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Streptozotocin Intracerebroventricular-Induced Neurotoxicity and Brain Insulin Resistance: a Therapeutic Intervention for Treatment of Sporadic Alzheimer’s Disease (sAD)-Like Pathology

Molecular Neurobiology volume 53, pages 4548–4562 (2016)Cite this article

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder that is remarkably characterized by pathological hallmarks which include amyloid plaques, neurofibrillary tangles, neuronal loss, and progressive cognitive loss. Several well-known genetic mutations which are being used for the development of a transgenic model of AD lead to an early onset familial AD (fAD)-like condition. However, these settings are only reasons for a small percentage of the total AD cases. The large majorities of AD cases are considered as a sporadic in origin and are less influenced by a single mutation of a gene. The etiology of sporadic Alzheimer’s disease (sAD) remains unclear, but numerous risk factors have been identified that increase the chance of developing AD. Among these risk factors are insulin desensitization/resistance state, oxidative stress, neuroinflammation, synapse dysfunction, tau hyperphosphorylation, and deposition of Aβ in the brain. Subsequently, these risk factors lead to development of sAD. However, the underlying molecular mechanism is not so clear. Streptozotocin (STZ) produces similar characteristic pathology of sAD such as altered glucose metabolism, insulin signaling, synaptic dysfunction, protein kinases such as protein kinase B/C, glycogen synthase-3β (GSK-3β) activation, tau hyperphosphorylation, Aβ deposition, and neuronal apoptosis. Further, STZ also leads to inhibition of Akt/PKB, insulin receptor (IR) signaling molecule, and insulin resistance in brain. These alterations mediated by STZ can be used to explore the underlying molecular and pathophysiological mechanism of AD (especially sAD) and their therapeutic intervention for drug development against AD pathology.

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Abbreviations

sAD:

Sporadic Alzheimer’s disease

CNS:

Central nervous system

NMDA:

N-methyl-D-aspartate receptor

Aβ:

Beta amyloid

APP:

Amyloid precursor protein

NFT:

Neurofibrillary tangle

STZ:

Streptozotocin

IRS:

Insulin receptor signaling

IR:

Insulin receptor

GLT:

Glucose transporter

IRBS:

Insulin-resistant brain state

OGlcNAc:

O-glucose-N-acetyl

ICV:

Intracerebroventricular

GSK-3β:

Glycogen synthase-3β

PKC:

Protein kinase C

References

  1. Mehla J, Pahuja M, Gupta P, Dethe S, Agarwal A, Gupta YK (2013) Clitoria ternatea ameliorated the intracerebroventricularly injected streptozotocin induced cognitive impairment in rats: behavioral and biochemical evidence. Psychopharmacology 230:589–605

    Article  CAS  PubMed  Google Scholar 

  2. Chen Y, Liang Z, Tian Z, Blanchard J, Dai CL, Chalbot S, Iqbal K, Liu F et al (2014) Intracerebroventricular streptozotocin exacerbates Alzheimer-like changes of 3xTg-AD mice. Mol Neurobiol 49:547–562

    Article  CAS  PubMed  Google Scholar 

  3. Lee Y, Kim YH, Park SJ, Huh JW, Kim SH, Kim SU, Kim JS, Jeong KJ et al (2014) Insulin/IGF signaling-related gene expression in the brain of a sporadic Alzheimer's disease monkey model induced by intracerebroventricular injection of streptozotocin. J Alzheimer's Dis : JAD 38:251–267

    PubMed  Google Scholar 

  4. Baluchnejadmojarad T, Roghani M (2006) Effect of naringenin on intracerebroventricular streptozotocin-induced cognitive deficits in rat: a behavioral analysis. Pharmacology 78:193–197

    Article  CAS  PubMed  Google Scholar 

  5. Plaschke K, Kopitz J, Siegelin M, Schliebs R, Salkovic-Petrisic M, Riederer P, Hoyer S (2010) Insulin-resistant brain state after intracerebroventricular streptozotocin injection exacerbates Alzheimer-like changes in Tg2576 AbetaPP-overexpressing mice. J Alzheimer's Dis : JAD 19:691–704

