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 language | English |
|---|---|
| Article number | 391 |
| Journal | Frontiers in Neuroscience |
| Volume | 13 |
| Issue number | APR |
| DOIs | |
| Publication status | Published - 2019 Jan 1 |
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Keywords
- Appetite
- Body weight
- Depression
- Galanin receptor 2 agonist
- Intranasal administration
- Post-traumatic stress disorder
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Spexin-based galanin receptor type 2 agonist for comorbid mood disorders and abnormal body weight. / Yun, Seongsik; Reyes-Alcaraz, Arfaxad; Lee, Yoo Na; Yong, Hyo Jeong; Choi, Jeewon; Ham, Byung-Joo; Sohn, Jong Woo; Kim, Dong-Hun; Son, Gi Hoon; Kim, Hyun; Kwon, Soon Gu; Kim, Dong Sik; Kim, Bong Chul; Hwang, Jong-Ik; Seong, Jae Young.
In: Frontiers in Neuroscience, Vol. 13, No. APR, 391, 01.01.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Spexin-based galanin receptor type 2 agonist for comorbid mood disorders and abnormal body weight
AU - Yun, Seongsik
AU - Reyes-Alcaraz, Arfaxad
AU - Lee, Yoo Na
AU - Yong, Hyo Jeong
AU - Choi, Jeewon
AU - Ham, Byung-Joo
AU - Sohn, Jong Woo
AU - Kim, Dong-Hun
AU - Son, Gi Hoon
AU - Kim, Hyun
AU - Kwon, Soon Gu
AU - Kim, Dong Sik
AU - Kim, Bong Chul
AU - Hwang, Jong-Ik
AU - Seong, Jae Young
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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.
AB - 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.
KW - Appetite
KW - Body weight
KW - Depression
KW - Galanin receptor 2 agonist
KW - Intranasal administration
KW - Post-traumatic stress disorder
UR - http://www.scopus.com/inward/record.url?scp=85068361240&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85068361240&partnerID=8YFLogxK
U2 - 10.3389/fnins.2019.00391
DO - 10.3389/fnins.2019.00391
M3 - Article
AN - SCOPUS:85068361240
VL - 13
JO - Frontiers in Neuroscience
JF - Frontiers in Neuroscience
SN - 1662-4548
IS - APR
M1 - 391
ER -