Student ID: 6441

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The Regenerative capacity of the Axolotl

Demircan, Turan. “Dissecting the Molecular Signature of Spinal Cord Regeneration in the
Axolotl Model.” Cureus, Cureus, 16 Feb. 2020,
www.ncbi.nlm.nih.gov/pmc/articles/PMC7081738/.

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Introduction:

Spinal cord injuries have always been a difficult subject to approach in mammals and
there is a dearth in the research surrounding this topic. Despite the difficulty it is imperative
that better solutions to treatment and prevention of spinal cord injuries be developed. Each
year more than a quarter million people suffer from spinal cord injuries, hereafter referred to
as SCI, yet this number does not include any pets such as dogs and cats or even domestic
livestock (WHO, 2013). There are many causes for SCI but all lead to the similar complications.
Risk of mortality rises sharply after SCI and can give rise to secondary health complications in
the form of infections or muscle spasms. It is clear then that understanding the process by
which organisms can heal from SCI is critical to improving the lives of so many around the world
each year.
Due to the regenerative capacity in mammals being so low, especially in injuries
involving the Central Nervous System, hereafter referred to as CNS. This presents a large issue
as the physiological response to SCI and trauma is acute and quick in mammals. It is for this
reason that a different model organism was chosen to study the process of regeneration with
regards to SCI. To fill this position the axolotl or Mexican salamander was chosen for its ability
to retain several qualities from early life into adulthood that allow for complete regeneration.
This study aims to better understand the mechanisms of regeneration using Axolotls for
use in the healing process for mammals.

Methods:
In order to gather the relevant data, following a laminectomy, a procedure in which a
piece of the spinal canal covering is removed, a portion of the spinal column between two
vertebrae was removed. A sample of the cells involved in the healing process were collected on
the 7th day after the amputation. RNA sequences were then extracted from each sample, and
then each sequence was tested for any matching orthologues in mice. Those with no matching
orthologues in mice were filtered out.

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US National Library of Medicine National Institutes of Health,
www.ncbi.nlm.nih.gov/pmc/articles/PMC7081738/figure/FIG1/.

Shown above is just after the laminectomy, shortly after the amputation, and four weeks after
the regeneration process was completed respectively.

Results:

After a careful analysis of the RNA sequences, 363 genes were found to be expressed
during the healing process. Of those 363 initial genes found 352 genes were found to have a
significant fold change, the rest were filtered out. After looking for those with significant fold
changes a second filtering process was undertaken, this time looking for those that have
matching mouse orthologues. This process left just 148 remaining genes. A final list of genes
was acquired by filtering out redundancies in downstream signaling. This final list yielded a total
of 129 expressed genes, 2 of which were upregulated and 127 were downregulated. Many of
the genes expressed during the process were found to be enriched by the downregulation of
other genes.

Discussion:

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 As previously stated, SCI is a widespread issue that can lead to long-term health issues
that affect not only humans but all mammals. However, the mechanisms by which this damage
is healed or mitigated is difficult to study using mammalian models. Through the use of the
Axolotl model, we have gained a deeper understanding of the issues facing recovery from this
type of injury. While the results from this study do not provide any immediate solutions, it does
provide work from which other studies can scaffold from.
There have not been many studies regarding the process of regeneration as it relates to
mammals, instead focusing on therapeutic remedies for adults in species as mammalian
capacity for regeneration ceases quickly in adults (Huang, D et al, 2001; NCSU, 2018). The
results therefore are illuminating as the enrichment of certain genes to enhance specific
processes involved in the regeneration give us an insight into how this can be applied to other
organisms.
While this study focused on the overall mechanisms behind regeneration an interesting
interaction with the immune system was observed. The immune system was repressed during
the study to better facilitate the creation of blastema tissue where needed. It has been thought
that overactive immune system responses are responsible for interference in the healing of
mammals (Sibai, Mustafa et al,2019).
This study does provide a good springboard for further inquiry. However, it is not
without its flaws. With only 15 subjects involved in the study the sample size is rather small. In
addition, only 2 samples were collected for each subject, one during the first day of the
amputation and a second sample on the 7th day post amputation. This lapse in samples leaves a
gap in the observed mechanism. However, there is a simple lack in research regarding this
process.
Conclusions:

As mentioned above this study is truly novel but provides no advancements on its own. Instead,
this work is to be used as the basis for further inquiry into the topic of regenerative capacity in
adult mammals. Such research could truly advance medical and veterinary practices and help to
alleviate an immense issue facing the world over today.

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 Works Cited

Demircan, Turan. “Dissecting the Molecular Signature of Spinal Cord Regeneration in the
Axolotl Model.” Cureus, Cureus, 16 Feb. 2020,
www.ncbi.nlm.nih.gov/pmc/articles/PMC7081738/.
Huang, D.W, et al. “A Therapeutic Vaccine Approach to Stimulate Axon Regeneration in the
Adult Mammalian Spinal Cord.” Neuron, Cell Press, 11 Apr. 2001,
www.sciencedirect.com/science/article/pii/S0896627300811186.
“Labs: Canine Spinal Cord Injury.” NC State Veterinary Medicine, 30 Oct. 2018,
cvm.ncsu.edu/research/labs/clinical-sciences/canine-spinal-cord-injury/.

Sibai, Mustafa, et al. “Comparison of Protein Expression Profile of Limb Regeneration between
Neotenic and Metamorphic Axolotl.” Biochemical and Biophysical Research
Communications, Academic Press, 22 Nov. 2019,
www.sciencedirect.com/science/article/abs/pii/S0006291X19322466
“Spinal Cord Injury.” World Health Organization, World Health Organization, 19 Nov. 2013,
www.who.int/news-room/fact-sheets/detail/spinal-cord-injury.
Themes, UFO. “Animal Models of Spinal Cord Injury.” Musculoskeletal Key, 21 Aug. 2016,
musculoskeletalkey.com/animal-models-of-spinal-cord-injury/.