Effects of ghrelin knock-out and age on spatial learning, neurogenesis, and spine density in the dentate gryus of rats

S.P. Cahill, T. Hatchard, A. Abizaid, M.R. Holahan

Location: Halls B-H
Presentation Time: Tuesday, Nov 12, 2013, 9:00 AM – 10:00 AM
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Work has revealed a high density of ghrelin receptors distributed throughout the hippocampal CA1 and dentate gyrus (DG) subregions. Binding of ghrelin to these receptors is associated with elevated dendritic spine density in the CA1 region and increased neurogenesis in the DG. These ghrelin-induced neuronal changes are paralleled by enhanced learning and memory on a variety of hippocampal and non-hippocampal dependent tasks such as the water maze after administration of ghrelin. While elevations in ghrelin appear to have consistent enhancing effects on spatial learning and hippocampal connectivity, the effect of decreasing ghrelin, either through antagonists or knock-out, has been less clear.

In the present experiment, we investigated how knock-out of the ghrelin receptor impacted spatial learning and memory as well as how ghrelin knock-out affected neurogenesis and spine density in the DG of the hippocampus. In this experiment, we used genetically modified rats, as opposed to mice, where previous work has been concentrated. To this end, we used both wild type (WT) and ghrelin receptor deficient (KO) Fawn Hooded Hypertensive (FHH) rats and tested them on two water maze (WM) tasks as well as an 8 arm radial arm maze task (8-RAM). To examine neurogenesis, we used double cortin immunohistochemistry to evaluate the number of immature neurons in the DG. Golgi- Cox impregnation was used to evaluate spine density in the DG. As aging is associated with decreased levels of ghrelin and has been shown to contribute to decreased neurogenesis and lead to impairments in learning and memory, we also tested theses WT and KO rats when they were aged.

Results showed there was no difference in acquisition on the water maze task between groups. Age was found to decrease learning and memory on the 8-RAM task, and this effect was exasperated in the aged KO rats. Both spine density and neurogenesis were decreased in the aged groups, with young WT rats having the highest spine density and levels of neurogenesis. Overall, results demonstrate a lack of an effect of ghrelin KO on water maze performance. An effect of ghrelin KO does appear to produce deficits in the performance of the 8-RAM food-motivated task, but only in aged rats. While in aging, there was an overall decrease in immature neurons and spine density, decreased neurogenesis and spine density was also evident in the young ghrelin KO rats. Data suggest that ghrelin KO disrupts hippocampal structural integrity that may manifest in non-spatial-related aspects of hippocampal function.