Anxiolytic Impact of Apelin-13 in a Rat Model of Alzheimer's Disease: Involvement of Glucocorticoid Receptor and FKBP5.

Apelin-13 is known to be one of the predominant neuropeptides with marked protective role in circuits involved in mood disturbances. The most putative hypothesis in pathophysiology of Alzheimer's disease (AD) is Amyloid beta (Aβ) aggregation which interrupt proper function of hypothalamic-pituitary-adrenal (HPA) axis and are associated with anxiety. Here, we assessed the potential anxiolytic effect of Apelin-13 in a rodent cognitive impairment model induced by intrahippocampal Aβ25-35 administration. We evaluated the memory impairment and anxiogenic behavior using shuttle box and Elevated plus maze apparatuses. We also measured the glucocorticoid receptor (GR) and FK506 binding protein 51 (FKBP5) expression as important markers showing the proper feedback mechanism within the HPA axis. Our findings showed that Aβ25-35 administration induced memory impairment and anxiety behaviors. Apelin-13 exerted the anxiolytic effects and provided protection against Aβ25-35-induced passive avoidance memory impairment. Moreover, Apelin-13 caused an increase in GR and a decrease in FKBP5 expression levels in Aβ25-35 treated animals. Taken together, these findings showed the anxiolytic effect of Apelin-13. This effect at least in part, may be mediated through the regulation of GR and FKBP5 expression levels which have a pivotal role in the appropriate negative feedback mechanism within the HPA axis. These data suggest that Apelin-13 might be considered as a potential neuropeptide defense that reduces anxiety along with neuroprotective effect against the Aβ25-35-induced injury.