Taketoshi Ishii, Yasuko Shimpo, Yuzo Matsuoka and Kiyoshi Kinoshita
Pharmacology Department, Discovery Research Laboratory, Tanabe Seiyaku
Co., Ltd.,
Kawagishi 2ﾐ2ﾐ50, Todaﾐshi, Saitama 335ﾐ8505, Japan
Abstract: Although exogenously administered acetylﾐlﾐcarnitine
(ALCAR, (2ﾐacetoxyﾐ3ﾐcarboxypropyl)ﾐtrimethylammonium) and lﾐcarnitine
(LC, (3ﾐcarboxyﾐ2ﾐhydroxypropyl)ﾐtrimethylammonium) prevent brain damage
in several ischemic models, the protective mechanism of these compounds
remains unclear. Here, we evaluated the effect of ALCAR and LC in primary
cultured neurons from the cerebral cortex, striatum and thalamus of 18ﾐdayﾐold
rat embryos. Deprivation of the serum from cultured medium for 3ﾊdays reduced
the number of viable cells and mitochondrial activity and induced cell death
with characteristics of apoptosis such as DNA fragmentation, nuclear condensation
and histoneﾐDNA release into the cytoplasm. ALCAR (1-100ﾊmM)
and LC (1-100ﾊmM) promoted neuronal survival
and mitochondrial activity in a concentrationﾐdependent manner. Moreover,
these compounds attenuated DNA fragmentation and nuclear condensation in
cultured neurons and significantly decreased histoneﾐDNA release into the
cytoplasm. These results indicate that antiﾐapoptotic actions of ALCAR and
LC contribute to their neuroprotective effect.
Keywords: Primary cultured neuron, Apoptosis, Neuroprotective, Acetylﾐlﾐcarnitine,
lﾐCarnitine