Effects of adropin on learning and memory in rats tested in the Morris water maze

Abstract

Adropin is a secreted peptide, which is composed of 43 amino acids and shows an effective role in regulating energy metabolism and insulin resistance. Motor coordination and locomotor activity were improved by adropin in the cerebellum. However, it is not known whether adropin administration has an effect on spatial learning and memory. In this study, we investigated the effect of adropin on spatial learning and memory and characterized the biochemical properties of adropin in the hippocampus. Thirty male Sprague–Dawley rats were randomly divided into two groups as control and adropin groups. The control group received 0.9% NaCl intracerebroventricular for 6 days, while the adropin groups received 1 nmol of adropin dissolved in 0.9% NaCl (for 6 days). The Morris water maze, Y maze, and object location recognition tests were performed to evaluate learning and memory. Also, the locomotor activity tests were measured to assess the motor function. The expression of Akt, phospho‐Akt, CREB, phospho‐CREB, Erk1/2, phospho‐Erk1/2, glycogen synthase kinase 3 β (GSK3β), phospho‐GSK3β, brain‐derived neurotrophic factor (BDNF), and N‐methyl‐d‐aspartate receptor NR2B subunit were determined in the hippocampal tissues by using western blot. Behavior tests showed that adropin significantly increase spatial memory performance. Meanwhile, the western blot analyses revealed that the phosphorylated form of the Akt and CREB were enhanced with adropin administration in the hippocampus. Also, the expression of BDNF showed an enhancement in adropin group in comparison to the control group. In conclusion, we have shown for the first time that adropin exerts its enhancing effect on spatial memory capacity through Akt/CREB/BDNF signaling pathways.

Potential of food-derived bioactive peptides in alleviation and prevention of Alzheimer's disease

“…131,132 Ozkan et al (2022) comprehensively explored the neuroprotective effect of adropin participating in the Akt/CREB/brain-derived neurotrophic factor (BDNF) signaling pathway using the Morris water maze, Y-maze, and object location recognition tests. 133 Wang et al (2013) found that intraventricular injection of the neuroprotective peptide humanin in mice could reduce Beclin-1-positive cells in hippocampal CA1, CA3, and DG by immunofluorescence detection. 134 Considering all of this evidence, it can be seen that the combination of chemical analysis, molecular docking, cells, and animal models has become a common method to evaluate the efficacy of food-derived peptides in the treatment of AD.…”

“…131,132 Ozkan et al (2022) comprehensively explored the neuroprotective effect of adropin participating in the Akt/CREB/brain-derived neurotrophic factor (BDNF) signaling pathway using the Morris water maze, Y-maze, and object location recognition tests. 133 Wang et al (2013) found that intraventricular injection of the neuroprotective peptide humanin in mice could reduce Beclin-1-positive cells in hippocampal CA1, CA3, and DG by immunofluorescence detection. 134…”

Sleeve gastrectomy attenuated diabetes-related cognitive decline in diabetic rats

“…MWM test was used to measure hippocampus-dependent cognitive function as previously described ( 25 ). All behavioral tests were performed during the active period of the photoperiod.…”

Adropin’s Role in Energy Homeostasis and Metabolic Disorders

“…In contrast, a study utilizing insulin-resistant hepatocytes showed that adropin could reduce glucose production in the liver. Adropin treatment downregulated the transcription of hepatic gluconeogenesis genes by inhibiting the binding site of transcription factors forkhead box protein O1(FoxO1) and cAMP-response element binding protein (CREB), along with their co-activators, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) and CREB regulated transcription coactivator 2 (CRTC2), respectively, to the promoter of gluconeogenesis genes [ 47 , 66 ]. FoxO1-PGC1α and CREB-CRTC2 complex promoter binding is required to activate the transcription of genes that are involved in hepatic glucose production [ 67 , 68 ].…”

“…Interestingly, this effect of adropin was not observed in insulin-sensitive hepatocytes [ 66 ]. This research team earlier reported that a downregulation in adropin expression led to systemic insulin resistance in mice that were introduced to a high-fat diet for a long period [ 16 ].…”