Ninjinyoeito improves social behavior disorder in neuropeptide Y deficient zebrafish
Sociability is an essential component of the linkage structure in human and other vertebrate communication. Low sociability is defined as a poor social approach, including social withdrawal and apathy, and is implicated in a variety of psychiatric disorders. Ninjinyoeito (NYT), a traditional Japanes...
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| Format: | Article |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.905711/full |
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| author | Momoko Kawabe Takumi Nishida Chihoko Horita Asami Ikeda Ryuji Takahashi Akio Inui Kazuhiro Shiozaki Kazuhiro Shiozaki |
| author_facet | Momoko Kawabe Takumi Nishida Chihoko Horita Asami Ikeda Ryuji Takahashi Akio Inui Kazuhiro Shiozaki Kazuhiro Shiozaki |
| author_sort | Momoko Kawabe |
| collection | DOAJ |
| description | Sociability is an essential component of the linkage structure in human and other vertebrate communication. Low sociability is defined as a poor social approach, including social withdrawal and apathy, and is implicated in a variety of psychiatric disorders. Ninjinyoeito (NYT), a traditional Japanese herbal medicine, has been used in the medical field. This study aimed to determine the effect of NYT on low sociality in NPY-KO zebrafish. NPY-KO zebrafish were fed a 3% NYT-supplemented diet for 4 days and subjected to behavioral tests. In the mirror test, NPY-KO zebrafish fed a control diet showed avoidance behavior toward their mirror counterparts. In contrast, the treatment of NPY-KO zebrafish with NYT significantly increased their interaction with their counterparts in the mirror. In addition, a 3-chambers test was conducted to confirm the effect of NYT on the low sociality of NPY-KO zebrafish. NPY-KO zebrafish fed the control diet showed less interaction with fish chambers, while NYT treatment increased the interaction. Phosphorylation of ERK, a marker of neuronal activity, was significantly reduced in the whole brain of NYT-fed NPY-KO zebrafish, compared to the control diet. NYT treatment significantly suppressed hypothalamic-pituitary-adrenal-related genes (gr, pomc, and crh) and sympathetic-adrenal-medullary-related genes (th1, th2, and cck) in NPY-KO zebrafish. NYT administration significantly reduced mRNA levels of gad1b compared to the control diet, suggesting the involvement of GABAergic neurons in NYT-induced improvement of low sociability. Furthermore, the expression of CREB was suppressed when NPY-KO zebrafish were fed NYT. Next, we attempted to identify the effective herb responsible for the NYT-induced improvement of low sociability. NPY-KO zebrafish were fed an experimental diet containing the target herb for 4 days, and its effect on sociability was evaluated using the 3-chambers test. Results showed that Cinnamon Bark and Polygala Root treatments significantly increased time spent in the fish tank area compared to the control diet, while the other 10 herbs did not. We confirmed that these two herbs suppressed the activity of HPA-, SAM-, and GABAergic neurons, as well as NYT-treated zebrafish, accompanied by downregulation of CREB signaling. This study suggests the potential use of NYT as a drug for sociability disorders. |
| first_indexed | 2024-04-13T18:21:33Z |
| format | Article |
| id | doaj.art-517a934af1a340d3964abb039f69eff6 |
| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-04-13T18:21:33Z |
| publishDate | 2022-08-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-517a934af1a340d3964abb039f69eff62022-12-22T02:35:25ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-08-011310.3389/fphar.2022.905711905711Ninjinyoeito improves social behavior disorder in neuropeptide Y deficient zebrafishMomoko Kawabe0Takumi Nishida1Chihoko Horita2Asami Ikeda3Ryuji Takahashi4Akio Inui5Kazuhiro Shiozaki6Kazuhiro Shiozaki7Course of Biological Science and Technology, The United Graduate School of Agricultural Sciences, Kagoshima University, Kagoshima, JapanDepartment of Food Life Sciences, Faculty of Fisheries, Kagoshima University, Kagoshima, JapanDepartment of Food Life Sciences, Faculty of Fisheries, Kagoshima