Cerebral ischemia combined with beta-amyloid impairs spatial memory in the eight-arm radial maze task in rats.

Abstract

beta-Amyloid (Abeta), a major component of senile plaques in Alzheimer's disease, has been implicated in neuronal cell death, a characteristic feature of this condition. In our previous experiments using primary cultures of hippocampal neurons, Abeta treatment induced neuronal cell death, displaying morphological characteristics of apoptosis that was significantly enhanced by hypoxia. Based on these results, we developed a simple in vivo rat model of Alzheimer's disease using cerebral ischemia, instead of hypoxia, combined with continuous intracerebroventricular administration of Abeta. The combination of cerebral ischemia and Abeta administration, but not either treatment alone, significantly impaired spatial memory in an eight-arm radial maze. A microdialysis study showed that spontaneous release of acetylcholine (ACh) from the dorsal hippocampus had a tendency to decrease in response to Abeta treatment alone or the combination of ischemia and Abeta. High K(+)-evoked increase in ACh release had a tendency to be inhibited by either ischemia or Abeta treatment alone and was significantly inhibited by the combination of both. Moreover, combination of ischemia and Abeta induced apoptosis of pyramidal neurons in the CA1 region of the hippocampus. Donepezil, a drug currently in clinical use for Alzheimer's disease, improved the impairment of spatial memory induced by cerebral ischemia combined with Abeta. These findings suggest that ischemia is an important factor facilitating the symptoms of Alzheimer's disease, and this model may be useful for developing new drugs for the treatment of Alzheimer's disease.

• Authors: Katsunori Iwasaki, Nobuaki Egashira, Izzettin Hatip-Al-Khatib, Yuki Akiyoshi, Takashi Arai, Yuki Takagaki, Takuya Watanabe, Kenichi Mishima, Michihiro Fujiwara
• Journal: Brain research (Brain Res) Vol. 1097 Issue 1 Pg. 216-23 (Jun 30 2006) ISSN: 0006-8993 [Print] Netherlands
• PMID: 16729978 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides

Topics

• Amyloid beta-Peptides (toxicity)
• Animals
• Brain Ischemia (physiopathology)
• Male
• Maze Learning (drug effects, physiology)
• Memory (drug effects, physiology)
• Rats
• Rats, Wistar
• Space Perception (drug effects, physiology)