Research Progress on the Correlation Between Diabetes and Alzheimer’s Disease

Abstract

Abstract: The incidence of Alzheimer’s disease (AD) is largely increased in the recent years. However, no available therapeutic regimens are successful treatment on the symptoms or altering the disease course of AD due to its undisclosed molecular mechanisms. Epidemiological data shows that diabetes mellitus is closely associated with AD incidence. Meanwhile, some antidiabetic drugs were found effectively to prevent or alleviate the symptom of AD, which may provide a new therapeutic strategy for future AD treatment. This article reviews the correlation between diabetes and AD, the mechanism about how diabetes causes AD, and the research progress of glucagon-like peptide 1 (GLP-1) analogues on AD treatment.

Key words: Alzheimer&, rsquo, s disease, diabetes mellitus, glucagon-like peptide 1, GLP-1R

PEI Shuang-chao, AI Jing. Research Progress on the Correlation Between Diabetes and Alzheimer’s Disease[J]. Acta Neuropharmacologica, 2015, 5(4): 55-64.

References

Cheng-zhi Mou, Tao Han, Min Wang, et al. Correlation of polymorphism of APOE and LRP genes to cognitive impairment and behavioral and psychological symptoms of dementia in Alzheimer's disease and vascular dementia [J]. Int J Clin Med, 2015, 8(11): 21679-21683.

2. Moritz M Hettich, Frank Matthes, Devon Ryan, et al. The anti-diabetic drug metformin reduces BACE1 protein level by interfering with the MID1 complex [J]. PLos One, 2014, 9(7): 1-8.

3. De la Monte S M. Type 3 diabetes is sporadic Alzheimers disease: mini-review [J]. Eur Neuropsychopharmacol, 2014, 24(12): 1954-1960.

4. Renata C Alencar, Roberta A Cobas, Marilia B Gomes. Assessment of cognitive status in patients with type 2 diabetes through the Mini-Mental Status Examination: a cross-sectional study [J]. Diabetol Metab Syndr, 2010, 2(10):1-6.

5. Hiroyuki Umegaki, TaKahiko wamura, Naoko Kawano, et al. Factors associated with cognitive decline in elderly diabetics [J]. Dement Geriatr Cogn Dis Extra, 2011, 1(1):1-9.

6. Andreea M Rawlings, A Richay Schneider, Andrea Lauren Coresh, et al. Diabetes in midlife and cognitive change over 20 years: a cohort study [J]. Ann Intern Med, 2014, 161(11):785-793.

7. Li Zhen-guo, Zhang Wei-xian, Anders A Sima. Alzheimer-like changes in rat models of spontaneous diabetes [J]. Diabetes, 2007, 56(7):1817-1824.

8. Sung Wook Jung, Ock Kyung Han, Sung-Jin Kim. Increased expression of beta amyloid precursor gene in the hippocampus of streptozotocin-induced diabetic mice with memory deficit and anxiety induction [J]. J Neural Transm, 2010, 117(12): 1411-1418.

9. Corinne G Jolivalt, Rosemarie Hurford, Corinne A Lee, et al. Type 1 diabetes exaggerates features of Alzheimer's disease in APP transgenic mice [J]. Experimental Neurology, 2010, 223(2): 422-431.

10. Juan Jose Ramos-Rodriguez, Sara Molina Gil, Oscar Ortiz-Barajas, et al. Central proliferation and neurogenesis is impaired in type 2 diabetes and prediabetes animal models [J]. PLoS One, 2014, 9(2): 1-8.

11. Sachi Okabayashi, Nobuhiro Shimozawa, Yasuhiro Yasutomi, et al. Diabetes mellitus accelerates Abeta pathology in brain accompanied by enhanced GAbeta generation in nonhuman primates [J]. PLoS One, 2015, 10(2): 1-19.

