The mammalian brain contains neurogenic niches comprising neural stem cells (NSCs) and other cell types. Neurogenic niches become less functional with age, but how they change during aging remains unclear. Here we perform single cell RNA-sequencing of young and old neurogenic Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the

Aging has a profound and devastating effect on the brain. Old age is accompanied by declining cognitive function and enhanced risk of brain diseases, including cancer and neurodegenerative disorders. A key question is whether cells with regenerative potential contribute to brain health and even brain ''rejuvenation.'' This review discusses mechanisms that regulate neural stem cells (NSCs) during aging, focusing on the effect of metabolism, genetic regulation, and the surrounding niche. We also explore emerging rejuvenating strategies for old NSCs. Finally, we consider how new technologies may help harness NSCs' potential to restore healthy brain function during physiological and pathological aging. ll

Acidic clusters act as sorting signals for packaging cargo into clathrin-coated vesicles. Navarro Negredo et al. show that the clathrin adaptor AP-1 subunit µ1 interacts with endogenous acidic cluster cargo as well as with the HIV-1 acidic cluster protein Nef, and they tease out the contribution of this interaction to acidic cluster protein trafficking.

Vesicluar transport of proteins from endosomes to the trans-Golgi network (TGN) is an essential cellular pathway, but much of its machinery is still unknown. A screen for genes involved in endosome-to-TGN trafficking produced two hits, the adaptor protein-1 (AP-1 complex), which facilitates vesicle budding, and WDR11. Here we demonstrate that WDR11 forms a stable complex with two other proteins, which localises to the TGN region and does not appear to be associated with AP-1, suggesting it may act downstream from budding. In a vesicle tethering assay, capture of vesicles by golgin-245 was substantially reduced in WDR11-knockout cells. Moreover, structured illumination microscopy and relocation assays indicate that the WDR11 complex is initially recruited onto vesicles rather than the TGN, where it may in turn recruit the golgin binding partner TBC1D23. We propose that the complex acts together with TBC1D23 to facilitate the golgin-mediated capture of vesicles that were generated using AP-1.

Complexins (Cplxs) are small, soluble, regulatory proteins that bind reversibly to the SNARE complex and modulate synaptic vesicle release. Cplx1 knockout mice (Cplx1−/−) have the earliest known onset of ataxia seen in a mouse model, although hitherto no histopathology has been described in these mice. Nevertheless, the profound neurological phenotype displayed by Cplx1−/− mutants suggests that significant functional abnormalities must be present in these animals. In this study, MRI was used to automatically detect regions where structural differences were not obvious when using a traditional histological approach. Tensor-based morphometry of Cplx1−/− mouse brains showed selective volume loss from the thalamus and cerebellum. Stereological analysis of Cplx1−/− and Cplx1+/+ mice brain slices confirmed the volume loss in the thalamus as well as loss in some lobules of the cerebellum. Finally, stereology was used to show that there was loss of cerebellar granule cells in Cplx1−/− mice when compared to Cplx1+/+ animals. Our study is the first to describe pathological changes in Cplx1−/− mouse brain. We suggest that the ataxia in Cplx1−/− mice is likely to be due to pathological changes in both cerebellum and thalamus. Reduced levels of Cplx proteins have been reported in brains of patients with neurodegenerative diseases. Therefore, understanding the effects of Cplx depletion in brains from Cplx1−/− mice may also shed light on the mechanisms underlying pathophysiology in disorders in which loss of Cplx1 occurs.