Functional Regrowth of Norepinephrine Axons in the Adult Mouse Brain Following Injury

eNeuro, 2025 · DOI: https://doi.org/10.1523/ENEURO.0418-24.2024 · Published: January 1, 2025

Neurology Medical Imaging Regenerative Medicine & Stem Cells

Simple Explanation

It has been a long-held belief that the central nervous system of adult mammals is unable to regrow axons following injury. This study challenges that idea, presenting evidence of structural and functional regrowth of norepinephrine axons in the adult mouse brain after injury. Using in vivo two-photon microscopy, researchers monitored norepinephrine axons after inducing injury with a selective neurotoxin. They observed that the axons were significantly depleted but then slowly and partially recovered their density over several weeks. The study also measured norepinephrine release using a calcium indicator in astrocytes and found that the ability to release norepinephrine returned to pre-injury levels, suggesting that the regrown axons are functional.

Study Duration

16 weeks

Participants

DBH-cre mice crossed with reporter lines, both male and female, aged 9–25 weeks

Evidence Level

Level II, Experimental study using in vivo two-photon microscopy

Key Findings

1
Norepinephrine axons in the adult mouse brain can regrow following injury induced by DSP4.
2
The regrowth of norepinephrine axons is primarily due to new axons entering the imaged area rather than local sprouting.
3
Regrown norepinephrine axons are capable of releasing neurotransmitters in response to a physiological stimulus.

Research Summary

This study demonstrates that norepinephrine axons in the adult mouse brain are capable of regrowth following injury induced by the neurotoxin DSP4, challenging the widely held belief that axons in the central nervous system cannot regenerate. Using in vivo two-photon microscopy, the study found that this regrowth is primarily due to new axons entering the imaged area, with little contribution from local sprouting or guidance from existing axons. The study also showed that these regrown axons are functional, capable of releasing norepinephrine in response to physiological stimuli, suggesting a potential for functional recovery after brain injury.

Practical Implications

Therapeutic Potential

Understanding the mechanisms behind monoaminergic axon regrowth could lead to therapies that promote axon regeneration and functional recovery after CNS injuries.

Common Program for Axon Regrowth

The similar regrowth patterns of norepinephrine and serotonin axons suggest a shared molecular and genetic program that can be targeted for therapeutic interventions.

Challenging Dogma

This study challenges the traditional view that axons in the adult mammalian CNS cannot regrow, opening new avenues for research and treatment strategies.

Study Limitations

1
Air puff-evoked Ca2+ transients were variable, making quantification of amplitude or kinetics challenging.
2
The recording room was not entirely soundproof, potentially affecting the startle response.
3
It is formally possible that DSP4 inhibits NE release from survived axons for several weeks after DSP4 administration.

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