Ninjin'yoeito Targets Distinct Ca2+ Channels to Activate Ghrelin-Responsive vs. Unresponsive NPY Neurons in the Arcuate Nucleus
Appetite loss or anorexia substantially deteriorates quality of life in various diseases, and stand upstream of frailty. Neuropeptide Y (NPY) in the hypothalamic arcuate nucleus (ARC) and ghrelin released from stomach are potent inducers of appetite. We previously reported that Ninjin'yoeito, a...
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| Format: | Article |
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Frontiers Media S.A.
2020-07-01
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| Series: | Frontiers in Nutrition |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnut.2020.00104/full |
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| author | Chayon Goswami Chayon Goswami Chayon Goswami Chayon Goswami Katsuya Dezaki Katsuya Dezaki Lei Wang Lei Wang Lei Wang Akio Inui Yutaka Seino Yutaka Seino Toshihiko Yada Toshihiko Yada Toshihiko Yada Toshihiko Yada |
| author_facet | Chayon Goswami Chayon Goswami Chayon Goswami Chayon Goswami Katsuya Dezaki Katsuya Dezaki Lei Wang Lei Wang Lei Wang Akio Inui Yutaka Seino Yutaka Seino Toshihiko Yada Toshihiko Yada Toshihiko Yada Toshihiko Yada |
| author_sort | Chayon Goswami |
| collection | DOAJ |
| description | Appetite loss or anorexia substantially deteriorates quality of life in various diseases, and stand upstream of frailty. Neuropeptide Y (NPY) in the hypothalamic arcuate nucleus (ARC) and ghrelin released from stomach are potent inducers of appetite. We previously reported that Ninjin'yoeito, a Japanese kampo medicine comprising twelve herbs, restores food intake, and body weight in cisplatin-treated anorectic mice. Furthermore, Ninjin'yoeito increased cytosolic Ca2+ concentration ([Ca2+]i) in not only ghrelin-responsive but ghrelin-unresponsive NPY neurons in ARC. The cellular lineage/differentiation of ghrelin-unresponsive neuron is less defined but might alter along with aging and diet. This study examined the occupancy of ghrelin-unresponsive neurons among ARC NPY neurons in adult mice fed normal chow, and explored the mechanisms underlying Ninjin'yoeito-induced [Ca2+]i increases in ghrelin-unresponsive vs. ghrelin-responsive NPY neurons. Single ARC neurons were subjected to [Ca2+]i measurement and subsequent immunostaining for NPY. Ghrelin failed to increase [Ca2+]i in 42% of ARC NPY neurons. Ninjin'yoeito (10 μg/ml)-induced increases in [Ca2+]i were abolished in Ca2+ free condition in ghrelin-responsive and ghrelin-unresponsive ARC NPY neurons. Ninjin'yoeito-induced [Ca2+]i increases were inhibited by N-type Ca2+ channel blocker ω-conotoxin in the majority (17 of 20), while by L-type Ca2+ channel blocker nitrendipine in the minority (2 of 23), of ghrelin-responsive neurons. In contrast, Ninjin'yoeito-induced [Ca2+]i increases were inhibited by nitrendipine in the majority (14 of 17), while by ω-conotoxin in the minority (8 of 24), of ghrelin-unresponsive neurons. These results indicate that ghrelin-unresponsive neurons occur substantially among NPY neurons of ARC in adult mice fed normal chow. Ninjin'yoeito preferentially target N-type and L-type Ca2+ channels in the majority of ghrelin-responsive and ghrelin-unresponsive neurons, respectively, to increase [Ca2+]i. We suggest ARC N- and L-type Ca2+ channels as potential targets for activating, respectively, ghrelin-responsive, and unresponsive NPY neurons to treat anorexia. |
| first_indexed | 2024-12-13T04:10:44Z |
| format | Article |
| id | doaj.art-63bfb3c8aa6e444c9d73bee6f31fac98 |
| institution | Directory Open Access Journal |
| issn | 2296-861X |
| language | English |
| last_indexed | 2024-12-13T04:10:44Z |
| publishDate | 2020-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Nutrition |
| spelling | doaj.art-63bfb3c8aa6e444c9d73bee6f31fac982022-12-22T00:00:03ZengFrontiers Media S.A.Frontiers in Nutrition2296-861X2020-07-01710.3389/fnut.2020.00104548394Ninjin'yoeito Targets Distinct Ca2+ Channels to Activate Ghrelin-Responsive vs. Unresponsive NPY Neurons in the Arcuate NucleusChayon Goswami0Chayon Goswami1Chayon Goswami2Chayon Goswami3Katsuya Dezaki4Katsuya Dezaki5Lei Wang6Lei Wang7Lei Wang8Akio Inui9Yutaka Seino10Yutaka Seino11Toshihiko Yada12Toshihiko Yada13Toshihiko Yada14Toshihiko Yada15Division of Integrative Physiology, Center for Integrative Physiology, Kansai Electric Power Medical Research Institute, Kobe, JapanDivision of Diabetes, Metabolism and Endocrinology, Kobe University Graduate School of Medicine, Kobe, JapanDivision of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, Tochigi, JapanDepartment of Biochemistry and Molecular Biology, Bangladesh Agricultural University, Mymensingh, BangladeshDivision of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, Tochigi, JapanFaculty of Pharmacy, Iryo Sosei University, Iwaki, JapanDivision of Integrative Physiology, Center for Integrative