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Frontiers in Neuroanatomy 2024The red nucleus is part of the motor system controlling limb movements. While this seems to be a function common in many vertebrates, its organization and circuitry have...
INTRODUCTION
The red nucleus is part of the motor system controlling limb movements. While this seems to be a function common in many vertebrates, its organization and circuitry have undergone massive changes during evolution. In primates, it is sub-divided into the magnocellular and parvocellular parts that give rise to rubrospinal and rubro-olivary connection, respectively. These two subdivisions are subject to striking variation within the primates and the size of the magnocellular part is markedly reduced in bipedal primates including humans. The parvocellular part is part of the olivo-cerebellar circuitry that is prominent in humans. Despite the well-described differences between species in the literature, systematic comparative studies of the red nucleus remain rare.
METHODS
We therefore mapped the red nucleus in cytoarchitectonic sections of 20 primate species belonging to 5 primate groups including prosimians, new world monkeys, old world monkeys, non-human apes and humans. We used Ornstein-Uhlenbeck modelling, ancestral state estimation and phylogenetic analysis of covariance to scrutinize the phylogenetic relations of the red nucleus volume.
RESULTS
We created openly available high-resolution cytoarchitectonic delineations of the human red nucleus in the microscopic BigBrain model and human probabilistic maps that capture inter-subject variations in quantitative terms. Further, we compared the volume of the nucleus across primates and showed that the parvocellular subdivision scaled proportionally to the brain volume across the groups while the magnocellular part deviated significantly from the scaling in humans and non-human apes. These two groups showed the lowest size of the magnocellular red nucleus relative to the whole brain volume and the largest relative difference between the parvocellular and magnocellular subdivision.
DISCUSSION
That is, the red nucleus has transformed from a magnocellular-dominated to a parvocellular-dominated station. It is reasonable to assume that these changes are intertwined with evolutionary developments in other brain regions, in particular the motor system. We speculate that the interspecies variations might partly reflect the differences in hand dexterity but also the tentative involvement of the red nucleus in sensory and cognitive functions.
PubMed: 38550712
DOI: 10.3389/fnana.2024.1331305 -
Neurochemistry International Jun 2024Our previous study has identified that glutamate in the red nucleus (RN) facilitates the development of neuropathic pain through metabotropic glutamate receptors...
Our previous study has identified that glutamate in the red nucleus (RN) facilitates the development of neuropathic pain through metabotropic glutamate receptors (mGluR). Here, we further explored the actions and possible molecular mechanisms of red nucleus mGluR Ⅰ (mGluR1 and mGluR5) in the development of neuropathic pain induced by spared nerve injury (SNI). Our data indicated that both mGluR1 and mGluR5 were constitutively expressed in the RN of normal rats. Two weeks after SNI, the expressions of mGluR1 and mGluR5 were significantly boosted in the RN contralateral to the nerve injury. Administration of mGluR1 antagonist LY367385 or mGluR5 antagonist MTEP to the RN contralateral to the nerve injury at 2 weeks post-SNI significantly ameliorated SNI-induced neuropathic pain. However, unilateral administration of mGluRⅠ agonist DHPG to the RN of normal rats provoked a significant mechanical allodynia, this effect could be blocked by LY367385 or MTEP. Further studies indicated that the expressions of TNF-α and IL-1β in the RN were also elevated at 2 weeks post-SNI. Administration of mGluR1 antagonist LY367385 or mGluR5 antagonist MTEP to the RN at 2 weeks post-SNI significantly inhibited the elevations of TNF-α and IL-1β. However, administration of mGluR Ⅰ agonist DHPG to the RN of normal rats significantly enhanced the expressions of TNF-α and IL-1β, these effects were blocked by LY367385 or MTEP. These results suggest that activation of red nucleus mGluR1 and mGluR5 facilitate the development of neuropathic pain by stimulating the expressions of TNF-α and IL-1β. mGluR Ⅰ maybe potential targets for drug development and clinical treatment of neuropathic pain.
PubMed: 38843952
DOI: 10.1016/j.neuint.2024.105786 -
Journal of Neuroinflammation Jul 2021Our recent studies have identified that the red nucleus (RN) dual-directionally modulates the development and maintenance of mononeuropathic pain through secreting...
BACKGROUND
Our recent studies have identified that the red nucleus (RN) dual-directionally modulates the development and maintenance of mononeuropathic pain through secreting proinflammatory and anti-inflammatory cytokines. Here, we further explored the action of red nucleus IL-33 in the early development of mononeuropathic pain.
METHODS
In this study, male rats with spared nerve injury (SNI) were used as mononeuropathic pain model. Immunohistochemistry, Western blotting, and behavioral testing were used to assess the expressions, cellular distributions, and actions of red nucleus IL-33 and its related downstream signaling molecules.
