Open AccessSuppressed Expression of Autophagosomal Protein LC3 in Cortical Tubers of Tuberous Sclerosis Complex
Author(s) -
Miyahara Hiroaki,
Natsumeda Manabu,
Shiga Atsushi,
Aoki Hiroshi,
Toyoshima Yasuko,
Zheng Yingjun,
Takeuchi Ryoko,
Murakami Hiroatsu,
Masuda Hiroshi,
Kameyama Shigeki,
Izumi Tatsuro,
Fujii Yukihiko,
Takahashi Hitoshi,
Kakita Akiyoshi
Publication year - 2013
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/j.1750-3639.2012.00634.x
Subject(s) - tuberous sclerosis , autophagy , pi3k/akt/mtor pathway , microbiology and biotechnology , tsc2 , biology , immunoelectron microscopy , tsc1 , cytoplasm , cancer research , pathology , immunohistochemistry , signal transduction , medicine , immunology , biochemistry , apoptosis
Tuberous sclerosis complex ( TSC ) is characterized by benign tumors and hamartomas, including cortical tubers. Hamartin and tuberin, encoded by the TSC 1 and 2 genes, respectively, constitute a functional complex that negatively regulates the mammalian target of rapamycin ( mTOR ) signaling pathway, eventually promoting the induction of autophagy. In the present study, we assessed the induction of autophagy in cortical tubers surgically removed from seven patients with TSC in comparison with five controls of cortical tissue taken from non‐ TSC patients with epilepsy. Immunoblotting demonstrated a marked reduction of LC3B ‐ I and LC3B ‐ II in tubers relative to the controls. In tubers, strong, diffuse and dot‐like immunoreactivity ( IR ) for LC3B was observed in dysmorphic neurons and balloon cells, but LC3B ‐ IR in other neurons with normal morphology was significantly weaker than that in neurons in the controls. Immunoelectron microscopy revealed diffuse distribution of LC3B ‐ IR within the cytoplasm of balloon cells. The dot‐like pattern may correspond to abnormal aggregation bodies involving LC3 . In an autopsy patient with TSC , we observed that LC3B ‐ IR in neurons located outside of the tubers was preserved. Thus, autophagy is suppressed in tubers presumably through the mTOR pathway, and possibly a pathological autophagy reaction occurs in the dysmorphic neurons and balloon cells.