[Abstract Title]. - Society for Neuroscience

Sciences Research Grants from MHLW, B. Research Grant (principal investigator, collaborator
or consultant and pending grants as well as grants already received).
Poster
293. Startle and Modulation of Startle
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 293.11/SS39
Topic: F.02.d. Cognitive learning and memory systems
Support: HKU7327/03M
Title: Transgenic mice with over-expression of endothelin-1 in endothelial cells have increased
locomotor activity, impaired startle response and mild cognitive deficit
Authors: *X. ZHANG 1 , Y. ZHOU 2 , J. F. CHIU 2 , V. K. L. HUNG 2 , S. M. CHUNG 3 , S. K.
CHUNG 2,4 ;
1 LiKa Shing Fac Med., Hong Kong, Hong Kong; 2 Anat., Li Ka Shing Fac Med., Hong Kong,
China; 3 Physiol., Li Ka Shing Fac. of Medicine, The Univ. of Hong Kong, Hong Kong, China;
4 Res. centre of Heart, Brain, Hormone and Healthy Aging, Li Ka Shing Fac. of Med., Hong
Kong, China
Abstract: Intracerebroventricular administration of low doses of endothelin-1 (ET-1), which is a
potent vasoconstrictor, has been shown to markedly increase the spontaneous locomotor activity
of rats. Previously, we have generated transgenic mice with over-expressing ET-1 in endothelial
cells (TET-1) and showed that these TET-1 mice have hypertension and left ventricular
hypertrophy. Here, we investigated the behavioral changes and cognitive function in adult (5~6
months) and aged (21~23 months) TET-1 mice under normal condition. Adult TET-1 mice
showed significantly increased spontaneous locomotor activity in Figure 8 maze than nontransgenic
mice. The difference was even more obvious in aged mice. On the other hand, TET-1
mice showed significantly lower response to acoustic startle stimulus than non-transgenic mice.
These behavioral changes are similar to those of spontaneously hypertensive rat (SHR), which is
used as an attention-deficit hyperactivity disorder (ADHD) model. In addition, TET-1 mice
showed a trend of cognitive deficit in spatial learning and memory, though not significant. By
two-dimensional electrophoresis, altered antioxidant protein was found in the cerebral cortex of
aged TET-1 mice and immunohistochemistry analysis showed increased heat-shock protein 70
(Hsp-70) expression in the cerebral blood vessels in the brain of aged TET-1 mice compared to
non-transgenic mice. Thus, it is possible that the behavioral changes in aged TET-1 mice might
be the consequence of oxidative stress.