    CAS  PubMed  Google Scholar 

  6. Rai S, Kamat PK, Nath C, Shukla R (2013) A study on neuroinflammation and NMDA receptor function in STZ (ICV) induced memory impaired rats. J Neuroimmunol 254:1–9

    Article  CAS  PubMed  Google Scholar 

  7. Deshmukh R, Sharma V, Mehan S, Sharma N, Bedi KL (2009) Amelioration of intracerebroventricular streptozotocin induced cognitive dysfunction and oxidative stress by vinpocetine—a PDE1 inhibitor. Eur J Pharmacol 620:49–56

    Article  CAS  PubMed  Google Scholar 

  8. Mistur R, Mosconi L, Santi SD, Guzman M, Li Y, Tsui W, de Leon MJ (2009) Current challenges for the early detection of Alzheimer's disease: brain imaging and CSF studies. J Clin Neurol 5:153–166

    Article  PubMed  PubMed Central  Google Scholar 

  9. Lester-Coll N, Rivera EJ, Soscia SJ, Doiron K, Wands JR, de la Monte SM (2006) Intracerebral streptozotocin model of type 3 diabetes: relevance to sporadic Alzheimer's disease. J Alzheimer's Dis : JAD 9:13–33

    CAS  PubMed  Google Scholar 

  10. Mosconi L, Mistur R, Switalski R, Brys M, Glodzik L, Rich K, Pirraglia E, Tsui W et al (2009) Declining brain glucose metabolism in normal individuals with a maternal history of Alzheimer disease. Neurology 72:513–520

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Selkoe DJ (2001) Alzheimer's disease results from the cerebral accumulation and cytotoxicity of amyloid beta-protein. J Alzheimer's Dis : JAD 3:75–80

    CAS  PubMed  Google Scholar 

  12. Mancuso M, Calsolaro V, Orsucci D, Carlesi C, Choub A, Piazza S, Siciliano G (2009) Mitochondria, cognitive impairment, and Alzheimer's disease. Int J Alzheimer's Dis

  13. Lewis C, Barbiers AR (1959) Streptozotocin, a new antibiotic in vitro and in vivo evaluation. Antibiot Annu 7:247–254

    PubMed  Google Scholar 

  14. Roos MD, Xie W, Su K, Clark JA, Yang X, Chin E, Paterson AJ, Kudlow JE (1998) Streptozotocin, an analog of N-acetylglucosamine, blocks the removal of O-GlcNAc from intracellular proteins. Proc Assoc Am Physicians 110:422–432

    CAS  PubMed  Google Scholar 

  15. Liu K, Paterson AJ, Chin E, Kudlow JE (2000) Glucose stimulates protein modification by O-linked GlcNAc in pancreatic beta cells: linkage of O-linked GlcNAc to beta cell death. Proc Natl Acad Sci U S A 97:2820–2825

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Hoyer S, Lannert H (2007) Long-term abnormalities in brain glucose/energy metabolism after inhibition of the neuronal insulin receptor: implication of tau-protein. J Neural Transm Suppl 195-202

  17. Saxena G, Bharti S, Kamat PK, Sharma S, Nath C (2010) Melatonin alleviates memory deficits and neuronal degeneration induced by intracerebroventricular administration of streptozotocin in rats. Pharmacol Biochem Behav 94:397–403

    Article  CAS  PubMed  Google Scholar 

  18. Labak M, Foniok T, Kirk D, Rushforth D, Tomanek B, Jasinski A, Grieb P (2010) Metabolic changes in rat brain following intracerebroventricular injections of streptozotocin: a model of sporadic Alzheimer's disease. Acta Neurochir Suppl 106:177–181

    Article  CAS  PubMed  Google Scholar 

  19. Szkudelski T (2001) The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol Res / Acad Sci Bohemoslovaca 50:537–546

    CAS  Google Scholar 

  20. Wang Z, Gleichmann H (1998) GLUT2 in pancreatic islets: crucial target molecule in diabetes induced with multiple low doses of streptozotocin in mice. Diabetes 47:50–56

    Article  CAS  PubMed  Google Scholar 

  21. Schnedl WJ, Ferber S, Johnson JH, Newgard CB (1994) STZ transport and cytotoxicity. Specific enhancement in GLUT2-expressing cells. Diabetes 43:1326–1333

