Local iron deficiency in the substantia nigra directly contributes to hyperlocomotion phenotypes
Local iron deficiency in the substantia nigra directly contributes to hyperlocomotion phenotypes
复制标题
黑质局部缺铁直接导致过度运动表型
DOI：
10.1016/j.nbd.2022.105693
复制
发表时间：
2022
影响因子：
6.1
通讯作者：
Pingming Qiu
中科院分区：
文献类型：
--
作者：
Zhuo Wang;Yanjun Huang;Zhihua Zhou;Jian Huang;Yitong He;Pingming Qiu
Brain iron is precisely regulated, and disrupted brain iron homeostasis is implicated in neuropsychological disease. Mounting evidence connects the iron status of the substantia nigra (SN) with locomotion-related neural symptomatology. Researchers in this field have long speculated that iron deficiency in the SN directly causes the high-locomotion symptoms observed in neuropsychiatric disorders. However, no direct experimental evidence of a causal relationship has been presented. To explore the relationship between iron deficiency in the SN and locomotion-related phenotypes, we stereotaxically injected the well-documented iron chelator, deferiprone (DFP) into the SN of mice to induce regional brain iron deprivation and subsequently performed behavioral tests. Altered expression of iron metabolism-related molecules was detected in the brain regions with interventions, and behavioral changes were observed. Targeted iron chelation effectively decreased the local iron content of the SN. Among the brain regions examined, only DFP injected into the SN resulted in the hyperlocomotion phenotype. Upon SN iron chelation, transferrin receptor (Tfr) expression was found to be upregulated. Conversely, viral vector-mediated SN-Tfr knockdown was sufficient to induce SN iron deficiency and mimic the hyperlocomotion phenotype. All locomotion changes had a significant negative correlation with iron alteration in the SN. Furthermore, SN iron disturbance also contributed to poor sleep efficiency. Thus, SN iron deficiency directly contributed to triggering both hyperlocomotion and sleep disturbances. This study offers a promising research and therapeutic direction for iron-linked neuropsychiatric diseases.
影响因子：
10.6
作者：
Anika-Maria Zimmermann;T. Jene;Michael Wolf;Andreas Görlich;C. Gurniak;M. Sassoè-Pognetto;W. Witke;E. Friauf;M. Rust
通讯作者：
Anika-Maria Zimmermann;T. Jene;Michael Wolf;Andreas Görlich;C. Gurniak;M. Sassoè-Pognetto;W. Witke;E. Friauf;M. Rust
DOI：
10.1152/ajpendo.00369.2011
发表时间：
2012-02
期刊：
American journal of physiology. Endocrinology and metabolism
影响因子：
--
作者：
P. Tran;Stephanie J. B. Fretham;J. Wobken;B. Miller;M. Georgieff
通讯作者：
P. Tran;Stephanie J. B. Fretham;J. Wobken;B. Miller;M. Georgieff