After function and exercise (). This was


analyzing this study and others it is evident that irisin is a promising
treatment method for depressive behaviours. Polyzes et al. as well as Moreno et
al. observed in their studies that stress causes an inhibition in mitochondrial
respiratory chain complexes I, III and IV in rat brains. What Wang & Pan concluded
was that in CUS rats an injection of irisin elevated the activity of these
mitochondrial complexes, which evidently altered their behaviour by reducing
depressive-like reactions. Similarly they determined that irisin promotes the
uptake of glucose and ATP by acting on the AMPK pathways in the brain. It does
so by increasing the enzymes necessarily for glucose metabolism, therefore
inducing antidepressant-like behaviours.

presence of irisin in cerebral spinal fluid and prefrontal cortex tissues has
been thoroughly investigated in a multitude of papers. Its been heavily
expressed in neural elements such as microglia, neurons and astrocytes and has
been closely related to neural differentiation and neurogenesis along with
FNDC5 (). Irisin has also been recognized in playing a role in relating brain
function and exercise (). This was supported by the results of the FST tests
run by Wang & Pan, where the irisin injections caused an increase in
mobility. Wang & Pan also noted that the irisin injections reversed the
depressive-like behaviours induced in CUS rats. These findings correlate with
another study done by Zhang et al. that involved the use of irisin as a
treatment to increase the locomotion of rats and decrease their overall rest
time. Both studies showed how irisin functions to induce antidepressant-like

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Criticisms and future directions:


& Pan have a few strengths to their paper, one being the various
physiological and behavioural factors they measured. They looked at the effects
irisin had on various deficits induced by the disorder or in this case the
chronic unpredictable stressors. As well, the fact that multiple behavioural
tests were done as opposed to just one makes their study more reliable as there
are various ways to validate their conclusion. Many studies often choose one
way to test their study and validate it through repetition as opposed to
studying different components that may be influenced by their experiment. Another
strength (though also a limitation) was the use of an animal model. This made it
easy to manipulate and thoroughly test the effects of irisin without the same
ethical concerns there would be in a human study.

using an animal model is beneficial in terms of flexibility one of the studies
biggest limitations was the fact that it was done on Sprague-Dawley rats.

Although rats are thought to be a good human representation it cannot be
assumed that the effects irisin had on the specimen will directly translate to
how it will affect humans. This is especially true because irisin is a
neurologically associated myokine. The only way to be sure would be to develop
another study that tested the same thing but on individuals with depression.

Another limitation was the lack of neural imaging done. To test the levels of
irisin, ATP and other molecules in areas such as the prefrontal cortex pieces
of tissue were excised, homogenized and centrifuged. While this is a good
determinant of the enzymatic function there were no tests completed that looked
at the overall brain function of the test subjects.

study similar to the one conducted by Wang & Pan should be done on humans
and should include neurological imaging. This study should begin with an
analysis of the brain function of each individual (both test and control,
before and after the experiment) so researchers are able to get a better idea
of the neurological affects the irisin has. This can be achieved through
functional MRI imaging, SPECT (single photon emission computed tomography) and
PET (positron emission tomography) scans, which are able to show a detailed
visual of the anatomical circuitry involved. As well, completing the study on
humans allows for a better indication of whether or not irisin is a successful,
long-term therapeutic antidepressant treatment, as it will be tested on the
test group it is meant for. Due to the fact that it has already been tested
using an animal model progressing to a human model is not that big of a risk. This
study will provide researchers with a more in depth understanding of how irisin
impacts the human brain and its effect on energy metabolism. 

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