LIVIVO - Search results -

Search results

Result 1 - 10 of total 18

Search options

Article ; Online: Differential Effects of Yeast NADH Dehydrogenase (Ndi1) Expression on Mitochondrial Function and Inclusion Formation in a Cell Culture Model of Sporadic Parkinson's Disease.

Cronin-Furman, Emily N / Barber-Singh, Jennifer / Bergquist, Kristen E / Yagi, Takao / Trimmer, Patricia A

2019 Volume 9, Issue 4

Abstract: Parkinson's disease (PD) is a neurodegenerative disorder that exhibits aberrant protein aggregation and mitochondrial dysfunction. Ndi1, the yeast mitochondrial NADH dehydrogenase (complex I) enzyme, is a single subunit, internal matrix-facing protein. ... ...

Abstract	Parkinson's disease (PD) is a neurodegenerative disorder that exhibits aberrant protein aggregation and mitochondrial dysfunction. Ndi1, the yeast mitochondrial NADH dehydrogenase (complex I) enzyme, is a single subunit, internal matrix-facing protein. Previous studies have shown that Ndi1 expression leads to improved mitochondrial function in models of complex I-mediated mitochondrial dysfunction. The trans-mitochondrial cybrid cell model of PD was created by fusing mitochondrial DNA-depleted SH-SY5Y cells with platelets from a sporadic PD patient. PD cybrid cells reproduce the mitochondrial dysfunction observed in a patient's brain and periphery and form intracellular, cybrid Lewy bodies comparable to Lewy bodies in PD brain. To improve mitochondrial function and alter the formation of protein aggregates, Ndi1 was expressed in PD cybrid cells and parent SH-SY5Y cells. We observed a dramatic increase in mitochondrial respiration, increased mitochondrial gene expression, and increased PGC-1α gene expression in PD cybrid cells expressing Ndi1. Total cellular aggregated protein content was decreased but Ndi1 expression was insufficient to prevent cybrid Lewy body formation. Ndi1 expression leads to improved mitochondrial function and biogenesis signaling, both processes that could improve neuron survival during disease. However, other aspects of PD pathology such as cybrid Lewy body formation were not reduced. Consequently, resolution of mitochondrial dysfunction alone may not be sufficient to overcome other aspects of PD-related cellular pathology.
MeSH term(s)	Cell Line, Tumor ; Coculture Techniques ; Electron Transport Complex I/genetics ; Electron Transport Complex I/metabolism ; Humans ; Mitochondria/metabolism ; Models, Biological ; Parkinson Disease/metabolism ; Saccharomyces cerevisiae/enzymology ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism
Chemical Substances	Ndi1 protein, S cerevisiae ; Saccharomyces cerevisiae Proteins ; Electron Transport Complex I (EC 1.6.5.3)
Language	English
Publishing date	2019-03-27
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom9040119
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Article ; Online: Targeting Kv1.3 channels to reduce white matter pathology after traumatic brain injury.

Reeves, Thomas M / Trimmer, Patricia A / Colley, Beverly S / Phillips, Linda L

Experimental neurology

2016 Volume 283, Issue Pt A, Page(s) 188–203

Abstract: Axonal injury is present in essentially all clinically significant cases of traumatic brain injury (TBI). While no effective treatment has been identified to date, experimental TBI models have shown promising axonal protection using immunosuppressants ... ...

