Testing efficacy of the nicotine protection of the substantia nigra pars compacta in a rat Parkinson disease model. Ultrastructure study

2022 ◽  
pp. 1-17
Author(s):  
S A M Elgayar ◽  
Ola A Hussein ◽  
Heba A Mubarak ◽  
Amany M Ismaiel ◽  
Asmaa M.S. Gomaa
Keyword(s):  
Substantia Nigra ◽  
Parkinson Disease ◽  
Disease Model ◽  
Substantia Nigra Pars Compacta ◽  
Ultrastructure Study

scholarly journals Substantia nigra neuromelanin magnetic resonance imaging in patients with different subtypes of Parkinson disease

2021 ◽  
Author(s):  
Lu Wang ◽  
Yayun Yan ◽  
Liyao Zhang ◽  
Yan Liu ◽  
Ruirui Luo ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Substantia Nigra ◽  
Parkinson Disease ◽  
Clinical Symptoms ◽  
Dopamine Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Resonance Imaging ◽  
Mean Values

AbstractNeuromelanin (NM) is a dark pigment that mainly exists in neurons of the substantia nigra pars compacta (SNc). In Parkinson disease (PD) patients, NM concentration decreases gradually with degeneration and necrosis of dopamine neurons, suggesting potential use as a PD biomarker. We aimed to evaluate associations between NM concentration in in vivo SN and PD progression and different motor subtypes using NM magnetic resonance imaging (NM-MRI). Fifty-four patients with idiopathic PD were enrolled. Patients were divided into groups by subtypes with different clinical symptoms: tremor dominant (TD) group and postural instability and gait difficulty (PIGD) group. Fifteen healthy age-matched volunteers were enrolled as controls. All subjects underwent clinical assessment and NM-MRI examination. PD patients showed significantly decreased contrast-to-noise ratio (CNR) values in medial and lateral SN (P < 0.05) compared to controls. CNR values in lateral SN region decreased linearly with PD progression (P = 0.001). PIGD patients showed significant decreases in CNR mean values in lateral SN compared to TD patients (P = 0.004). Diagnostic accuracy of using lateral substantia nigra (SN) in TD and PIGD groups was 79% (sensitivity 76.5%, specificity 78.6%). NM concentration in PD patients decreases gradually during disease progression and differs significantly between PD subtypes. NM may be a reliable biomarker for PD severity and subtype identification.

Toxic Equine Parkinsonism: An Immunohistochemical Study of 10 Horses With Nigropallidal Encephalomalacia

2011 ◽  
Vol 49 (2) ◽  
pp. 398-402 ◽  
Author(s):  
H. T. Chang ◽  
W. K. Rumbeiha ◽  
J. S. Patterson ◽  
B. Puschner ◽  
A. P. Knight
Keyword(s):  
Tyrosine Hydroxylase ◽  
Substantia Nigra ◽  
Parkinson Disease ◽  
Globus Pallidus ◽  
Dopaminergic Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Large Animal Model ◽  
Substantia Nigra Pars Reticulata ◽  
Large Animal ◽  
Cytoplasmic Inclusions

Chronic ingestion of yellow star thistle ( Centaurea solstitialis) or Russian knapweed ( Acroptilon repens) causes nigropallidal encephalomalacia (NPE) in horses with an abrupt onset of neurologic signs characterized by dystonia of lips and tongue, inability to prehend food, depression, and locomotor deficits. The objectives of this study were to reexamine the pathologic alterations of NPE and to conduct an immunohistochemistry study using antibodies to tyrosine hydroxylase and α-synuclein, to determine whether NPE brains show histopathologic features resembling those in human Parkinson disease. Results confirm that the NPE lesions are located within the substantia nigra pars reticulata, sparing the cell bodies of the dopaminergic neurons in the substantia nigra pars compacta, and in the rostral portion of the globus pallidus, with partial disruption of dopaminergic (tyrosine hydroxylase–positive) fibers passing through the globus pallidus. No abnormal cytoplasmic inclusions like the Lewy bodies of human Parkinson disease were seen in these NPE brains. These findings indicate that equine NPE may serve as a large animal model of environmentally acquired toxic parkinsonism, with clinical phenotype directly attributable to lesions in globus pallidus and substantia nigra pars reticulata rather than to the destruction of dopaminergic neurons.