RESULTS
IL-33 and its receptor ST2 were constitutively expressed in the RN in naive rats. After SNI, both IL-33 and ST2 were upregulated significantly at 3 days and peaked at 1 week post-injury, especially in RN neurons, oligodendrocytes, and microglia. Blockade of red nucleus IL-33 with anti-IL-33 neutralizing antibody attenuated SNI-induced mononeuropathic pain, while intrarubral administration of exogenous IL-33 evoked mechanical hypersensitivity in naive rats. Red nucleus IL-33 generated an algesic effect in the early development of SNI-induced mononeuropathic pain through activating NF-κB, ERK, p38 MAPK, and JAK2/STAT3, suppression of NF-κB, ERK, p38 MAPK, and JAK2/STAT3 with corresponding inhibitors markedly attenuated SNI-induced mononeuropathic pain or IL-33-evoked mechanical hypersensitivity in naive rats. Red nucleus IL-33 contributed to SNI-induced mononeuropathic pain by stimulating TNF-α expression, which could be abolished by administration of inhibitors against ERK, p38 MAPK, and JAK2/STAT3, but not NF-κB.
CONCLUSIONS
These results suggest that red nucleus IL-33 facilitates the early development of mononeuropathic pain through activating NF-κB, ERK, p38 MAPK, and JAK2/STAT3. IL-33 mediates algesic effect partly by inducing TNF-α through activating ERK, p38 MAPK and JAK2/STAT3.
Topics: Animals; Interleukin-33; Janus Kinase 2; MAP Kinase Signaling System; Male; Mononeuropathies; Neuralgia; Rats; Rats, Sprague-Dawley; Red Nucleus; STAT3 Transcription Factor; Tumor Necrosis Factor-alpha; p38 Mitogen-Activated Protein Kinases
PubMed: 34225736
DOI: 10.1186/s12974-021-02198-9 -
Frontiers in Neuroscience 2021The knowledge about how different subsystems participate and interplay in sensorimotor control is fundamental to understand motor deficits associated with CNS injury and... (Review)
Review
The knowledge about how different subsystems participate and interplay in sensorimotor control is fundamental to understand motor deficits associated with CNS injury and movement recovery. The role of corticospinal (CS) and rubrospinal (RS) projections in motor control has been extensively studied and compared, and it is clear that both systems are important for skilled movement. However, during phylogeny, the emerging cerebral cortex took a higher hierarchical role controlling rubro-cerebellar circuits. Here, we present anatomical, neurophysiological, and behavioral evidence suggesting that both systems modulate complex segmental neuronal networks in a parallel way, which is important for sensorimotor integration at spinal cord level. We also highlight that, although specializations exist, both systems could be complementary and potentially subserve motor recovery associated with CNS damage.
PubMed: 34177458
DOI: 10.3389/fnins.2021.686481 -
Journal of Nuclear Medicine : Official... Aug 2015The red nucleus (RN) is a pair of small gray matter structures located in the midbrain and involved in muscle movement and cognitive functions. This retrospective study...
UNLABELLED
The red nucleus (RN) is a pair of small gray matter structures located in the midbrain and involved in muscle movement and cognitive functions. This retrospective study aimed to investigate the metabolism of human RN and its correlation to other brain regions.
METHODS
We developed a high-resolution semiconductor PET system to image small brain structures. Twenty patients without neurologic disorders underwent whole-brain scanning after injection of 400 MBq of (18)F-FDG. The individual brain (18)F-FDG PET images were spatially normalized to generate a surface projection map using a 3-dimensional stereotactic surface projection technique. The correlation between the RN and each voxel on the cerebral and cerebellar cortices was estimated with Pearson product-moment correlation analysis.
RESULTS
Both right and left RNs were visualized with higher uptake than that in the background midbrain. The maximum standardized uptake values of RN were 7.64 ± 1.92; these were higher than the values for the dentate nucleus but lower than those for the caudate nucleus, putamen, and thalamus. The voxel-by-voxel analysis demonstrated that the right RN was correlated more with ipsilateral association cortices than contralateral cortices, whereas the left RN was equally correlated with ipsilateral and contralateral cortices. The left RN showed a stronger correlation with the motor cortices and cerebellum than the right RN did.
CONCLUSION
Although nonspecific background activity around RNs might have influenced the correlation patterns, these metabolic relationships suggested that RN cooperates with association cortices and limbic areas to conduct higher brain functions.