Abstract	Axonal injury is present in essentially all clinically significant cases of traumatic brain injury (TBI). While no effective treatment has been identified to date, experimental TBI models have shown promising axonal protection using immunosuppressants FK506 and Cyclosporine-A, with treatment benefits attributed to calcineurin inhibition or protection of mitochondrial function. However, growing evidence suggests neuroprotective efficacy of these compounds may also involve direct modulation of ion channels, and in particular Kv1.3. The present study tested whether blockade of Kv1.3 channels, using Clofazimine (CFZ), would alleviate TBI-induced white matter pathology in rodents. Postinjury CFZ administration prevented suppression of compound action potential (CAP) amplitude in the corpus callosum of adult rats following midline fluid percussion TBI, with injury and treatment effects primarily expressed in unmyelinated CAPs. Kv1.3 protein levels in callosal tissue extracts were significantly reduced postinjury, but this loss was prevented by CFZ treatment. In parallel, CFZ also attenuated the injury-induced elevation in pro-inflammatory cytokine IL1-β. The effects of CFZ on glial function were further studied using mixed microglia/astrocyte cell cultures derived from P3-5 mouse corpus callosum. Cultures of callosal glia challenged with lipopolysaccharide exhibited a dramatic increase in IL1-β levels, accompanied by reactive morphological changes in microglia, both of which were attenuated by CFZ treatment. These results support a cell specific role for Kv1.3 signaling in white matter pathology after TBI, and suggest a treatment approach based on the blockade of these channels. This therapeutic strategy may be especially efficacious for normalizing neuro-glial interactions affecting unmyelinated axons after TBI.
MeSH term(s)	Action Potentials/drug effects ; Animals ; Animals, Newborn ; Brain Injuries, Traumatic/complications ; Brain Injuries, Traumatic/pathology ; Calcium-Binding Proteins/metabolism ; Cells, Cultured ; Clofazimine/pharmacology ; Corpus Callosum/drug effects ; Corpus Callosum/metabolism ; Cyclosporine/therapeutic use ; Disease Models, Animal ; Electric Stimulation ; Gene Expression Regulation/drug effects ; Gene Expression Regulation/physiology ; Immunosuppressive Agents/therapeutic use ; Kv1.3 Potassium Channel/metabolism ; Leukoencephalopathies/drug therapy ; Leukoencephalopathies/etiology ; Leukoencephalopathies/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Microfilament Proteins/metabolism ; Potassium Channel Blockers/pharmacology ; Rats ; Rats, Sprague-Dawley ; Tacrolimus/therapeutic use
Chemical Substances	Aif1 protein, rat ; Calcium-Binding Proteins ; Immunosuppressive Agents ; Kv1.3 Potassium Channel ; Microfilament Proteins ; Potassium Channel Blockers ; Cyclosporine (83HN0GTJ6D) ; Clofazimine (D959AE5USF) ; Tacrolimus (WM0HAQ4WNM)
Language	English
Publishing date	2016-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	207148-4
ISSN	1090-2430 ; 0014-4886
ISSN (online)	1090-2430
ISSN	0014-4886
DOI	10.1016/j.expneurol.2016.06.011
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 184: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: The cybrid model of sporadic Parkinson's disease.

Trimmer, Patricia A / Bennett, James P

Experimental neurology

2009 Volume 218, Issue 2, Page(s) 320–325

Abstract: Parkinson's disease (PD) is the eponym attached to the most prevalent neurodegenerative movement disorder of adults, derived from observations of an early nineteenth century physician and paleontologist, James Parkinson, and is now recognized to ... ...

