| Autor: |
Teresa Torre-Muruzabal, Jens Devoght, Chris Van den Haute, Bert Brône, Anke Van der Perren, Veerle Baekelandt |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
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| Zdroj: |
Acta Neuropathologica Communications, Vol 7, Iss 1, Pp 1-13 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
2051-5960 |
| DOI: |
10.1186/s40478-019-0814-3 |
| Popis: |
Abstract Aggregation of alpha-synuclein (α-SYN) is the pathological hallmark of several diseases named synucleinopathies, including Parkinson’s disease (PD), which is the most common neurodegenerative motor disorder. Alpha-SYN has been linked to synaptic function both in physiological and pathological conditions. However, the exact link between neuronal activity, α-SYN toxicity and disease progression in PD is not clear. In this study, we aimed to investigate the effect of chronic neuromodulation in an α-SYN-based rat model for PD using chemogenetics. To do this, we expressed excitatory Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) combined with mutant A53T α-SYN, using two different recombinant adeno-associated viral (rAAV) vectors (serotypes 2/7 and 2/8) in rat substantia nigra (SN) and investigated the effect on motor behavior, synapses and neuropathology. We found that chronic neuromodulation aggravates motor deficits induced by α-SYN, without altering dopaminergic neurodegeneration. In addition, neuronal activation led to changes in post-translational modification and subcellular localization of α-SYN, linking neuronal activity to the pathophysiological role of α-SYN in PD. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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