TY - JOUR
T1 - Anhedonic- and anxiogenic-like behaviors and neurochemical alterations are abolished by a single administration of a selenium-containing compound in chronically stressed mice
AU - Casaril, Angela Maria
AU - Lourenço, Darling de Andrade
AU - Domingues, Micaela
AU - Smaniotto, Thiago Ângelo
AU - Birmann, Paloma Taborda
AU - Vieira, Beatriz
AU - Sonego, Mariana Souza
AU - Seixas, Fabiana Kömmling
AU - Collares, Tiago
AU - Lenardão, Eder João
AU - Savegnago, Lucielli
N1 - Publisher Copyright:
© 2021 The Author(s)
PY - 2021/5
Y1 - 2021/5
N2 - Despite the severity and the high prevalence of depression and anxiety and the efforts that have been done to improve their treatment, the available pharmacotherapy still has several limitations. Therefore, the investigation of novel agents and the characterization of the molecular signaling pathways underlying their effects are needed. The organoselenium compound 3-[(4-chlorophenyl)selanyl]-1-methyl-1H-indole (CMI) has emerged as a promising antidepressant and anxiolytic molecule in several animal models of depression through the modulation of neuroinflammation and oxidative stress. In light of this, the present study aimed to dive into the mechanism of action of CMI in ameliorating anhedonic- and anxiogenic-like behaviors induced by repeated corticosterone administration in mice. A single administration of CMI (1 mg/kg, i.g.) abrogated the behavioral alterations induced by corticosterone in the open field test, splash test, and elevated plus maze test. Additionally, CMI treatment decreased the levels of reactive species and lipid peroxidation in the plasma of corticosterone-treated mice and normalized the expression of GR, BDNF, synaptophysin, GSK-3β, Nrf2, and IDO in the hippocampi of stressed mice. Noteworthy, the pre-treatment of mice with LY294002 (PI3K inhibitor) and rapamycin (mTOR inhibitor) abrogated the anti-anhedonic- and anxiolytic-like effects elicited by CMI in corticosterone-treated mice, while ZnPP (HO-1 inhibitor) counteracted the anxiolytic-like effect of CMI. These findings suggest that CMI might ameliorate behavioral and biochemical alterations in the depression-anxiety comorbidity induced by corticosterone, highlighting the potential of CMI as a possible adjuvant therapy.
AB - Despite the severity and the high prevalence of depression and anxiety and the efforts that have been done to improve their treatment, the available pharmacotherapy still has several limitations. Therefore, the investigation of novel agents and the characterization of the molecular signaling pathways underlying their effects are needed. The organoselenium compound 3-[(4-chlorophenyl)selanyl]-1-methyl-1H-indole (CMI) has emerged as a promising antidepressant and anxiolytic molecule in several animal models of depression through the modulation of neuroinflammation and oxidative stress. In light of this, the present study aimed to dive into the mechanism of action of CMI in ameliorating anhedonic- and anxiogenic-like behaviors induced by repeated corticosterone administration in mice. A single administration of CMI (1 mg/kg, i.g.) abrogated the behavioral alterations induced by corticosterone in the open field test, splash test, and elevated plus maze test. Additionally, CMI treatment decreased the levels of reactive species and lipid peroxidation in the plasma of corticosterone-treated mice and normalized the expression of GR, BDNF, synaptophysin, GSK-3β, Nrf2, and IDO in the hippocampi of stressed mice. Noteworthy, the pre-treatment of mice with LY294002 (PI3K inhibitor) and rapamycin (mTOR inhibitor) abrogated the anti-anhedonic- and anxiolytic-like effects elicited by CMI in corticosterone-treated mice, while ZnPP (HO-1 inhibitor) counteracted the anxiolytic-like effect of CMI. These findings suggest that CMI might ameliorate behavioral and biochemical alterations in the depression-anxiety comorbidity induced by corticosterone, highlighting the potential of CMI as a possible adjuvant therapy.
KW - Antidepressant
KW - Anxiolytic
KW - Corticosterone
KW - HPA axis
KW - Organoselenium
KW - PI3K/mTOR
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UR - http://www.scopus.com/inward/citedby.url?scp=85126066551&partnerID=8YFLogxK
U2 - 10.1016/j.cpnec.2021.100054
DO - 10.1016/j.cpnec.2021.100054
M3 - Article
C2 - 35757368
AN - SCOPUS:85126066551
SN - 2666-4976
VL - 6
JO - Comprehensive Psychoneuroendocrinology
JF - Comprehensive Psychoneuroendocrinology
M1 - 100054
ER -