Abstract	Parkinson's disease (PD) is the eponym attached to the most prevalent neurodegenerative movement disorder of adults, derived from observations of an early nineteenth century physician and paleontologist, James Parkinson, and is now recognized to encompass much more than a movement disorder clinically or dopamine neuron death pathologically. Most PD ( approximately 90%) is sporadic (sPD), is associated with mitochondrial deficiencies and has been studied in cell and animal models arising from the use of mitochondrial toxins that unfortunately have not predicted clinical efficacy to slow disease progression in humans. We have extensively studied the cytoplasmic hybrid ("cybrid") model of sPD in which donor mtDNAs are introduced into and expressed in neural tumor cells with identical nuclear genetic and environmental backgrounds. sPD cybrids demonstrate many abnormalities in which increased oxidative stress drives downstream antioxidant response and cell death activating signaling pathways. sPD cybrids regulate mitochondrial ETC genes and gene ontology families like sPD brain. sPD cybrids spontaneously form Lewy bodies and Lewy neurites, linking mtDNA expression to neuropathology, and demonstrate impaired organelle transport in processes and reduced mitochondrial respiration. Our recent studies show that near-infrared laser light therapy normalizes mitochondrial movement and can stimulate respiration in sPD cybrid neurons, and mitochondrial gene therapy can restore respiration and stimulate mitochondrial ETC gene and protein expression. sPD cybrids have provided multiple lines of circumstantial evidence linking mtDNA to sPD pathogenesis and can serve as platforms for therapy development. sPD cybrid models can be improved by the use of non-tumor human stem cell-derived neural precursor cells and by an introduction of postmortem brain mtDNA to test its causality directly.
MeSH term(s)	Animals ; Cell Death ; Cell Line, Tumor ; DNA, Mitochondrial/genetics ; DNA, Mitochondrial/metabolism ; Gene Expression ; Humans ; Hybrid Cells/metabolism ; Hybrid Cells/pathology ; Neurons/metabolism ; Neurons/pathology ; Oxidative Stress ; Parkinson Disease/genetics ; Parkinson Disease/metabolism ; Parkinson Disease/pathology ; Signal Transduction
Chemical Substances	DNA, Mitochondrial
Language	English
Publishing date	2009-03-26
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	207148-4
ISSN	1090-2430 ; 0014-4886
ISSN (online)	1090-2430
ISSN	0014-4886
DOI	10.1016/j.expneurol.2009.03.016
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 184: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Differentiated Alzheimer's disease transmitochondrial cybrid cell lines exhibit reduced organelle movement.

Trimmer, Patricia A / Borland, M Kathleen

Antioxidants & redox signaling

2005 Volume 7, Issue 9-10, Page(s) 1101–1109

Abstract: The axonal transport and function of organelles like mitochondria and lysosomes may be impaired and play an important role in the pathogenesis of Alzheimer's disease (AD). Unique cybrid cell lines that model AD pathology were created by fusing platelets ... ...

Abstract	The axonal transport and function of organelles like mitochondria and lysosomes may be impaired and play an important role in the pathogenesis of Alzheimer's disease (AD). Unique cybrid cell lines that model AD pathology were created by fusing platelets containing mitochondria from age-matched AD and control volunteers with mitochondrial DNA-free SH-SY5Y human neuroblastoma cells. These cybrid lines were differentiated to form process-bearing neuronal cells. Mitochondria and lysosomes in the neurites of each cybrid line were fluorescently labeled to determine the kinetics of organelle movement. The mitochondria in AD cybrid neurites were elongate, whereas the mitochondria in control cybrid neurites were short and more punctate. The mean velocity of mitochondrial movement, as well as the percentage of moving mitochondria, was significantly reduced in AD cybrids. The velocity of lysosomal movement was also reduced in the processes of AD cybrid cells, suggesting that the axonal transport machinery may be compromised in cybrid cell lines that contain mitochondrial DNA derived from AD patients. Reduced mitochondrial and lysosomal movement in susceptible neurons may compromise function in metabolically demanding structures like synaptic terminals and participate in the terminal degeneration that is characteristic of AD.
MeSH term(s)	Aged ; Alzheimer Disease/metabolism ; Axons/metabolism ; Blood Platelets ; Case-Control Studies ; Cell Culture Techniques ; Cell Differentiation ; Cell Line ; Cell Line, Tumor ; DNA/chemistry ; DNA, Mitochondrial/metabolism ; Electron Transport ; Female ; Humans ; Kinetics ; Lysosomes/metabolism ; Male ; Middle Aged ; Mitochondria/metabolism ; Neurons/metabolism ; Presynaptic Terminals ; Reactive Oxygen Species ; Synapses/pathology
Chemical Substances	DNA, Mitochondrial ; Reactive Oxygen Species ; DNA (9007-49-2)
Language	English
Publishing date	2005-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	1483836-9
ISSN	1557-7716 ; 1523-0864
ISSN (online)	1557-7716
ISSN	1523-0864
DOI	10.1089/ars.2005.7.1101
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5488: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Mitochondrial quality, dynamics and functional capacity in Parkinson's disease cybrid cell lines selected for Lewy body expression.

