NDLI: The Role of Autophagy Dysregulation in Manganese-Induced Dopaminergic Neurodegeneration

Please wait, while we are loading the content...

The Role of Autophagy Dysregulation in Manganese-Induced Dopaminergic Neurodegeneration

Content Provider	PubMed Central
Author	Zhang, Jianbin Cao, Rui Cai, Tongjian Aschner, Michael Zhao, Fang Yao, Ting Chen, Yaoming Cao, Zipeng Luo, Wenjing Chen, Jingyuan
Abstract	The etiological role of dysregulated autophagy in neurodegenerative diseases has been a subject of intense investigation. While manganese (Mn) is known to cause dopaminergic (DAergic) neurodegeneration, it has yet to be determined whether the dysregulation of autophagy plays a role in Mn-induced neuronal injury. In this study, we investigated the effect of Mn on autophagy in a rat model of manganism, a neurodegenerative disease associated with excessive exposure to Mn. After a single intrastriatal injection of Mn, the short- (4–12 h) and long-term (1–28 days) effect of Mn on DAergic neurons and autophagy were examined. Marked reduction in the number of TH-immunoreactive neurons in the substantia nigra pars compacta (SNpc) as well as TH protein expression, and a significant increase of apomorphine-induced rotations were observed in rats after Mn injection. Manganese also induced the down-regulation of dopamine levels and D1 dopamine receptor expression. In addition, autophagy was dysregulated and inhibited, as evidenced by increased number of abnormal lysosomes, decreased protein expression of Beclin1, and decreased ratio of microtubule-associated protein 1 light chain 3 (LC3) II over LC3 I, concomitant with activated mammalian target of rapamycin (mTOR)/p70 ribosomal protein S6 kinase (p70s6k) signaling. In contrast, in the early phase of Mn exposure, the level of autophagy was not be suppressed but compensatorily activated. Although the morphology of the DAergic neuron was intact in the early phase, Mn caused a significant decrease in TH-immunoreactivity and a significant increase in apomorphine-induced rotations in the presence of wortmannin, an inhibitor of autophagy. Taken together, these results demonstrate, for the first time, that autophagy may play a protective role against Mn-induced neuronal damage, whilst dysregulation of autophagy at later phases may mediate DAergic neurodegeneration.
Related Links	http://dx.doi.org/10.1007/s12640-013-9392-5
Ending Page	490
Page Count	13
Starting Page	478
File Format	PDF
ISSN	10298428
e-ISSN	14763524
Journal	Neurotoxicity Research
Issue Number	4
Volume Number	24
Language	English
Publisher	Springer US
Publisher Date	2013-11-01
Access Restriction	Open
Rights Holder	Springer US
Subject Keyword	Toxicology Neuroscience(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Neuroscience Toxicology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Erratum to: The Role of Autophagy Dysregulation in Manganese-Induced Dopaminergic Neurodegeneration

The role of autophagy dysregulation in manganese-induced dopaminergic neurodegeneration.

The Role of Autophagy Dysregulation in Manganese-Induced Dopaminergic Neurodegeneration

Erratum to: The Role of Autophagy Dysregulation in Manganese-Induced Dopaminergic Neurodegeneration

Microglia enhance manganese chloride-induced dopaminergic neurodegeneration: role of free radical generation

Manganese Potentiates LPS-Induced Heme-Oxygenase 1 in Microglia but not Dopaminergic Cells: Role in Controlling Microglial Hydrogen Peroxide and Inflammatory Cytokine Output

MANGANESE IN EUKARYOTES: THE ROLE OF DMT1

Parkin Protects Against LRRK2 G2019S Mutant-induced Dopaminergic Neurodegeneration in Drosophila

Emerging Neurotoxic Mechanisms in Environmental Factors-Induced Neurodegeneration

The Role of Autophagy Dysregulation in Manganese-Induced Dopaminergic Neurodegeneration

Similar Documents

Erratum to: The Role of Autophagy Dysregulation in Manganese-Induced Dopaminergic Neurodegeneration

The role of autophagy dysregulation in manganese-induced dopaminergic neurodegeneration.

The Role of Autophagy Dysregulation in Manganese-Induced Dopaminergic Neurodegeneration

Erratum to: The Role of Autophagy Dysregulation in Manganese-Induced Dopaminergic Neurodegeneration

Microglia enhance manganese chloride-induced dopaminergic neurodegeneration: role of free radical generation

Manganese Potentiates LPS-Induced Heme-Oxygenase 1 in Microglia but not Dopaminergic Cells: Role in Controlling Microglial Hydrogen Peroxide and Inflammatory Cytokine Output

MANGANESE IN EUKARYOTES: THE ROLE OF DMT1

Parkin Protects Against LRRK2 G2019S Mutant-induced Dopaminergic Neurodegeneration in Drosophila

Emerging Neurotoxic Mechanisms in Environmental Factors-Induced Neurodegeneration

The Role of Autophagy Dysregulation in Manganese-Induced Dopaminergic Neurodegeneration