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Motor nerve terminal restoration after focal destruction in young and old mice
N Robbins1, M Kuchynski, J Polak
1Center for Neurosciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106.
Abstract:
Regeneration of soleus motor nerve terminals after focal destruction by black widow spider venom (BWSV) or its active factor alpha-latrotoxin (LTx) was compared in young and old CBF-1 mice. The object was to determine whether previously reported delayed regeneration after nerve injury in old rodents was due to altered removal of debris, or delay or aberrancy in structural or functional restoration of the neuromuscular junction. In addition, the use of a new fluorescent technique permitted for the first time quantitation of the accuracy of early nerve terminal regeneration in mammalian muscle. Immunohistochemical and electron micrographic studies showed no age difference in destruction of terminals and removal of debris 2 days after toxin application. The indirect twitch and structural reinnervation (measured with flourescent techniques) returned to an equal extent in young and old mice beginning at 3 days after LTx treatment. BWSV (as opposed to LTx) delayed regeneration 1 day in young but not in old mice. On the first day of reinnervation, there was perisynaptic outgrowth in both young and old mice, although in the latter, there was a higher incidence of aberrant outgrowth. The relation between return of twitch strength and recovery of nerve terminal area (measured in teased zinc iodide-stained preparations) showed no age dependency. We conclude that factors cited to explain altered reactive sprouting in the aging CNS do not apply to regeneration of peripheral motor nerve terminals. However, it is possible that the aberrant regrowth observed at the neuromuscular junction in old mice will pertain to the aging CNS. Altered axonal rather than nerve terminal regeneration is the likely source of delayed peripheral nerve regeneration in old animals.
Insights
Peripheral nerve regeneration in old mice is not delayed by debris clearance or neuromuscular junction restoration. Aberrant regrowth at the neuromuscular junction may impact the aging central nervous system.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Aging Research
Background:
- Peripheral nerve injury and regeneration are critical areas in neuroscience.
- Aging is associated with altered neural repair processes, but the precise mechanisms remain unclear.
- Previous studies suggest delayed nerve regeneration in older rodents, necessitating investigation into underlying causes.
Purpose of the Study:
- To compare soleus motor nerve terminal regeneration in young and old mice following focal destruction.
- To investigate if age-related delays in nerve regeneration are due to altered debris removal or neuromuscular junction (NMJ) restoration.
- To quantify the accuracy of early nerve terminal regeneration using a novel fluorescent technique.
Main Methods:
- Focal destruction of soleus motor nerve terminals using black widow spider venom (BWSV) or alpha-latrotoxin (LTx).
- Immunohistochemistry and electron microscopy to assess terminal destruction and debris removal.
- Fluorescent techniques to quantify structural reinnervation and nerve terminal regeneration.
- Measurement of indirect twitch strength and nerve terminal area recovery.
Main Results:
- No age-related differences were observed in nerve terminal destruction or debris removal at 2 days post-toxin application.
- Functional (twitch) and structural reinnervation occurred to an equal extent in young and old mice starting at 3 days after LTx treatment.
- While BWSV delayed regeneration in young mice, it did not affect old mice. Aberrant nerve outgrowth was more frequent in older mice at the NMJ.
Conclusions:
- Factors influencing CNS aging do not appear to affect peripheral motor nerve terminal regeneration.
- Aberrant nerve regrowth at the NMJ in aged mice may be relevant to aging in the central nervous system.
- Delayed peripheral nerve regeneration in older animals is likely due to altered axonal regeneration, not nerve terminal issues.