Cronin-Furman, Emily N / Borland, M Kathleen / Bergquist, Kristen E / Bennett, James P / Trimmer, Patricia A

Molecular neurodegeneration

2013 Volume 8, Page(s) 6

Abstract: Background: Lewy bodies (LB) are a neuropathological hallmark of Parkinson's disease (PD) and other synucleinopathies. The role their formation plays in disease pathogenesis is not well understood, in part because studies of LB have been limited to ... ...

Abstract	Background: Lewy bodies (LB) are a neuropathological hallmark of Parkinson's disease (PD) and other synucleinopathies. The role their formation plays in disease pathogenesis is not well understood, in part because studies of LB have been limited to examination of post-mortem tissue. LB formation may be detrimental to neuronal survival or merely an adaptive response to other ongoing pathological processes. In a human cytoplasmic hybrid (cybrid) neural cell model that expresses mitochondrial DNA from PD patients, we observed spontaneous formation of intracellular protein aggregates ("cybrid LB" or CLB) that replicate morphological and biochemical properties of native, cortical LB. We studied mitochondrial morphology, bioenergetics and biogenesis signaling by creating stable sub-clones of three PD cybrid cell lines derived from cells expressing CLB. Results: Cloning based on CLB expression had a differential effect on mitochondrial morphology, movement and oxygen utilization in each of three sub-cloned lines, but no long-term change in CLB expression. In one line (PD63(CLB)), mitochondrial function declined compared to the original PD cybrid line (PD63(Orig)) due to low levels of mtDNA in nucleoids. In another cell line (PD61(Orig)), the reverse was true, and cellular and mitochondrial function improved after sub-cloning for CLB expression (PD61(CLB)). In the third cell line (PD67(Orig)), there was no change in function after selection for CLB expression (PD67(CLB)). Conclusions: Expression of mitochondrial DNA derived from PD patients in cybrid cell lines induced the spontaneous formation of CLB. The creation of three sub-cloned cybrid lines from cells expressing CLB resulted in differential phenotypic changes in mitochondrial and cellular function. These changes were driven by the expression of patient derived mitochondrial DNA in nucleoids, rather than by the presence of CLB. Our studies suggest that mitochondrial DNA plays an important role in cellular and mitochondrial dysfunction in PD. Additional studies will be needed to assess the direct effect of CLB expression on cellular and mitochondrial function.
MeSH term(s)	Adult ; Aged ; DNA, Mitochondrial/metabolism ; Energy Metabolism ; Female ; Humans ; Hybrid Cells/metabolism ; Hybrid Cells/ultrastructure ; Lewy Bodies/metabolism ; Lewy Bodies/pathology ; Male ; Microscopy, Electron, Transmission ; Middle Aged ; Mitochondria/metabolism ; Mitochondria/ultrastructure ; Neurons ; Parkinson Disease/genetics ; Parkinson Disease/metabolism ; Parkinson Disease/pathology ; Reverse Transcriptase Polymerase Chain Reaction
Chemical Substances	DNA, Mitochondrial
Language	English
Publishing date	2013-01-26
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1750-1326
ISSN (online)	1750-1326
DOI	10.1186/1750-1326-8-6
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article: Nitric oxide impairs mitochondrial movement in cortical neurons during hypoxia.

Zanelli, Santina A / Trimmer, Patricia A / Solenski, Nina J

Journal of neurochemistry

2006 Volume 97, Issue 3, Page(s) 724–736

Abstract: Cortical nitric oxide (NO) production increases during hypoxia/ischemia in the immature brain and is associated with both neurotoxicity and mitochondrial dysfunction. Mitochondrial redistribution within the cell is critical to normal neuronal function, ... ...