12. Li Lin. Commonality between diabetes and Alzheimer’s disease and a new strategy for the therapy [J]. Clinical Medicine: Pathology, 2008, 1: 83-91.

13. Omorogieva Ojo, Joanne Brooke. Evaluating the association between diabetes, cognitive decline and dementia [J]. Int J Environ Res Public Health, 2015, 12(7): 8281-8294.

14. Hiroyuki Umegaki, Takahiko Kawamura, Toshitaka Umemura, et al. Factors associated with cognitive decline in older adults with type 2 diabetes mellitus during a 6-year observation [J]. Geriatr Gerontol Int, 2015, 15(3): 302-310.

15.   Sho-Ichi Yamagishi, Nobutaka Nakamura, Mika Suematsu, et al. Advanced glycation end products: a molecular target for vascular complications in diabetes [J]. Mol Med, 2015, 21(1): 32-40.

16. Wang Pin, Huang Rong, Lu Sen, et al. RAGE and AGEs in mild cognitive impairment of diabetic patients: a cross-sectional study [J]. PLoS One, 2016, 11(1): 1-15.

17. Yamagishi S, Nakamura K, Inoue H, et al. Serum or cerebrospinal fluid levels of glyceraldehyde-derived advanced glycation end products (AGEs) may be a promising biomarker for early detection of Alzheimer's disease [J]. Med Hypotheses, 2005, 64(6): 1205-1207.

18. Chen Song, An Feng-mao, Yin Lei, et al. Glucagon-like peptide-1 protects hippocampal neurons against advanced glycation end product-induced tau hyperphosphorylation [J]. Neuroscience, 2014, 256: 137-146.

19. Barbagallo M, L J Dominguez. Type 2 diabetes mellitus and Alzheimer's disease [J]. World J Diabetes, 2014, 5(6): 889-893.

20. Katharina Mattishent, Yoon K Loke. Bi-directional interaction between hypoglycaemia and cognitive impairment in elderly patients treated with glucose-lowering agents a systematic review and meta-analysis [J]. Diabetic,Obesity and Metabolism, 2016, 18(2): 135-141.

21.   A Sherin, J Anu, K T Peeyush, et al. Cholinergic and GABAergic receptor functional defecit in the hippocampus of insulin-induced hypoglycemic and streptozotocin-induced diabetic rats [J]. Neuroscience, 2012, 202(2012): 69-76.

22. Noura B El Khoury, Maud Gratuze, Franck R Petry，et al. Hypothermia mediates age-dependent increase of tau phosphorylation in db/db mice [J]. Neurobiology Disease, 2016, 88: 55-65.

23. Cui Xing-ran, Amir Abduljalil, Brad D Manor, et al. Multi-scale glycemic variability: a link to gray matter atrophy and cognitive decline in type 2 diabetes [J]. PLoS One, 2014, 9(1): 1-12.

24. Chulho Kim, Jong-Hee Sohn, Min Uk Jang, et al. Association between visit-to-visit glucose variability and cognitive function in aged type 2 diabetic patients: a cross-sectional study [J]. PLoS One, 2015, 10(7): 1-9.

25. Richard H Tuligenga, Aline Dugravot, Adam G Tabak, et al. Midlife type 2 diabetes and poor glycaemic control as risk factors for cognitive decline in early old age: a post-hoc analysis of the Whitehall II cohort study [J]. The Lancet Diabetes & Endocrinology, 2014, 2(3): 228-235.

26. Bhumsoo Kim, Eva L Feldman. Insulin resistance as a key link for the increased risk of cognitive impairment in the metabolic syndrome [J]. Exp Mol Med, 2015, 47(3): 1-10.

27. Katrin Morgen, Lutz Frolich. The metabolism hypothesis of Alzheimer's disease: from the concept of central insulin resistance and associated consequences to insulin therapy[J]. J Neural Transm, 2015, 122(4): 499-504.

