Patodia, Smriti;
Lim, Yau Mun;
Chung, Freda;
Stylianou, Irene;
El Hachami, Hanaa;
Thom, Maria;
(2022)
Cortical neuronal hypertrophy and MTOR pathway activation in CAN regions in SUDEP.
Epilepsia
, 63
(9)
pp. 2427-2438.
10.1111/epi.17335.
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Abstract
Objectives: Dysfunctional connectivity and preexisting structural abnormalities of central autonomic network (CAN) regions have been shown on magnetic resonance imaging (MRI) in sudden unexpected death in epilepsy (SUDEP) and may be mechanistically relevant. In a previous postmortem study we reported increased microglia in CAN regions, including the superior temporal gyrus (STG) in SUDEP. In this current study we investigated mammalian target of rapamycin (mTOR) pathway activation and neuronal c-Fos activation in CAN regions in SUDEP compared to control groups. Methods: In a series of 59 postmortem cases (SUDEP, n = 26; epilepsy controls [EPCs], n = 14; and nonepilepsy controls [NECs], n = 19), we quantified pS6-240/4, pS6-235/6 (markers of mTOR activation) and c-Fos neuronal densities and labeling index in the STG, anterior cingulate, insula, frontobasal, and pulvinar regions using immunohistochemistry with whole-slide automated image analysis. Results: Significantly more pS6-positive neurons were present in the STG in cases with a history of recent seizures prior to death and also in SUDEP compared to other cause of death groups. No differences were noted for c-Fos neuronal labeling in any region between cause of death groups. Cortical neuronal hypertrophy in the STG was observed in some SUDEP cases and associated with pS6-240/4 expression. pS6-235/6 highlighted neuronal intranuclear inclusions, mainly in SUDEP cases and in the STG region. Significance: Neuronal labeling for pS6 in the STG correlated with both seizure activity in the period prior to death and SUDEP. Further investigations are required to explore the significance of this region in terms of autonomic network dysfunction that may increase the vulnerability for SUDEP.
| Type: | Article |
|---|---|
| Title: | Cortical neuronal hypertrophy and MTOR pathway activation in CAN regions in SUDEP |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1111/epi.17335 |
| Publisher version: | https://doi.org/10.1111/epi.17335 |
| Language: | English |
| Additional information: | © 2022 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
| Keywords: | C-Fos, mTOR, SUDEP, superior temporal gyrus |
| 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 > Clinical and Experimental Epilepsy 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-pp.ucl.ac.uk/id/eprint/10150459 |
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