Abstract	Cortical nitric oxide (NO) production increases during hypoxia/ischemia in the immature brain and is associated with both neurotoxicity and mitochondrial dysfunction. Mitochondrial redistribution within the cell is critical to normal neuronal function, however, the effects of hypoxia on mitochondrial dynamics are not known. This study tested the hypothesis that hypoxia impairs mitochondrial movement via NO-mediated pathways. Fluorescently labeled mitochondria were studied using time-lapse digital video microscopy in cultured cortical neurons exposed either to hypoxia/re-oxygenation or to diethyleneamine/nitric oxide adduct, DETA-NO (100-500 microm). Two NO synthase inhibitors, were used to determine NO specificity. Mitochondrial mean velocity, the percentage of movement (i.e. the time spent moving) and mitochondrial morphology were analyzed. Exposure to hypoxia reduced mitochondrial movement to 10.4 +/- 1.3% at 0 h and 7.4 +/- 1.7% at 1 h of re-oxygenation, versus 25.6 +/- 1.4% in controls (p < 0.05). Mean mitochondrial velocity (microm s(-1)) decreased from 0.374 +/- 0.01 in controls to 0.146 +/- 0.01 at 0 h and 0.177 +/- 0.02 at 1 h of re-oxygenation (p < 0.001). Exposure to DETA-NO resulted in a significant decrease in mean mitochondrial velocity at all tested time points. Treatment with NG-nitro-L-arginine methyl ester (L-NAME) prevented the hypoxia-induced decrease in mitochondrial movement at 0 h (30.1 +/- 1.6%) and at 1 h (26.1 +/- 9%) of re-oxygenation. Exposure to either hypoxia/re-oxygenation or NO also resulted in the rapid decrease in mitochondrial size. Both hypoxia and NO exposure result in impaired mitochondrial movement and morphology in cultured cortical neurons. As the effect of hypoxia on mitochondrial movement and morphology can be partially prevented by a nitric oxide synthase (NOS) inhibitor, these data suggest that an NO-mediated pathway is at least partially involved.
MeSH term(s)	Animals ; Cell Hypoxia/drug effects ; Cell Survival/drug effects ; Cells, Cultured ; Cerebral Cortex/cytology ; Dose-Response Relationship, Drug ; Embryo, Mammalian ; Enzyme Inhibitors/pharmacology ; Free Radical Scavengers/pharmacology ; Luminescent Agents/pharmacokinetics ; Microscopy, Video/methods ; Mitochondria/drug effects ; Mitochondria/metabolism ; Mitochondria/physiology ; NG-Nitroarginine Methyl Ester/pharmacology ; Neurons/drug effects ; Nitric Oxide/pharmacology ; Organic Chemicals/pharmacokinetics ; Oxygen/pharmacology ; Rats ; Rats, Sprague-Dawley ; Time Factors ; Triazenes/pharmacology
Chemical Substances	1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene ; Enzyme Inhibitors ; Free Radical Scavengers ; Luminescent Agents ; Organic Chemicals ; Triazenes ; red dye CMXRos ; Nitric Oxide (31C4KY9ESH) ; Oxygen (S88TT14065) ; NG-Nitroarginine Methyl Ester (V55S2QJN2X)
Language	English
Publishing date	2006-05
Publishing country	England
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80158-6
ISSN	1471-4159 ; 0022-3042 ; 1474-1644
ISSN (online)	1471-4159
ISSN	0022-3042 ; 1474-1644
DOI	10.1111/j.1471-4159.2006.03767.x
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ui II Zs.170: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Mitochondrial quality, dynamics and functional capacity in Parkinson’s disease cybrid cell lines selected for Lewy body expression

Cronin-Furman Emily N / Borland M Kathleen / Bergquist Kristen E / Bennett James P / Trimmer Patricia A

Molecular Neurodegeneration, Vol 8, Iss 1, p

2013 Volume 6

Abstract: Abstract Background Lewy bodies (LB) are a neuropathological hallmark of Parkinson’s disease (PD) and other synucleinopathies. The role their formation plays in disease pathogenesis is not well understood, in part because studies of LB have been limited ... ...

