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1. Introduction
2. Amyotrophic lateral sclerosis
3. ALS - classification
4. Death of motor neurons
5. Gene discovery in ALS
6. ALS – SOD1 mutations overview
7. Abundance of ALS models: mice/rats/flys/fish
8. The mechanisms of neuron/glial toxicity
9. Astroglial cells contribute to ALS pathogenesis
10. Evidence for astroglial dysfunction in ALS
11. Astroglial defect in ALS
12. ALS is disorder of oligodendroglial function
13. Neural/glial stem cell lineages
14. An enigmatic population of glial cells in CNS
15. NG2+ cells in the adult spinal cord
16. Gliosis in the spinal cord of ALS mice
17. Enhanced proliferation of NG2+ cells in ALS mice
18. PDGFalphaR-CreER BAC transgenic mice
19. Enhanced cell proliferation in ALS mice
20. NG2+ cells remain lineage restricted
21. Human cortical ALS NG2 altered morphology
22. Myelin protein(s) in motor cortex of ALS patients
23. Human ALS: cortical demyelination
24. ALS spinal cord ventral gray demyelination
25. Loss of myelin basic protein (MBP)
26. MTR abnormalities in human ALS
27. Is there evidence for oligo injury in ALS?
28. Oligodendroglia metabolically support axons
29. Astrocyte-oligodendrocyte-neuron lactate shuttle
30. Topology of MCT1
31. MCT1 is widely expressed in oligodendroglia
32. MCT1-TdTom is not expressed by astroglia
33. Immunolocalization confirms MCT1 to Oligo
34. MCT1 is present only in oligodendrocytes
35. Loss of MCT1 leads to MN degeneration
36. Lactate rescues MCT1i mediated neuronal toxicity
37. Lactate also rescues neuronal toxicity in vivo
38. MCT1 het mice show axonal degeneration
39. MCT1 knockdown leads to axonal degeneration
40. Hypothesis
41. MCT1 in affected areas of ALS patients
42. MCT1 expression in ALS gray matter oligos
43. Oligodendroglia: metabolic stabilizers of axons
44. C14-lactate uptake and block by MCTi
45. More questions should be explored…
46. Acknowledgements

Topics Covered

• The variety of cellular pathways causing Amyotrophic Lateral Sclerosis (ALS)
• A new ALS-causing cellular pathway implicating oligodendroglia and their newly discovered property of metabolic support neurons via lactate transport
• Unexpected major cellular injury in ALS gray matter and the relationship to newly discovered ALS-causing pathway – Current and future targets for therapeutic intervention in ALS

Links

Series:

• Physiology and Pathophysiology of Neuroglia

Categories:

• Biochemistry
• Cell Biology
• Clinical Practice
• Neuroscience

Therapeutic Areas:

• Neurology

Talk Citation

Rothstein, J.D. (2013, August 19). Oligodendroglia/MCT1 are an unexpected contributor to CNS toxicity/neurodegeneration [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 30, 2024, from https://doi.org/10.69645/NOCT4579.
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Publication History

• Published on August 19, 2013

Financial Disclosures

• Prof. Jeffrey D. Rothstein has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.