Physiology, Kansai Electric Power Medical Research Institute, Kobe, JapanDivision of Diabetes, Metabolism and Endocrinology, Kobe University Graduate School of Medicine, Kobe, JapanDivision of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, Tochigi, JapanPharmacological Department of Herbal Medicine, Kagoshima University Graduate School of Medical & Dental Sciences, Kagoshima, JapanDivision of Integrative Physiology, Center for Integrative Physiology, Kansai Electric Power Medical Research Institute, Kobe, JapanCenter for Diabetes Research, Division of Diabetes and Endocrinology, Kansai Electric Power Medical Research Institute, Kobe, JapanDivision of Integrative Physiology, Center for Integrative Physiology, Kansai Electric Power Medical Research Institute, Kobe, JapanDivision of Diabetes, Metabolism and Endocrinology, Kobe University Graduate School of Medicine, Kobe, JapanDivision of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, Tochigi, JapanPharmacological Department of Herbal Medicine, Kagoshima University Graduate School of Medical & Dental Sciences, Kagoshima, JapanAppetite loss or anorexia substantially deteriorates quality of life in various diseases, and stand upstream of frailty. Neuropeptide Y (NPY) in the hypothalamic arcuate nucleus (ARC) and ghrelin released from stomach are potent inducers of appetite. We previously reported that Ninjin'yoeito, a Japanese kampo medicine comprising twelve herbs, restores food intake, and body weight in cisplatin-treated anorectic mice. Furthermore, Ninjin'yoeito increased cytosolic Ca2+ concentration ([Ca2+]i) in not only ghrelin-responsive but ghrelin-unresponsive NPY neurons in ARC. The cellular lineage/differentiation of ghrelin-unresponsive neuron is less defined but might alter along with aging and diet. This study examined the occupancy of ghrelin-unresponsive neurons among ARC NPY neurons in adult mice fed normal chow, and explored the mechanisms underlying Ninjin'yoeito-induced [Ca2+]i increases in ghrelin-unresponsive vs. ghrelin-responsive NPY neurons. Single ARC neurons were subjected to [Ca2+]i measurement and subsequent immunostaining for NPY. Ghrelin failed to increase [Ca2+]i in 42% of ARC NPY neurons. Ninjin'yoeito (10 μg/ml)-induced increases in [Ca2+]i were abolished in Ca2+ free condition in ghrelin-responsive and ghrelin-unresponsive ARC NPY neurons. Ninjin'yoeito-induced [Ca2+]i increases were inhibited by N-type Ca2+ channel blocker ω-conotoxin in the majority (17 of 20), while by L-type Ca2+ channel blocker nitrendipine in the minority (2 of 23), of ghrelin-responsive neurons. In contrast, Ninjin'yoeito-induced [Ca2+]i increases were inhibited by nitrendipine in the majority (14 of 17), while by ω-conotoxin in the minority (8 of 24), of ghrelin-unresponsive neurons. These results indicate that ghrelin-unresponsive neurons occur substantially among NPY neurons of ARC in adult mice fed normal chow. Ninjin'yoeito preferentially target N-type and L-type Ca2+ channels in the majority of ghrelin-responsive and ghrelin-unresponsive neurons, respectively, to increase [Ca2+]i. We suggest ARC N- and L-type Ca2+ channels as potential targets for activating, respectively, ghrelin-responsive, and unresponsive NPY neurons to treat anorexia.https://www.frontiersin.org/article/10.3389/fnut.2020.00104/fullNinjin-yoeitoanorexiaarcuate nucleusneuropeptide YghrelinN-type Ca2+ channel |
| spellingShingle | Chayon Goswami Chayon Goswami Chayon Goswami Chayon Goswami Katsuya Dezaki Katsuya Dezaki Lei Wang Lei Wang Lei Wang Akio Inui Yutaka Seino Yutaka Seino Toshihiko Yada Toshihiko Yada Toshihiko Yada Toshihiko Yada Ninjin'yoeito Targets Distinct Ca2+ Channels to Activate Ghrelin-Responsive vs. Unresponsive NPY Neurons in the Arcuate Nucleus Frontiers in Nutrition Ninjin-yoeito anorexia arcuate nucleus neuropeptide Y ghrelin N-type Ca2+ channel |
| title | Ninjin'yoeito Targets Distinct Ca2+ Channels to Activate Ghrelin-Responsive vs. Unresponsive NPY Neurons in the Arcuate Nucleus |
| title_full | Ninjin'yoeito Targets Distinct Ca2+ Channels to Activate Ghrelin-Responsive vs. Unresponsive NPY Neurons in the Arcuate Nucleus |
| title_fullStr | Ninjin'yoeito Targets Distinct Ca2+ Channels to Activate Ghrelin-Responsive vs. Unresponsive NPY Neurons in the Arcuate Nucleus |
| title_full_unstemmed | Ninjin'yoeito Targets Distinct Ca2+ Channels to Activate Ghrelin-Responsive vs. Unresponsive NPY Neurons in the Arcuate Nucleus |
| title_short | Ninjin'yoeito Targets Distinct Ca2+ Channels to Activate Ghrelin-Responsive vs. Unresponsive NPY Neurons in the Arcuate Nucleus |
| title_sort | ninjin yoeito targets distinct ca2 channels to activate ghrelin responsive vs unresponsive npy neurons in the arcuate nucleus |
| topic | Ninjin-yoeito anorexia arcuate nucleus neuropeptide Y ghrelin N-type Ca2+ channel |
| url | https://www.frontiersin.org/article/10.3389/fnut.2020.00104/full |
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