Endoplasmic reticulum stress/autophagy pathway is involved in diabetes-induced neuronal apoptosis and cognitive decline in mice

Fei-Juan Kong; Lei-Lei Ma; Jun-Jie Guo; Lin-Hao Xu; Yun Li; Shen Qu

doi:10.1042/cs20171432

journal article Jan 11, 2018

Endoplasmic reticulum stress/autophagy pathway is involved in diabetes-induced neuronal apoptosis and cognitive decline in mice

Fei-Juan Kong Lei-Lei Ma Jun-Jie Guo Lin-Hao Xu Yun Li

Shen Qu

Clinical Science Vol. 132 No. 1 pp. 111-125 · Portland Press Ltd.

View at Publisher Save 10.1042/cs20171432

Abstract

Diabetes mellitus is a significant global public health problem depicting a rising prevalence worldwide. As a serious complication of diabetes, diabetes-associated cognitive decline is attracting increasing attention. However, the underlying mechanisms are yet to be fully determined. Both endoplasmic reticulum (ER) stress and autophagy have been reported to modulate neuronal survival and death and be associated with several neurodegenerative diseases. Here, a streptozotocin-induced diabetic mouse model and primary cultured mouse hippocampal neurons were employed to investigate the possible role of ER stress and autophagy in diabetes-induced neuronal apoptosis and cognitive impairments, and further explore the potential molecular mechanisms. ER stress markers GRP78 and CHOP were both enhanced in diabetic mice, as was phosphorylation of PERK, IRE1α, and JNK. In addition, the results indicated an elevated level of autophagy in diabetic mice, as demonstrated by up-regulated expressions of autophagy markers LC3-II, beclin 1 and down-regulated level of p62, and increased formation of autophagic vacuoles and LC3-II aggregates. Meanwhile, we found that these effects could be abolished by ER stress inhibitor 4-phenylbutyrate or JNK inhibitor SP600125 in vitro. Furthermore, neuronal apoptosis of diabetic mice was attenuated by pretreatment with 4-phenylbutyrate, while aggravated by application of inhibitor of autophagy bafilomycin A1 in vitro. These results suggest that ER stress pathway may be involved in diabetes-mediated neurotoxicity and promote the following cognitive impairments. More important, autophagy was induced by diabetes possibly through ER stress-mediated JNK pathway, which may protect neurons against ER stress-associated cell damages.

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References

61

[1]

Northam "Therapy insight: the impact of type 1 diabetes on brain development and function" Nat. Clin. Pract. Neurol. (2006) 10.1038/ncpneuro0097

[2]

Brismar "Predictors of cognitive impairment in type 1 diabetes" Psychoneuroendocrinology (2007) 10.1016/j.psyneuen.2007.08.002

[3]

Revsin "Glucocorticoid receptor blockade normalizes hippocampal alterations and cognitive impairment in streptozotocin-induced type 1 diabetes mice" Neuropsychopharmacology (2009) 10.1038/npp.2008.136

[4]

Brands "The effects of type 1 diabetes on cognitive performance: a meta-analysis" Diabetes Care (2005) 10.2337/diacare.28.3.726

[5]

Sinclair "Cognitive dysfunction in older subjects with diabetes mellitus: impact on diabetes self-management and use of care services. All Wales Research into Elderly (AWARE) Study" Diabetes Res. Clin. Pract. (2000) 10.1016/s0168-8227(00)00195-9

[6]

Kapoor "Endoplasmic reticulum stress and the unfolded protein response" Clin. Liver Dis. (2009) 10.1016/j.cld.2009.07.004

[7]

Roles of CHOP/GADD153 in endoplasmic reticulum stress

S Oyadomari, M Mori

Cell Death & Differentiation 2004 10.1038/sj.cdd.4401373

[8]

Kakizuka "Protein precipitation: a common etiology in neurodegenerative disorders?" Trends Genet. (1998) 10.1016/s0168-9525(98)01559-5

[9]

Hoyer-Hansen "Connecting endoplasmic reticulum stress to autophagy by unfolded protein response and calcium" Cell Death Differ. (2007) 10.1038/sj.cdd.4402200

[10]

Xie "Autophagosome formation: core machinery and adaptations" Nat. Cell Biol. (2007) 10.1038/ncb1007-1102

[11]

Macroautophagy—a novel β-amyloid peptide-generating pathway activated in Alzheimer's disease

