1. Alpha-synuclein oligomers impair memory through glial cell activation and via Toll-like receptor 2.
- Author
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La Vitola, Pietro, Balducci, Claudia, Cerovic, Milica, Santamaria, Giulia, Brandi, Edoardo, Grandi, Federica, Caldinelli, Laura, Colombo, Laura, Morgese, Maria Grazia, Trabace, Luigia, Pollegioni, Loredano, Albani, Diego, and Forloni, Gianluigi
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FLUORINATION , *FASCIOLA hepatica , *NIELSEN'S form , *TUBERCULARIACEAE , *CYLINDROCLADIUM - Abstract
Alpha-synuclein oligomers (α-synOs) are emerging as crucial factors in the pathogenesis of synucleinopathies. Although the connection between neuroinflammation and α-syn still remains elusive, increasing evidence suggests that extracellular moieties activate glial cells leading to neuronal damage. Using an acute mouse model, we explored whether α-synOs induce memory impairment in association to neuroinflammation, addressing Toll-like receptors 2 and 4 (TLR2 and TLR4) involvement. We found that α-synOs abolished mouse memory establishment in association to hippocampal glial activation. On brain slices α-synOs inhibited long-term potentiation. Indomethacin and Ibuprofen prevented the α-synOs-mediated detrimental actions. Furthermore, while the TLR2 functional inhibitor antibody prevented the memory deficit, oligomers induced memory deficits in the TLR4 knockout mice. In conclusion, solely α-synOs induce memory impairment likely inhibiting synaptic plasticity. α-synOs lead to hippocampal gliosis that is involved in memory impairment. Moreover, while the oligomer-mediated detrimental actions are TLR2 dependent, the involvement of TLR4 was ruled out. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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