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<h2 id ="Subtitle1">Background</h2> | <h2 id ="Subtitle1">Background</h2> | ||
<p>   According to the World Health Organization (WHO), depression is becoming the leading cause of disability worldwide, affecting more than 264 million people worldwide<sup>[<a href="#ref1">1</a>]</sup>. | <p>   According to the World Health Organization (WHO), depression is becoming the leading cause of disability worldwide, affecting more than 264 million people worldwide<sup>[<a href="#ref1">1</a>]</sup>. | ||
− | <p> Exposure to prolonged chronic stress induces heightened vulnerability to anxiety, depression, and several mood disorders. Chronic stress-induced depression (CSID) is characterized by the dysfunction of the medial prefrontal cortex (mPFC) in the brain, linked to cognitive and emotional deficiencies induced by long-term stress exposure<sup>[<a href="#ref2">2</a>]</sup>.</p> | + | <p>   Exposure to prolonged chronic stress induces heightened vulnerability to anxiety, depression, and several mood disorders. Chronic stress-induced depression (CSID) is characterized by the dysfunction of the medial prefrontal cortex (mPFC) in the brain, linked to cognitive and emotional deficiencies induced by long-term stress exposure<sup>[<a href="#ref2">2</a>]</sup>.</p> |
− | <p> Research has shown that chronic stress is closely related to the dysregulation of the gut-brain axis. In addition, gut-modifying substances, such as immune-inflammatory cytokines and Reactive oxygen species (ROS), cause detrimental effects on the gute<sup>[<a href="#ref3">3</a>]</sup>. The immune-inflammatory and oxidative stress pathways will be further discussed in the following sections.</p> | + | <p>   Research has shown that chronic stress is closely related to the dysregulation of the gut-brain axis. In addition, gut-modifying substances, such as immune-inflammatory cytokines and Reactive oxygen species (ROS), cause detrimental effects on the gute<sup>[<a href="#ref3">3</a>]</sup>. The immune-inflammatory and oxidative stress pathways will be further discussed in the following sections.</p> |
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<h3>Immune-inflammatory Pathway in Depression</h3> | <h3>Immune-inflammatory Pathway in Depression</h3> | ||
− | <p> <b>Interferon-gamma (IFN-γ) is known to be positively correlated with depressive symptoms<sup>[<a href="#ref4">4</a>]</sup></b>. Research indicates that the activation of immune-inflammatory pathways and neural-immune interactions are closely involved in the pathophysiology of depressive disorders.</p> | + | <p> <b>  Interferon-gamma (IFN-γ) is known to be positively correlated with depressive symptoms<sup>[<a href="#ref4">4</a>]</sup></b>. Research indicates that the activation of immune-inflammatory pathways and neural-immune interactions are closely involved in the pathophysiology of depressive disorders.</p> |
<p> Below are two immune-inflammatory pathways :</p> | <p> Below are two immune-inflammatory pathways :</p> | ||
<ol> | <ol> | ||
− | <li><b>Higher serum levels of inflammatory cytokines.</b><br> | + | <li><b>Higher serum levels of inflammatory cytokines.</b><br>Interleukin-6 (IL-6), IL-1β, and TNF-α could cause depressive disorders by disrupting neurotransmitter synthesis and signal transduction.</li> |
<li><b>T-cell abnormal activation.</b><br>Elevated serum levels of neopterin, as well as activation of Th1-like and Th-17-like cells, including increased production of IL-2 and IFN-γ, will activate more inflammatory cytokines production.</li> | <li><b>T-cell abnormal activation.</b><br>Elevated serum levels of neopterin, as well as activation of Th1-like and Th-17-like cells, including increased production of IL-2 and IFN-γ, will activate more inflammatory cytokines production.</li> | ||
</ol> | </ol> | ||
<h3>Oxidative Stress Pathway in Depression</h3> | <h3>Oxidative Stress Pathway in Depression</h3> | ||
− | <p> Oxidative stress (OS) is defined as the intracellular biological imbalance between ROS (reactive oxygen species) and antioxidants, leading to the dysregulation of redox signaling pathways. Both neuronal OS and intestinal OS could lead to the occurrence of CSID. The following are physiological effects caused by excessive ROS<sup>[<a href="#ref3">3</a>]</sup>:</p> | + | <p>   Oxidative stress (OS) is defined as the intracellular biological imbalance between ROS (reactive oxygen species) and antioxidants, leading to the dysregulation of redox signaling pathways. Both neuronal OS and intestinal OS could lead to the occurrence of CSID. The following are physiological effects caused by excessive ROS<sup>[<a href="#ref3">3</a>]</sup>:</p> |
<ol> | <ol> | ||
<li>Excessive oxidative stress can induce neuronal inflammation, which often leads to abnormal brain function in patients with depression<sup>[<a href="#ref5">5</a>]</sup>.</li> | <li>Excessive oxidative stress can induce neuronal inflammation, which often leads to abnormal brain function in patients with depression<sup>[<a href="#ref5">5</a>]</sup>.</li> | ||
<li>Chronic intestinal inflammation is strongly related to increased ROS, composed of superoxide, hydrogen peroxide, and hydroxyl radical, which leads to depressive symptoms through the gut-brain axis.</li> | <li>Chronic intestinal inflammation is strongly related to increased ROS, composed of superoxide, hydrogen peroxide, and hydroxyl radical, which leads to depressive symptoms through the gut-brain axis.</li> | ||
</ol> | </ol> | ||
− | <p> | + | <p> <b>  To sum up, depression is highly correlated with inflammatory response and oxidative stress. </b> However, current medication cannot effectively deal with CSID due to its difficult detection. Therefore, we try to utilize a novel synthetic biological approach to deal with this problem. After surfing previous research, <b>we found that ROS and IFN-γ are two potential biomarkers of CSID.</b> As for taurine, a kind of amino acid, it has both anti-inflammatory and ROS-scavenging effects. As a result, we use these agents to develop our project.</p> |
<h3>Taurine</h3> | <h3>Taurine</h3> | ||
− | <p> Taurine is a semi-essential amino acid appreciated for its role in neural development and neurogenesis as a neuroprotective agent. In chronically stress-induced depressive mice models, taurine dietary has increased the L-arginine concentrations in the hypothalamus with a significant decrease in the duration of immobility in forced swimming tests.<sup>[<a href="#ref6">6</a>]</sup></p> | + | <p>   Taurine is a semi-essential amino acid appreciated for its role in neural development and neurogenesis as a neuroprotective agent. In chronically stress-induced depressive mice models, taurine dietary has increased the L-arginine concentrations in the hypothalamus with a significant decrease in the duration of immobility in forced swimming tests.<sup>[<a href="#ref6">6</a>]</sup></p> |
− | <p> Moreover, studies have shown that taurine with its metabolites could significantly reduce the level of both reactive oxygen species such as HOCL and IFN-γ. Further mechanisms will be discussed in the <a href="https://2021.igem.org/Team:NCKU_Tainan/Model">Model part</a>.</p> | + | <p>   Moreover, studies have shown that taurine with its metabolites could significantly reduce the level of both reactive oxygen species such as HOCL and IFN-γ. Further mechanisms will be discussed in the <b><a href="https://2021.igem.org/Team:NCKU_Tainan/Model">Model part</a>.</</b>p> |
− | <p> These results strongly suggest taurine’s capability in reducing stress-induced depressive symptoms.</p> | + | <p>   These results strongly suggest taurine’s capability in reducing stress-induced depressive symptoms.</p> |
</section> | </section> | ||
<hr> | <hr> |
Revision as of 15:38, 19 October 2021