Fol. Biol. 2021, 67, 49-61
Acylated Ghrelin Administration Inhibits Sleeve Gastrectomy - Induced Hippocampal Oxidative Stress, Apoptosis and Tau-Hyperphosphorylation by Activating the PI3K/Akt Pathway
This study investigated the impact of exogenous replacement therapy with acylated ghrelin (AG) post sleeve gastrectomy (SG) on the memory function in rats. In addition, we investigated the possible underlying mechanisms, including the effects on markers of oxidative stress, tau phosphorylation, and apoptosis. Adult male Wistar rats were divided into four groups (N = 18/group) as follows: sham (control), SG, SG+AG (100 μM), and SG+AG+LY294002 (0.25 μg/100 g). We continued all treatments daily for four weeks post-surgery. SG impaired the spatial, retention, and recognition memories as tested by the Morris water maze test, passive avoidance test, and novel object recognition test, respectively. Also, it enhanced the levels of reactive oxygen species and lipid peroxides, reduced glutathione and protein levels of Bcl-2, and increased the levels of Bax and cleaved caspase-3 in the hippocampus. In addition, SG reduced the hippocampal levels of acetylcholine and brain-derived neurotrophic factor. Concomitantly, it inhibited the hippocampal activity of Akt and increased the activity of glycogen synthase kinase 3β and tau protein phosphorylation. Exogenous administration of acylated ghrelin to rats that had undergone SG prevented memory deficits. Also, it prevented the alteration in the above-mentioned biochemical parameters, an effect that was abolished by co-administration of LY294002 (phosphoinositide 3-kinase inhibitor). In conclusion, AG replacement therapy after SG in rats protects them against memory deficits and hippocampal damage by suppressing tau protein phosphorylation, mediated by activating PI3K/Aktinduced inhibition of glycogen synthase kinase 3β.
Keywords
ghrelin, gastrectomy, Tau, hippocampus, Alzheimer’s disease.
Funding
This research was fully funded by the Deanship of the Scientific Research, King Khalid University, KSA (grant number GRP-99-41).
References
Copyright
This is an open-access article distributed under the terms of the Creative Commons Attribution License.