    Article  CAS  PubMed  Google Scholar 

  22. Kumar A, Naidu PS, Seghal N, Padi SS (2007) Neuroprotective effects of resveratrol against intracerebroventricular colchicine-induced cognitive impairment and oxidative stress in rats. Pharmacology 79:17–26

    Article  CAS  PubMed  Google Scholar 

  23. Kamat PK, Tota S, Shukla R, Ali S, Najmi AK, Nath C (2011) Mitochondrial dysfunction: a crucial event in okadaic acid (ICV) induced memory impairment and apoptotic cell death in rat brain. Pharmacol Biochem Behav 100:311–319

    Article  CAS  PubMed  Google Scholar 

  24. Saxena G, Singh SP, Agrawal R, Nath C (2008) Effect of donepezil and tacrine on oxidative stress in intracerebral streptozotocin-induced model of dementia in mice. Eur J Pharmacol 581:283–289

    Article  CAS  PubMed  Google Scholar 

  25. Shoham S, Bejar C, Kovalev E, Schorer-Apelbaum D, Weinstock M (2007) Ladostigil prevents gliosis, oxidative-nitrative stress and memory deficits induced by intracerebroventricular injection of streptozotocin in rats. Neuropharmacology 52:836–843

    Article  CAS  PubMed  Google Scholar 

  26. Ishrat T, Hoda MN, Khan MB, Yousuf S, Ahmad M, Khan MM, Ahmad A, Islam F (2009) Amelioration of cognitive deficits and neurodegeneration by curcumin in rat model of sporadic dementia of Alzheimer's type (SDAT). Eur Neuropsychopharmacol 19:636–647

    Article  CAS  PubMed  Google Scholar 

  27. Ishrat T, Parveen K, Khan MM, Khuwaja G, Khan MB, Yousuf S, Ahmad A, Shrivastav P et al (2009) Selenium prevents cognitive decline and oxidative damage in rat model of streptozotocin-induced experimental dementia of Alzheimer's type. Brain Res 1281:117–127

    Article  CAS  PubMed  Google Scholar 

  28. Agrawal R, Mishra B, Tyagi E, Nath C, Shukla R (2010) Effect of curcumin on brain insulin receptors and memory functions in STZ (ICV) induced dementia model of rat. Pharmacol Res 61:247–252

    Article  CAS  PubMed  Google Scholar 

  29. Awasthi H, Tota S, Hanif K, Nath C, Shukla R (2010) Protective effect of curcumin against intracerebral streptozotocin induced impairment in memory and cerebral blood flow. Life Sci 86:87–94

    Article  CAS  PubMed  Google Scholar 

  30. Tota S, Kamat PK, Awasthi H, Singh N, Raghubir R, Nath C, Hanif K (2009) Candesartan improves memory decline in mice: involvement of AT1 receptors in memory deficit induced by intracerebral streptozotocin. Behav Brain Res 199:235–240

    Article  CAS  PubMed  Google Scholar 

  31. Rai S, Kamat PK, Nath C, Shukla R (2014) Glial activation and post-synaptic neurotoxicity: the key events in Streptozotocin (ICV) induced memory impairment in rats. Pharmacol Biochem Behav 117:104–117

    Article  CAS  PubMed  Google Scholar 

  32. Tesch GH, Allen TJ (2007) Rodent models of streptozotocin-induced diabetic nephropathy. Nephrology 12:261–266

    Article  PubMed  Google Scholar 

  33. Rajasekar N, Dwivedi S, Nath C, Hanif K, Shukla R (2014) Protection of streptozotocin induced insulin receptor dysfunction, neuroinflammation and amyloidogenesis in astrocytes by insulin. Neuropharmacology 86:337–352

    Article  CAS  PubMed  Google Scholar 

  34. Zilka N, Ferencik M, Hulin I (2006) Neuroinflammation in Alzheimer's disease: protector or promoter? Bratisl Lek Listy 107:374–383

    CAS  PubMed  Google Scholar 

  35. Kamat PK, Tota S, Rai S, Swarnkar S, Shukla R, Nath C (2012) A study on neuroinflammatory marker in brain areas of okadaic acid (ICV) induced memory impaired rats. Life Sci 90:713–720

