Adenosine monophosphate-activated protein kinase activation mediates the leptin-induced attenuation of cognitive impairment in a streptozotocin-induced rat model

Zhu,Bin; Jiang,Ri‑Yue; Yang,Chun; Liu,Ning

doi:10.3892/etm.2015.2317

Adenosine monophosphate-activated protein kinase activation mediates the leptin-induced attenuation of cognitive impairment in a streptozotocin-induced rat model

Authors:
- Bin Zhu
- Ri‑Yue Jiang
- Chun Yang
- Ning Liu
View Affiliations

Affiliations: Department of Critical Care Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, P.R. China, Department of Radiotherapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, P.R. China, Department of Anesthesiology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, P.R. China
Published online on: February 25, 2015 https://doi.org/10.3892/etm.2015.2317
Pages: 1998-2002

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Several lines of evidence have shown that the incidence of cognitive impairment in diabetic patients is significantly higher than that in healthy individuals, but the exact pathogenesis has not been fully elucidated. Furthermore, it has been suggested that leptin may have a therapeutic effect in cognitive dysfunction. The aim of the present study was to observe the effect of leptin on cognitive dysfunction in streptozotocin (STZ)‑induced diabetic rats, and to explore whether adenosine monophosphate‑activated protein kinase (AMPK) activation was involved in any potential therapeutic effect of leptin. Compared with control rats, STZ rats exhibited decreased levels of AMPK and a poor performance in the Morris water maze, while these changes were reversed by leptin. Furthermore, Compound C, an AMPK antagonist, significantly attenuated the leptin‑induced cognitive function improvement in the STZ rats. In conclusion, these results suggest that AMPK activation may play a critical role in the leptin‑induced attenuation of STZ‑induced cognitive impairment.

