Chronic lesions differentially decrease tyrosine hydroxylase messenger RNA in dopaminergic neurons of the substantia nigra

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.

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Subpopulations of mesencephalic dopaminergic neurons express different levels of tyrosine hydroxylase messenger RNA

The Journal of Comparative Neurology ◽

10.1002/cne.903030312 ◽

1991 ◽

Vol 303 (3) ◽

pp. 478-488 ◽

Cited By ~ 39

Author(s):

Linda T. Weiss-Wunder ◽

Marie-Fran�loise Chesselet

Keyword(s):

Tyrosine Hydroxylase ◽

Dopaminergic Neurons ◽

Messenger Rna ◽

Different Levels

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Effect of the weaver mutation on the expression of dopamine membrane transporter, tyrosine hydroxylase and vesicular monoamine transporter in dopaminergic neurons of the substantia nigra and the ventral tegmental area

Molecular Brain Research ◽

10.1016/s0169-328x(96)00214-8 ◽

1996 ◽

Vol 43 (1-2) ◽

pp. 291-300 ◽

Cited By ~ 10

Author(s):

Christine Adelbrecht ◽

Yves Agid ◽

Rita Raisman-Vozari

Keyword(s):

Tyrosine Hydroxylase ◽

Substantia Nigra ◽

Ventral Tegmental Area ◽

Dopaminergic Neurons ◽

Vesicular Monoamine Transporter ◽

Membrane Transporter ◽

Monoamine Transporter ◽

Ventral Tegmental

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Transplanted Neural Stem Cells: Playing a Neuroprotective Role by Ceruloplasmin in the Substantia Nigra of PD Model Rats?

Oxidative Medicine and Cellular Longevity ◽

10.1155/2015/618631 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Jia-Jia Xiao ◽

Ming Yin ◽

Ze-Jian Wang ◽

Xiao-Ping Wang

Keyword(s):

Stem Cells ◽

Tyrosine Hydroxylase ◽

Substantia Nigra ◽

Neural Stem Cells ◽

Dopaminergic Neurons ◽

Wilson’S Disease ◽

Wilson's Disease ◽

Iron Deposition ◽

Common Mechanism ◽

Stereotaxic Technique

Although mounting evidence suggests that ceruloplasmin (CP) deficiency and iron deposition are pivotal factors responsible for exacerbating demise of dopaminergic neurons in the substantia nigra (SN) of the Parkinsonism and neural stem cells (NSCs) are believed to be excellent candidates for compensating the lost dopaminergic neurons, there are few researches to explore the change of CP expression and of iron deposition in the pathological microenvironment of SN after NSCs transplantation and the ability of grafted NSCs to differentiate directionally into dopaminergic neurons under the changed homeostasis. With substantia nigral stereotaxic technique and NSCs transplantation, we found that tyrosine hydroxylase and CP expression decreased and iron deposition increased in the lesioned SN after 6-OHDA administration compared with control, while tyrosine hydroxylase and CP expression increased and iron deposition decreased after NSCs transplantation compared to 6-OHDA administration alone. Only a small number of embedding NSCs are able to differentiate into dopaminergic neurons. These results suggest that grafted NSCs have an influence on improving the content of CP expression, which may play a neuroprotective role by decreasing iron deposition and ameliorating damage of dopaminergic neurons and possibly underline the iron-related common mechanism of Parkinson’s disease and Wilson’s disease.

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Programming of Dopaminergic Neurons by Neonatal Sex Hormone Exposure: Effects on Dopamine Content and Tyrosine Hydroxylase Expression in Adult Male Rats

Neural Plasticity ◽

10.1155/2016/4569785 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 8

Author(s):

Pedro Espinosa ◽

Roxana A. Silva ◽

Nicole K. Sanguinetti ◽

Francisca C. Venegas ◽

Raul Riquelme ◽

...

Keyword(s):

Nucleus Accumbens ◽

Tyrosine Hydroxylase ◽

Substantia Nigra ◽

Ventral Tegmental Area ◽

Dopaminergic Neurons ◽

Dopamine Release ◽

Male Rats ◽

Midbrain Dopaminergic Neurons ◽

Dopamine Content ◽

Ventral Tegmental

We sought to determine the long-term changes produced by neonatal sex hormone administration on the functioning of midbrain dopaminergic neurons in adult male rats. Sprague-Dawley rats were injected subcutaneously at postnatal day 1 and were assigned to the following experimental groups: TP (testosterone propionate of 1.0 mg/50 μL); DHT (dihydrotestosterone of 1.0 mg/50 μL); EV (estradiol valerate of 0.1 mg/50 μL); and control (sesame oil of 50 μL). At postnatal day 60, neurochemical studies were performed to determine dopamine content in substantia nigra-ventral tegmental area and dopamine release in nucleus accumbens. Molecular (mRNA expression of tyrosine hydroxylase) and cellular (tyrosine hydroxylase immunoreactivity) studies were also performed. We found increased dopamine content in substantia nigra-ventral tegmental area of TP and EV rats, in addition to increased dopamine release in nucleus accumbens. However, neonatal exposure to DHT, a nonaromatizable androgen, did not affect midbrain dopaminergic neurons. Correspondingly, compared to control rats, levels of tyrosine hydroxylase mRNA and protein were significantly increased in TP and EV rats but not in DHT rats, as determined by qPCR and immunohistochemistry, respectively. Our results suggest an estrogenic mechanism involving increased tyrosine hydroxylase expression, either by direct estrogenic action or by aromatization of testosterone to estradiol in substantia nigra-ventral tegmental area.

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