28. Li Xiao-hua, D. Song, and S.X. Leng. Link between type 2 diabetes and Alzheimer's disease: from epidemiology to mechanism and treatment [J]. Clin Interv Aging, 2015, 10: 549-560.

29.    Ekaterina G Kochkina, Svetlana A Plesneva, Dmitrii S Vasilev, et al. Effects of ageing and experimental diabetes on insulin-degrading enzyme expression in male rat tissues [J]. Biogerontology, 2015, 16(4): 473-484.

30. Ines Sebastiao, Emanuel Candeias, Maria S Santos, et al. Insulin as a bridge between type 2 diabetes and Alzheimer disease - how anti-diabetics could be a solution for dementia [J]. Front Endocrinol (Lausanne), 2014, 5: 1-13.

31. Yang Yan, Delin Ma, Xu Wei-jie, et al. Exendin-4 reduces tau hyperphosphorylation in type 2 diabetic rats via increasing brain insulin level [J]. Mol Cell Neurosci, 2016, 70: 68-75.

32. Yang Yan, Ma De-lin, Xu Wu-ping, et al. Intranasal insulin ameliorates tau hyperphosphorylation in a rat model of type 2 diabetes [J]. J Alzheimers Dis, 2013, 33(2): 329-338.

33. Giuseppe Verdile, Kevin N Keane, Vinicius F Cruzat, et al. Inflammation and oxidative stress: the molecular connectivity between insulin resistance, obesity, and Alzheimer's disease [J]. Mediators Inflamm, 2015, 2015(6): 1-17.

34. Gohar Mushtaq, Jalauddin A Khan, Taha A Kumosani, et al. Alzheimer's disease and type 2 diabetes via chronic inflammatory mechanisms [J]. Saudi J Biol Sci, 2015, 22(1): 4-13.

35. Wang Chuang, Yang Xue-mei, Zhuo Ye-ye, et al. The phosphodiesterase-4 inhibitor rolipram reverses Abeta-induced cognitive impairment and neuroinflammatory and apoptotic responses in rats [J]. Int J Neuropsychopharmacol, 2012, 15(6): 749-766.

36. Miao Ya, He Ting, Zhu Yi-tong, et al. Activation of hippocampal CREB by rolipram partially recovers balance between TNF-alpha and IL-10 levels and improves cognitive deficits in diabetic rats [J]. Cell Mol Neurobiol, 2015, 35(8): 1157-1164.

37. Michael H Yan, Wang Xing-long, Zhu Xiong-wei. Mitochondrial defects and oxidative stress in Alzheimer disease and Parkinson disease [J]. Free Radic Biol Med, 2013, 62: 90-101.

38. Siddhartha Mondragon-Rodriguez, George Perry, Zhu Xiong-wei, et al. Phosphorylation of tau protein as the link between oxidative stress, mitochondrial dysfunction, and connectivity failure: implications for Alzheimer's disease [J]. Oxid Med Cell Longev, 2013, 2013(7): 1-6.

39. Sheng-bin Huang, Y Wang, Xue-qi Gan, et al. Drp1-mediated mitochondrial abnormalities link to synaptic injury in diabetes model [J]. Diabetes, 2015, 64(5): 1728-1742.

40. Ji Xue-fei, Chi Tian-yan, Xu Qian, et al. Xanthoceraside ameliorates mitochondrial dysfunction contributing to the improvement of learning and memory impairment in mice with intracerebroventricular injection of abeta1-42 [J]. Evid Based Complement Alternat Med, 2014, 2014(2): 1-11.

41. Naoyuki Sato, Ryuichi Morishita. The roles of lipid and glucose metabolism in modulation of β-amyloid, tau, and neurodegeneration in the pathogenesis of Alzheimer disease [J]. Frontiers in Aging Neuroscience, 2015, 7: 1-9.

42. Jean-Christophe Devedjian, Monica George, Alba Casellas, et al. Transgenic mice overexpressing insulin-like growth factor-II in β cells develop type 2 diabetes [J]. J Clinical Investigation, 2000, 105(6): 731-740.

