Vulnerability for Apoptosis in the Hippocampal Dentate Gyrus of STZ-induced Diabetic Rats with Cognitive Impairment

Overview

Journal J Endocrinol Invest

Publisher Springer

Specialty Endocrinology

Date 2014 Jan 28

PMID 24464455

Citations 7

Authors

Yi-Jing Guo

Shao-Hua Wang

Yang Yuan

Feng-Fei Li

Kuan-ping Ye

Yan Huang

Wen-Qing Xia

Yi Zhou

Affiliations

Soon will be listed here.

Abstract

Background: Hyperglycemia impaired hippocampal network via triggering suicide program of immanent neurons, this is regarded as an etiological factor for diabetic cognition deficits.

Aim: To investigate the occurrence of apoptosis in the hippocampal dentate gyrus of streptozotocin (STZ)-induced diabetic rats with cognitive impairment and assess the gene and protein expression of the apoptotic proteins bax, bcl-2, and caspase-3.

Materials And Methods: Four weeks after the verification of STZ-induced diabetes, diabetic rats with and without cognitive decline subgroups were subsequently assigned according to Morris water maze test. The expression levels of apoptotic proteins were measured using real-time RT-PCR and western blotting, respectively. Neuronal apoptosis was detected by TUNEL staining and electron microscopy.

Results: In the dentate gyrus of the rats with cognitive decline, Bcl-2 exhibited lower gene and protein levels, whereas a higher expression of bax was detected contributing to a significant increase in their mean bax/bcl-2 ratio. However, caspase-3 was not activated. Statistically different numbers of TUNEL-staining cells and features of apoptosis were no found.

Conclusions: The higher bax/bcl ratio probably represents neurons of dentate gyrus vulnerable to apoptosis in the diabetes with cognitive decline. However, the normal caspase-3 level suggests that apoptosis is not active in this illness phase.

Citing Articles

Pyruvate dehydrogenase kinase 1 protects against neuronal injury and memory loss in mouse models of diabetes.

Yao Y, Shi J, Zhang C, Gao W, Huang N, Liu Y Cell Death Dis. 2023; 14(11):722.

PMID: 37935660 PMC: 10630521. DOI: 10.1038/s41419-023-06249-2.

"Adjust Zang and arouse spirit" electroacupuncture ameliorates cognitive impairment by reducing endoplasmic reticulum stress in db/db mice.

Li M, Yao L, He M, Huang H, Zheng H, Ma S Front Endocrinol (Lausanne). 2023; 14:1185022.

PMID: 37152933 PMC: 10154981. DOI: 10.3389/fendo.2023.1185022.

TIGAR Attenuates High Glucose-Induced Neuronal Apoptosis an Autophagy Pathway.

Zhou W, Yao Y, Li J, Wu D, Zhao M, Yan Z Front Mol Neurosci. 2019; 12:193.

PMID: 31456661 PMC: 6700368. DOI: 10.3389/fnmol.2019.00193.

Activation of Sirtuin 1 Attenuates High Glucose-Induced Neuronal Apoptosis by Deacetylating p53.

Shi X, Pi L, Zhou S, Li X, Min F, Wang S Front Endocrinol (Lausanne). 2018; 9:274.

PMID: 29892266 PMC: 5985296. DOI: 10.3389/fendo.2018.00274.

Neonatal hyperglycemia induces cell death in the rat brain.

Rosa A, Mescka C, Catarino F, de Castro A, Teixeira R, Campos C Metab Brain Dis. 2017; 33(1):333-342.

PMID: 29260360 DOI: 10.1007/s11011-017-0170-6.

References

Sawa A, Oyama F, Cairns N, Amano N, Matsushita M . Aberrant expression of bcl-2 gene family in Down's syndrome brains. Brain Res Mol Brain Res. 1997; 48(1):53-9. DOI: 10.1016/s0169-328x(97)00078-8. View

Tuitoek P, Ziari S, Tsin A, Rajotte R, Suh M, Basu T . Streptozotocin-induced diabetes in rats is associated with impaired metabolic availability of vitamin A (retinol). Br J Nutr. 1996; 75(4):615-22. DOI: 10.1079/bjn19960164. View

Masliah E, Mallory M, Alford M, Tanaka S, Hansen L . Caspase dependent DNA fragmentation might be associated with excitotoxicity in Alzheimer disease. J Neuropathol Exp Neurol. 1998; 57(11):1041-52. DOI: 10.1097/00005072-199811000-00007. View

