Oligodendrocytes in amyotrophic lateral sclerosis and frontotemporal dementia: the new players on stage.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are fatal adult-onset neurodegenerative disorders that share clinical, neuropathological and genetic features, which forms part of a multi-system disease spectrum. The pathological process leading to ALS and FTD is the result of the combination of multiple mechanisms that operate within specific populations of neurons and glial cells. The implication of oligodendrocytes has been the subject of a number of studies conducted on patients and related animal models. In this review we summarize our current knowledge on the alterations specific to myelin and the oligodendrocyte lineage occurring in ALS and FTD. We also consider different ways by which specific oligodendroglial alterations influence neurodegeneration and highlight the important role of oligodendrocytes in these two intrinsically associated neurodegenerative diseases.

Cytoplasmic FUS triggers early behavioral alterations linked to cortical neuronal hyperactivity and inhibitory synaptic defects.

Gene mutations causing cytoplasmic mislocalization of the RNA-binding protein FUS lead to severe forms of amyotrophic lateral sclerosis (ALS). Cytoplasmic accumulation of FUS is also observed in other diseases, with unknown consequences. Here, we show that cytoplasmic mislocalization of FUS drives behavioral abnormalities in knock-in mice, including locomotor hyperactivity and alterations in social interactions, in the absence of widespread neuronal loss. Mechanistically, we identified a progressive increase in neuronal activity in the frontal cortex of Fus knock-in mice in vivo, associated with altered synaptic gene expression. Synaptic ultrastructural and morphological defects were more pronounced in inhibitory than excitatory synapses and associated with increased synaptosomal levels of FUS and its RNA targets. Thus, cytoplasmic FUS triggers synaptic deficits, which is leading to increased neuronal activity in frontal cortex and causing related behavioral phenotypes. These results indicate that FUS mislocalization may trigger deleterious phenotypes beyond motor neuron impairment in ALS, likely relevant also for other neurodegenerative diseases characterized by FUS mislocalization.

Authentication of pharmaceutical vials.

Packaging analysis is an important step in the authentication of medicines. All types of medicines are nowadays targeted by the counterfeiters, and among them, vials of injectable medicines. This type of pharmaceutical product is often a combination of fake parts and genuine but stolen, expired, reused and/or manipulated parts. For this reason, while the visual comparison with references is necessary to identify the packaging, it is sometimes difficult to see visual differences for each of the parts that compose a pharmaceutical vial. Several analytical tools were successfully tested to support the investigation of 31 counterfeited vials. Moreover eight counterfeited vials originating from different seizures could be linked based on the chemical or elemental composition of the different vial parts. Raman spectroscopy and microscopy, X-ray fluorescence spectroscopy, Infrared spectroscopy and optical microscopy proved especially efficient to support the visual comparison for the authentication of counterfeited flip off caps, aluminium crimping caps, stoppers, glass vials and vial labels and to detect links between the counterfeits at each of these levels. This last information can be especially useful for on-going investigations. The understanding of how the packaging was faked and manipulated could also be provided, which is also very valuable for prevention purposes, for example for the design of a more robust - and therefore more difficult to counterfeit - packaging.