Intracerebroventricular (i.c.v.) injection of angiotensin IV (Ang IV) enhances the acquisition of hippocampus dependent spatial memory tasks. It has been hypothesized that Ang IV exerts its effects, independently of AT1 or AT2 receptors, through interaction with a high affinity binding site, denominated as 'AT4 receptor', which was purified and identified as insulin-regulated aminopeptidase (IRAP). This enzyme shows a high expression in the hippocampus, where it shows intracellular co-localization with the insulin-responsive glucose transporter GLUT4 in pyramidal cells. Ang IV may, by binding to IRAP, facilitate the uptake of glucose in hippocampal neurons. Alternatively, Ang IV has been demonstrated to enhance cerebral blood flow and may as such enhance the transport of glucose towards the hippocampus. The purpose of this study is to examine the effect of a single i.c.v. injection of Ang IV on spatial working memory and a possible role of modulation of hippocampal glucose levels in the cognitive effects of Ang IV. Spatial working memory was tested in a plus maze spontaneous alternation task and hippocampal glucose levels were simultaneously monitored using the microdialysis technique. Rats receiving a single i.c.v. injection of Ang IV (1 nmol) had significantly higher alternation scores without an effect on the number of arm visits. This indicates that the Ang IV treated rats had a higher capability to remember previously visited arms, but motoric or motivational factors did not contribute to this effect. In control rats, a drop in hippocampal glucose levels was observed when the rats were placed in the plus maze but no change was observed when the rats were placed in a novel control box. However, Ang IV did not affect hippocampal glucose levels compared to control. These data suggest that facilitation of hippocampal glucose uptake is not involved in the effects of Ang IV on spatial working memory.
|Name||IBRO 7th World Congress on Neuroscience, Melbourne, Australia, 12-17 July 2007|
|Conference||Finds and Results from the Swedish Cyprus Expedition: A Gender Perspective at the Medelhavsmuseet|
|Period||21/09/09 → 25/09/09|
- Angiotensin IV
- spatial working memory