the effect of neuropeptide y y2 receptor blockade on memory impairment and autophagy in a rat model of alzheimer’s disease

Introduction: while the involvement of neuropeptide y (npy) in learning and memory, as well as the role of the y1 receptor, are well established, the function of the y2 receptor remains a topic of debate. while the involvement of neuropeptide y (npy) in learning and memory, as well as the role of the y1 receptor, are well established, the function of the y2 receptor remains a topic of debate. some studies suggest that npy may also play a role in autophagy. in our investigation, we aimed to explore whether npy and its y2 receptor inhibitor could influence memory modulation or affect beclin-1 expression in a rat model of alzheimer’s disease (ad). npy may also have a role in autophagy, according to some studies.methods: intracerebroventricular (i.c.v) injections of amyloid-beta (aβ1-42, 2µg/µl/ side) were used to establish an animal model of ad. npy (10 ng/µl, 10 µl, i.c.v) was administered 30 minutes before the retrieval. y2 antagonist biie-0246 was injected 15 minutes before npy administration in the targeted groups. biie-0246 was used at three different concentrations (20 nm, 200 nm, and 2 µm). passive avoidance memory and novel object recognition were both evaluated. subsequently, beclin-1 protein expression in the hippocampus was determined using western blot analysis.results: it was found that npy administration improved passive avoidance and cognitive memory in animals treated with aβ. injecting biie-0246 before npy did not reverse the improving effect of npy on passive avoidance and novel object recognition memories. furthermore, compared to sham-operated animals, aβ treatment significantly reduced the hippocampal expression of beclin-1 protein (p≤0.05), and neither npy nor npy y2 receptor inhibitors affected beclin-1. conclusion: in aβ-induced memory impairment, it is thought that npy can improve both aversive and cognitive memory. blocking npy y2 receptors with biie-0246 did not alter npy’s memory-enhancing effect