Spexin-based galanin receptor type 2 agonist for comorbid mood disorders and abnormal body weight

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

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number391
JournalFrontiers in Neuroscience
Volume13
Issue numberAPR
DOIs
Publication statusPublished - 2019

Bibliographical note

Funding Information:
This work was supported by grants from the National Natural Science Foundation of China No. 81422051, 81402853 and 81472593, the National Key Basic Research Program (2015CB910700), the Project of Innovation-driven Plan in Central South University (502211812), and the Hunan Natural Science Foundation of China No. 2016JJ1020.

Funding Information:
This work was supported by grants from the Research Program of the National Research Foundation of Korea (NRF-2015M3A9E7029172) funded by the Ministry of Science, ICT, and Future Planning. Neuracle Science Co., Ltd., holds a Korean patent (10-1885238 and 10-1885241), United States (15/771,078), EPO (16871028.3), Australian (2016361783), Brazilian (11 2018 008315 1), Canada (3003262), China (201680062527.4), and Japan (2018-523789) patents.

Publisher Copyright:
© 2019 Yun, Reyes-Alcaraz, Lee, Yong, Choi, Ham, Sohn, Kim, Son, Kim, Kwon, Kim, Kim, Hwang and Seong.

Keywords

  • Appetite
  • Body weight
  • Depression
  • Galanin receptor 2 agonist
  • Intranasal administration
  • Post-traumatic stress disorder

ASJC Scopus subject areas

  • General Neuroscience

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