scholarly journals Paraquat Toxicogenetics: Strain-Related Reduction of Tyrosine Hydroxylase Staining in Substantia Nigra in Mice

2021 ◽  
Vol 3 ◽  
Author(s):  
Carolina Torres-Rojas ◽  
Wenyuan Zhao ◽  
Daming Zhuang ◽  
James P. O’Callaghan ◽  
Lu Lu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Risk Factor ◽  
Individual Differences ◽  
Tyrosine Hydroxylase ◽  
Substantia Nigra ◽  
Genetic Basis ◽  
Substantia Nigra Pars Compacta ◽  
Genetic Modulation ◽  
Putative Risk Factor ◽  
Sporadic Parkinson’S Disease

Paraquat (PQ) is a putative risk factor for the development of sporadic Parkinson’s disease. To model a possible genetic basis for individual differences in susceptibility to exposure to PQ, we recently examined the effects of paraquat on tyrosine hydroxylase (TH)-containing neurons in the substantia nigra pars compacta (SNc) of six members of the BXD family of mice (n = 2–6 per strain). We injected males with 5 mg/kg paraquat weekly three times. The density of TH+ neurons counted by immunocytochemistry at 200x in eight or more sections through the SNc is reduced in five of the six strains relative to control (N = 4 ± 2 mice per strain). TH+ loss ranged from 0 to 20% with an SEM of 1%. The heritability was estimated using standard ANOVA and jackknife resampling and is 0.37 ± 0.05 in untreated animals and 0.47 ± 0.04 in treated animals. These results demonstrate genetic modulation and GxE variation in susceptibility to PQ exposure and the loss of TH staining in the substantia nigra.

scholarly journals Daily Subacute Paraquat Exposure Decreases Muscle Function and Substantia Nigra Dopamine Level

2013 ◽  
pp. 313-321 ◽  
Author(s):  
M. A. FAHIM ◽  
S. SHEHAB ◽  
A. NEMMAR ◽  
A. ADEM ◽  
S. DHANASEKARAN ◽  
...  
Keyword(s):  
Tyrosine Hydroxylase ◽  
Substantia Nigra ◽  
High Performance ◽  
Motor Coordination ◽  
Neuronal Loss ◽  
Male Rats ◽  
Substantia Nigra Pars Compacta ◽  
Motor Deficit ◽  
Dopamine Level ◽  
Dopaminergic Neurodegeneration

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.

scholarly journals Proteomic Characterization of Synaptosomes from Human Substantia Nigra Indicates Altered Mitochondrial Translation in Parkinson’s Disease

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2580
Author(s):  
Sarah Plum ◽  
Britta Eggers ◽  
Stefan Helling ◽  
Markus Stepath ◽  
Carsten Theiss ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Gradient Centrifugation ◽  
Synaptic Function ◽  
Substantia Nigra Pars Compacta ◽  
Differential Analysis ◽  
Mitochondrial Translation ◽  
Control Subjects ◽  
Core Proteome

The pathological hallmark of Parkinson’s disease (PD) is the loss of neuromelanin-containing dopaminergic neurons within the substantia nigra pars compacta (SNpc). Additionally, numerous studies indicate an altered synaptic function during disease progression. To gain new insights into the molecular processes underlying the alteration of synaptic function in PD, a proteomic study was performed. Therefore, synaptosomes were isolated by density gradient centrifugation from SNpc tissue of individuals at advanced PD stages (N = 5) as well as control subjects free of pathology (N = 5) followed by mass spectrometry-based analysis. In total, 362 proteins were identified and assigned to the synaptosomal core proteome. This core proteome comprised all proteins expressed within the synapses without regard to data analysis software, gender, age, or disease. The differential analysis between control subjects and PD cases revealed that CD9 antigen was overrepresented and fourteen proteins, among them Thymidine kinase 2 (TK2), mitochondrial, 39S ribosomal protein L37, neurolysin, and Methionine-tRNA ligase (MARS2) were underrepresented in PD suggesting an alteration in mitochondrial translation within synaptosomes.

Loss of insulin receptor immunoreactivity from the substantia nigra pars compacta neurons in Parkinson's disease

1994 ◽  
Vol 87 (4) ◽  
pp. 343-348
Author(s):  
I. Moroo ◽  
T. Yamada ◽  
H. Makino ◽  
I. Tooyama ◽  
P. L. McGeer ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Insulin Receptor ◽  
Substantia Nigra Pars Compacta

Neurofilament mRNA is reduced in Parkinson's disease substantia nigra pars compacta neurons

1993 ◽  
Vol 329 (3) ◽  
pp. 328-336 ◽  
Author(s):  
William D. Hill ◽  
Motomi Arai ◽  
Jeffrey A. Cohen ◽  
John Q. Trojanowski
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Substantia Nigra Pars Compacta

scholarly journals Passiflora cincinnata Extract Delays the Development of Motor Signs and Prevents Dopaminergic Loss in a Mice Model of Parkinson’s Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Luiz Eduardo Mateus Brandão ◽  
Diana Aline Morais Ferreira Nôga ◽  
Aline Lima Dierschnabel ◽  
Clarissa Loureiro das Chagas Campêlo ◽  
Ywlliane da Silva Rodrigues Meurer ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Tyrosine Hydroxylase ◽  
Native Species ◽  
Biological Effects ◽  
Neuroprotective Effect ◽  
Substantia Nigra Pars Compacta ◽  
Concomitant Treatment ◽  
Mice Model ◽  
Neuroprotective Effects

Passiflora cincinnata Masters is a Brazilian native species of passionflower. This genus is known in the American continent folk medicine for its diuretic and analgesic properties. Nevertheless, few studies investigated possible biological effects of P. cincinnata extracts. Further, evidence of antioxidant actions encourages the investigation of possible neuroprotective effects in animal models of neurodegenerative diseases. This study investigates the effect of the P. cincinnata ethanolic extract (PAS) on mice submitted to a progressive model of Parkinson’s disease (PD) induced by reserpine. Male (6-month-old) mice received reserpine (0.1 mg/kg, s.c.), every other day, for 40 days, with or without a concomitant treatment with daily injections of PAS (25 mg/kg, i.p.). Catalepsy, open field, oral movements, and plus-maze discriminative avoidance evaluations were performed across treatment, and immunohistochemistry for tyrosine hydroxylase was conducted at the end. The results showed that PAS treatment delayed the onset of motor impairments and prevented the occurrence of increased catalepsy behavior in the premotor phase. However, PAS administration did not modify reserpine-induced cognitive impairments. Moreover, PAS prevented the decrease in tyrosine hydroxylase immunostaining in the substantia nigra pars compacta (SNpc) induced by reserpine. Taken together, our results suggested that PAS exerted a neuroprotective effect in a progressive model of PD.

Sign in / Sign up

Export Citation Format

Share Document