Elevated vesicular Zn2+ in dorsal root ganglion neurons expressing the transporter TMEM163 causes age-associated itchy skin in mice.
The prevalent itching condition associated with aging, historically referred to as senile pruritus, diminishes quality of life. Despite its impact, effective treatments remain elusive, largely due to an incomplete understanding of its pathological cause. In this study, we reveal a subset of dorsal r...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2024-11-01
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| Series: | PLoS Biology |
| Online Access: | https://doi.org/10.1371/journal.pbio.3002888 |
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| author | Fang Tong Shuai Liu Chen Zhang Xicheng Gu Huan Yang Bin Zhou Yun-Yun Wang Jianwei Chen Qianhui Qu Ye Gong Haili Pan Chen Liang Changlin Li Xin Zhang Qingjian Han |
| author_facet | Fang Tong Shuai Liu Chen Zhang Xicheng Gu Huan Yang Bin Zhou Yun-Yun Wang Jianwei Chen Qianhui Qu Ye Gong Haili Pan Chen Liang Changlin Li Xin Zhang Qingjian Han |
| author_sort | Fang Tong |
| collection | DOAJ |
| description | The prevalent itching condition associated with aging, historically referred to as senile pruritus, diminishes quality of life. Despite its impact, effective treatments remain elusive, largely due to an incomplete understanding of its pathological cause. In this study, we reveal a subset of dorsal root ganglion neurons enriched with Zn2+ that express the vesicular Zn2+ transporter TMEM163. These neurons form direct synapses with and modulate the activity of spinal NPY+ inhibitory interneurons. In aged mice, both the expression of TMEM163 and the concentration of vesicular Zn2+ within the central terminals of TMEM163+ primary afferents show marked elevation. Importantly, the excessive release of vesicular Zn2+ significantly dampens the activity of NPY+ neurons, triggering the disinhibition of itch-transmitting neural circuits and resulting in chronic itch. Intriguingly, chelating Zn2+ within the spinal dorsal horn effectively relieves itch in aged mice. Our study thus unveils a novel molecular mechanism underlying senile pruritus. |
| format | Article |
| id | doaj-art-545d5ce49da14f258e152b8382cf530d |
| institution | Kabale University |
| issn | 1544-9173 1545-7885 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj-art-545d5ce49da14f258e152b8382cf530d2024-12-04T05:30:34ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852024-11-012211e300288810.1371/journal.pbio.3002888Elevated vesicular Zn2+ in dorsal root ganglion neurons expressing the transporter TMEM163 causes age-associated itchy skin in mice.Fang TongShuai LiuChen ZhangXicheng GuHuan YangBin ZhouYun-Yun WangJianwei ChenQianhui QuYe GongHaili PanChen LiangChanglin LiXin ZhangQingjian HanThe prevalent itching condition associated with aging, historically referred to as senile pruritus, diminishes quality of life. Despite its impact, effective treatments remain elusive, largely due to an incomplete understanding of its pathological cause. In this study, we reveal a subset of dorsal root ganglion neurons enriched with Zn2+ that express the vesicular Zn2+ transporter TMEM163. These neurons form direct synapses with and modulate the activity of spinal NPY+ inhibitory interneurons. In aged mice, both the expression of TMEM163 and the concentration of vesicular Zn2+ within the central terminals of TMEM163+ primary afferents show marked elevation. Importantly, the excessive release of vesicular Zn2+ significantly dampens the activity of NPY+ neurons, triggering the disinhibition of itch-transmitting neural circuits and resulting in chronic itch. Intriguingly, chelating Zn2+ within the spinal dorsal horn effectively relieves itch in aged mice. Our study thus unveils a novel molecular mechanism underlying senile pruritus.https://doi.org/10.1371/journal.pbio.3002888 |
| spellingShingle | Fang Tong Shuai Liu Chen Zhang Xicheng Gu Huan Yang Bin Zhou Yun-Yun Wang Jianwei Chen Qianhui Qu Ye Gong Haili Pan Chen Liang Changlin Li Xin Zhang Qingjian Han Elevated vesicular Zn2+ in dorsal root ganglion neurons expressing the transporter TMEM163 causes age-associated itchy skin in mice. PLoS Biology |
| title | Elevated vesicular Zn2+ in dorsal root ganglion neurons expressing the transporter TMEM163 causes age-associated itchy skin in mice. |
| title_full | Elevated vesicular Zn2+ in dorsal root ganglion neurons expressing the transporter TMEM163 causes age-associated itchy skin in mice. |
| title_fullStr | Elevated vesicular Zn2+ in dorsal root ganglion neurons expressing the transporter TMEM163 causes age-associated itchy skin in mice. |
| title_full_unstemmed | Elevated vesicular Zn2+ in dorsal root ganglion neurons expressing the transporter TMEM163 causes age-associated itchy skin in mice. |
| title_short | Elevated vesicular Zn2+ in dorsal root ganglion neurons expressing the transporter TMEM163 causes age-associated itchy skin in mice. |
| title_sort | elevated vesicular zn2 in dorsal root ganglion neurons expressing the transporter tmem163 causes age associated itchy skin in mice |
| url | https://doi.org/10.1371/journal.pbio.3002888 |
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