Differential Expression of Genes at Stages When Regeneration Can and Cannot Occur after Injury to Immature Mammalian Spinal Cord

Cellular and Molecular Neurobiology, 2005 · DOI: 10.1007/s10571-005-3150-z · Published: April 1, 2005

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This study investigates why the central nervous system (CNS) in mammals loses its ability to regenerate after injury as they mature. The researchers focused on a critical period in newborn opossums when this regenerative capacity disappears. The study compares gene expression in spinal cord regions that can regenerate (young opossums) with those that cannot (older opossums), aiming to identify genes that are either turned on or off during this transition. By identifying these genes, the researchers hope to find potential targets for therapies that could restore the ability of the mammalian CNS to repair itself after spinal cord injuries.

Study Duration

Not specified

Participants

Neonatal opossums (Monodelphis domestica)

Evidence Level

Not specified

Key Findings

1
The study identified a set of genes that are differentially expressed in regenerating versus non-regenerating spinal cords of neonatal opossums, including novel sequences and genes involved in cell growth, motility, and myelin formation.
2
Genes like cadherin, catenin, and NAV3 were found to be upregulated in tissues capable of regeneration, suggesting their potential role in promoting axon outgrowth and repair.
3
Myelin-associated genes such as myelin basic protein (MBP) and CNP were found to be upregulated in older spinal cords that had lost their regenerative capacity, indicating their potential involvement in inhibiting regeneration.

Research Summary

The study comprehensively screens for genes that change their expression during the brief critical period in development when the neonatal mammalian central nervous system (CNS) loses its capacity to regenerate. By using polymerase chain reaction-based subtractive hybridization, the researchers analyzed mRNAs extracted from cervical cords of animals aged 9 and 12 days, as well as lumbar regions of 12-day-old cords, and identified differentially expressed sequences related to cell growth, proliferation, and differentiation. The results revealed novel sequences and genes involved in transcription, cell signaling, myelin formation, and growth cone motility as potential candidates for neuroregeneration, setting the stage for testing their efficacy in turning on or off the capacity for spinal cord regeneration.

Practical Implications

Therapeutic Targets

Identified genes could be potential targets for therapies aimed at promoting spinal cord regeneration.

Understanding Regeneration

Provides insights into the molecular mechanisms underlying the loss of regenerative capacity in the mammalian CNS.

Drug Development

The opossum spinal cord in vitro model can be used as a reliable and rapid assay for testing the efficacy of candidate genes and molecules in promoting axon outgrowth and synapse formation.

Study Limitations

1
The study acknowledges the possibility of contaminants being amplified during subtractive hybridization.
2
The blotting technique may not detect differences in gene expression of less than 30%.
3
The study is limited by the fact that some genes may have shifted distributions rather than changes in total amount.

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