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.
| Original language | English |
|---|---|
| Pages (from-to) | 591-602 |
| Number of pages | 12 |
| Journal | Brain, Behavior, and Immunity |
| Volume | 69 |
| DOIs | |
| Publication status | Published - Mar 2018 |
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Alpha-synuclein oligomers impair memory through glial cell activation and via Toll-like receptor 2. / 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; Forloni, Gianluigi.
In: Brain, Behavior, and Immunity, Vol. 69, 03.2018, p. 591-602.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Alpha-synuclein oligomers impair memory through glial cell activation and via Toll-like receptor 2
AU - La Vitola, Pietro
AU - Balducci, Claudia
AU - Cerovic, Milica
AU - Santamaria, Giulia
AU - Brandi, Edoardo
AU - Grandi, Federica
AU - Caldinelli, Laura
AU - Colombo, Laura
AU - Morgese, Maria Grazia
AU - Trabace, Luigia
AU - Pollegioni, Loredano
AU - Albani, Diego
AU - Forloni, Gianluigi
N1 - Copyright © 2018 Elsevier Inc. All rights reserved.
PY - 2018/3
Y1 - 2018/3
N2 - 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.
AB - 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.
U2 - 10.1016/j.bbi.2018.02.012
DO - 10.1016/j.bbi.2018.02.012
M3 - Article
C2 - 29458199
VL - 69
SP - 591
EP - 602
JO - Brain, Behavior, and Immunity
JF - Brain, Behavior, and Immunity
SN - 0889-1591
ER -