Paradis E, Douillard H, Koutroumanis M, Goodyer C, Leblanc A . Amyloid beta peptide of Alzheimer's disease downregulates Bcl-2 and upregulates bax expression in human neurons. J Neurosci. 1996; 16(23):7533-9. PMC: 6579094. View

Stranahan A, Arumugam T, Cutler R, Lee K, Egan J, Mattson M . Diabetes impairs hippocampal function through glucocorticoid-mediated effects on new and mature neurons. Nat Neurosci. 2008; 11(3):309-17. PMC: 2927988. DOI: 10.1038/nn2055. View

Jafari Anarkooli I, Sankian M, Ahmadpour S, Varasteh A, Haghir H . Evaluation of Bcl-2 family gene expression and Caspase-3 activity in hippocampus STZ-induced diabetic rats. Exp Diabetes Res. 2008; 2008:638467. PMC: 2566751. DOI: 10.1155/2008/638467. View

Gould E, Gross C . Neurogenesis in adult mammals: some progress and problems. J Neurosci. 2002; 22(3):619-23. PMC: 6758509. View

Hartmann A, Hunot S, Michel P, Muriel M, Vyas S, Faucheux B . Caspase-3: A vulnerability factor and final effector in apoptotic death of dopaminergic neurons in Parkinson's disease. Proc Natl Acad Sci U S A. 2000; 97(6):2875-80. PMC: 16023. DOI: 10.1073/pnas.040556597. View

Bredesen D . Neural apoptosis. Ann Neurol. 1995; 38(6):839-51. DOI: 10.1002/ana.410380604. View

10.

Rodrigues L, Biasibetti R, Swarowsky A, Leite M, Quincozes-Santos A, Quilfeldt J . Hippocampal alterations in rats submitted to streptozotocin-induced dementia model are prevented by aminoguanidine. J Alzheimers Dis. 2009; 17(1):193-202. DOI: 10.3233/JAD-2009-1034. View

11.

Oltvai Z, Milliman C, Korsmeyer S . Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell. 1993; 74(4):609-19. DOI: 10.1016/0092-8674(93)90509-o. View

12.

Livak K, Schmittgen T . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2002; 25(4):402-8. DOI: 10.1006/meth.2001.1262. View

13.

Whitmer R, Gunderson E, Barrett-Connor E, Quesenberry Jr C, Yaffe K . Obesity in middle age and future risk of dementia: a 27 year longitudinal population based study. BMJ. 2005; 330(7504):1360. PMC: 558283. DOI: 10.1136/bmj.38446.466238.E0. View

14.

Thornberry N, Lazebnik Y . Caspases: enemies within. Science. 1998; 281(5381):1312-6. DOI: 10.1126/science.281.5381.1312. View

15.

Su J, Deng G, Cotman C . Bax protein expression is increased in Alzheimer's brain: correlations with DNA damage, Bcl-2 expression, and brain pathology. J Neuropathol Exp Neurol. 1997; 56(1):86-93. DOI: 10.1097/00005072-199701000-00009. View

16.

Festoff B, Suo Z, Citron B . Plasticity and stabilization of neuromuscular and CNS synapses: interactions between thrombin protease signaling pathways and tissue transglutaminase. Int Rev Cytol. 2001; 211:153-77. DOI: 10.1016/s0074-7696(01)11018-1. View

17.

Kempermann G, Kronenberg G . Depressed new neurons--adult hippocampal neurogenesis and a cellular plasticity hypothesis of major depression. Biol Psychiatry. 2003; 54(5):499-503. DOI: 10.1016/s0006-3223(03)00319-6. View

18.

Wang S, Sun Z, Guo Y, Yuan Y, Yang B . Diabetes impairs hippocampal function via advanced glycation end product mediated new neuron generation in animals with diabetes-related depression. Toxicol Sci. 2009; 111(1):72-9. DOI: 10.1093/toxsci/kfp126. View

19.

Zhang L, Jiang C, Liu D . Hydrogen sulfide attenuates neuronal injury induced by vascular dementia via inhibiting apoptosis in rats. Neurochem Res. 2009; 34(11):1984-92. DOI: 10.1007/s11064-009-0006-9. View

20.

Vekrellis K, McCarthy M, Watson A, Whitfield J, Rubin L, Ham J . Bax promotes neuronal cell death and is downregulated during the development of the nervous system. Development. 1997; 124(6):1239-49. DOI: 10.1242/dev.124.6.1239. View