43. Mari Takalo, Annakaisa Haapasalo, Henna Martiskainen, et al. High-fat diet increases tau expression in the brain of T2DM and AD mice independently of peripheral metabolic status [J]. J Nutr Biochem, 2014, 25(6): 634-641.

44. Gao Lei, Cui Zhen, Shen Liang, et al. Shared genetic etiology between type 2 diabetes and Alzheimer's disease identified by bioinformatics analysis [J]. J Alzheimers Dis, 2016, 50: 13-17.

45. Mun-Gwan Hong, Chandra Reynolds, Margaret Gatz, et al. Evidence that the gene encoding insulin degrading enzyme influences human lifespan [J]. Hum Mol Genet, 2008, 17(15): 2370-2378.

46. Xu Wei-li, Nancy L Pedersen, Lina Keller, et al. HHEX_23 AA Genotype Exacerbates Effect of Diabetes on Dementia and Alzheimer Disease: A Population-Based Longitudinal Study[J]. PLoS Med, 2015, 12(7): 1-20.

47. Shikha Prasad, Ravi Sajja, Pooja Naik, et al. Diabetes mellitus and blood-brain barrier dysfunction: an overview [J]. J Pharmacovigil, 2014, 2(2): 125-149.

48. Wang Fu-zhou, Guo Xirong, Shen Xiao-feng, et al. Vascular dysfunction associated with type 2 diabetes and Alzheimer's disease: a potential etiological linkage [J]. Med Sci Monit Basic Res, 2014, 20: 118-129.

49. Noura B El Khoury, Maud Gratuze, Franck Petry, et al. Hypothermia mediates age-dependent increase of tau phosphorylation in db/db mice [J]. Neurobiol Dis, 2016, 88: 55-65.

50. Rachael Lennox, David W Porter, Peter R Flatt, et al. Comparison of the independent and combined effects of sub-chronic therapy with metformin and a stable GLP-1 receptor agonist on cognitive function, hippocampal synaptic plasticity and metabolic control in high-fat fed mice [J]. Neuropharmacology, 2014, 86: 22-30.

51. Jiang Li-ying, Tang Su-su, Wang Xiao-yun, et al. PPARgamma agonist pioglitazone reverses memory impairment and biochemical changes in a mouse model of type 2 diabetes mellitus [J]. CNS Neurosci Ther, 2012, 18(8): 659-666.

52.    Eileen M Moore, Alastair G Mander, David Ames, et al. Increased risk of cognitive impairment in patients with diabetes is associated with metformin [J]. Diabetes Care, 2013, 36(10): 2981-2987.

53. Laurie L Baggio, Daniel J Drucker. Biology of incretins: GLP-1 and GIP [J]. Gastroenterology, 2007, 132(6): 2131-2157.

54. Filip K Knop, Tina Vilsboll, Jens J Holst. Incretin-based therapy of type 2 diabetes mellitus [J]. Current Protein and Peptide Science, 2009, 10(1): 46-55.

55. Michael J Riedel, Patrick E MacDonald, Wasim El-kholy, et al. The multiple Actions of GLP-1 on the process of Glucose-Stimulated Insulin release [J]. Diabetes, 2002, 5(Suppl 3): 434-442.

56. Agus Lastya, Made Ratna Saraswati, Ketut Suastika. The low level of glucagon-like peptide-1 (glp-1) is a risk factor of type 2 diabetes mellitus [J]. BMC Res Notes, 2014, 7(849): 1-4.

57. Linda Ahlkvist, K Brown, B Ahren. Upregulated insulin secretion in insulin-resistant mice: evidence of increased islet GLP1 receptor levels and GPR119-activated GLP1 secretion[J]. Endocr Connect, 2013, 2(2): 69-78.

