TY - JOUR
T1 - Indoleamine-2,3-dioxygenase-1 is a molecular target for the protective activity of mood stabilizers against mania-like behavior induced by d-amphetamine
AU - Tran, Hai Quyen
AU - Shin, Eun Joo
AU - Saito, Kuniaki
AU - Tran, The Vinh
AU - Phan, Dieu Hien
AU - Sharma, Naveen
AU - Kim, Dae Won
AU - Choi, Soo Young
AU - Jeong, Ji Hoon
AU - Jang, Choon Gon
AU - Cheong, Jae Hoon
AU - Nabeshima, Toshitaka
AU - Kim, Hyoung Chun
N1 - Funding Information:
This study was supported by a grant (# 19182MFDS410 ) from the Korea Food and Drug Administration , and by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (# NRF-2019R1I1A3A01063609 and # NRF-2019R1A2C4070161 ), Republic of Korea, and by a grant of the Private University Research Branding Project from the Ministry of Education, Culture, Sports, Science and Technology of Japan ( MEXT ) and by JSPS ( 17H04252 ). Hai-Quyen Tran, The-Vinh Tran, Dieu-Hien Phan, and Naveen Sharma were supported by the BK21 PLUS program. The English in this document has been checked by at least two professional editors, both native speakers of English. Appendix A
Funding Information:
This study was supported by a grant (#19182MFDS410) from the Korea Food and Drug Administration, and by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (#NRF-2019R1I1A3A01063609 and #NRF-2019R1A2C4070161), Republic of Korea, and by a grant of the Private University Research Branding Project from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT) and by JSPS (17H04252). Hai-Quyen Tran, The-Vinh Tran, Dieu-Hien Phan, and Naveen Sharma were supported by the BK21 PLUS program. The English in this document has been checked by at least two professional editors, both native speakers of English.
Publisher Copyright:
© 2019 Elsevier Ltd
PY - 2020/2
Y1 - 2020/2
N2 - It is recognized that d-amphetamine (AMPH)-induced hyperactivity is thought to be a valid animal model of mania. In the present study, we investigated whether a proinflammatory oxidative gene indoleamine-2,3-dioxygenase (IDO) is involved in AMPH-induced mitochondrial burden, and whether mood stabilizers (i.e., lithium and valproate) modulate IDO to protect against AMPH-induced mania-like behaviors. AMPH-induced IDO-1 expression was significantly greater than IDO-2 expression in the prefrontal cortex of wild type mice. IDO-1 expression was more pronounced in the mitochondria than in the cytosol. AMPH treatment activated intra-mitochondrial Ca2+ accumulation and mitochondrial oxidative burden, while inhibited mitochondrial membrane potential and activity of the mitochondrial complex (I > II), mitochondrial glutathione peroxidase, and superoxide dismutase, indicating that mitochondrial burden might be contributable to mania-like behaviors induced by AMPH. The behaviors were significantly attenuated by lithium, valproate, or IDO-1 knockout, but not in IDO-2 knockout mice. Lithium, valproate administration, or IDO-1 knockout significantly attenuated mitochondrial burden. Neither lithium nor valproate produced additive effects above the protective effects observed in IDO-1 KO in mice. Collectively, our results suggest that mood stabilizers attenuate AMPH-induced mania-like behaviors via attenuation of IDO-1-dependent mitochondrial stress, highlighting IDO-1 as a novel molecular target for the protective potential of mood stabilizers.
AB - It is recognized that d-amphetamine (AMPH)-induced hyperactivity is thought to be a valid animal model of mania. In the present study, we investigated whether a proinflammatory oxidative gene indoleamine-2,3-dioxygenase (IDO) is involved in AMPH-induced mitochondrial burden, and whether mood stabilizers (i.e., lithium and valproate) modulate IDO to protect against AMPH-induced mania-like behaviors. AMPH-induced IDO-1 expression was significantly greater than IDO-2 expression in the prefrontal cortex of wild type mice. IDO-1 expression was more pronounced in the mitochondria than in the cytosol. AMPH treatment activated intra-mitochondrial Ca2+ accumulation and mitochondrial oxidative burden, while inhibited mitochondrial membrane potential and activity of the mitochondrial complex (I > II), mitochondrial glutathione peroxidase, and superoxide dismutase, indicating that mitochondrial burden might be contributable to mania-like behaviors induced by AMPH. The behaviors were significantly attenuated by lithium, valproate, or IDO-1 knockout, but not in IDO-2 knockout mice. Lithium, valproate administration, or IDO-1 knockout significantly attenuated mitochondrial burden. Neither lithium nor valproate produced additive effects above the protective effects observed in IDO-1 KO in mice. Collectively, our results suggest that mood stabilizers attenuate AMPH-induced mania-like behaviors via attenuation of IDO-1-dependent mitochondrial stress, highlighting IDO-1 as a novel molecular target for the protective potential of mood stabilizers.
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U2 - 10.1016/j.fct.2019.110986
DO - 10.1016/j.fct.2019.110986
M3 - Article
C2 - 31760073
AN - SCOPUS:85076212108
VL - 136
JO - Food and Chemical Toxicology
JF - Food and Chemical Toxicology
SN - 0278-6915
M1 - 110986
ER -