    Article  CAS  PubMed  Google Scholar 

  36. Mrak RE, Griffin WS (2001) Interleukin-1, neuroinflammation, and Alzheimer's disease. Neurobiol Aging 22:903–908

    Article  CAS  PubMed  Google Scholar 

  37. Ifuku M, Katafuchi T, Mawatari S, Noda M, Miake K, Sugiyama M, Fujino T (2012) Anti-inflammatory/anti-amyloidogenic effects of plasmalogens in lipopolysaccharide-induced neuroinflammation in adult mice. J Neuroinflammation 9:197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Skaper SD (2007) The brain as a target for inflammatory processes and neuroprotective strategies. Ann N Y Acad Sci 1122:23–34

    Article  CAS  PubMed  Google Scholar 

  39. Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM, Cooper NR, Eikelenboom P et al (2000) Inflammation and Alzheimer's disease. Neurobiol Aging 21:383–421

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Ricci S, Fuso A, Ippoliti F, Businaro R (2012) Stress-induced cytokines and neuronal dysfunction in Alzheimer's disease. J Alzheimer's Dis : JAD 28:11–24

    CAS  PubMed  Google Scholar 

  41. Bryan KJ, Zhu X, Harris PL, Perry G, Castellani RJ, Smith MA, Casadesus G (2008) Expression of CD74 is increased in neurofibrillary tangles in Alzheimer's disease. Mol Neurodegener 3:13

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Chen J, Buchanan JB, Sparkman NL, Godbout JP, Freund GG, Johnson RW (2008) Neuroinflammation and disruption in working memory in aged mice after acute stimulation of the peripheral innate immune system. Brain Behav Immun 22:301–311

    Article  CAS  PubMed  Google Scholar 

  43. Ownby RL (2010) Neuroinflammation and cognitive aging. Curr Psychiatry Rep 12:39–45

    Article  PubMed  Google Scholar 

  44. Banks WA (2004) Neuroimmune networks and communication pathways: the importance of location. Brain Behav Immun 18:120–122

    Article  PubMed  Google Scholar 

  45. Schechter R, Abboud M (2001) Neuronal synthesized insulin roles on neural differentiation within fetal rat neuron cell cultures. Brain Res Dev Brain Res 127:41–49

    Article  CAS  PubMed  Google Scholar 

  46. Raizada MK, Shemer J, Judkins JH, Clarke DW, Masters BA, LeRoith D (1988) Insulin receptors in the brain: structural and physiological characterization. Neurochem Res 13:297–303

    Article  CAS  PubMed  Google Scholar 

  47. Abbott MA, Wells DG, Fallon JR (1999) The insulin receptor tyrosine kinase substrate p58/53 and the insulin receptor are components of CNS synapses. J Neurosci : Off J Soc Neurosci 19:7300–7308

    CAS  Google Scholar 

  48. Moreira PI, Santos MS, Sena C, Seica R, Oliveira CR (2005) Insulin protects against amyloid beta-peptide toxicity in brain mitochondria of diabetic rats. Neurobiol Dis 18:628–637

    Article  CAS  PubMed  Google Scholar 

  49. Grunblatt E, Salkovic-Petrisic M, Osmanovic J, Riederer P, Hoyer S (2007) Brain insulin system dysfunction in streptozotocin intracerebroventricularly treated rats generates hyperphosphorylated tau protein. J Neurochem 101:757–770

    Article  PubMed  CAS  Google Scholar 

  50. Steen E, Terry BM, Rivera EJ, Cannon JL, Neely TR, Tavares R, Xu XJ, Wands JR et al (2005) Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer's disease—is this type 3 diabetes? J Alzheimer's Dis : JAD 7:63–80

    CAS  PubMed  Google Scholar 

  51. Dong J, Xu H, Xu H, Wang PF, Cai GJ, Song HF, Wang CC, Dong ZT et al (2013) Nesfatin-1 stimulates fatty-acid oxidation by activating AMP-activated protein kinase in STZ-induced type 2 diabetic mice. PLoS One 8:e83397

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Shaw CA, Hoglinger GU (2008) Neurodegenerative diseases: neurotoxins as sufficient etiologic agents? Neruomol Med 10:1–9

