NMJG

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)

Collateral Sprouting

Collateral Sprouting: Features

Nerve Sprouts
- New growth: Terminal branches to different NMJs from a single preterminal axon
- Surrounding myelin: None or Thin
- Diameter: Narrow
- 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 reinnervating a group of muscle fibers dies, or becomes inactive
  - ALS: Regions of grouped atrophy may contain mixed fiber types

Terminal sprouting In ALS

Silver-P₀-Esterase stain

Collateral Sprouts after Partial Denervation of rat muscle

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

Collateral 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

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

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

Axon Atrophy

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

Botulinum Toxin

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

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)

Acrylamide

Silver-Esterase stain

Acrylamide intoxication (Rat)
Motor nerve terminals: Focal Enlargements

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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3/15/2023