Organotypic cultures of cerebellar slices as a model to investigate demyelinating disorders

Expert Opin Drug Discov. 2017 Oct;12(10):1011-1022. doi: 10.1080/17460441.2017.1356285. Epub 2017 Jul 20.

Abstract

Demyelinating disorders, characterized by a chronic or episodic destruction of the myelin sheath, are a leading cause of neurological disability in young adults in western countries. Studying the complex mechanisms involved in axon myelination, demyelination and remyelination requires an experimental model preserving the neuronal networks and neuro-glial interactions. Organotypic cerebellar slice cultures appear to be the best alternative to in vivo experiments and the most commonly used model for investigating etiology or novel therapeutic strategies in multiple sclerosis. Areas covered: This review gives an overview of slice culture techniques and focuses on the use of organotypic cerebellar slice cultures on semi-permeable membranes for studying many aspects of axon myelination and cerebellar functions. Expert opinion: Cerebellar slice cultures are probably the easiest way to faithfully reproduce all stages of axon myelination/demyelination/remyelination in a three-dimensional neuronal network. However, in the cerebellum, neurological disability in multiple sclerosis also results from channelopathies which induce changes in Purkinje cell excitability. Cerebellar cultures offer easy access to electrophysiological approaches which are largely untapped and we believe that these cultures might be of great interest when studying changes in neuronal excitability, axonal conduction or synaptic properties that likely occur during multiple sclerosis.

Keywords: Organotypic brain slice cultures; cerebellum; epsilon toxin; multiple sclerosis; myelin.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism
  • Cerebellum / pathology*
  • Demyelinating Diseases / physiopathology*
  • Humans
  • Multiple Sclerosis / physiopathology
  • Myelin Sheath / pathology
  • Organ Culture Techniques / methods*
  • Purkinje Cells / metabolism