A novel in vitro model for investigating oligodendroglial maturation and myelin deposition under demyelinating and remyelinating conditions: Impact of microglial depletion and repopulation

• Published in: Molecular and cellular neuroscience 2024-06, Vol.129, p.103937-103937, Article 103937
• Main Authors: Di Pietro, Anabella Ayelen, Pasquini, Laura Andrea
• Format: Article
• Language: English
• Subjects: Animals; Cell Differentiation - physiology; Cells, Cultured; Demyelinating Diseases - metabolism; Demyelinating Diseases - pathology; Demyelination; In vitro model; Mice; Microglia - metabolism; Microglial depletion; Microglial repopulation; Multiple sclerosis; Myelin Sheath - metabolism; Oligodendroglia - metabolism; Oligodendroglial differentiation; Remyelination; Remyelination - physiology
• ISSN: 1044-7431; 1095-9327
• DOI: 10.1016/j.mcn.2024.103937

Experimental models of multiple sclerosis (MS) have significantly contributed to our understanding of pathophysiology and the development of therapeutic interventions. Various in vivo animal models have successfully replicated key features of MS and associated pathophysiological processes, shedding light on the sequence of events leading to disease initiation, progression, and resolution. Nevertheless, these models often entail substantial costs and prolonged treatment periods. In contrast, in vitro models offer distinct advantages, including cost-effectiveness and precise control over experimental conditions, thereby facilitating more reproducible results. We have developed a novel in vitro model tailored to the study of oligodendroglial maturation and myelin deposition under demyelinating and remyelinating conditions, which encompasses all the cell types present in the central nervous system (CNS). Of note, our model enables the evaluation of microglial cell commitment through a protocol involving their depletion and subsequent repopulation. Given that the development and survival of microglia are critically reliant on colony-stimulating factor-1 receptor (CSF-1R) signaling, we have employed CSF-1R inhibition to effectively deplete microglia. This versatile model holds promise for the assessment of potential therapies aimed at promoting oligodendroglial differentiation to safeguard and repair myelin, hence mitigate neurodegenerative processes. The Mixed Neuronal Glial Culture (MNGC) is an innovative in vitro model that includes all cell types present in the central nervous system (CNS): astrocytes (AST), oligodendrocytes (OLG), microglia (MG) and neurons. It has been designed to explore oligodendroglial maturation and myelin deposition in demyelinating and remyelinating conditions. This model allows for the evaluation of MG commitment through a protocol involving depletion and subsequent repopulation. This versatile model shows significant potential in assessing potential therapies aimed at promoting oligodendroglial differentiation to safeguard and repair myelin, hence mitigate neurodegenerative processes. [Display omitted] •The Mixed Neuronal Glial Culture is an innovative in vitro model that includes all cell types present in the CNS.•This model has been designed to explore oligodendroglial maturation and myelin deposition in de/remyelinating conditions.•This model allows for the evaluation of MG commitment through a protocol involving depletion and s