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@@ -3,10 +3,17 @@ title: Effect of Sulfakinin/Cholecystokinin-type Peptide ArSK/CCK1 on Satiety an
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abstract: |
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Depression is the persistent sadness or lack of interest in previously rewarding activities and has devastating effects on much of the global population. The neuropeptide cholecystokinin (CCK) controls satiety in humans and travels along a signaling pathway related to the brain-gut axis in humans. This suggests a relationship between the pathway and experienced emotions in relation to depression. Increased levels of CCK have been correlated with increased suicide attempts, and the effects of CCK-like pathways in arthropods have exhibited an increased correlation between peptide levels and feelings of satiety. Though a similar pathway (using the ArSK/CCK neuropeptide) has been identified in the evolutionarily proximal echinoderm Asterias rubens, little is known about the effects of these peptide levels on depressive symptoms through observation of feeding and energy metabolism. This study observed the effect of injected ArSK/CCK1 peptide on satiety and energy homeostasis through examination of initial and final stomach eversion areas of Asterias vulgaris, synonymous with A. rubens. Energy homeostasis was observed using a constructed open-flow respirometer taking measurements, which predicted energy creation using the rate of dissolved oxygen consumption to be used for cellular respiration. Exposure to ArSK/CCK1 was found to yield lower rates of dissolved oxygen decrease compared to basal rate and control measurements, suggesting a resulting decreased satiety and rate of energy metabolism.
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## Introduction
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Depression, defined as the persistent sadness and lack of interest or pleasure in previously rewarding activities, affects much of the world today. It is one of the most prevalent mental health disorders in the United States and the second leading cause of disability worldwide, proving to be an immense global and economic burden in addition to the emotional distress felt by those affected. Some symptoms of the disease include feelings of sadness or hopelessness, sudden angry outbursts, reduced appetite, and anxiety. Despite the large quantity of research done on the topic, the exact mechanisms underlying depression are unknown. However, research has shown that changes in the gut microbiome (the variety of microorganisms living in the digestive tract) play an important role in the brain-gut axis, and thus hold influence in the neural and immune systems. More specifically, changes in the composition of the gut microbiome in mice have caused the demonstration of resilience when exposed to stress {cite:p}`https://doi.org/10.1016/j.brainresbull.2022.02.004`.
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Cholecystokinin (CCK) is a neuropeptide, or chemical messenger, synthesized by neurons and involved in a signaling pathway along the brain-gut axis. The peptide hormone was discovered and named due to its stimulatory effects on gallbladder contraction as well as the gastric secretion of pepsin and acid in mammals {cite:p}`https://doi.org/10.1152/ajplegacy.1928.86.3.599`. Neuropeptides such as CCK are composed of small chains of amino acids and are synthesized and released by neurons, binding to G protein-coupled receptors to modulate tissue activity. CCK is an important moderator of food intake and energy homeostasis, having been found to generate anxiety and aggression once simulated in mice {cite:p}`https://doi.org/10.1073/pnas.88.4.1130`. Increased levels of CCK are related to stronger feelings of satiety as well. In human patients suffering from depression, significant inverse correlations were found between CCK levels and depression and anxiety parameters. Patients who had made one or more suicide attempts generally had higher CCK levels in their cerebrospinal fluid (CSF) than those who had not {cite:p}`https://doi.org/10.1016/s0924-977x(97)00046-1` .
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Cholecystokinin (CCK) is a neuropeptide, or chemical messenger, synthesized by neurons and involved in a signaling pathway along the brain-gut axis. The peptide hormone was discovered and named due to its stimulatory effects on gallbladder contraction as well as the gastric secretion of pepsin and acid in mammals {cite:p}`https://doi.org/10.1152/ajplegacy.1928.86.3.599`. Neuropeptides such as CCK are composed of small chains of amino acids and are synthesized and released by neurons, binding to G protein-coupled receptors to modulate tissue activity. CCK is an important moderator of food intake and energy homeostasis, having been found to generate anxiety and aggression once simulated in mice {cite:p}`https://doi.org/10.1073/pnas.88.4.1130`. Increased levels of CCK are related to stronger feelings of satiety as well. In human patients suffering from depression, significant inverse correlations were found between CCK levels and depression and anxiety parameters. Patients who had made one or
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more suicide attempts generally had higher CCK levels in their cerebrospinal fluid (CSF) than those who had not {cite:p}`https://doi.org/10.1016/s0924-977x(97)00046-1` .
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A CCK-type pathway has been discovered in a variety of insects, with similar G Protein Coupled Receptors that act as receptors for these CCK-like signaling molecules. Named sulfakinins (SKs), these neuropeptides have proven to be a family of neuropeptides homologous to mammalian CCK and caused the reduction of food intake by either direct peptide injection {cite:p}`https://doi.org/10.1016/s0022-1910(00)00046-9` or sk gene silencing {cite:p}`https://doi.org/10.1016/j.jinsphys.2007.04.003` , similar to the effect of CCK in mammals. The homologous nature of CCK and SK suggests that insects with SK signaling pathways can serve as model organisms utilized in the study of CCK signaling pathways {cite:p}`https://doi.org/10.1016/j.ygcen.2013.03.006`. Its inhibitory action on feeding in insects has been quantified and discovered to affect the regulation of insulin-like peptides and carbohydrates in insect hemolymph {cite:p}`https://doi.org/10.1007/s00360-020-01300-6`.
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The prospect of these signaling pathways in modeling depression opens up further questions regarding prospective treatments that target its behavior. With the establishment of A. vulgaris as an adequate model organism for studying ArSK/CCK1 signaling with its impact on satiety, this study observed its impact on the energy loss aspect of depression. Further research that could be done would include the observation of ancient herbal medicinal extracts such as Ziziphus jujube that had previously exhibited antidepressant effects in stress-related studies involving mammals {cite:p}`https://doi.org/10.3390/app10207374; https://doi.org/10.1016/j.jep.2018.12.043`. Oral administrations or a filtered extract administered by injection can be utilized to observe its impact on satiety and energy metabolism measurements {cite:p}`https://doi.org/10.1007/7854_2016_470`.
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The author would like to thank Jennifer Williams, North Carolina School of Science and Mathematics-Morganton, and Ana B. Tinoco for their guidance and support throughout the course of this project.
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## Acknowledgments
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The author would like to thank Jennifer Williams, North Carolina School of Science and Mathematics-Morganton, and Ana B. Tinoco for their guidance and support throughout the course of this project.
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