Abstract	Abstract Background Lewy bodies (LB) are a neuropathological hallmark of Parkinson’s disease (PD) and other synucleinopathies. The role their formation plays in disease pathogenesis is not well understood, in part because studies of LB have been limited to examination of post-mortem tissue. LB formation may be detrimental to neuronal survival or merely an adaptive response to other ongoing pathological processes. In a human cytoplasmic hybrid (cybrid) neural cell model that expresses mitochondrial DNA from PD patients, we observed spontaneous formation of intracellular protein aggregates (“cybrid LB” or CLB) that replicate morphological and biochemical properties of native, cortical LB. We studied mitochondrial morphology, bioenergetics and biogenesis signaling by creating stable sub-clones of three PD cybrid cell lines derived from cells expressing CLB. Results Cloning based on CLB expression had a differential effect on mitochondrial morphology, movement and oxygen utilization in each of three sub-cloned lines, but no long-term change in CLB expression. In one line (PD63 CLB ), mitochondrial function declined compared to the original PD cybrid line (PD63 Orig ) due to low levels of mtDNA in nucleoids. In another cell line (PD61 Orig ), the reverse was true, and cellular and mitochondrial function improved after sub-cloning for CLB expression (PD61 CLB ). In the third cell line (PD67 Orig ), there was no change in function after selection for CLB expression (PD67 CLB ). Conclusions Expression of mitochondrial DNA derived from PD patients in cybrid cell lines induced the spontaneous formation of CLB. The creation of three sub-cloned cybrid lines from cells expressing CLB resulted in differential phenotypic changes in mitochondrial and cellular function. These changes were driven by the expression of patient derived mitochondrial DNA in nucleoids, rather than by the presence of CLB. Our studies suggest that mitochondrial DNA plays an important role in cellular and mitochondrial dysfunction in PD. Additional studies will be needed to assess the direct effect of CLB expression on cellular and mitochondrial function.
Keywords	Neurology. Diseases of the nervous system ; RC346-429 ; Neurosciences. Biological psychiatry. Neuropsychiatry ; RC321-571 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Neurology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Subject code	570
Language	English
Publishing date	2013-01-01T00:00:00Z
Publisher	BioMed Central
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Reduced axonal transport in Parkinson's disease cybrid neurites is restored by light therapy.

Trimmer, Patricia A / Schwartz, Kathleen M / Borland, M Kathleen / De Taboada, Luis / Streeter, Jackson / Oron, Uri

Molecular neurodegeneration

2009 Volume 4, Page(s) 26

Abstract: Background: It has been hypothesized that reduced axonal transport contributes to the degeneration of neuronal processes in Parkinson's disease (PD). Mitochondria supply the adenosine triphosphate (ATP) needed to support axonal transport and contribute ... ...

Abstract	Background: It has been hypothesized that reduced axonal transport contributes to the degeneration of neuronal processes in Parkinson's disease (PD). Mitochondria supply the adenosine triphosphate (ATP) needed to support axonal transport and contribute to many other cellular functions essential for the survival of neuronal cells. Furthermore, mitochondria in PD tissues are metabolically and functionally compromised. To address this hypothesis, we measured the velocity of mitochondrial movement in human transmitochondrial cybrid "cytoplasmic hybrid" neuronal cells bearing mitochondrial DNA from patients with sporadic PD and disease-free age-matched volunteer controls (CNT). The absorption of low level, near-infrared laser light by components of the mitochondrial electron transport chain (mtETC) enhances mitochondrial metabolism, stimulates oxidative phosphorylation and improves redox capacity. PD and CNT cybrid neuronal cells were exposed to near-infrared laser light to determine if the velocity of mitochondrial movement can be restored by low level light therapy (LLLT). Axonal transport of labeled mitochondria was documented by time lapse microscopy in dopaminergic PD and CNT cybrid neuronal cells before and after illumination with an 810 nm diode laser (50 mW/cm2) for 40 seconds. Oxygen utilization and assembly of mtETC complexes were also determined. Results: The velocity of mitochondrial movement in PD cybrid neuronal cells (0.175 +/- 0.005 SEM) was significantly reduced (p < 0.02) compared to mitochondrial movement in disease free CNT cybrid neuronal cells (0.232 +/- 0.017 SEM). For two hours after LLLT, the average velocity of mitochondrial movement in PD cybrid neurites was significantly (p < 0.003) increased (to 0.224 +/- 0.02 SEM) and restored to levels comparable to CNT. Mitochondrial movement in CNT cybrid neurites was unaltered by LLLT (0.232 +/- 0.017 SEM). Assembly of complexes in the mtETC was reduced and oxygen utilization was altered in PD cybrid neuronal cells. PD cybrid neuronal cell lines with the most dysfunctional mtETC assembly and oxygen utilization profiles were least responsive to LLLT. Conclusion: The results from this study support our proposal that axonal transport is reduced in sporadic PD and that a single, brief treatment with near-infrared light can restore axonal transport to control levels. These results are the first demonstration that LLLT can increase axonal transport in model human dopaminergic neuronal cells and they suggest that LLLT could be developed as a novel treatment to improve neuronal function in patients with PD.
Language	English
Publishing date	2009-06-17
Publishing country	England
Document type	Journal Article
ISSN	1750-1326
ISSN (online)	1750-1326
DOI	10.1186/1750-1326-4-26
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Chronic, low-dose rotenone reproduces Lewy neurites found in early stages of Parkinson's disease, reduces mitochondrial movement and slowly kills differentiated SH-SY5Y neural cells.

