Miki, Yasuo;
Tanji, Kunikazu;
Shinnai, Kana;
Tanaka, Makoto;
Altay, Firat;
Foti, Sandrine C;
Strand, Catherine;
... Wakabayashi, Koichi; + view all
(2022)
Pathological substrate of memory impairment in multiple system atrophy.
Neuropathology and Applied Neurobiology
, 48
(7)
, Article e12844. 10.1111/nan.12844.
Preview |
Text
Neuropathology Appl Neurobio - 2022 - Miki - Pathological substrate of memory impairment in multiple system atrophy.pdf - Accepted Version Download (2MB) | Preview |
Abstract
AIMS AND METHODS: Synaptic dysfunction in Parkinson's disease is caused by propagation of pathogenic α-synuclein between neurons. Previously, in multiple system atrophy (MSA), pathologically characterised by ectopic deposition of abnormal α-synuclein predominantly in oligodendrocytes, we demonstrated that the occurrence of memory impairment was associated with the number of α-synuclein-positive neuronal cytoplasmic inclusions (NCIs) in the hippocampus. Here, using a mouse model of adult-onset MSA and human cases (MSA, N = 25; Parkinson's disease, N = 3, Alzheimer's disease, N = 2; normal controls, N = 11), we aimed to investigate how abnormal α-synuclein in the hippocampus can lead to memory impairment. RESULTS: In the MSA model, inducible human α-synuclein was first expressed in oligodendrocytes, and subsequently accumulated in the cytoplasm of excitatory hippocampal neurons (NCI-like structures) and their presynaptic nerve terminals with the development of memory impairment. α-Synuclein oligomers increased simultaneously in the hippocampus of the MSA model. Hippocampal dendritic spines also decreased in number, followed by suppression of long-term potentiation. Consistent with these findings obtained in the MSA model, post-mortem analysis of human MSA brain tissues showed that cases of MSA with memory impairment developed more NCIs in excitatory hippocampal neurons along with α-synuclein oligomers than those without. CONCLUSIONS: our results provide new insights into the role of α-synuclein oligomers as a possible pathological cause of memory impairment in MSA.
| Type: | Article |
|---|---|
| Title: | Pathological substrate of memory impairment in multiple system atrophy |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1111/nan.12844 |
| Publisher version: | https://doi.org/10.1111/nan.12844 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | memory impairment, multiple system atrophy, neuronal cytoplasmic inclusion, α-synuclein, α-synuclein oligomer |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10153082 |
Archive Staff Only
 |
View Item |
