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Characteristics of neurons

Characteristics of neurons. Cytoskeletal organization Microtubules and motors Neuronal intermediate filaments Neurofilaments Peripherin, Nestin Microfilaments Actins Axonal transport Fast transport Slow transport. Neurofilaments (EM). Neurofilaments (EM). Neurofilaments (biochemistry).

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Characteristics of neurons

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

  2. Neurofilaments (EM)

  3. Neurofilaments (EM)

  4. Neurofilaments (biochemistry)

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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. Transgenic mice with no NF

  12. 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

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

  14. Filamentous pathology in neuronal cell bodies

  15. Filamentous pathology in proximal axons

  16. 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

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

  18. 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

  19. 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

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

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

  22. 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)

  23. 神經再生

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