58. Zhang J, Tokui Y, Yamagata K, et al. Continuous stimulation of human glucagon-like peptide-1 (7-36) amide in a mouse model (NOD) delays onset of autoimmune type 1 diabetes [J]. Diabetologia, 2007, 50(9): 1900-1909.

59. Jorsal T, Joergen Rungby, Filip K Knop, et al. GLP-1 and amylin in the treatment of obesity [J]. Curr Diab Rep, 2016, 16(1): 1-7.

60. Livia X S Farah, Vanessa Valentini, Thaissa D Pessoa, et al. The physiological role of glucagon-like peptide-1 in the regulation of renal function [J]. Am J Physiol Renal Physiol, 2015, 310(2): 1-20.

61. Hemant Poudyal. Mechanisms for the cardiovascular effects of glucagon-like peptide-1 [J]. Acta Physiol (Oxf), 2015, 216(3): 1-112

62. Isidro Salcedo, David Tweedie, Li Ya-zhou, et al. Neuroprotective and neurotrophic actions of glucagon-like peptide-1: an emerging opportunity to treat neurodegenerative and cerebrovascular disorders [J]. Br J Pharmacol, 2012, 166(5): 1586-1599.

63. Christian Holscher. Central effects of GLP-1: new opportunities for treatments of neurodegenerative diseases [J]. J Endocrinol, 2014, 221(1): 31-41.

64. Tracy Ann Perry, Norman J Haughey, Mark P Mattson, et al. Protection and reversal of excitotoxic neuronal damage by glucagon-like peptide-1 and exendin-4 [J]. J Pharmacol Exp Ther, 2002, 302(3): 881-888.

65. Henrik H Hansen, Katrine Fabricius, Pernille Barkholt, et al. The GLP-1 receptor agonist liraglutide improves memory function and increases hippocampal CA1 neuronal numbers in a senescence-accelerated mouse model of Alzheimer's disease [J]. J Alzheimers Dis, 2015, 46(4): 877-888.

66. Kerry Hunter, Christian Holscher. Drugs developed to treat diabetes, liraglutide and lixisenatide, cross the blood brain barrier and enhance neurogenesis [J]. BMC Neurosci, 2012, 13(33): 1-6.

67. Vadivel Parthsarathy, Christian Holscher. Chronic treatment with the GLP-1 analogue liraglutide increases cell differention into neurons in AD mouse model [J]. PLoS One, 2013, 8(3): 1-10.

68. Ma De-lin, Chen Fu-qiong, Xu Wei-jie, et al. Early intervention with glucagon-like peptide 1 analog liraglutide prevents tau hyperphosphorylation in diabetic db/db mice [J]. J Neurochem, 2015, 135(2): 301-308.

69. Yang, Yan, Zhang Jing, Ma De-lin, et al. Subcutaneous administration of liraglutide ameliorates Alzheimer-associated tau hyperphosphorylation in rats with type 2 diabetes [J]. J Alzheimers Dis, 2013, 37(3): 637-648.

70. Paula Lousie McClean, Vadivel Parthsarathy, Emilie Faivre, et al. The diabetes drug liraglutide prevents degenerative processes in a mouse model of Alzheimer's disease [J]. J Neurosci, 2011. 31(17): 6587-6594.

71. Ma Tao, Du Xue-liang, Joseph E Pick, et al. Glucagon-like peptide-1 cleavage product GLP-1(9-36) amide rescues synaptic plasticity and memory deficits in Alzheimer's disease model mice [J]. J Neurosci, 2012, 32(40): 13701-13708.

72. Jayasankar Kosaraju, Chaitanya Chakravarthi Gali, et al. Saxagliptin: a dipeptidyl peptidase-4 inhibitor ameliorates streptozotocin induced Alzheimer's disease [J]. Neuropharmacology, 2013, 72: 291-300.

