| First Author | Valera E | Year | 2014 |
| Journal | Glia | Volume | 62 |
| Issue | 2 | Pages | 317-37 |
| PubMed ID | 24310907 | Mgi Jnum | J:207162 |
| Mgi Id | MGI:5554615 | Doi | 10.1002/glia.22610 |
| Citation | Valera E, et al. (2014) Antidepressants reduce neuroinflammatory responses and astroglial alpha-synuclein accumulation in a transgenic mouse model of multiple system atrophy. Glia 62(2):317-37 |
| abstractText | Multiple system atrophy (MSA) is a neurodegenerative disease characterized by the pathological accumulation of alpha-synuclein (alpha-syn) within oligodendroglial cells. This accumulation is accompanied by neuroinflammation with astrogliosis and microgliosis, that leads to neuronal death and subsequent parkinsonism and dysautonomia. Antidepressants have been explored as neuroprotective agents as they normalize neurotrophic factor levels, increase neurogenesis and reduce neurodegeneration, but their anti-inflammatory properties have not been fully characterized. We analyzed the anti-inflammatory profiles of three different antidepressants (fluoxetine, olanzapine and amitriptyline) in the MBP1-halpha-syn transgenic (tg) mouse model of MSA. We observed that antidepressant treatment decreased the number of alpha-syn-positive cells in the basal ganglia of 11-month-old tg animals. This reduction was accompanied with a similar decrease in the colocalization of alpha-syn with astrocyte markers in this brain structure. Consistent with these results, antidepressants reduced astrogliosis in the hippocampus and basal ganglia of the MBP1-halpha-syn tg mice, and modulated the expression levels of key cytokines that were dysregulated in the tg mouse model, such as IL-1beta. In vitro experiments in the astroglial cell line C6 confirmed that antidepressants inhibited NF-kappaB translocation to the nucleus and reduced IL-1beta protein levels. We conclude that the anti-inflammatory properties of antidepressants in the MBP1-halpha-syn tg mouse model of MSA might be related to their ability to inhibit alpha-syn propagation from oligodendrocytes to astroglia and to regulate transcription factors involved in cytokine expression. Our results suggest that antidepressants might be of interest as anti-inflammatory and alpha-syn-reducing agents for MSA and other alpha-synucleinopathies. |
