Levodopa induces apoptosis in cultured neuronal cells—A possible accelerator of nigrostriatal degeneration in Parkinson's disease?

1997 ◽  
Vol 12 (1) ◽  
pp. 17-23 ◽  
Author(s):  
Ilan Ziv ◽  
Rina Zilkha-Falb ◽  
Daniel Offen ◽  
Anat Shirvan ◽  
Ari Barzilai ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neuronal Cells ◽  
Nigrostriatal Degeneration

scholarly journals 22(R)-hydroxycholesterol for dopaminergic neuronal specification of MSCs and amelioration of Parkinsonian symptoms in rats

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Manisha Singh ◽  
Manish Jain ◽  
Samrat Bose ◽  
Ashutosh Halder ◽  
Tapas Chandra Nag ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Stem Cells ◽  
Parkinson's Disease ◽  
Dental Pulp ◽  
Neuronal Cells ◽  
Human Mesenchymal Stem Cells ◽  
Wistar Rat ◽  
Human Mscs ◽  
In Vitro Differentiation

AbstractOxysterols play vital roles in the human body, ranging from cell cycle regulation and progression to dopaminergic neurogenesis. While naïve human mesenchymal stem cells (hMSCs) have been explored to have neurogenic effect, there is still a grey area to explore their regenerative potential after in vitro differentiation. Hence, in the current study, we have investigated the neurogenic effect of 22(R)-hydroxycholesterol (22-HC) on hMSCs obtained from bone marrow, adipose tissue and dental pulp. Morphological and morphometric analysis revealed physical differentiation of stem cells into neuronal cells. Detailed characterization of differentiated cells affirmed generation of neuronal cells in culture. The percentage of generation of non-DA cells in the culture confirmed selective neurogenic potential of 22-HC. We substantiated the efficacy of these cells in neuro-regeneration by transplanting them into Parkinson’s disease Wistar rat model. MSCs from dental pulp had maximal regenerative effect (with 80.20 ± 1.5% in vitro differentiation efficiency) upon transplantation, as shown by various behavioural examinations and immunohistochemical tests. Subsequential analysis revealed that 22-HC yields a higher percentage of functional DA neurons and has differential effect on various tissue-specific primary human MSCs. 22-HC may be used for treating Parkinson’s disease in future with stem cells.

Asymmetric Dopaminergic Dysfunction in Brain-First versus Body-First Parkinson’s Disease Subtypes

2021 ◽  
pp. 1-11
Author(s):  
Karoline Knudsen ◽  
Tatyana D. Fedorova ◽  
Jacob Horsager ◽  
Katrine B. Andersen ◽  
Casper Skjærbæk ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
De Novo ◽  
Specific Binding ◽  
Asymmetry Index ◽  
The Body ◽  
Specific Binding Ratio ◽  
Dat Spect ◽  
Vagal Innervation ◽  
Nigrostriatal Degeneration

Background: We have hypothesized that Parkinson’s disease (PD) comprises two subtypes. Brain-first, where pathogenic α-synuclein initially forms unilaterally in one hemisphere leading to asymmetric nigrostriatal degeneration, and body-first with initial enteric pathology, which spreads through overlapping vagal innervation leading to more symmetric brainstem involvement and hence more symmetric nigrostriatal degeneration. Isolated REM sleep behaviour disorder has been identified as a strong marker of the body-first type. Objective: To analyse striatal asymmetry in [18F]FDOPA PET and [123I]FP-CIT DaT SPECT data from iRBD patients, de novo PD patients with RBD (PD +RBD) and de novo PD patients without RBD (PD - RBD). These groups were defined as prodromal body-first, de novo body-first, and de novo brain-first, respectively. Methods: We included [18F]FDOPA PET scans from 21 iRBD patients, 11 de novo PD +RBD, 22 de novo PD - RBD, and 18 controls subjects. Also, [123I]FP-CIT DaT SPECT data from iRBD and de novo PD patients with unknown RBD status from the PPPMI dataset was analysed. Lowest putamen specific binding ratio and putamen asymmetry index (AI) was defined. Results: Nigrostriatal degeneration was significantly more symmetric in patients with RBD versus patients without RBD or with unknown RBD status in both FDOPA (p = 0.001) and DaT SPECT (p = 0.001) datasets. Conclusion: iRBD subjects and de novo PD +RBD patients present with significantly more symmetric nigrostriatal dopaminergic degeneration compared to de novo PD - RBD patients. The results support the hypothesis that body-first PD is characterized by more symmetric distribution most likely due to more symmetric propagation of pathogenic α-synuclein compared to brain-first PD.

scholarly journals Wild-type but Not Parkinson's Disease-related Ala-53 → Thr Mutant α-Synuclein Protects Neuronal Cells from Apoptotic Stimuli

2000 ◽  
Vol 275 (31) ◽  
pp. 24065-24069 ◽  
Author(s):  
Cristine Alves da Costa ◽  
Karine Ancolio ◽  
Frédéric Checler
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neuronal Cells ◽  
Wild Type

Pyrethroid and organophosphate insecticide exposure in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease: an immunohistochemical analysis of tyrosine hydroxylase and glial fibrillary acidic protein in dorsolateral striatum

2009 ◽  
Vol 25 (1) ◽  
pp. 25-39 ◽  
Author(s):  
CA Dodd ◽  
BG Klein
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Tyrosine Hydroxylase ◽  
Mouse Model ◽  
Glial Fibrillary Acidic Protein ◽  
Immunohistochemical Analysis ◽  
Acidic Protein ◽  
Nigrostriatal Pathway ◽  
Organophosphate Insecticide ◽  
Nigrostriatal Degeneration

