Elevated vesicular Zn2+ in dorsal root ganglion neurons expressing the transporter TMEM163 causes age-associated itchy skin in mice

• DOI: 10.1371/journal.pbio.3002888
• Publication Date: 2024-11-27T18:23:56Z
• Authors: 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
• Keywords: Dorsal root ganglion; Disinhibition; Itching

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 an incomplete understanding pathological cause. In this study, we reveal a subset dorsal root ganglion neurons enriched Zn 2+ that express the vesicular transporter TMEM163. These form direct synapses and modulate activity spinal NPY + inhibitory interneurons. aged mice, both expression TMEM163 concentration within central terminals primary afferents show marked elevation. Importantly, excessive release significantly dampens neurons, triggering disinhibition itch-transmitting neural circuits resulting in chronic itch. Intriguingly, chelating horn effectively relieves itch mice. Our study thus unveils novel molecular mechanism underlying pruritus.