A rat model of human FENIB (familial encephalopathy with neuroserpin inclusion bodies)

Katsura Takano, Yasuko Kitao, Reiko Inagi, Takashi Momoi, Tomohiro Matsuyama, Toshio Miyata, Yukio Yoneda, Hiroyuki Iso, David Stern, Osamu Hori, Satoshi Ogawa

Research output: Contribution to journalArticle

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Abstract

FENIB (familial encephalopathy with neuroserpin inclusion bodies) is caused by intracellular accumulation/polymerization of mutant neuroserpins in the endoplasmic reticulum (ER). Transgenic rats overexpressing megsin (Tg meg), a newly identified serine protease inhibitor (serpin), demonstrated intraneuronal periodic-acid Schiff (PAS)-positive inclusions distributed throughout deeper layers of cerebral cortex, CA1 of the hippocampus, and substantia nigra. Hippocampal extracts from Tg meg rats showed increased expression of ER stress proteins, and activation of caspases-12 and -3, associated with decreased neuronal density. Enhanced ER stress was also observed in dopaminergic neurons in the substantia nigra, in parallel with decreased neuronal viability and motor coordination. In each case, PAS-positive inclusions were also positive for megsin. These data suggest that overexpression of megsin results in ER stress, eventuating in the formation of PAS-positive inclusions. Tg meg rats provide a novel model of FENIB, where accumulation of serpins in the ER induces selective dysfunction/loss of specific neuronal populations.

Original languageEnglish (US)
Pages (from-to)1040-1047
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume346
Issue number3
DOIs
StatePublished - Aug 4 2006

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Periodic Acid
Endoplasmic Reticulum Stress
Rats
Substantia Nigra
Endoplasmic Reticulum
Caspase 12
Transgenic Rats
Serpins
Serine Proteinase Inhibitors
Dopaminergic Neurons
Heat-Shock Proteins
Caspase 3
Polymerization
Cerebral Cortex
Hippocampus
Neurons
Population
Chemical activation
Familial encephalopathy with neuroserpin inclusion bodies
neuroserpin

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

A rat model of human FENIB (familial encephalopathy with neuroserpin inclusion bodies). / Takano, Katsura; Kitao, Yasuko; Inagi, Reiko; Momoi, Takashi; Matsuyama, Tomohiro; Miyata, Toshio; Yoneda, Yukio; Iso, Hiroyuki; Stern, David; Hori, Osamu; Ogawa, Satoshi.

In: Biochemical and Biophysical Research Communications, Vol. 346, No. 3, 04.08.2006, p. 1040-1047.

Research output: Contribution to journalArticle

Takano, K, Kitao, Y, Inagi, R, Momoi, T, Matsuyama, T, Miyata, T, Yoneda, Y, Iso, H, Stern, D, Hori, O & Ogawa, S 2006, 'A rat model of human FENIB (familial encephalopathy with neuroserpin inclusion bodies)', Biochemical and Biophysical Research Communications, vol. 346, no. 3, pp. 1040-1047. https://doi.org/10.1016/j.bbrc.2006.06.016
Takano, Katsura ; Kitao, Yasuko ; Inagi, Reiko ; Momoi, Takashi ; Matsuyama, Tomohiro ; Miyata, Toshio ; Yoneda, Yukio ; Iso, Hiroyuki ; Stern, David ; Hori, Osamu ; Ogawa, Satoshi. / A rat model of human FENIB (familial encephalopathy with neuroserpin inclusion bodies). In: Biochemical and Biophysical Research Communications. 2006 ; Vol. 346, No. 3. pp. 1040-1047.
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