University, Kagoshima, JapanCourse of Biological Science and Technology, The United Graduate School of Agricultural Sciences, Kagoshima University, Kagoshima, JapanKampo Research Laboratories, Kracie Pharma Ltd., Toyama, JapanPharmacological Department of Herbal Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, JapanCourse of Biological Science and Technology, The United Graduate School of Agricultural Sciences, Kagoshima University, Kagoshima, JapanDepartment of Food Life Sciences, Faculty of Fisheries, Kagoshima University, Kagoshima, JapanSociability is an essential component of the linkage structure in human and other vertebrate communication. Low sociability is defined as a poor social approach, including social withdrawal and apathy, and is implicated in a variety of psychiatric disorders. Ninjinyoeito (NYT), a traditional Japanese herbal medicine, has been used in the medical field. This study aimed to determine the effect of NYT on low sociality in NPY-KO zebrafish. NPY-KO zebrafish were fed a 3% NYT-supplemented diet for 4 days and subjected to behavioral tests. In the mirror test, NPY-KO zebrafish fed a control diet showed avoidance behavior toward their mirror counterparts. In contrast, the treatment of NPY-KO zebrafish with NYT significantly increased their interaction with their counterparts in the mirror. In addition, a 3-chambers test was conducted to confirm the effect of NYT on the low sociality of NPY-KO zebrafish. NPY-KO zebrafish fed the control diet showed less interaction with fish chambers, while NYT treatment increased the interaction. Phosphorylation of ERK, a marker of neuronal activity, was significantly reduced in the whole brain of NYT-fed NPY-KO zebrafish, compared to the control diet. NYT treatment significantly suppressed hypothalamic-pituitary-adrenal-related genes (gr, pomc, and crh) and sympathetic-adrenal-medullary-related genes (th1, th2, and cck) in NPY-KO zebrafish. NYT administration significantly reduced mRNA levels of gad1b compared to the control diet, suggesting the involvement of GABAergic neurons in NYT-induced improvement of low sociability. Furthermore, the expression of CREB was suppressed when NPY-KO zebrafish were fed NYT. Next, we attempted to identify the effective herb responsible for the NYT-induced improvement of low sociability. NPY-KO zebrafish were fed an experimental diet containing the target herb for 4 days, and its effect on sociability was evaluated using the 3-chambers test. Results showed that Cinnamon Bark and Polygala Root treatments significantly increased time spent in the fish tank area compared to the control diet, while the other 10 herbs did not. We confirmed that these two herbs suppressed the activity of HPA-, SAM-, and GABAergic neurons, as well as NYT-treated zebrafish, accompanied by downregulation of CREB signaling. This study suggests the potential use of NYT as a drug for sociability disorders.https://www.frontiersin.org/articles/10.3389/fphar.2022.905711/fullsociabilityzebrafishherbal medicineNinjinyoeitoneuropeptide Y |
| spellingShingle | Momoko Kawabe Takumi Nishida Chihoko Horita Asami Ikeda Ryuji Takahashi Akio Inui Kazuhiro Shiozaki Kazuhiro Shiozaki Ninjinyoeito improves social behavior disorder in neuropeptide Y deficient zebrafish Frontiers in Pharmacology sociability zebrafish herbal medicine Ninjinyoeito neuropeptide Y |
| title | Ninjinyoeito improves social behavior disorder in neuropeptide Y deficient zebrafish |
| title_full | Ninjinyoeito improves social behavior disorder in neuropeptide Y deficient zebrafish |
| title_fullStr | Ninjinyoeito improves social behavior disorder in neuropeptide Y deficient zebrafish |
| title_full_unstemmed | Ninjinyoeito improves social behavior disorder in neuropeptide Y deficient zebrafish |
| title_short | Ninjinyoeito improves social behavior disorder in neuropeptide Y deficient zebrafish |
| title_sort | ninjinyoeito improves social behavior disorder in neuropeptide y deficient zebrafish |
| topic | sociability zebrafish herbal medicine Ninjinyoeito neuropeptide Y |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.905711/full |
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