Topics: Adult; Aged; Brain; Brain Mapping; Cerebellum; Cerebral Cortex; Cognition Disorders; Female; Fluorodeoxyglucose F18; Humans; Image Processing, Computer-Assisted; Imaging, Three-Dimensional; Male; Middle Aged; Positron-Emission Tomography; Radiopharmaceuticals; Red Nucleus; Reproducibility of Results; Retrospective Studies; Semiconductors
PubMed: 26045313
DOI: 10.2967/jnumed.114.152504 -
Neurology International Apr 2016Metronidazole is a very common antibacterial and antiprotozoal with wide usage across the globe, including the least developed countries. It is generally well-tolerated...
Metronidazole is a very common antibacterial and antiprotozoal with wide usage across the globe, including the least developed countries. It is generally well-tolerated with a low incidence of serious side-effects. Neurological toxicity is fairly common with this drug, however majority of these are peripheral neuropathy with very few cases of central nervous toxicity reported. We report the imaging findings in two patients with cerebellar dysfunction after Metronidazole usage. Signal changes in the dentate and red nucleus were seen on magnetic resonance imaging in these patients. Most of the cases reported in literature reported similar findings, suggesting high predilection for the dentate nucleus in metronidazole induced encephalopathy.
PubMed: 27127600
DOI: 10.4081/ni.2016.6365 -
Cureus Dec 2022Manganese (Mn) is an essential element used in many industries, such as welding, foundries, the production of metal alloys, especially stainless steel, and the... (Review)
Review
Manganese (Mn) is an essential element used in many industries, such as welding, foundries, the production of metal alloys, especially stainless steel, and the production of dry batteries, pesticides, paints, and explosives. Individuals are exposed to Mn through inhalation of fumes, dermal absorption, and ingestion. This metal is an essential trace element required for normal growth, development, and cellular homeostasis. It has also toxic effects on the central nervous system and can cause Parkinsonism symptoms in exposed patients. Studies on human and animal models reveal that neurons of the globus pallidus, the cerebellum, pons, red nucleus, the thalamus, cortex, and the anterior horn of the spinal cord could be affected by Mn toxicity. Although the diagnosis of manganese-induced Parkinsonism is primarily clinical, there are some supporting features on brain MRI images that may be helpful to objectively distinguish it. This study was designed to review the ways of exposure to Mn, clinical symptoms in case of exposure, and discover the relationship between exposure to Mn and Parkinsonism in the working population.
PubMed: 36601184
DOI: 10.7759/cureus.32161 -
EJNMMI Physics Oct 2022To confirm the performance of the first hemispherical positron emission tomography (PET) for the brain (Vrain) that we developed to visualise the small nuclei in the...
BACKGROUND
To confirm the performance of the first hemispherical positron emission tomography (PET) for the brain (Vrain) that we developed to visualise the small nuclei in the deep brain area, we compared F-fluorodeoxyglucose (FDG) brain images with whole-body PET images.
METHODS
Ten healthy male volunteers (aged 22-45 years) underwent a representative clinical whole-body PET, followed by Vrain each for 10 min. These two scans were initiated 30 min and 45 min after FDG injection (4.1 ± 0.5 MBq/kg), respectively. First, we visually identified the small nuclei and then compared their standardised uptake values (SUVs) with the participants' age. Next, the SUVs of each brain region, which were determined by applying a volume-of-interest template for anatomically normalised PET images, were compared between the brain images with the Vrain and those with the whole-body PET images.
RESULTS
Small nuclei, such as the inferior colliculus, red nucleus, and substantia nigra, were more clearly visualised in Vrain than in whole-body PET. The anterior nucleus and dorsomedial nucleus in the thalamus and raphe nucleus in the brainstem were identified in Vrain but not in whole-body PET. The SUVs of the inferior colliculus and dentate gyrus in the cerebellum positively correlated with age (Spearman's correlation coefficient r = 0.811, p = 0.004; r = 0.738, p = 0.015, respectively). The SUVs of Vrain were slightly higher in the mesial temporal and medial parietal lobes than those in whole-body PET.
CONCLUSIONS
This was the first time that the raphe nuclei, anterior nuclei, and dorsomedial nuclei were successfully visualised using the first hemispherical brain PET. TRIAL REGISTRATION : Japan Registry of Clinical Trials, jRCTs032210086, Registered 13 May 2021, https://jrct.niph.go.jp/latest-detail/jRCTs032210086 .
PubMed: 36209191
DOI: 10.1186/s40658-022-00498-4 -
The Journal of Physiology Jan 1985Correlation and regression analyses were performed on thirty-three of the magnocellular red nucleus cells described in the previous paper. We sought to test for reliable...
