Central nervous system regeneration: from leech to opossum

Area of Science:

• Neurobiology
• Regenerative Medicine
• Developmental Neuroscience

Background:

• Mammalian spinal cord injuries typically do not repair, posing a significant challenge in neurobiology.
• Regeneration research focuses on model systems where repair is possible, such as invertebrates and immature mammals.

Purpose of the Study:

• To elucidate the cellular and molecular mechanisms underlying spinal cord regeneration.
• To identify factors that promote or inhibit axon regrowth after injury.

Main Methods:

• Comparative analysis of regeneration in leech central nervous system (CNS) and neonatal opossum spinal cord.
• Gene expression profiling and location identification in opossum spinal cords at different developmental stages.
• In vitro culture of neonatal opossum brain and spinal cord explants.

Main Results:

• In leeches, successful axon regeneration and functional recovery are observed, with microglial cells and nitric oxide playing key roles.
• In neonatal opossums, axon regeneration across lesions occurs but ceases between postnatal days 9 and 12.
• Gene expression analysis reveals upregulation of growth-promoting factors at day 9 and increased expression of myelin-associated inhibitory molecules by day 12.

Conclusions:

• Specific cellular (microglia) and molecular (nitric oxide) factors are vital for regeneration in leeches.
• A critical developmental window exists for spinal cord regeneration in mammals, influenced by the switch from growth-promoting to inhibitory molecules.
• Further research utilizing opossum genome sequencing and gene transfection holds promise for identifying therapeutic targets for human spinal cord injury.