73. Holscher C. Incretin that have been Developed to Treat Type 2 Diabetes Hold promise as a treatment strategy for Alzheimer's disease [J]. Recent Patent on CNS Drug Discovery, 2010, 5: 109-117.

74. Bao Y, Jiang L, Chen H, et al. The neuroprotective effect of liraglutide is mediated by glucagon-like peptide 1 receptor-mediated activation of cAMP/PKA/CREB pathway [J]. Cell Physiol Biochem, 2015, 36(6): 2366-2378.

75. Simon C Cork, James E Richards, Marie K Holt, et al. Distribution and characterisation of Glucagon-like peptide-1 receptor expressing cells in the mouse brain [J]. Mol Metab, 2015, 4(10): 718-731.

76. Hamilton A, Hölscher C. Receptors for the incretin glucagon-like peptide-1 are expressed on neurons in the central nervous system [J]. NeuroReport, 2009, 20(13): 1161-1166.

77. Alexander Harkavyi, Peter S Whitton. Glucagon-like peptide 1 receptor stimulation as a means of neuroprotection [J]. Br J Pharmacol, 2010, 159(3): 495-501.

78. Amantha Thathiah, Bart De Strooper. The role of G protein-coupled receptors in the pathology of Alzheimer's disease [J]. Nature Reviews Neuroscience, 2011, 12(2): 73-87.

79. TracyAnn Perry, Nigel H Greig. Enhancing central nervous system endogenous GLP-1 receptor pathways for intervention in AD [J]. Current Alzheimer Res, 2005, 2(3): 377-385.

80. Joanthan Janssens, Harmonie Etienne, Sherif Idriss, et al. Systems-level G protein-coupled receptor therapy across a neurodegenerative continuum by the GLP-1 receptor system [J]. Front Endocrinol (Lausanne), 2014, 5: 1-15.

81. Talib Abbas, Emillie Faivre, Christian Hölscher. Impairment of synaptic plasticity and memory formation in GLP-1 receptor KO mice: Interaction between type 2 diabetes and Alzheimer's disease [J]. Behavioural Brain Research, 2009, 205(1): 265-271.

82. Matthew J During, David S Zuzga, Jeremy S Francis', et al. GLP-1R is involved in learning and neuroprotection [J]. Nature Medicine, 2003. 9(9): 1173-1179.

83. Li Ya-zhou, Tracy Ann Perry, Mark S Kindy, et al. GLP-1 receptor stimulation preserves primary cortical and dopaminergic neurons in cellular and rodent models of stroke and Parkinsonism [J]. Proc Natl Acad Sci USA, 2009, 106(4): 1285-1290.

84. Li Ya-zhou, David Tweedie, Mark P Mattson, et al. Enhancing the GLP-1 receptor signaling pathway leads to proliferation and neuroprotection in human neuroblastoma cells [J]. J Neurochem, 2010, 113(6): 1621-1631.

85. Jennifer S Ten Kulve, Liselotte van Bloemendaal, Rawien Balesar, et al. Decreased hypothalamic glucagon-like peptide-1 receptor expression in type 2 diabetes patients [J]. J Clin Endocrinol Metab, 2015, 100(12): 1-8.

86. Dong-ll Kim, Min-Jung Park, Joo-Hee Choi, et al. Hyperglycemia-induced GLP-1R downregulation causes RPE cell apoptosis [J]. Int J Biochem Cell Biol, 2015, 59(2): 41-51.