Heterotopic Mucosal Grafting Enables the Delivery of Therapeutic Neuropeptides Across the Blood Brain Barrier

Neurosurgery ◽  
2015 ◽  
Vol 78 (3) ◽  
pp. 448-457 ◽  
Author(s):  
Benjamin S. Bleier ◽  
Richie E. Kohman ◽  
Kevin Guerra ◽  
Angela L. Nocera ◽  
Shreshtha Ramanlal ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Parkinson Disease ◽  
Blood Brain Barrier ◽  
Disease Model ◽  
Brain Barrier ◽  
Saline Control ◽  
Skull Base Reconstruction ◽  
Blood Brain ◽  
Behavioral Assays ◽  
Intrastriatal Injection

Abstract BACKGROUND: The blood-brain barrier represents a fundamental limitation in treating neurological disease because it prevents all neuropeptides from reaching the central nervous system (CNS). Currently, there is no efficient method to permanently bypass the blood-brain barrier. OBJECTIVE: To test the feasibility of using nasal mucosal graft reconstruction of arachnoid defects to deliver glial-derived neurotrophic factor (GDNF) for the treatment of Parkinson disease in a mouse model. METHODS: The Institutional Animal Care and Use Committee approved this study in an established murine 6-hydroxydopamine Parkinson disease model. A parietal craniotomy and arachnoid defect was repaired with a heterotopic donor mucosal graft. The therapeutic efficacy of GDNF (2 μg/mL) delivered through the mucosal graft was compared with direct intrastriatal GDNF injection (2 μg/mL) and saline control through the use of 2 behavioral assays (rotarod and apomorphine rotation). An immunohistological analysis was further used to compare the relative preservation of substantia nigra cell bodies between treatment groups. RESULTS: Transmucosal GDNF was equivalent to direct intrastriatal injection at preserving motor function at week 7 in both the rotarod and apomorphine rotation behavioral assays. Similarly, both transmucosal and intrastriatal GDNF demonstrated an equivalent ratio of preserved substantia nigra cell bodies (0.79 ± 0.14 and 0.78 ± 0.09, respectively, P = NS) compared with the contralateral control side, and both were significantly greater than saline control (0.53 ± 0.21; P = .01 and P = .03, respectively). CONCLUSION: Transmucosal delivery of GDNF is equivalent to direct intrastriatal injection at ameliorating the behavioral and immunohistological features of Parkinson disease in a murine model. Mucosal grafting of arachnoid defects is a technique commonly used for endoscopic skull base reconstruction and may represent a novel method to permanently bypass the blood-brain barrier.

scholarly journals Neurotoxin-Induced Animal Models of Parkinson Disease: Pathogenic Mechanism and Assessment

ASN NEURO ◽  
2018 ◽  
Vol 10 ◽  
pp. 175909141877743 ◽  
Author(s):  
Xian-Si Zeng ◽  
Wen-Shuo Geng ◽  
Jin-Jing Jia
Keyword(s):  
Animal Models ◽  
Substantia Nigra ◽  
Parkinson Disease ◽  
Movement Disorder ◽  
Dopaminergic Neurons ◽  
Lewy Bodies ◽  
Substantia Nigra Pars Compacta ◽  
Progressive Loss ◽  
Key Features ◽  
6 Hydroxydopamine

Parkinson disease (PD) is the second most common neurodegenerative movement disorder. Pharmacological animal models are invaluable tools to study the pathological mechanisms of PD. Currently, invertebrate and vertebrate animal models have been developed by using several main neurotoxins, such as 6-hydroxydopamine, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, paraquat, and rotenone. These models achieve to some extent to reproduce the key features of PD, including motor defects, progressive loss of dopaminergic neurons in substantia nigra pars compacta, and the formation of Lewy bodies. In this review, we will highlight the pathogenic mechanisms of those neurotoxins and summarize different neurotoxic animal models with the hope to help researchers choose among them accurately and to promote the development of modeling PD.

Dopamine transporter imaging does not predict the number of nigral neurons in Parkinson disease

Neurology ◽  
2017 ◽  
Vol 88 (15) ◽  
pp. 1461-1467 ◽  
Author(s):  
Laura Saari ◽  
Katri Kivinen ◽  
Maria Gardberg ◽  
Juho Joutsa ◽  
Tommi Noponen ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Parkinson Disease ◽  
Dopamine Transporter ◽  
Specific Binding ◽  
Region Of Interest ◽  
Substantia Nigra Pars Compacta ◽  
Time Interval ◽  
Dat Spect ◽  
Axonal Dysfunction

Objective:To examine possible associations between in vivo brain dopamine transporter SPECT imaging and substantia nigra pars compacta (SNc) neuronal survival in Parkinson disease (PD).Methods:Nigral neuron numbers were calculated for 18 patients (11 patients with neuropathologically confirmed PD) who had been examined with dopamine transporter (DAT) SPECT before death. Correlation analyses between SNc tyrosine hydroxylase (TH)–positive and neuromelanin-containing neuron counts and DAT striatal specific binding ratios (SBRs) were performed with semiquantitative region of interest–based and voxel-based analyses.Results:Mean putamen SBR did not correlate with the number of substantia nigra TH-positive (r = −0.11, p = 0.66) or neuromelanin-containing (r = −0.07, p = 0.78) neurons. Correlations remained clearly nonsignificant when the time interval between SPECT and death was used as a covariate, when the voxel-based analysis was used, and when only patients with PD were included.Conclusions:This cohort study demonstrates that postmortem SNc neuron counts are not associated with striatal DAT binding in PD. These results fit with the theory that there is no correlation between the number of substantia nigra neurons and striatal dopamine after a certain level of damage has occurred. Striatal DAT binding in PD may reflect axonal dysfunction or DAT expression rather than the number of viable neurons.

scholarly journals The tectonigral pathway regulates appetitive locomotion in predatory hunting in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Meizhu Huang ◽  
Dapeng Li ◽  
Xinyu Cheng ◽  
Qing Pei ◽  
Zhiyong Xie ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Superior Colliculus ◽  
Dopamine Release ◽  
Dorsal Striatum ◽  
Dopamine Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Neuronal Circuitry ◽  
Locomotion Speed ◽  
Brain Circuit ◽  
Goal Directed Behavior

AbstractAppetitive locomotion is essential for animals to approach rewards, such as food and prey. The neuronal circuitry controlling appetitive locomotion is unclear. In a goal-directed behavior—predatory hunting, we show an excitatory brain circuit from the superior colliculus (SC) to the substantia nigra pars compacta (SNc) to enhance appetitive locomotion in mice. This tectonigral pathway transmits locomotion-speed signals to dopamine neurons and triggers dopamine release in the dorsal striatum. Synaptic inactivation of this pathway impairs appetitive locomotion but not defensive locomotion. Conversely, activation of this pathway increases the speed and frequency of approach during predatory hunting, an effect that depends on the activities of SNc dopamine neurons. Together, these data reveal that the SC regulates locomotion-speed signals to SNc dopamine neurons to enhance appetitive locomotion in mice.

Struktur und Efferenzen der Substantia nigra pars compacta beim idiopathischen Parkinson-Syndrom

2020 ◽  
Vol 88 (09) ◽  
pp. 591-599
Author(s):  
Peter Urban ◽  
Bjorn Falkenburger ◽  
Wolfgang H. Jost ◽  
Gerhard Ransmayr ◽  
Peter Riederer ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Substantia Nigra Pars Compacta

ZusammenfassungEs besteht Konsens, dass das neuropathologische Merkmal des idiopathischen Parkinson-Syndroms (IPS) der neuronale Zellverlust der Substantia nigra pars compacta (SNc) in Verbindung mit einer Lewy-Pathologie ist. Die transsynaptische Ausbreitung der Lewy-Pathologie wird als wesentlich in der Parkinson-Pathogenese angesehen. Daher ist die Kenntnis präexistenter neuroanatomischer Verbindungen der SNc wesentlich. Wir beschreiben hier neuere tierexperimentelle Befunde zu den afferenten und efferenten Projektionen der SNc und diskutieren die Evidenz für und gegen die sequentielle transsynaptische Ausbreitung der Lewy-Pathologie in der Pathogenese des IPS.

Sign in / Sign up

Export Citation Format

Share Document