Spexin-Based Galanin Receptor Type 2 Agonist for Comorbid Mood Disorders and Abnormal Body Weight
Despite the established comorbidity between mood disorders and abnormal eating behaviors, the underlying molecular mechanism and therapeutics remain to be resolved. Here, we show that a spexin-based galanin receptor type 2 agonist (SG2A) simultaneously normalized mood behaviors and body weight in co...
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doaj-3bd03b366ad241c68e3ed73f1eea03d42020-11-25T01:40:03ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2019-04-011310.3389/fnins.2019.00391455204Spexin-Based Galanin Receptor Type 2 Agonist for Comorbid Mood Disorders and Abnormal Body WeightSeongsik Yun0Arfaxad Reyes-Alcaraz1Yoo-Na Lee2Hyo Jeong Yong3Jeewon Choi4Byung-Joo Ham5Jong-Woo Sohn6Dong-Hoon Kim7Gi Hoon Son8Hyun Kim9Soon-Gu Kwon10Dong Sik Kim11Bong Chul Kim12Jong-Ik Hwang13Jae Young Seong14Graduate School of Medicine, Korea University, Seoul, South KoreaGraduate School of Medicine, Korea University, Seoul, South KoreaGraduate School of Medicine, Korea University, Seoul, South KoreaGraduate School of Medicine, Korea University, Seoul, South KoreaGraduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, South KoreaDepartment of Psychiatry, College of Medicine, Korea University, Seoul, South KoreaGraduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, South KoreaGraduate School of Medicine, Korea University, Seoul, South KoreaGraduate School of Medicine, Korea University, Seoul, South KoreaGraduate School of Medicine, Korea University, Seoul, South KoreaNeuracle Science Co., Ltd., Seoul, South KoreaNeuracle Science Co., Ltd., Seoul, South KoreaNeuracle Science Co., Ltd., Seoul, South KoreaGraduate School of Medicine, Korea University, Seoul, South KoreaGraduate School of Medicine, Korea University, Seoul, South KoreaDespite the established comorbidity between mood disorders and abnormal eating behaviors, the underlying molecular mechanism and therapeutics remain to be resolved. Here, we show that a spexin-based galanin receptor type 2 agonist (SG2A) simultaneously normalized mood behaviors and body weight in corticosterone pellet-implanted (CORTI) mice, which are underweight and exhibit signs of anhedonia, increased anxiety, and depression. Administration of SG2A into the lateral ventricle produced antidepressive and anxiolytic effects in CORTI mice. Additionally, SG2A led to a recovery of body weight in CORTI mice while it induced significant weight loss in normal mice. In Pavlovian fear-conditioned mice, SG2A decreased contextual and auditory fear memory consolidation but accelerated the extinction of acquired fear memory without altering innate fear and recognition memory. The main action sites of SG2A in the brain may include serotonergic neurons in the dorsal raphe nucleus for mood control, and proopiomelanocortin/corticotropin-releasing hormone neurons in the hypothalamus for appetite and body weight control. Furthermore, intranasal administration of SG2A exerted the same anxiolytic and antidepressant-like effects and decreased food intake and body weight in a dose-dependent manner. Altogether, these results indicate that SG2A holds promise as a clinical treatment for patients with comorbid mood disorders and abnormal appetite/body weight.https://www.frontiersin.org/article/10.3389/fnins.2019.00391/fullgalanin receptor 2 agonistdepressionpost-traumatic stress disorderbody weightappetiteintranasal administration |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Seongsik Yun Arfaxad Reyes-Alcaraz Yoo-Na Lee Hyo Jeong Yong Jeewon Choi Byung-Joo Ham Jong-Woo Sohn Dong-Hoon Kim Gi Hoon Son Hyun Kim Soon-Gu Kwon Dong Sik Kim Bong Chul Kim Jong-Ik Hwang Jae Young Seong |
spellingShingle |
Seongsik Yun Arfaxad Reyes-Alcaraz Yoo-Na Lee Hyo Jeong Yong Jeewon Choi Byung-Joo Ham Jong-Woo Sohn Dong-Hoon Kim Gi Hoon Son Hyun Kim Soon-Gu Kwon Dong Sik Kim Bong Chul Kim Jong-Ik Hwang Jae Young Seong Spexin-Based Galanin Receptor Type 2 Agonist for Comorbid Mood Disorders and Abnormal Body Weight Frontiers in Neuroscience galanin receptor 2 agonist depression post-traumatic stress disorder body weight appetite intranasal administration |
author_facet |
Seongsik Yun Arfaxad Reyes-Alcaraz Yoo-Na Lee Hyo Jeong Yong Jeewon Choi Byung-Joo Ham Jong-Woo Sohn Dong-Hoon Kim Gi Hoon Son Hyun Kim Soon-Gu Kwon Dong Sik Kim Bong Chul Kim Jong-Ik Hwang Jae Young Seong |
author_sort |
Seongsik Yun |
title |
Spexin-Based Galanin Receptor Type 2 Agonist for Comorbid Mood Disorders and Abnormal Body Weight |
title_short |
Spexin-Based Galanin Receptor Type 2 Agonist for Comorbid Mood Disorders and Abnormal Body Weight |
title_full |
Spexin-Based Galanin Receptor Type 2 Agonist for Comorbid Mood Disorders and Abnormal Body Weight |
title_fullStr |
Spexin-Based Galanin Receptor Type 2 Agonist for Comorbid Mood Disorders and Abnormal Body Weight |
title_full_unstemmed |
Spexin-Based Galanin Receptor Type 2 Agonist for Comorbid Mood Disorders and Abnormal Body Weight |
title_sort |
spexin-based galanin receptor type 2 agonist for comorbid mood disorders and abnormal body weight |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Neuroscience |
issn |
1662-453X |
publishDate |
2019-04-01 |
description |
Despite the established comorbidity between mood disorders and abnormal eating behaviors, the underlying molecular mechanism and therapeutics remain to be resolved. Here, we show that a spexin-based galanin receptor type 2 agonist (SG2A) simultaneously normalized mood behaviors and body weight in corticosterone pellet-implanted (CORTI) mice, which are underweight and exhibit signs of anhedonia, increased anxiety, and depression. Administration of SG2A into the lateral ventricle produced antidepressive and anxiolytic effects in CORTI mice. Additionally, SG2A led to a recovery of body weight in CORTI mice while it induced significant weight loss in normal mice. In Pavlovian fear-conditioned mice, SG2A decreased contextual and auditory fear memory consolidation but accelerated the extinction of acquired fear memory without altering innate fear and recognition memory. The main action sites of SG2A in the brain may include serotonergic neurons in the dorsal raphe nucleus for mood control, and proopiomelanocortin/corticotropin-releasing hormone neurons in the hypothalamus for appetite and body weight control. Furthermore, intranasal administration of SG2A exerted the same anxiolytic and antidepressant-like effects and decreased food intake and body weight in a dose-dependent manner. Altogether, these results indicate that SG2A holds promise as a clinical treatment for patients with comorbid mood disorders and abnormal appetite/body weight. |
topic |
galanin receptor 2 agonist depression post-traumatic stress disorder body weight appetite intranasal administration |
url |
https://www.frontiersin.org/article/10.3389/fnins.2019.00391/full |
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