W. Haung Yu, Ana Maria Cuervo, Asok Kumar et al.

The Journal of cell biology 2005 10.1083/jcb.200505082

[12]

Pickford "The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid beta accumulation in mice" J. Clin. Invest. (2008)

[13]

Tung "Autophagy: a double-edged sword in Alzheimer’s disease" J. Biosci. (2012) 10.1007/s12038-011-9176-0

[14]

Enhamre-Brolin "Growth hormone reverses streptozotocin-induced cognitive impairments in male mice" Behav. Brain Res. (2013) 10.1016/j.bbr.2012.10.036

[15]

Zhou "Inhibition of iNOS alleviates cognitive deficits and depression in diabetic mice through downregulating the NO/sGC/cGMP/PKG signal pathway" Behav. Brain Res. (2017) 10.1016/j.bbr.2016.12.046

[16]

Xu "Critical role of endoplasmic reticulum stress in chronic intermittent hypoxia-induced deficits in synaptic plasticity and long-term memory" Antioxid. Redox Signal. (2015) 10.1089/ars.2014.6122

[17]

Ricobaraza "Phenylbutyrate ameliorates cognitive deficit and reduces tau pathology in an Alzheimer’s disease mouse model" Neuropsychopharmacology (2009) 10.1038/npp.2008.229

[18]

Culturing hippocampal neurons

Stefanie Kaech, Gary Banker

Nature Protocols 2006 10.1038/nprot.2006.356

[19]

Zhang "Endoplasmic reticulum stress-mediated hippocampal neuron apoptosis involved in diabetic cognitive impairment" Biomed Res. Int. (2013)

[20]

Lee "Alteration of adolescent aversive nicotine response and anxiety-like behavior in nicotine-exposed rats during late lactation period" . Behav. Brain Res.

[21]

Ge "Endoplasmic reticulum stress pathway mediates isoflurane-induced neuroapoptosis and cognitive impairments in aged rats" Physiol. Behav. (2015) 10.1016/j.physbeh.2015.07.008

[22]

Kong "Fetal exposure to high isoflurane concentration induces postnatal memory and learning deficits in rats" Biochem. Pharmacol. (2012) 10.1016/j.bcp.2012.06.001

[23]

Kong "Minocycline attenuates cognitive impairment induced by isoflurane anesthesia in aged rats" PLoS One (2013) 10.1371/journal.pone.0061385

[24]

Grasshoff "Effects of cholinergic overstimulation on isoflurane potency and efficacy in cortical and spinal networks" Toxicology (2007) 10.1016/j.tox.2006.10.017

[25]

American Diabetes Association "Diagnosis and classification of diabetes mellitus" Diabetes Care (2014) 10.2337/dc14-s081

[26]

Sims-Robinson "How does diabetes accelerate Alzheimer disease pathology?" Nat. Rev. Neurol. (2010) 10.1038/nrneurol.2010.130

[27]

Biessels "Cerebral function in diabetes mellitus" Diabetologia (1994) 10.1007/bf00417687

[28]

Gispen "Cognition and synaptic plasticity in diabetes mellitus" Trends Neurosci. (2000) 10.1016/s0166-2236(00)01656-8

[29]

Yates "Impact of metabolic syndrome on cognition and brain: a selected review of the literature" Arterioscler. Thromb. Vasc. Biol. (2012) 10.1161/atvbaha.112.252759

[30]

Dutheil "High-fat diet induced anxiety and anhedonia: impact on brain homeostasis and inflammation" Neuropsychopharmacology (2016) 10.1038/npp.2015.357

[31]

Zemdegs "High-fat diet-induced metabolic disorders impairs 5-HT function and anxiety-like behavior in mice" Br. J. Pharmacol. (2016) 10.1111/bph.13343

[32]

Diabetes in Midlife and Cognitive Change Over 20 Years

Andreea M. Rawlings, A. Richey Sharrett, Andrea L.C. Schneider et al.

