Myriam Baes

Peroxisomes are organelles with diverse metabolic tasks including essential roles in lipid metabolism. They are of utmost importance for the normal functioning of the nervous system as most peroxisomal disorders are accompanied with neurological symptoms. Remarkably, the cerebellum exquisitely depends on intact peroxisomal function both during development and adulthood. In this review, we cover all aspects of cerebellar pathology that were reported in peroxisome biogenesis disorders and in diseases caused by dysfunction of the peroxisomal α‐oxidation, β‐oxidation or ether lipid synthesis pathways. We also discuss the phenotypes of mouse models in which cerebellar pathologies were recapitulated and search for connections with the metabolic abnormalities. It becomes increasingly clear that besides the most severe forms of peroxisome dysfunction that are associated with developmental cerebellar defects, milder impairments can give rise to ataxia later in life.

The functional diversity and molecular adaptations of reactive microglia in the chronically inflamed central nervous system (CNS) are poorly understood. We previously showed that mice lacking multifunctional protein 2 (MFP2), a pivotal enzyme in peroxisomal β‐oxidation, persistently accumulate reactive myeloid cells in the gray matter of the CNS. Here, we show that the increased numbers of myeloid cells solely derive from the proliferation of resident microglia and not from infiltrating monocytes. We defined the signature of Mfp2^−/− microglia by gene expression profiling after acute isolation, which was validated by quantitative polymerase reaction (qPCR), immunohistochemical, and flow cytometric analysis. The features of Mfp2^−/− microglia were compared with those from SOD1^G93A mice, an amyotrophic lateral sclerosis model. In contrast to the neurodegenerative milieu of SOD1^G93A spinal cord, neurons were intact in Mfp2^−/− brain and Mfp2^−/− microglia lacked signs of phagocytic and neurotoxic activity. The chronically reactive state of Mfp2^−/− microglia was accompanied by the downregulation of markers that specify the unique microglial signature in homeostatic conditions. In contrast, mammalian target of rapamycin (mTOR) and downstream glycolytic and protein translation pathways were induced, indicative of metabolic adaptations. Mfp2^−/− microglia were immunologically activated but not polarized to a pro‐ or anti‐inflammatory phenotype. A peripheral lipopolysaccharide challenge provoked an exaggerated inflammatory response in Mfp2^−/− brain, consistent with a primed state. Taken together, we demonstrate that chronic activation of resident microglia does not necessarily lead to phagocytosis nor overt neurotoxicity. GLIA 2015;63:1606–1620

Plastic materials are widely used in research laboratories. Disposable plasticware facilitates life science research in the storage, transportation and manipulation of biological samples. However, recent findings have shown that some disposable plasticwares release bioactive contaminants. The bioactive leachates from plastic tubes, used as Abl1 catalytic incubator in this report, were noticed to interfere with the activity of Abl1. Extraction of these bioactive leachates was performed, and their inhibitory activity against Abl1 and cytotoxicity were tested. Results indicated that the tube extracts had no significant cytotoxicity but could inhibit the activity of Abl1. Therefore, these bioactive leachates from plastic tubes might be a specific inhibitor of tyrosine kinase.

Although peroxisomes are ubiquitous organelles in all animal species, their importance for the functioning of tissues and organs remains largely unresolved. Because peroxins are essential for the biogenesis of peroxisomes, an obvious approach to investigate their physiological role is to inactivate a Pex gene or to suppress its translation. This has been performed in mice but also in more primitive organisms including D. melanogaster, C. elegans and D. rerio, and the major findings and abnormalities in these models will be highlighted. Although peroxisomes are generally not essential for embryonic development and organogenesis, a generalized inactivity of peroxisomes affects lifespan and posthatching/postnatal growth, proving that peroxisomal metabolism is necessary for the normal maturation of these organisms. Strikingly, despite the wide variety of model organisms, corresponding tissues are affected including the central nervous system and the testis. By inactivating peroxisomes in a cell type selective way in the brain of mice, it was also demonstrated that peroxisomes are necessary to prevent neurodegeneration. As these peroxisome deficient model organisms recapitulate pathologies of patients affected with peroxisomal diseases, their further analysis will contribute to the elucidation of still elusive pathogenic mechanisms.