Effects of ghrelin receptor knockout and age on spatial learning, neurogenesis, and spine density in the dentate gyrus of rats

Although ghrelin is best known for its effects on feeding and weight regulation, recent research has indicated that its effects are much more diverse. The receptor for ghrelin has been found throughout several regions of the brain, including the hippocampus. Work has revealed that binding of ghrelin to ghrelin receptors in the hippocampus is associated with elevated dendritic spine density in the CA 1 and increased neurogenesis in the DG. These ghrelin-induced neuronal changes are paralleled by enhanced learning and memory performance on a variety of hippocampal and nonhippocampal dependent tasks in mice. In the present experiment, we used ghrelin receptor deficient knock out (KO) and wild type (WT) Fawn Hooded Hypertensive rats, as opposed to mice which previous work has been concentrated. We investigated how the knock out of the ghrelin receptor impacted spatial learning and memory and neurogenesis and spine density in the DG of the hippocampus. As ageing is associated with decreased levels of ghrelin and contributes to decreased neurogenesis and learning and memory impairments, we incorporated an aged KO and WT group. Overall, our results demonstrated a lack of an effect of ghrelin receptor KO on water maze performance. Ghrelin receptor KO, however, did appear to produce deficits in performance on the radial arm maze food-motivated task, but only in aged rats. Both groups of aged rats, as weil as the young ghrelin KO rats exhibited attenuated levels of neurogenesis and spine density. Overall, our data suggest that ghrelin KO disrupts hippocampal structural integrity that may manifest in non-spatial-related aspects of hippocampal function.