[1]	XIE bin, HUANG Zhi-yuan, LIN Duo-duo, YANG Fu-long, XIE Yi-bin. Effect of Acupuncture Combined with Medicine on Depressive Symptoms of Alzheimer’s Disease [J]. ACTA NEUROPHARMACOLOGICA, 2020, 10(5): 5-8.
[2]	SUN Li-cong, ZHANG Dan-shen. Research Progress on Potential Treatment of Alzheimer’s Disease with Alkaloids [J]. ACTA NEUROPHARMACOLOGICA, 2020, 10(5): 33-37.
[3]	WANG Si-yi, LI Xian-xiang, LIU Yi-zhou, DU Shuang, GE Chao, LIU Si-si. Current Situation and Prospect of Alzeimer’s Disease Treatment [J]. ACTA NEUROPHARMACOLOGICA, 2020, 10(5): 38-42.
[4]	ZHAO Yu-wei, ZHEN Yan-jie, DAI Yue-ying, SHEN Li-xia. Study on the Neuroprotective Mechanism of Quercetin in Alzheimer’s Disease [J]. ACTA NEUROPHARMACOLOGICA, 2020, 10(5): 55-64.
[5]	HAI Ji-tao, LUO Huan-min. Progress on the Relationship between Pathogenic Microorganisms and Alzheimer’s Disease [J]. ACTA NEUROPHARMACOLOGICA, 2020, 10(4): 58-64.
[6]	ZHANG Hao-ting, SONG Gui-qin, CUI Ruo-tong, HAO Min, WANG Wen-dong. Mining Target Genes of Alzheimer’s Disease Associated with Biological Clock by Bioinformatics Analysis [J]. ACTA NEUROPHARMACOLOGICA, 2020, 10(3): 1-7.
[7]	YANG Xu-hua, DU Shuang, SHEN Li-xia, HAO Jun-rong. Research Progress in Drug Treatment of Alzheimer’s Disease [J]. ACTA NEUROPHARMACOLOGICA, 2020, 10(3): 47-53.
[8]	ZHEN Yan-jie, GUO Tong-lin, ZHAO Yu-wei, SHEN Li-xia. Study Progress on Phytoestrogen-Mediated Mitochondrial Pathway’s Neuroprotective Effects in Alzheimer’s Disease [J]. ACTA NEUROPHARMACOLOGICA, 2020, 10(1): 40-46.
[9]	QI Gi，WU Hong-li，QI Quan, et al. Correlation between Progesterone Supplementation in the Early Pregnancy and Incidence of Gestational Diabetes Mellitus [J]. Acta Neuropharmacologica, 2019, 9(6): 6-10.
[10]	YANG-Lin，AI-Jing. Research Progress of Brain-Derived Estrogen in Alzheimer’s Disease [J]. Acta Neuropharmacologica, 2019, 9(5): 50-64.
[11]	ZHANG Shuai，AI Jing. Glutamate Dysfunction and Alzheimer’s Disease [J]. Acta Neuropharmacologica, 2018, 8(6): 9-20.
[12]	王奇. Bushen-Yizhi Formula Inhibits the NLRP3/NFκB Mediated Neuroinflammation and Improves the Motor Dysfunction in a Mouse Model of Parkinson's Disease [J]. Acta Neuropharmacologica, 2018, 8(5): 71-72.
[13]	CUI Su-ying, SONG Jin-zhi, CUI Xiang-yu, HU Xiao, DING Hui, YE Hui, ZHANG Yong-he. Intracerebroventricular Streptozocin-induced Alzheimer’s Disease-like Sleep Disorders: Role of the GABAergic System in the Parabrachial Complex [J]. Acta Neuropharmacologica, 2018, 8(5): 96-97.
[14]	YU Li-li1，2，XU Li1，WANG Yi-nuo1，XUE Lu-ning1，Gou Ji-wei1，LI Hong-bo1，HOU Xue-qin1，ZHANG Han-ting1. Effects of Osthole on Learning and Memory and the Estrogen Pathway in Ovariectomized Rats [J]. Acta Neuropharmacologica, 2018, 8(4): 7-8.
[15]	SHEN li-xia1，LIU Liang-liang1，ZHANG Ming1，LIU Yang1，ZHANG Dan-shen 2. Research of Quercetin’s Estrogen-Like Action on Central Nervous System and Its Mechanisms* [J]. Acta Neuropharmacologica, 2018, 8(4): 23-25.