The pyrethroid insecticide permethrin and the organophosphate insecticide chlorpyrifos can experimentally produce Parkinson’s disease (PD)-associated changes in the dopaminergic nigrostriatal pathway, short of frank degeneration, although at doses considerably higher than from a likely environmental exposure. The ability of permethrin (200 mg/kg), chlorpyrifos (50 mg/kg), or combined permethrin + chlorpyrifos to facilitate nigrostriatal damage in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (30 mg/kg) C57BL/6 mouse model of PD was investigated in three separate experiments. Tyrosine hydroxylase (TH) and glial fibrillary acidic protein (GFAP) immunohistochemistry assessed nigrostriatal degeneration or nigrostriatal damage more subtle than frank degeneration. Four fields in the dorsolateral caudate-putamen were examined at two rostrocaudal locations. The dopaminergic neurotoxin MPTP decreased striatal TH immunopositive neuropil and increased GFAP immunopositive neuropil. Neither permethrin nor chlorpyrifos, alone or in combination, altered the effects of MPTP upon TH or GFAP immunostaining. Permethrin alone increased striatal GFAP immunopositive neuropil but not when combined with chlorpyrifos treatment. Therefore, combined administration of the two insecticides appeared to protect against an increase in a neuropathological indicator of striatal damage seen with permethrin treatment alone. Differences compared with analysis of entire striatum emphasize the value of varying the topographic focus used to assess nigrostriatal degeneration in studies of insecticides in PD.

Colour vision abnormalities do not correlate with dopaminergic nigrostriatal degeneration in Parkinson's disease

1998 ◽  
Vol 245 (10) ◽  
pp. 659-664 ◽  
Author(s):  
T. Müller ◽  
Wilfried Kuhn ◽  
Thomas Büttner ◽  
Ernst Eising ◽  
H. Coenen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Colour Vision ◽  
Nigrostriatal Degeneration

Time-Course of Nigrostriatal Degeneration in a Progressive MPTP-Lesioned Macaque Model of Parkinson's Disease

2003 ◽  
Vol 28 (3) ◽  
pp. 209-218 ◽  
Author(s):  
Wassilios Meissner ◽  
Caroline Prunier ◽  
Denis Guilloteau ◽  
Sylvie Chalon ◽  
Christian E. Gross ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Time Course ◽  
Macaque Model ◽  
Nigrostriatal Degeneration

P4-103: PARKINSON'S DISEASE: BRAIN METABOLIC CORRELATES OF NIGROSTRIATAL DEGENERATION IN STRIATAL SUBREGIONS DEFINED BY CORTICO-STRIATAL CONNECTIVITY

2006 ◽  
Vol 14 (7S_Part_28) ◽  
pp. P1477-P1478
Author(s):  
Ivayla Apostolova ◽  
Catharina Lange ◽  
Lars Frings ◽  
Janos Mester ◽  
Susanne Klutmann ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nigrostriatal Degeneration

BDNF levels and nigrostriatal degeneration in “drug naïve” Parkinson's disease patients. An “in vivo” study using I-123-FP-CIT SPECT

2020 ◽  
Vol 78 ◽  
pp. 31-35
Author(s):  
J. Hernández-Vara ◽  
N. Sáez-Francàs ◽  
C. Lorenzo-Bosquet ◽  
M. Corominas-Roso ◽  
G. Cuberas-Borròs ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
In Vivo Study ◽  
Drug Naïve ◽  
Nigrostriatal Degeneration

scholarly journals Amyloid aggregates of the deubiquitinase OTUB1 are neurotoxic, suggesting that they contribute to the development of Parkinson's disease

2020 ◽  
Vol 295 (11) ◽  
pp. 3466-3484 ◽  
Author(s):  
Raniki Kumari ◽  
Roshan Kumar ◽  
Sanjay Kumar ◽  
Abhishek Kumar Singh ◽  
Pranita Hanpude ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Neuronal Cells ◽  
Lewy Bodies ◽  
Cd Spectroscopy ◽  
Force Microscopy ◽  
Atomic Force ◽  
Biochemical Assays ◽  
Mammalian Cell Cultures

Parkinson's disease (PD) is a multifactorial malady and the second most common neurodegenerative disorder, characterized by loss of dopaminergic neurons in the midbrain. A hallmark of PD pathology is the formation of intracellular protein inclusions, termed Lewy bodies (LBs). Recent MS studies have shown that OTU deubiquitinase ubiquitin aldehyde-binding 1 (OTUB1), a deubiquitinating enzyme of the OTU family, is enriched together with α-synuclein in LBs from individuals with PD and is also present in amyloid plaques associated with Alzheimer's disease. In the present study, using mammalian cell cultures and a PD mouse model, along with CD spectroscopy, atomic force microscopy, immunofluorescence-based imaging, and various biochemical assays, we demonstrate that after heat-induced protein aggregation, OTUB1 reacts strongly with both anti-A11 and anti-osteocalcin antibodies, detecting oligomeric, prefibrillar structures or fibrillar species of amyloidogenic proteins, respectively. Further, recombinant OTUB1 exhibited high thioflavin-T and Congo red binding and increased β-sheet formation upon heat induction. The oligomeric OTUB1 aggregates were highly cytotoxic, characteristic of many amyloid proteins. OTUB1 formed inclusions in neuronal cells and co-localized with thioflavin S and with α-synuclein during rotenone-induced stress. It also co-localized with the disease-associated variant pS129-α-synuclein in rotenone-exposed mouse brains. Interestingly, OTUB1 aggregates were also associated with severe cytoskeleton damage, rapid internalization inside the neuronal cells, and mitochondrial damage, all of which contribute to neurotoxicity. In conclusion, the results of our study indicate that OTUB1 may contribute to LB pathology through its amyloidogenic properties.

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