Dataset Information

TRK-fused Gene Protein Localization Is Prominent in Serotonergic and Noradrenergic Cell Groups, and Some Lower Motor Neurons in the Corticospinal Tract of the Rat Brainstem.

ABSTRACT: The TRK-fused gene (TFG) is reported to be involved in the regulation of cell size, apoptosis, cell growth, ER-Golgi protein secretion, NF-?? pathway signaling, the ubiquitin-proteasome system, and pancreatic ?-cell mass and function. TFG mutations were reported in some neurodegenerative diseases affecting sensory and motor functions. However, the function of TFG in the nervous system and how TFG mutations lead to neurodegeneration remain unclear. In this study, we employed double immunohistochemistry to investigate the details of TFG localization patterns in monoaminergic and cholinergic neurons in the brainstem. Intense TFG immunoreactivity was observed in the dorsal raphe nucleus, the locus coeruleus, and the ventral horn of the spinal cord. TFG immunoreactivity was observed in some serotonergic neurons in all B1-B9 cell groups, and some noradrenergic neurons in all A1-A7 cell groups in the rat brainstem, while no immunoreactivity was observed in the dopaminergic neurons in A8-A10 cell groups. TFG immunoreactivity was observed in all ChAT-positive motor nuclei in the lower corticospinal tract of the rat brainstem.

SUBMITTER: Takeuchi S

PROVIDER: S-EPMC6066645 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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TRK-fused Gene Protein Localization Is Prominent in Serotonergic and Noradrenergic Cell Groups, and Some Lower Motor Neurons in the Corticospinal Tract of the Rat Brainstem.

Takeuchi Shigeko S Tooyama Ikuo I

Acta histochemica et cytochemica 20180523 3

The TRK-fused gene (TFG) is reported to be involved in the regulation of cell size, apoptosis, cell growth, ER-Golgi protein secretion, NF-κβ pathway signaling, the ubiquitin-proteasome system, and pancreatic β-cell mass and function. TFG mutations were reported in some neurodegenerative diseases affecting sensory and motor functions. However, the function of TFG in the nervous system and how TFG mutations lead to neurodegeneration remain unclear. In this study, we em ...[more]

PMID: 30083019

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Project description:ObjectivePeople with Parkinson disease (PD) frequently develop dementia, which is associated with neocortical deposition of alpha-synuclein (α-syn) in Lewy bodies and Lewy neurites. In addition, neuronal loss and deposition of aggregated α-syn also occur in multiple subcortical nuclei that project to neocortical, limbic, and basal ganglia regions. Therefore, we quantified regional deficits in innervation from these PD-affected subcortical nuclei, by measuring the neurotransmitters and neurotransmitter transporter proteins originating from projections of dopaminergic neurons in substantia nigra pars compacta, serotonergic neurons in dorsal raphé nuclei, noradrenergic neurons in locus coeruleus, and cholinergic neurons in nucleus basalis of Meynert.MethodsHigh-performance liquid chromatography and novel enzyme-linked immunosorbent assays were performed to quantify dopaminergic, serotonergic, noradrenergic, and cholinergic innervation in postmortem brain tissue. Eight brain regions from 15 PD participants (with dementia and Braak stage 6 α-syn deposition) and six age-matched controls were tested.ResultsPD participants compared to controls had widespread reductions of dopamine transporter in caudate, amygdala, hippocampus, inferior parietal lobule (IPL), precuneus, and visual association cortex (VAC) that exceeded loss of dopamine, which was only significantly reduced in caudate and amygdala. In contrast, PD participants had comparable deficits of both serotonin and serotonin transporter in caudate, middle frontal gyrus, IPL, and VAC. PD participants also had significantly reduced norepinephrine levels for all eight brain regions tested. Vesicular acetylcholine transporter levels were only quantifiable in caudate and hippocampus and did not differ between PD and control groups.InterpretationThese results demonstrate widespread deficits in dopaminergic, serotonergic, and noradrenergic innervation of neocortical, limbic, and basal ganglia regions in advanced PD with dementia.

Dataset Information

TRK-fused Gene Protein Localization Is Prominent in Serotonergic and Noradrenergic Cell Groups, and Some Lower Motor Neurons in the Corticospinal Tract of the Rat Brainstem.

Publications

TRK-fused Gene Protein Localization Is Prominent in Serotonergic and Noradrenergic Cell Groups, and Some Lower Motor Neurons in the Corticospinal Tract of the Rat Brainstem.

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