Indoleamine-2,3-dioxygenase-1 is a molecular target for the protective activity of mood stabilizers against mania-like behavior induced by d-amphetamine

Hai Quyen Tran, Eun Joo Shin, Kuniaki Saito, The Vinh Tran, Dieu Hien Phan, Naveen Sharma, Dae Won Kim, Soo Young Choi, Ji Hoon Jeong, Choon Gon Jang, Jae Hoon Cheong, Toshitaka Nabeshima, Hyoung Chun Kim

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number110986
JournalFood and Chemical Toxicology
DOIs
Publication statusAccepted/In press - 01-01-2019

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Indoleamine-Pyrrole 2,3,-Dioxygenase
amphetamine
Dextroamphetamine
emotions
Bipolar Disorder
Amphetamine
lithium
Valproic Acid
Lithium
mice
indoleamine 2,3-dioxygenase
Mitochondria
Mitochondrial Membrane Potential
Glutathione Peroxidase
Prefrontal Cortex
additive effect
membrane potential
Knockout Mice
cytosol
glutathione peroxidase

All Science Journal Classification (ASJC) codes

  • Food Science
  • Toxicology

Cite this

Tran, Hai Quyen ; Shin, Eun Joo ; Saito, Kuniaki ; Tran, The Vinh ; Phan, Dieu Hien ; Sharma, Naveen ; Kim, Dae Won ; Choi, Soo Young ; Jeong, Ji Hoon ; Jang, Choon Gon ; Cheong, Jae Hoon ; Nabeshima, Toshitaka ; Kim, Hyoung Chun. / Indoleamine-2,3-dioxygenase-1 is a molecular target for the protective activity of mood stabilizers against mania-like behavior induced by d-amphetamine. In: Food and Chemical Toxicology. 2019.
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abstract = "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.",
author = "Tran, {Hai Quyen} and Shin, {Eun Joo} and Kuniaki Saito and Tran, {The Vinh} and Phan, {Dieu Hien} and Naveen Sharma and Kim, {Dae Won} and Choi, {Soo Young} and Jeong, {Ji Hoon} and Jang, {Choon Gon} and Cheong, {Jae Hoon} and Toshitaka Nabeshima and Kim, {Hyoung Chun}",
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Indoleamine-2,3-dioxygenase-1 is a molecular target for the protective activity of mood stabilizers against mania-like behavior induced by d-amphetamine. / Tran, Hai Quyen; Shin, Eun Joo; Saito, Kuniaki; Tran, The Vinh; Phan, Dieu Hien; Sharma, Naveen; Kim, Dae Won; Choi, Soo Young; Jeong, Ji Hoon; Jang, Choon Gon; Cheong, Jae Hoon; Nabeshima, Toshitaka; Kim, Hyoung Chun.

In: Food and Chemical Toxicology, 01.01.2019.

Research output: Contribution to journalArticle

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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

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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.

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