Lactobacillus plantarum PS128 ameliorates 2,5-Dimethoxy-4-iodoamphetamine-induced tic-like behaviors via its influences on the microbiota-gut-brain-axis

Jian-Fu Liao; Yun-Fang Cheng; Shiao-Wen Li; Wang-Tso Lee; Chih-Chieh Hsu; Chien-Chen Wu; One-Jang Jeng; Sabrina Wang; Ying-Chieh Tsai

doi:10.1016/j.brainresbull.2019.07.027

Lactobacillus plantarum PS128 ameliorates 2,5-Dimethoxy-4-iodoamphetamine-induced tic-like behaviors via its influences on the microbiota-gut-brain-axis

Brain Res Bull. 2019 Nov:153:59-73. doi: 10.1016/j.brainresbull.2019.07.027. Epub 2019 Jul 25.

Authors

Jian-Fu Liao¹, Yun-Fang Cheng², Shiao-Wen Li³, Wang-Tso Lee⁴, Chih-Chieh Hsu⁵, Chien-Chen Wu⁶, One-Jang Jeng⁷, Sabrina Wang⁸, Ying-Chieh Tsai⁹

Affiliations

¹ Institute of Biochemistry and Molecular Biology, National Yang-Ming University, 155, Section 2, Linong Street, Beitou Dist., Taipei City 11221, Taiwan, ROC. Electronic address: ckjackboy@gmail.com.
² Institute of Biochemistry and Molecular Biology, National Yang-Ming University, 155, Section 2, Linong Street, Beitou Dist., Taipei City 11221, Taiwan, ROC; Microbiome Research Center, National Yang-Ming University, 155, Section 2, Linong Street, Beitou Dist., Taipei City 11221, Taiwan, ROC; Bened Biomedical Co., Ltd., 2F-2, No. 129, Sec. 2, Zhongshan N. Rd., Zhongshan Dist., Taipei City 104, Taiwan, ROC. Electronic address: hiyunfang@gmail.com.
³ Molecular Medicine Research Center, Chang Gung University, No. 259, Wenhua 1st Rd., Guishan District, Taoyuan City 33302, Taiwan, ROC. Electronic address: winncesnow@gmail.com.
⁴ Department of Pediatrics, National Taiwan University Hospital, No. 8, Zhongshan S. Rd., Zhongzheng Dist., Taipei City 100, Taiwan, ROC. Electronic address: leeped@hotmail.com.
⁵ Institute of Biochemistry and Molecular Biology, National Yang-Ming University, 155, Section 2, Linong Street, Beitou Dist., Taipei City 11221, Taiwan, ROC; Bened Biomedical Co., Ltd., 2F-2, No. 129, Sec. 2, Zhongshan N. Rd., Zhongshan Dist., Taipei City 104, Taiwan, ROC. Electronic address: cchsu2000@gmail.com.
⁶ Institute of Biochemistry and Molecular Biology, National Yang-Ming University, 155, Section 2, Linong Street, Beitou Dist., Taipei City 11221, Taiwan, ROC; Bened Biomedical Co., Ltd., 2F-2, No. 129, Sec. 2, Zhongshan N. Rd., Zhongshan Dist., Taipei City 104, Taiwan, ROC. Electronic address: allen@benedbiomed.com.
⁷ Bened Biomedical Co., Ltd., 2F-2, No. 129, Sec. 2, Zhongshan N. Rd., Zhongshan Dist., Taipei City 104, Taiwan, ROC. Electronic address: onejang@benedbiomed.com.
⁸ Institute of Anatomy and Cell Biology, National Yang-Ming University, 155, Section 2, Linong Street, Beitou Dist., Taipei City 11221, Taiwan, ROC. Electronic address: sabrina@ym.edu.tw.
⁹ Institute of Biochemistry and Molecular Biology, National Yang-Ming University, 155, Section 2, Linong Street, Beitou Dist., Taipei City 11221, Taiwan, ROC; Microbiome Research Center, National Yang-Ming University, 155, Section 2, Linong Street, Beitou Dist., Taipei City 11221, Taiwan, ROC. Electronic address: tsaiyc@ym.edu.tw.

PMID: 31351942
DOI: 10.1016/j.brainresbull.2019.07.027

Abstract

We previously reported a novel psychobiotic strain of Lactobacillus plantarum PS128 (PS128) which could ameliorate anxiety-like& depression-like behaviors and modulate cerebral dopamine (DA) and serotonin (5-HT) in mice. Here, we examine the possibility of using PS128 administration to improve tic-like behaviors by using a 5-HT_2A and 5-HT_2C receptor agonist 2,5-Dimethoxy-4-iodoamphetamine (DOI). PS128 was orally administered to male Wistar rat for 2 weeks before two daily DOI injections. We recorded the behaviors immediately after the second DOI injection and compared the results with control and haloperidol treatment groups. PS128 significantly reduced tic-like behaviors and pre-pulse inhibition deficit in a threshold-dose of 10⁹ CFU per day. Brain tissue analysis showed that DOI induced abnormal DA efflux in the striatum and prefrontal cortex, while PS128 ingestion improved DA metabolism and increased norepinephrine (NE) levels in these two regions. In addition, PS128 ingestion increased DA transporter and β-arrestin expressions and decreased DOI-induced phosphorylation of DA and cAMP regulated phosphoprotein of molecular weight 32 kDa (DARPP-32) at Thr34 and extracellular regulated protein kinases (ERK). PS128 ingestion also modulated peripheral 5-HT levels and shaped the cecal microbiota composition, which helps to alleviate DOI-induced dysbiosis. These results suggested that PS128 ameliorated DOI-induced tic-like hyper-active behaviors via stabilizing cerebral dopaminergic pathways through its modulation of host's microbiota-gut-brain axis. Thus, we believe there are potentials for utilizing psychobiotics to improve syndromes caused by DA dysregulation in DA-related neurological disorders and movement disorders such as Tourette syndrome.

Keywords: Dopamine; Lactobacillus plantarum PS128; Microbiome-gut-brain-axis; Psychobiotic; Tics; Tourette syndrome.

MeSH terms

Amphetamines / pharmacology
Animals
Brain / metabolism
Corpus Striatum / metabolism
Dopamine / metabolism
Gastrointestinal Microbiome / physiology
Haloperidol / pharmacology
Lactobacillus plantarum / metabolism*
Male
Prefrontal Cortex / metabolism
Rats
Rats, Wistar
Serotonin / metabolism
Tics / chemically induced
Tics / microbiology*

Substances

Amphetamines
Serotonin
Haloperidol
4-iodo-2,5-dimethoxyphenylisopropylamine
Dopamine