Borland, M Kathleen / Trimmer, Patricia A / Rubinstein, Jeremy D / Keeney, Paula M / Mohanakumar, Kp / Liu, Lei / Bennett, James P

Molecular neurodegeneration

2008 Volume 3, Page(s) 21

Abstract: Background: Parkinson's disease, the most common adult neurodegenerative movement disorder, demonstrates a brain-wide pathology that begins pre-clinically with alpha-synuclein aggregates ("Lewy neurites") in processes of gut enteric and vagal motor ... ...

Abstract	Background: Parkinson's disease, the most common adult neurodegenerative movement disorder, demonstrates a brain-wide pathology that begins pre-clinically with alpha-synuclein aggregates ("Lewy neurites") in processes of gut enteric and vagal motor neurons. Rostral progression into substantia nigra with death of dopamine neurons produces the motor impairment phenotype that yields a clinical diagnosis. The vast majority of Parkinson's disease occurs sporadically, and current models of sporadic Parkinson's disease (sPD) can utilize directly infused or systemic neurotoxins. Results: We developed a differentiation protocol for human SH-SY5Y neuroblastoma that yielded non-dividing dopaminergic neural cells with long processes that we then exposed to 50 nM rotenone, a complex I inhibitor used in Parkinson's disease models. After 21 days of rotenone, ~60% of cells died. Their processes retracted and accumulated ASYN-(+) and UB-(+) aggregates that blocked organelle transport. Mitochondrial movement velocities were reduced by 8 days of rotenone and continued to decline over time. No cytoplasmic inclusions resembling Lewy bodies were observed. Gene microarray analyses showed that the majority of genes were under-expressed. qPCR analyses of 11 mtDNA-encoded and 10 nDNA-encoded mitochondrial electron transport chain RNAs' relative expressions revealed small increases in mtDNA-encoded genes and lesser regulation of nDNA-encoded ETC genes. Conclusion: Subacute rotenone treatment of differentiated SH-SY5Y neuroblastoma cells causes process retraction and partial death over several weeks, slowed mitochondrial movement in processes and appears to reproduce the Lewy neuritic changes of early Parkinson's disease pathology but does not cause Lewy body inclusions. The overall pattern of transcriptional regulation is gene under-expression with minimal regulation of ETC genes in spite of rotenone's being a complex I toxin. This rotenone-SH-SY5Y model in a differentiated human neural cell mimics changes of early Parkinson's disease and may be useful for screening therapeutics for neuroprotection in that disease stage.
Language	English
Publishing date	2008-12-29
Publishing country	England
Document type	Journal Article
ISSN	1750-1326
ISSN (online)	1750-1326
DOI	10.1186/1750-1326-3-21
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article: Parkinson's disease transgenic mitochondrial cybrids generate Lewy inclusion bodies.