    Article  CAS  Google Scholar 

  53. Szkudelski T, Zywert A, Szkudelska K (2013) Metabolic disturbances and defects in insulin secretion in rats with streptozotocin-nicotinamide-induced diabetes. Physiol Res / Acad Sci Bohemoslovaca 62:663–670

    CAS  Google Scholar 

  54. Nelson DW, Murali SG, Liu X, Koopmann MC, Holst JJ, Ney DM (2008) Insulin-like growth factor I and glucagon-like peptide-2 responses to fasting followed by controlled or ad libitum refeeding in rats. Am J Physiol Regul, Integr Comp Physiol 294:R1175–R1184

    Article  CAS  Google Scholar 

  55. Salkovic-Petrisic M, Osmanovic-Barilar J, Bruckner MK, Hoyer S, Arendt T, Riederer P (2011) Cerebral amyloid angiopathy in streptozotocin rat model of sporadic Alzheimer's disease: a long-term follow up study. J Neural Transm 118:765–772

    Article  CAS  PubMed  Google Scholar 

  56. Shingo AS, Kanabayashi T, Murase T, Kito S (2012) Cognitive decline in STZ-3V rats is largely due to dysfunctional insulin signalling through the dentate gyrus. Behav Brain Res 229:378–383

    Article  CAS  PubMed  Google Scholar 

  57. Sharma M, Gupta YK (2001) Intracerebroventricular injection of streptozotocin in rats produces both oxidative stress in the brain and cognitive impairment. Life Sci 68:1021–1029

    Article  CAS  PubMed  Google Scholar 

  58. Kang EB, Cho JY (2014) Effects of treadmill exercise on brain insulin signaling and beta-amyloid in intracerebroventricular streptozotocin induced-memory impairment in rats. J Exerc Nutrition Biochem 18:89–96

    Article  PubMed  PubMed Central  Google Scholar 

  59. Avila J, Hernandez F (2007) GSK-3 inhibitors for Alzheimer's disease. Expert Rev Neurother 7:1527–1533

    Article  CAS  PubMed  Google Scholar 

  60. Salkovic-Petrisic M, Hoyer S (2007) Central insulin resistance as a trigger for sporadic Alzheimer-like pathology: an experimental approach. J Neural Transm Suppl 217-233

  61. Pabbidi RM, Yu SQ, Peng S, Khardori R, Pauza ME, Premkumar LS (2008) Influence of TRPV1 on diabetes-induced alterations in thermal pain sensitivity. Mol Pain 4:9

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Zhu SQ, Kum W, Ho SK, Young JD, Cockram CS (1990) Structure-function relationships of insulin receptor interactions in cultured mouse astrocytes. Brain Res 529:329–332

    Article  CAS  PubMed  Google Scholar 

  63. Burette AC, Park H, Weinberg RJ (2014) Postsynaptic distribution of IRSp53 in spiny excitatory and inhibitory neurons. J Comp Neurol 522:2164–2178

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Heras-Sandoval D, Ferrera P, Arias C (2012) Amyloid-beta protein modulates insulin signaling in presynaptic terminals. Neurochem Res 37:1879–1885

    Article  CAS  PubMed  Google Scholar 

  65. Gerozissis K (2003) Brain insulin: regulation, mechanisms of action and functions. Cell Mol Neurobiol 23:1–25

    Article  PubMed  Google Scholar 

  66. Skeberdis VA, Lan J, Zheng X, Zukin RS, Bennett MV (2001) Insulin promotes rapid delivery of N-methyl-D- aspartate receptors to the cell surface by exocytosis. Proc Natl Acad Sci U S A 98:3561–3566

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. van der Heide LP, Kamal A, Artola A, Gispen WH, Ramakers GM (2005) Insulin modulates hippocampal activity-dependent synaptic plasticity in a N-methyl-d-aspartate receptor and phosphatidyl-inositol-3-kinase-dependent manner. J Neurochem 94:1158–1166

    Article  PubMed  CAS  Google Scholar 

  68. Hooper PL (2007) Insulin signaling, GSK-3, heat shock proteins and the natural history of type 2 diabetes mellitus: a hypothesis. Metab Syndr Relat Disord 5:220–230