Correlation and regression analyses were performed on thirty-three of the magnocellular red nucleus cells described in the previous paper. We sought to test for reliable relations between the parameters of individual tracking movements and corresponding bursts of neural discharge. High correlations were found between the following burst and movement parameters: (i) burst latency versus movement latency; (ii) burst duration versus movement duration; (iii) burst frequency versus movement velocity and (iv) number of spikes in the burst versus movement amplitude. Cells were ranked according to the average of the duration, velocity and amplitude correlation coefficients. The top twenty cells had average correlation coefficients ranging from 0.69 to 0.88 for their preferred movement. These cases were judged most likely to reveal the control functions of the red nucleus, and the following points refer to this sample. Burst onset led movement onset by 118 +/- 23 ms, and burst offset led movement offset by 50 +/- 38 ms. Burst duration increased as the duration of the movement increased (r = 0.87 +/- 0.11). The duration of the burst was approximately equal to movement duration (slope of 0.99 +/- 0.16) plus a constant (72 +/- 34 ms) throughout a broad range. Average discharge rate during the burst increased with average movement velocity (r = 0.69 +/- 0.15). The slope of the relation was 0.36 +/- 0.21 (pulses/s)/(deg/s) of joint rotation. The regression lines had consistent upward offsets (56 +/- 15 pulses/s) that exceeded the spontaneous discharge rate (17 +/- 10 pulses/s). The number of spikes in the burst increased with movement amplitude independent of velocity (r = 0.72 +/- 0.11). The slope of the relation was 0.62 spikes/deg and the offset was 13 +/- 4 spikes. The preferred movement was co-ordinated hand in fifteen cases, digit in three, elbow in one and shoulder in one. When these cells were tested with an alternate movement, the failure rate (cases in which a burst did not accompany a movement) increased from 1.4 to 20%, and the correlation coefficients generally were low and lacked significance. Cells in the top twenty had directionally specific responses, low variance in lead time, large depths of modulation (41-118 pulses/s) and low failure rates. Cells that failed to show strong parametric correlations often had one or more of the former attributes. It appears that high parametric correlations with individual movements are particularly restrictive criteria of relatedness.(ABSTRACT TRUNCATED AT 400 WORDS)
Topics: Action Potentials; Animals; Extremities; Macaca fascicularis; Macaca mulatta; Male; Movement; Neurons; Red Nucleus; Time Factors
PubMed: 3981473
DOI: 10.1113/jphysiol.1985.sp015566 -
NeuroImage. Clinical 2019Differential diagnosis between Parkinson's disease (PD) and Atypical Parkinsonisms, mainly Progressive Supranuclear Palsy (PSP) and Multiple System Atrophy (MSA),...
BACKGROUND AND PURPOSE
Differential diagnosis between Parkinson's disease (PD) and Atypical Parkinsonisms, mainly Progressive Supranuclear Palsy (PSP) and Multiple System Atrophy (MSA), remains challenging. The low sensitivity of macroscopic findings at imaging might limit early diagnosis. The availability of iron-sensitive MR techniques and high magnetic field MR scanners provides new insights in evaluating brain structures in degenerative parkinsonisms. Quantitative Susceptibility Mapping (QSM) allows quantifying tissue iron content and could be sensitive to microstructural abnormalities which precede the appearence of regional atrophy. We measured the magnetic susceptibility (χ) of nigral and extranigral regions in patients with PD, PSP and MSA to evaluate the potential utility of the QSM technique for differential diagnosis.
MATERIALS AND METHODS
65 patients (36 PD, 14 MSA, 15 PSP) underwent clinical and radiological evaluation with 3 T MRI. QSM maps were obtained from GRE sequences. ROI were drawn on substantia nigra (SN), red nucleus (RN), subthalamic nucleus (STN), putamen, globus pallidus and caudate. χ values were compared to detect inter-group differences.
RESULTS
The highest diagnostic accuracy for PSP (area under the ROC curve, AUC, range 0.9-0.7) was observed for increased χ values in RN, STN and medial part of SN whereas in MSA (AUC range 0.8-0.7) iron deposition was significantly higher in the putamen, according to the patterns of pathological involvement that characterize the different diseases.
CONCLUSION
QSM could be used for iron quantification of nigral and extranigral structures in all degenerative parkinsonisms and should be tested longitudinally in order to identify early microscopical changes.
Topics: Aged; Corpus Striatum; Diagnosis, Differential; Female; Humans; Iron; Magnetic Resonance Imaging; Male; Middle Aged; Multiple System Atrophy; Parkinson Disease; Red Nucleus; Substantia Nigra; Subthalamic Nucleus; Supranuclear Palsy, Progressive
PubMed: 31539801
DOI: 10.1016/j.nicl.2019.101999