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It
is well known that depression is an extremely common and serious mood disorder.

It produces various damaging symptoms that affect how an individual
thinks, feels, acts and functions throughout the day. Unfortunately, there is
very little known about successful, long-term therapeutic anti-depression
treatments. Wang and Pan set out to determine whether the hormone irisin, plays
a role in the modulation of depressive behaviours in rats exposed to chronic
unpredictable stress (CUS). They performed a series of tests such as forced
swim tests (FST) and sucrose preference tests (SPT) to evaluate the rat’s
depressive like behaviours after being CUS-induced. The rats were then injected
with irisin at different concentrations and the ATP, creatine kinase,
respiratory chain enzymes and 2-deoxyglucose levels were monitored. It was
discovered that irisin caused an increase in mitochondrial complex activity,
sucrose preference, creatine kinase presence, ATP levels and glucose transport
and phosphorylation. It also reduced the immobility time in the CUS rats.

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Continued studies also proved that the AMPK pathway is involved in the regulation
of irisin and its role in influencing depressive-like behaviours. Pan and Wang
demonstrated that irisin plays an important role in producing antidepressant
behavioural effects in CUS rats through the regulation of energy metabolism in
their prefrontal cortex (PFC). Not only does this aid with developing a
treatment for depression but it also provides an understanding of the
biological mechanics of the disorder.

 

Background

 

            Depression
is the most common and one of the most significant psychiatric disorders today.

It affects millions of people globally of all ages, races and genders. Those
affected can suffer indefinitely if the disorder or its symptoms go untreated.

What is unclear is the pathogenesis of depression but elements such as
environment, psychological influence and genetics are thought to be the major
sources of this neurological disorder. Scientists are constantly identifying different
hormones and proteins that may explain the physiological cause of this disorder
and its effects on the body.

            Research
has been done to prove the effects irisin has on a multitude of disorders
including obesity, depression and many neurodegenerative disorders. In the
Wrann C. article (2013) it was shown that irisin works in conjunction with
other myokines to positively effect the brain as well as the rest of the body.

Irisin is secreted when an individual exercises but its natural effects and
naturally existing quantity can be insufficient when neurodegenerative or mood
disorders have developed. It is expected to increase energy metabolism and
works on many neural components such as neurons, microglia and astrocytes,
which is what drove researchers to study the hormone as a potential long-term
treatment solution for depression. It is because there are no existing
long-term therapeutic antidepressant treatments that studies like the one
completed by Wang & Pan are so important.

            Wang
& Pan focused their study on how an injection of irisin affected both the
physiological and behavioural deficits in rats that had been exposed to a
series chronic unpredictable stressors and compared the outcomes to unstressed
rats. The CUS rats were found to express
many depressed-like behaviours and once injected with the irisin these
behaviours began to resolve themselves. After thorough analysis via irisin and
ATP assays, western blot tests, cell culture analysis and more it was
determined that irisin can be used as an effective, long-term therapeutic
antidepressant treatment as it played as crucial role in generating antidepressant-like behaviours in the
CUS rats. These results are credited to
the myokines ability to regulate energy metabolism in the prefrontal cortex.

           

Methods/Results

 

Wang
and Pan chose to use rats induced by CUS to see how irisin effected the development of depressive-like behaviours in the
species. They examined the behavioural effects first through alterations in the
rat’s behaviours. They conducted FST and SPT behaviour tests on days 0, 7, 14
and 21 of the CUS procedure. During the FST test there was a clear increase in
the CUS rat’s immobility times which was discerning, especially when compared
to the results of the unstressed rats. They also established that there was a
reduction in sucrose consumption over time in the CUS rats when compared with
the controls. In furthering their study investigation, Pan and Wang measured
(using ELISA analysis) the levels of irisin in the prefrontal cortex and
cerebrospinal fluid (CSF) of CUS rats as well as unstressed rats. They
discovered that the irisin levels in the CSF and PFC were higher in the CUS
rats than the control. Then the CUS rats were injected subcutaneously with varying
concentrations of irisin or saline solution (control) for two weeks. Their
results showed that the CUS depressive-like
behaviours induced in rats can be reversed through dose dependent irisin treatments.

Irisin was also discovered to be an important regulator of lipid and glucose metabolism in adipose tissue and skeletal
muscle. As well it increases the activity of mitochondrial complexes I, II and
IV. Finally, irisin also affects glucose and ATP uptake into the PFC. In CUS
rats these processes were inhibited but after exposure to irisin there was an
increase in glucose uptake as well as a significant increase in ATP levels. Wang
and Pan also discovered that irisin treatment significantly enhanced AMPK
phosphorylation in prefrontal cortex of CUS rats. To be sure they released
compound C (which is an AMPK pathway inhibitor). The inhibitor eliminated the
behavioural effects of irisin proving that irisin acts as a regulator when absorbing
glucose and in the metabolism of the prefrontal cortex via the AMPK pathway.

 

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