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Terminal Motor Axons & Neuromuscular Junctions

Acrylamide Age Atrophy Axon Regrowth   Ultraterminal sprouts (Botulinum toxin)   Collateral sprouts   Regeneration Demyelination   CIDP   MMN Dimethyaminopropionitrile (DMAPN) Myasthenia Gravis Normal

Normal Human: Silver-P0-Esterase stain

Rat: Silver-P0-Esterase stain

Neuromuscular Junctions: Normal

• Axon stained black (Silver), innervates a single NMJ
  • Terminal axon: Branches within NMJ (Blue) area
• Myelin is rust colored (P₀ antibody)
• NMJ region is blue (Esterase stain)

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Collateral Sprouting

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Collateral Sprouting: Features

• Nerve Sprouts
  • New growth: Terminal branches to different NMJs from a single preterminal axon
  • Diameter: Narrow
  • Surrounding myelin: None or Thin
  • Sprout Origin
    • Ultraterminal: From terminal axon branches within NMJ
    • Preterminal: From Node of Ranvier or most distal part of axon before NMJ
  • Sprout Target: Neighboring neuromuscular junctions
• Effects of sprouting on Muscle
  • Fiber type grouping
    • Occurs with reinnervation by intact axons
    • Collateral sprouts: Produce small regions of type grouping
    • Regenerating axons: Produce larger regions of type grouping
    • ALS: More common with slowly progressive or chronic disease
  • Grouped atrophy
    • Occurs when axon that has reinnervated a group of neighboring muscle fibers degenerates, or becomes less active
    • ALS: Regions of grouped atrophy may contain mixed fiber types

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Terminal (Collateral) sprouting in ALS

Silver-P0-Esterase stain

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Terminal (Collateral) Sprouts after Partial Denervation of rat muscle

Silver (Black)-Esterase (Blue) stain: Rat muscle

Collateral (Pre-Terminal & Terminal) Sprouting (Rat)
  Collateral sprouts: Several sprouts reinnervate one NMJ
    From Intact axons to Denervated NMJ (Arrow)
    May originate from
      Terminal axon branches (Above), or
      Preterminal axon (Below)

Silver (Blue)-Esterase (Blue) stain: Rat muscle

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Collateral sprouts (Arrow) after Partial Denervation of rat muscle
  Preterminal axon origin: Arise from Nodes of Ranvier
  Size: Thin compared to original axon

Silver (Black)-Esterase (Blue) stain: Rat muscle

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Axon Regeneration

Single Regrowing Axon (Left)

• May develop several branches
• Branches
  • May be myelinated or non-myelinated
  • Origin:
    • Often pre-terminal axon
    • May appear as regenerating clusters in proximal nerve
• Single proximal axon
  • Innervates several NMJs (Below)
  • May, or may not, convert fiber type
    • Type conversion less likely conversion in ALS

Silver (Black)-Esterase (Blue) stain: Rat muscle

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Axon Atrophy

Silver-P0-Esterase stain
Loss of myelin sheath toward end of an atrophic (thin) axon

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Botulinum Toxin

Silver-Esterase stain Botulinum treatment (Rat) NMJ: Enlarged   Elongated   2 segments   Motor axon terminal: Increased branching

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Botulinum Toxin Treatment (Rat): Ultraterminal sprouts

Silver-Esterase stain

Terminal axons at Neuromuscular junctions (Rat)
  Botulinum toxin induces
    Enlargement of NMJs (middle) &
    Ultraterminal sprouts (Arrows) extending from nerve terminals at NMJs (middle & top)
  Control NMJ (Bottom)

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Acrylamide

Silver-Esterase stain Acrylamide intoxication (Rat)   Motor nerve terminals: Focal Enlargements

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Dimethyaminopropionitrile

Silver-Esterase stain Dimethyaminopropionitrile (DMAPN) intoxication (Rat)   Swelling in sprout & axon terminal branches in NMJ   Ultraterminal sprout with swelling (Top left)

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7/27/2023