首页|The raphe nuclei are the early lesion site of gastric α-synuclein propagation to the substantia nigra

The raphe nuclei are the early lesion site of gastric α-synuclein propagation to the substantia nigra

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Parkinson's disease(PD)is a neurodegeneration disease with α-synuclein accumulated in the substantia nigra pars compacta(SNpc)and most of the dopaminergic neurons are lost in SNpc while pa-tients are diagnosed with PD.Exploring the pathology at an early stage contributes to the development of the disease-modifying strategy.Although the"gut-brain"hypothesis is proposed to explain the underly-ing mechanism,where the earlier lesioned site in the brain of gastric α-synuclein and how α-synuclein further spreads are not fully understood.Here we report that caudal raphe nuclei(CRN)are the early lesion site of gastric α-synuclein propagating through the spinal cord,while locus coeruleus(LC)and substantia nigra pars compacta(SNpc)were further affected over a time frame of 7 months.Pathologicalα-synuclein propagation via CRN leads to neuron loss and disordered neuron activity,accompanied by abnormal motor and non-motor behavior.Potential neuron circuits are observed among CRN,LC,and SNpc,which contribute to the venerability of dopaminergic neurons in SNpc.These results show that CRN is the key region for the gastric α-synuclein spread to the midbrain.Our study provides valuable details for the"gut-brain"hypothesis and proposes a valuable PD model for future research on early PD intervention.

Raphe nucleiα-SynucleinGastrointestinal tractElectrophysiologyLocus coeruleusSubstantia nigra pars compactaParkinson's diseaseSpinal cord

Chenglu Zhang、Ruxue Bo、Tiantian Zhou、Naihong Chen、Yuhe Yuan

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State Key Laboratory of Bioactive Substances and Functions of Natural Medicines,Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Materia Medica,Beijing 100050,China

北京市自然科学基金CAMS Innovation Fund for Medical Sciences,ChinaCAMS Innovation Fund for Medical Sciences,China国家自然科学基金

7212156CIFMS2021-I2M-1-02682373852

2024

10.1016/j.apsb.2024.01.015

药学学报(英文版)

药学学报(英文版)

CSTPCD
ISSN：
年,卷(期)：2024.14(5)
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