Parkinson's disease(PD)is a neurodegeneration disease withα-synuclein accumulated in the substantia nigra pars compacta(SNpc)and most of the dopaminergic neurons are lost in SNpc while patients are diagnosed with...Parkinson's disease(PD)is a neurodegeneration disease withα-synuclein accumulated in the substantia nigra pars compacta(SNpc)and most of the dopaminergic neurons are lost in SNpc while patients 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 underlying mechanism,where the earlier lesioned site in the brain of gastricα-synuclein and howα-synuclein further spreads are not fully understood.Here we report that caudal raphe nuclei(CRN)are the early lesion site of gastricα-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 gastricα-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.展开更多
Obstructive sleep apnea syndrome (OSAS) was a disease of breath obstacle happened in the process of sleep. The central mechanism of OSAS has not yet been fully elucidated. Most of studies focused on raphe nuclei and...Obstructive sleep apnea syndrome (OSAS) was a disease of breath obstacle happened in the process of sleep. The central mechanism of OSAS has not yet been fully elucidated. Most of studies focused on raphe nuclei and 5-hydroxytryptamine (5-HT), and showed that brain serotonergic activity might be decreased in OSAS. It is well known that the dorsal and medial raphe nuclei provide almost all the serotonergic innervation to the forebrain. A previous study evaluated the stimulation of the dorsal raphe nuclei (DRN) in the rat inducing mainly pressor and sympathoexcitatory responses.展开更多
Using a combined microsphere retrograde transport with immunofluorescence technique,the glutamate-immunoreactive neurons in the medullary raphe nuclei that project to the cerebellar cortex were investigated in the pre...Using a combined microsphere retrograde transport with immunofluorescence technique,the glutamate-immunoreactive neurons in the medullary raphe nuclei that project to the cerebellar cortex were investigated in the present study.The cells double-labeled by glutamate-immunoresctivity and microspheres were found in all medullary raphe nuclei.Among all the cerebellar projection neurons in the medullary raphe nuclei,(49. 49±2.78)% (±)in pallidus (NRP),(62.02±3. 62) % in obscures (NRD),(3. 03±3. 03) % in magnus (NRM) were immunoreactive to glutamate.The results raise the possibility that the cerehellar vermal cortex (lobules Ⅴ-Ⅶ) may receive some excitatory input from medullary raphe nuclei to affect the function of the cerebellum.展开更多
基金This work was supported by the Natural Science Foundation of Beijing Municipality(No.7212156,China)CAMS Innovation Fund for Medical Sciences(CIFMS,2021-I2M-1–026,China)National Natural Science Foundation of China,China(82373852).
文摘Parkinson's disease(PD)is a neurodegeneration disease withα-synuclein accumulated in the substantia nigra pars compacta(SNpc)and most of the dopaminergic neurons are lost in SNpc while patients 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 underlying mechanism,where the earlier lesioned site in the brain of gastricα-synuclein and howα-synuclein further spreads are not fully understood.Here we report that caudal raphe nuclei(CRN)are the early lesion site of gastricα-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 gastricα-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.
基金This study was supported by a grant from the National Natural Science Foundation of China(No.30270502)
文摘Obstructive sleep apnea syndrome (OSAS) was a disease of breath obstacle happened in the process of sleep. The central mechanism of OSAS has not yet been fully elucidated. Most of studies focused on raphe nuclei and 5-hydroxytryptamine (5-HT), and showed that brain serotonergic activity might be decreased in OSAS. It is well known that the dorsal and medial raphe nuclei provide almost all the serotonergic innervation to the forebrain. A previous study evaluated the stimulation of the dorsal raphe nuclei (DRN) in the rat inducing mainly pressor and sympathoexcitatory responses.
文摘Using a combined microsphere retrograde transport with immunofluorescence technique,the glutamate-immunoreactive neurons in the medullary raphe nuclei that project to the cerebellar cortex were investigated in the present study.The cells double-labeled by glutamate-immunoresctivity and microspheres were found in all medullary raphe nuclei.Among all the cerebellar projection neurons in the medullary raphe nuclei,(49. 49±2.78)% (±)in pallidus (NRP),(62.02±3. 62) % in obscures (NRD),(3. 03±3. 03) % in magnus (NRM) were immunoreactive to glutamate.The results raise the possibility that the cerehellar vermal cortex (lobules Ⅴ-Ⅶ) may receive some excitatory input from medullary raphe nuclei to affect the function of the cerebellum.