Trimmer, Patricia A / Borland, M Kathleen / Keeney, Paula M / Bennett, James P / Parker, W Davis

Journal of neurochemistry

2003 Volume 88, Issue 4, Page(s) 800–812

Abstract: Many models of Parkinson's disease (PD) have succeeded in replicating dopaminergic neuron loss or alpha-synuclein aggregation but not the formation of classical Lewy bodies, the pathological hallmark of PD. Our cybrid model of sporadic PD was created by ... ...

Abstract	Many models of Parkinson's disease (PD) have succeeded in replicating dopaminergic neuron loss or alpha-synuclein aggregation but not the formation of classical Lewy bodies, the pathological hallmark of PD. Our cybrid model of sporadic PD was created by introducing the mitochondrial genes from PD patients into neuroblastoma cells that lack mitochondrial DNA. Previous studies using cybrids have shown that information encoded by mitochondrial DNA in patients contributes to many pathogenic features of sporadic PD. In this paper, we report the generation of fibrillar and vesicular inclusions in a long-term cybrid cell culture model that replicates the essential antigenic and structural features of Lewy bodies in PD brain without the need for exogenous protein expression or inhibition of mitochondrial or proteasomal function. The inclusions generated by PD cybrid cells stained with eosin, thioflavin S, and antibodies to alpha-synuclein, ubiquitin, parkin, synphilin-1, neurofilament, beta-tubulin, the proteasome, nitrotyrosine, and cytochrome c. Future studies of these cybrids will enable us to better understand how Lewy bodies form and what role they play in the pathogenesis of PD.
MeSH term(s)	Aged ; Blotting, Western ; Carrier Proteins/metabolism ; Case-Control Studies ; Cell Line ; Cysteine Endopeptidases/metabolism ; Cytochromes c/metabolism ; DNA, Mitochondrial/genetics ; DNA, Mitochondrial/physiology ; Electron Transport Complex I/metabolism ; Female ; Humans ; Immunohistochemistry ; Lewy Bodies/genetics ; Lewy Bodies/metabolism ; Lewy Bodies/ultrastructure ; Male ; Microscopy, Confocal ; Microscopy, Electron/methods ; Middle Aged ; Multienzyme Complexes/metabolism ; Nerve Tissue Proteins/metabolism ; Neuroblastoma ; Neurofilament Proteins/metabolism ; Neurons/metabolism ; Neurons/pathology ; Parkinson Disease/genetics ; Parkinson Disease/metabolism ; Precipitin Tests ; Proteasome Endopeptidase Complex ; Staining and Labeling ; Synucleins ; Transgenes/physiology ; Tubulin/metabolism ; Tyrosine/analogs & derivatives ; Tyrosine/metabolism ; Ubiquitin/metabolism ; Ubiquitin-Protein Ligases/metabolism ; alpha-Synuclein
Chemical Substances	Carrier Proteins ; DNA, Mitochondrial ; Multienzyme Complexes ; Nerve Tissue Proteins ; Neurofilament Proteins ; SNCA protein, human ; SNCAIP protein, human ; Synucleins ; Tubulin ; Ubiquitin ; alpha-Synuclein ; 3-nitrotyrosine (3604-79-3) ; Tyrosine (42HK56048U) ; Cytochromes c (9007-43-6) ; Electron Transport Complex I (EC 1.6.5.3) ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; parkin protein (EC 2.3.2.27) ; Cysteine Endopeptidases (EC 3.4.22.-) ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
Language	English
Publishing date	2003-12-15
Publishing country	England
Document type	Comparative Study ; Journal Article ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	80158-6
ISSN	1471-4159 ; 0022-3042 ; 1474-1644
ISSN (online)	1471-4159
ISSN	0022-3042 ; 1474-1644
DOI	10.1046/j.1471-4159.2003.02168.x
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ui II Zs.170: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

To top

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito