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

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.

Author(s):  
Edith G. McGeer ◽  
William A. Staines ◽  
Patrick L. McGeer

ABSTRACTThe literature is reviewed on the afferents and efferents of the caudate/putamen, globus pallidus and substantia nigra, and on the neurotransmitters occurring in the various tracts. Emphasis is placed upon the diverse roles played by GABA and glutamate as transmitters in motor pathways and upon the probability that the substantia nigra pars reticulata plays a pivotal role in the output of the basal ganglia. Excessive stimulation of the projection from the pedunculopontine tegmental area to the substantia nigra is shown to cause destruction of dopaminergic neurons in the latter nucleus, suggesting another possible mechanism for cell death in Parkinson’s disease.


ASN NEURO ◽  
2018 ◽  
Vol 10 ◽  
pp. 175909141877743 ◽  
Author(s):  
Xian-Si Zeng ◽  
Wen-Shuo Geng ◽  
Jin-Jing Jia

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.


2007 ◽  
Vol 26 (3) ◽  
pp. 203-211 ◽  
Author(s):  
S Y Baek ◽  
Y H Kim ◽  
S O Oh ◽  
C-R Lee ◽  
C I Yoo ◽  
...  

We utilized a mice model of Parkinsonism: (1) to evaluate 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity; and (2) to evaluate whether manganese (Mn) exposure can affect MPTP-induced neurotoxicity. A 2 × 3 experimental design (MPTP ×± Mn) was as follows: SS, MPTP(-) × Mn(-); SLMn, MPTP(-) × low Mn(+); SHMn, MPTP(-) × high Mn(+); MpS, MPTP(+) × Mn(-); MpLMn, MPTP(+) × low Mn(+); MpHMn, MPTP(+) × high Mn(+). We administered MPTP (30 mg/kg per day) to male C57BL/6 mice intraperitoneally, once a day for 5 days. Subsequently, mice were treated with either 2 or 8 mg/kg of MnCl2.4H2O intraperitoneally, once a day for 3 weeks. Blood and striatal Mn levels were elevated in the Mnexposed groups. The number of tyrosine hydroxylase (TH)-immunoreactive (ir) neurons in the substantia nigra pars compacta were decreased significantly in the MPTP-exposed groups. The densities of TH-ir axon terminals in caudate-putamen (CPU) were significantly decreased in the MPTP-treated groups. However, Mn treatment did not affect MPTP neurotoxicity. The densities of glial fibrillary acidic protein (GFAP)-ir astrocytes in the CPU or globus pallidus were significantly increased in the MPTP-treated groups. Concentrations of dopamine in the striatum were decreased significantly in the MPTP-exposed groups only, but Mn had no effect.


Author(s):  
Lu Wang ◽  
Yayun Yan ◽  
Liyao Zhang ◽  
Yan Liu ◽  
Ruirui Luo ◽  
...  

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.


2013 ◽  
pp. 313-321 ◽  
Author(s):  
M. A. FAHIM ◽  
S. SHEHAB ◽  
A. NEMMAR ◽  
A. ADEM ◽  
S. DHANASEKARAN ◽  
...  

The use of the herbicide paraquat (1,1'-dimethyl-4,4'-bipyridylium dichloride; PQ) which is widely used in agriculture is known to cause dopaminergic neurotoxicity. However, the mechanisms underlying this effect are not fully understood. This present study investigated the behavioral manifestations, motor coordination, and dopaminergic neurodegeneration following exposure to PQ. Male rats were injected with PQ (10 mg/kg i.p.) daily for three weeks. Rotarod systems were used for measuring locomotor activity and motor coordination. The effects of PQ on dorsiflexor, electrophysiologically-induced muscle contraction were studied. Dopamine concentrations in the ventral mesencephalon were measured by high performance liquid chromatography and the number of dopaminergic neurons in substantia nigra pars compacta was estimated by tyrosine hydroxylase immunohistochemistry. PQ induced difficulty in movement and significant reduction in motor activity and twitch tension at the dorsiflexor skeletal muscle. The number of tyrosine hydroxylase positive neurons was significantly less in the substantia nigra pars compacta and nigral dopamine level was significantly reduced in PQ treated animals (20.4±3.4 pg/mg) when compared with control animals (55.0±2.4 pg/mg wet tissue). Daily treatment of PQ for three weeks induces selective dopaminergic neuronal loss in the substantia nigra and significant behavioral and peripheral motor deficit effects.


2021 ◽  
pp. 576-582
Author(s):  
Sarah M. Tisel ◽  
Bryan T. Klassen

Parkinson disease (PD) is the classic hypokinetic movement disorder and one of the most common and widely recognized neurodegenerative conditions. PD is distinct from parkinsonism, a term that refers to a syndrome of rest tremor, bradykinesia, rigidity, and postural instability. The mechanism behind the progressive degeneration and cell death that result in PD is not precisely understood. Substantia nigra depigmentation occurs on a macroscopic level and loss of dopaminergic neurons and gliosis on a microscopic level.


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