Annals of Internal Medicine 2014 10.7326/m14-0737

[33]

van den Berg "A 4 year follow-up study of cognitive functioning in patients with type 2 diabetes mellitus" Diabetologia (2010) 10.1007/s00125-009-1571-9

[34]

Kanaya "Change in cognitive function by glucose tolerance status in older adults: a 4-year prospective study of the Rancho Bernardo study cohort" Arch. Intern. Med. (2004) 10.1001/archinte.164.12.1327

[35]

Moheet "Impact of diabetes on cognitive function and brain structure" Ann. N. Y. Acad. Sci. (2015) 10.1111/nyas.12807

[36]

Biessels "Risk of dementia in diabetes mellitus: a systematic review" Lancet Neurol. (2006) 10.1016/s1474-4422(05)70284-2

[37]

Grunblatt "The link between iron, metabolic syndrome, and Alzheimer’s disease" J. Neural. Transm. (Vienna) (2011) 10.1007/s00702-010-0426-3

[38]

Chatterjee "Type 2 diabetes as a risk factor for dementia in women compared with men: a pooled analysis of 2.3 million people comprising more than 100,000 cases of dementia" Diabetes Care (2016) 10.2337/dc15-1588

[39]

Ascher-Svanum "Cognitive and functional decline in patients with mild alzheimer dementia with or without comorbid diabetes" Clin. Ther. (2015) 10.1016/j.clinthera.2015.01.002

[40]

Kwon "Diabetes augments cognitive dysfunction in chronic cerebral hypoperfusion by increasing neuronal cell death: implication of cilostazol for diabetes mellitus-induced dementia" Neurobiol. Dis. (2015) 10.1016/j.nbd.2014.08.034

[41]

Bannerman "Distinct components of spatial learning revealed by prior training and NMDA receptor blockade" Nature (1995) 10.1038/378182a0

[42]

Zhou "Expression changes of growth-associated protein-43 (GAP-43) and mitogen-activated protein kinase phosphatase-1 (MKP-1) and in hippocampus of streptozotocin-induced diabetic cognitive impairment rats" Exp. Neurol. (2007) 10.1016/j.expneurol.2007.04.013

[43]

A synaptic model of memory: long-term potentiation in the hippocampus

T. V. P. Bliss, G. L. Collingridge

Nature 1993 10.1038/361031a0

[44]

Malenka "Long-term potentiation–a decade of progress?" Science (1999) 10.1126/science.285.5435.1870

[45]

Muller "LTP, memory and structural plasticity" Curr. Mol. Med. (2002) 10.2174/1566524023362041

[46]

van der Kallen "Endoplasmic reticulum stress-induced apoptosis in the development of diabetes: is there a role for adipose tissue and liver?" Apoptosis (2009) 10.1007/s10495-009-0400-4

[47]

Nitric oxide-induced apoptosis in pancreatic β cells is mediated by the endoplasmic reticulum stress pathway

Seiichi Oyadomari, Kiyoshi Takeda, Masaki Takiguchi et al.

Proceedings of the National Academy of Sciences 2001 10.1073/pnas.191207498

[48]

Rani "Alzheimer’s disease: is this a brain specific diabetic condition?" Physiol. Behav. (2016) 10.1016/j.physbeh.2016.05.041

[49]

Martindale "Endoplasmic reticulum stress gene induction and protection from ischemia/reperfusion injury in the hearts of transgenic mice with a tamoxifen-regulated form of ATF6" Circ. Res. (2006) 10.1161/01.res.0000220643.65941.8d

[50]

Liu "Disrupted autophagy after spinal cord injury is associated with ER stress and neuronal cell death" Cell Death Dis. (2015) 10.1038/cddis.2014.527

Showing 50 of 61 references

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Details

Published: Jan 11, 2018
Vol/Issue: 132(1)
Pages: 111-125

Authors

F

Fei-Juan Kong

Department of Endocrinology and Metabolism, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China

L

Lei-Lei Ma

Department of Critical Care Medicine, Zhejiang Provincial People’s Hospital and People’s Hospitalof Hangzhou Medical College, Hangzhou, China; Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao, China; Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China

J

Jun-Jie Guo

Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao, China

L

Lin-Hao Xu

Department of Anatomy, Faculty of Basic Medicine, Hangzhou Medical College, Hangzhou, China

Y

Yun Li

Department of Ophthalmology, The Second Affiliated Hospital of Nanchang University, Nanchang, China

S

Shen Qu

Department of Endocrinology and Metabolism, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China

Cite This Article

Fei-Juan Kong, Lei-Lei Ma, Jun-Jie Guo, et al. (2018). Endoplasmic reticulum stress/autophagy pathway is involved in diabetes-induced neuronal apoptosis and cognitive decline in mice. Clinical Science, 132(1), 111-125. https://doi.org/10.1042/cs20171432

Endoplasmic reticulum stress/autophagy pathway is involved in diabetes-induced neuronal apoptosis and cognitive decline in mice

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