliomas, the authors report that exhausted CD8+ T lymphocytes (PD1+/TIGIT+) are restricted to tumor tissues, where they express paracrine factors essential for tumor cell growth. Importantly, in these models, anti-PD1 (α-PD1) and anti-TIGIT (α-TIGIT) antibodies reduce tumor proliferation by inhibiting the chemotaxis of CD8 T lymphocytes rather than enhancing their cytotoxic activity.