View Figures

View References

1	Arvanitakis Z, Wilson RS, Bienias JL, Evans DA and Bennett DA: Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function. Arch Neurol. 61:661–666. 2004. View Article : Google Scholar : PubMed/NCBI
2	Engelgau MM, Geiss LS, Saaddine JB, et al: The evolving diabetes burden in the United States. Ann Intern Med. 140:945–950. 2004. View Article : Google Scholar : PubMed/NCBI
3	van den Berg E, Reijmer YD, de Bresser J, et al: Utrecht Diabetic Encephalopathy Study Group: A 4 year follow-up study of cognitive functioning in patients with type 2 diabetes mellitus. Diabetologia. 53:58–65. 2010. View Article : Google Scholar : PubMed/NCBI
4	Huber JD: Diabetes, cognitive function, and the blood-brain barrier. Curr Pharm Des. 14:1594–1600. 2008. View Article : Google Scholar : PubMed/NCBI
5	Strachan MW, Price JF and Frier BM: Diabetes, cognitive impairment, and dementia. BMJ. 336:62008. View Article : Google Scholar : PubMed/NCBI
6	Peila R, Rodriguez BL and Launer LJ: Honolulu-Asia Aging Study: Type 2 diabetes, APOE gene and the risk for dementia and related pathologies: The Honolulu-Asia Aging Study. Diabetes. 51:1256–1262. 2002. View Article : Google Scholar : PubMed/NCBI
7	Breteler MM: Vascular risk factors for Alzheimer's disease: An epidemiologic perspective. Neurobiol Aging. 21:153–160. 2000. View Article : Google Scholar : PubMed/NCBI
8	Gispen WH and Biessels GJ: Cognition and synaptic plasticity in diabetes mellitus. Trends Neurosci. 23:542–549. 2000. View Article : Google Scholar : PubMed/NCBI
9	Anarkooli Jafari I, Sankian M, Ahmadpour S, Varasteh AR and Haghir H: Evaluation of Bcl-2 family gene expression and Caspase-3 activity in hippocampus STZ-induced diabetic rats. Exp Diabetes Res. 2008:6384672008.PubMed/NCBI
10	Revsin Y, Rekers NV, Louwe MC, et al: Glucocorticoid receptor blockade normalizes hippocampal alterations and cognitive impairment in streptozotocin-induced type 1 diabetes mice. Neuropsychopharmacology. 34:747–758. 2009. View Article : Google Scholar : PubMed/NCBI
11	Yang C, Zhu B, Ding J and Wang ZG: Isoflurane anesthesia aggravates cognitive impairment in streptozotocin-induced diabetic rats. Int J Clin Exp Med. 7:903–910. 2014.PubMed/NCBI
12	Denver RJ, Bonett RM and Boorse GC: Evolution of leptin structure and function. Neuroendocrinology. 94:21–38. 2011. View Article : Google Scholar : PubMed/NCBI
13	Singh A, Wirtz M, Parker N, et al: Leptin-mediated changes in hepatic mitochondrial metabolism, structure and protein levels. Proc Natl Acad Sci USA. 106:13100–13105. 2009. View Article : Google Scholar : PubMed/NCBI
14	Harvey J, Shanley LJ, O'Malley D and Irving AJ: Leptin: A potential cognitive enhancer? Biochem Soc Trans. 33:1029–1032. 2005. View Article : Google Scholar : PubMed/NCBI
15	Minokoshi Y, Kim YB, Peroni OD, et al: Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature. 415:339–343. 2002. View Article : Google Scholar : PubMed/NCBI
16	Minokoshi Y and Kahn BB: Role of AMP-activated protein kinase in leptin-induced fatty acid oxidation in muscle. Biochem Soc Trans. 31:196–201. 2003. View Article : Google Scholar : PubMed/NCBI
17	Yi X, Cao S, Chang B, et al: Effects of acute exercise and chronic exercise on the liver leptin-AMPK-ACC signaling pathway in rats with type 2 diabetes. J Diabetes Res. 2013:9464322013. View Article : Google Scholar : PubMed/NCBI
18	Namkoong C, Kim MS, Jang PG, et al: Enhanced hypothalamic AMP-activated protein kinase activity contributes to hyperphagia in diabetic rats. Diabetes. 54:63–68. 2005. View Article : Google Scholar : PubMed/NCBI
19	Sharma B and Singh N: Attenuation of vascular dementia by sodium butyrate in streptozotocin diabetic rats. Psychopharmacology (Berl). 215:677–687. 2011. View Article : Google Scholar : PubMed/NCBI
20	Zhu X, Raina AK, Lee HG, Casadesus G, Smith MA and Perry G: Oxidative stress signalling in Alzheimer's disease. Brain Res. 1000:32–39. 2004. View Article : Google Scholar : PubMed/NCBI
21	Davis C, Mudd J and Hawkins M: Neuroprotective effects of leptin in the context of obesity and metabolic disorders. Neurobiol Dis. 72:61–71. 2014. View Article : Google Scholar : PubMed/NCBI
22	Salminen A, Kaarniranta K, Haapasalo A, Soininen H and Hiltunen M: AMP-activated protein kinase: A potential player in Alzheimer's disease. J Neurochem. 118:460–474. 2011. View Article : Google Scholar : PubMed/NCBI
23	Cai Z, Yan LJ, Li K, Quazi SH and Zhao B: Roles of AMP-activated protein kinase in Alzheimer's disease. Neuromolecular Med. 14:1–14. 2012. View Article : Google Scholar : PubMed/NCBI
24	Greco SJ, Sarkar S, Johnston JM and Tezapsidis N: Leptin regulates tau phosphorylation and amyloid through AMPK in neuronal cells. Biochem Biophys Res Commun. 380:98–104. 2009. View Article : Google Scholar : PubMed/NCBI
25	Greco SJ, Hamzelou A, Johnston JM, Smith MA, Ashford JW and Tezapsidis N: Leptin boosts cellular metabolism by activating AMPK and the sirtuins to reduce tau phosphorylation and β-amyloid in neurons. Biochem Biophys Res Commun. 414:170–174. 2011. View Article : Google Scholar : PubMed/NCBI
26	Praticò D, Clark CM, Liun F, Rokach J, Lee VY and Trojanowski JQ: Increase of brain oxidative stress in mild cognitive impairment: a possible predictor of Alzheimer disease. Arch Neurol. 59:972–976. 2002. View Article : Google Scholar : PubMed/NCBI
27	Fukui K, Omoi NO, Hayasaka T, et al: Cognitive impairment of rats caused by oxidative stress and aging and its prevention by vitamin E. Ann NY Acad Sci. 959:275–284. 2002. View Article : Google Scholar : PubMed/NCBI
28	Padurariu M, Ciobica A, Hritcu L, Stoica B, Bild W and Stefanescu C: Changes of some oxidative stress markers in the serum of patients with mild cognitive impairment and Alzheimer's disease. Neurosci Lett. 469:6–10. 2010. View Article : Google Scholar : PubMed/NCBI