Characteristics of neurons

1. Characteristics of neurons • Cytoskeletal organization • Microtubules and motors • Neuronal intermediate filaments • Neurofilaments • Peripherin, Nestin • Microfilaments • Actins • Axonal transport • Fast transport • Slow transport

4. Neurofilaments (EM)

5. Neurofilaments (EM)

6. Neurofilaments (biochemistry)

7. Neurofilaments • Functions • Maintenance of the axonal organization • Radial growth • Mechanisms • Phosphorylation • Glycosylation?

8. Axonal growth • Longitudinal growth • To establish the connection with targets • Growth cone • Early phase of Regeneration/Development • Actin and microtubules • Radial growth • To increase axonal caliber • Late phase of Regeneration/Development • Neurofilaments

9. Neurofilaments and Axonal caliber • Inherent neuronal characteristics • Large targets with large axons • Developmental stage • Smaller caliber, less NF • Somatofugal axonal atrophy • Atrophy of the axons in the proximal stump after nerve injury • Related to NF synthesis, transport and phosphorylation

10. Neurofilaments and Axonal caliber(Experimental evidence) • Correlation between caliber and NF number • Development • Degeneration/Regeneration • Genetics • Transgenic mice to delete NFs • Spontaneous mutant: Japanese quail

13. NF: Spontaneous mutant • Mutant Japanese quail • Lack of neurofilaments in axons; small axonal caliber • Growth normally, with some unsteadiness • Still susceptible to acrylamide: a model of neurofilamentous pathology • Mechanism: mutation in NF-L with a premature stop codon

14. Transgenic mice with no NF • Absence of NFs due to deletion of NF-L gene • Small caliber with absence of NFs • Grow normally with neuronal swelling in spinal cords and axonal degeneration

15. Transgenic mice with no NF

19. Neuronal swelling in NF transgenics • Over-expression of NFs • NF-H, NF-M, NF-L (ref) • Mutant or normal NFs • Pathology • Neuronal aggregates of NFs leading to neurodegeneration • Axonal atrophy and degeneration

21. Filamentous neuropathology • NF pathology • Neuronal • Early stage of ALS • Transgenics: NF, SOD • Axonal • Proximal: IDPN • Distal: 2,5-HD • Consequence: Neuronal death (Neurodegeneration)

22. Filamentous pathology in neuronal cell bodies

25. Filamentous pathology in proximal axons

28. Wallerian degeneration • In the stump distal to the site of nerve injury • Degeneration of axons • Disintegration of axonal cytoskeleton and organization • Proliferation of Schwann cells • Infiltration of macrophages

29. Neuronal response in Wallerian degeneration • Chromatolysis • Alteration in the patterns of mRNA • Somatofugal atrophy • Neuronal death in some situations

31. Neurodegenerative diseases • Cortex • Alzheimer disease • Frontotemporal dementia • Motor and coordination system • Motor neuron disease, Amyotrophic lateral sclerosis (ALS) • Parkinson’s disease • Spinocerebellar atrophy (SCA) • Autonomic system • Multiple system atrophy

32. Filamentous neuropathology • MT pathology • Acrylamide • NF pathology • Neuronal • Early stage of ALS • Transgenics: NF, SOD • Axonal • Proximal: IDPN • Distal: 2,5-HD • Tau pathology • NFT in Alzheimer disease

33. Alzheimer disease • Progressive dementia, particularly over age 65 • Basal foregbrain cholinergic hypothesis • Pathological hallmarks • Senile plaque • Neurofibrillary tangle

34. Regenerative strategy for neurodegenerative diseases • Supplement of deficiency: cholinergic medications • Replacement of cells: stem cells, adrenergic cells • Establishment of connections: repulsive and attractive molecules

35. 神經再生 神經突起的再生 生長錐 (growth cones) 相吸物質(attractants) 相斥物質(repulsants)

36. 神經再生