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Axonal iron transport in the brain modulates anxiety-related behaviors.

Nature chemical biology (2019-10-09)
Zhuo Wang, Yuan-Ning Zeng, Peng Yang, Li-Qiang Jin, Wen-Chao Xiong, Min-Zhen Zhu, Jun-Zhe Zhang, Xiao He, Xin-Hong Zhu
要旨

Iron is essential for a broad range of biochemical processes in the brain, but the mechanisms of iron metabolism in the brain remain elusive. Here we show that iron functionally translocates among brain regions along specific axonal projections. We identified two pathways for iron transport in the brain: a pathway from ventral hippocampus (vHip) to medial prefrontal cortex (mPFC) to substantia nigra; and a pathway from thalamus (Tha) to amygdala (AMG) to mPFC. While vHip-mPFC transport modulates anxiety-related behaviors, impairment of Tha-AMG-mPFC transport did not. Moreover, vHip-mPFC iron transport is necessary for the behavioral effects of diazepam, a well-known anxiolytic drug. By contrast, genetic or pharmacological promotion of vHip-mPFC transport produced anxiolytic-like effects and restored anxiety-like behaviors induced by repeated restraint stress. Taken together, these findings provide key insights into iron metabolism in the brain and identify the mechanisms underlying iron transport in the brain as a potential target for development of novel anxiety treatments.

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Sigma-Aldrich
塩化鉄(III), reagent grade, 97%
Sigma-Aldrich
ヘキサシアノ鉄(II)酸カリウム 三水和物, ACS reagent, 98.5-102.0%
Sigma-Aldrich
ジフテリア毒素 ジフテリア菌由来, lyophilized powder, Product is in unnicked form
Sigma-Aldrich
塩化リチウム, BioUltra, for molecular biology, anhydrous, ≥99.0% (AT)
Sigma-Aldrich
Iron-57Fe solution, 95 atom %, 99.9% (trace metals analysis)
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3-ヒドロキシ-1,2-ジメチル-4(1H)-ピリドン, 98%
Sigma-Aldrich
イボテン酸, ~95%, solid
Sigma-Aldrich
クエン酸三ナトリウム 二水和物, for molecular biology, ≥99%