- Title
- Reconsidering the role of glial cells in chronic stress-induced dopaminergic neurons loss within the substantia nigra? Friend or foe?
- Creator
- Ong, Lin Kooi; Zhao, Zidan; Kluge, Murielle; TeBay, Clifford; Zalewska, Katarzyna; Dickson, Phillip W.; Johnson, Sarah J.; Nilsson, Michael; Walker, Frederick R.
- Relation
- Brain, Behavior, and Immunity Vol. 60, Issue February, p. 117-125
- Publisher Link
- http://dx.doi.org/10.1016/j.bbi.2016.10.001
- Publisher
- Academic Press
- Resource Type
- journal article
- Date
- 2017
- Description
- Exposure to psychological stress is known to seriously disrupt the operation of the substantia nigra (SN) and may in fact initiate the loss of dopaminergic neurons within the SN. In this study, we aimed to investigate how chronic stress modified the SN in adult male mice. Using a paradigm of repeated restraint stress (an average of 20 h per week for 6 weeks), we examined changes within the SN using western blotting and immunohistochemistry. We demonstrated that chronic stress was associated with a clear loss of dopaminergic neurons within the SN. The loss of dopaminergic neurons was accompanied by higher levels of oxidative stress damage, indexed by levels of protein carbonylation and strong suppression of both microglial and astrocytic responses. In addition, we demonstrated for the first time, that chronic stress alone enhanced the aggregation of a-synuclein into the insoluble protein fraction. These results indicate that chronic stress triggered loss of dopaminergic neurons by increasing oxidative stress, suppressing glial neuroprotective functions and enhancing the aggregation of the neurotoxic protein, a-synuclein. Collectively, these results reinforce the negative effects of chronic stress on the viability of dopaminergic cells within the SN.
- Subject
- α-Synuclein; astrocytes; chronic stress; microglia; neurodegeneration; oxidative stress; substantia nigra
- Identifier
- http://hdl.handle.net/1959.13/1390588
- Identifier
- uon:33093
- Identifier
- ISSN:0889-1591
- Rights
- © 2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/.
- Language
- eng
- Full Text
- Reviewed
- Hits: 6033
- Visitors: 5394
- Downloads: 374
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT02 | Author final version | 1 MB | Adobe Acrobat PDF | View Details Download |