Premium
Brefeldin A‐induced neurotoxicity in cultured spinal cord neurons
Author(s) -
Kikuchi Seiji,
Shinpo Kazuyoshi,
Tsuji Sachiko,
Yabe Ichiro,
Niino Masaaki,
Tashiro Kunio
Publication year - 2002
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.10479
Subject(s) - brefeldin a , neurotoxicity , spinal cord , golgi apparatus , amyotrophic lateral sclerosis , apoptosis , neuroprotection , microbiology and biotechnology , in vitro , biology , neuroscience , chemistry , pharmacology , medicine , pathology , disease , toxicity , biochemistry , endoplasmic reticulum
Brefeldin A (BFA) is a fungus metabolite that is known to cause the disassembly of the Golgi complex and apoptosis in exposed cells, both of which have been suggested as playing roles in the pathogenesis of neurodegenerative diseases, particularly amyotrophic lateral sclerosis (ALS). This study showed that BFA caused neurotoxicity and apoptotic nuclear changes in cultured spinal neurons of rat spinal cord in a dose‐ and time‐dependent manner. The spinal motor neurons were more vulnerable to this neurotoxicity. The cultured spinal neurons showed irreversible disassembly of the Golgi apparatus as early as 1 hr after exposure to BFA. BFA induced the expression and activation of caspase‐12 beginning 8 hr after exposure. The level of the cleaved form of caspase‐3 had increased 12 hr after the addition of BFA. Free radical generation and loss of mitochondrial membrane potential were observed in the later stages of neurotoxicity caused by BFA. Collectively, our data suggests that BFA is an excellent agent for reproducing the pathophysiological features of ALS. This in vitro model may be useful in attempts to study the mechanisms of this neurodegenerative disease and to examine therapeutic potentials. © 2002 Wiley‐Liss, Inc.