Cortical neuronal hypertrophy and mTOR pathway activation in CAN regions in SUDEP

SUDEP 中 CAN 区域的皮质神经元肥大和 mTOR 通路激活

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作者:Smriti Patodia, Yau Mun Lim, Freda Chung, Irene Stylianou, Hanaa El Hachami, Maria Thom

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.

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.

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