    Article  CAS  PubMed  Google Scholar 

  69. Johnson-Farley NN, Patel K, Kim D, Cowen DS (2007) Interaction of FGF-2 with IGF-1 and BDNF in stimulating Akt, ERK, and neuronal survival in hippocampal cultures. Brain Res 1154:40–49

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Sui W, Zou H, Zou G, Yan Q, Chen H, Che W, Xie S (2008) Clinical study of the risk factors of insulin resistance and metabolic syndrome after kidney transplantation. Transpl Immunol 20:95–98

    Article  CAS  PubMed  Google Scholar 

  71. Peineau S, Taghibiglou C, Bradley C, Wong TP, Liu L, Lu J, Lo E, Wu D et al (2007) LTP inhibits LTD in the hippocampus via regulation of GSK3beta. Neuron 53:703–717

    Article  CAS  PubMed  Google Scholar 

  72. Zhu LQ, Wang SH, Liu D, Yin YY, Tian Q, Wang XC, Wang Q, Chen JG et al (2007) Activation of glycogen synthase kinase-3 inhibits long-term potentiation with synapse-associated impairments. J Neurosci : Off J Soc Neurosci 27:12211–12220

    Article  CAS  Google Scholar 

  73. Shonesy BC, Thiruchelvam K, Parameshwaran K, Rahman EA, Karuppagounder SS, Huggins KW, Pinkert CA, Amin R et al (2012) Central insulin resistance and synaptic dysfunction in intracerebroventricular-streptozotocin injected rodents. Neurobiol Aging 33(430):e435–418

    Google Scholar 

  74. Terwel D, Prickaerts J, Meng F, Jolles J (1995) Brain enzyme activities after intracerebroventricular injection of streptozotocin in rats receiving acetyl-L-carnitine. Eur J Pharmacol 287:65–71

    Article  CAS  PubMed  Google Scholar 

  75. Prickaerts J, De Vente J, Honig W, Steinbusch H, Ittersum MMV, Blokland A, Steinbusch HW (2000) Nitric oxide synthase does not mediate neurotoxicity after an i.c.v. injection of streptozotocin in the rat. J Neural Transm 107:745–766

    Article  CAS  PubMed  Google Scholar 

  76. Prickaerts J, Fahrig T, Blokland A (1999) Cognitive performance and biochemical markers in septum, hippocampus and striatum of rats after an i.c.v. injection of streptozotocin: a correlation analysis. Behav Brain Res 102:73–88

    Article  CAS  PubMed  Google Scholar 

  77. Weinstock M, Shoham S (2004) Rat models of dementia based on reductions in regional glucose metabolism, cerebral blood flow and cytochrome oxidase activity. J Neural Transm 111:347–366

    Article  CAS  PubMed  Google Scholar 

  78. Greenfield JP, Tsai J, Gouras GK, Hai B, Thinakaran G, Checler F, Sisodia SS, Greengard P et al (1999) Endoplasmic reticulum and trans-Golgi network generate distinct populations of Alzheimer beta-amyloid peptides. Proc Natl Acad Sci U S A 96:742–747

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Bernardi L, Geracitano S, Colao R, Puccio G, Gallo M, Anfossi M, Frangipane F, Curcio SA et al (2009) AbetaPP A713T mutation in late onset Alzheimer's disease with cerebrovascular lesions. J Alzheimer's Dis : JAD 17:383–389

    CAS  PubMed  Google Scholar 

  80. Bamburg JR, Bloom GS (2009) Cytoskeletal pathologies of Alzheimer disease. Cell Motil Cytoskeleton 66:635–649

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Liu F, Iqbal K, Grundke-Iqbal I, Rossie S, Gong CX (2005) Dephosphorylation of tau by protein phosphatase 5: impairment in Alzheimer's disease. J Biol Chem 280:1790–1796

    Article  CAS  PubMed  Google Scholar 

  82. Iqbal K, Alonso Adel C, Chen S, Chohan MO, El-Akkad E, Gong CX, Khatoon S, Li B et al (2005) Tau pathology in Alzheimer disease and other tauopathies. Biochim Biophys Acta 1739:198–210

    Article  CAS  PubMed  Google Scholar 

  83. Chu WZ, Qian CY (2005) [Expressions of Abeta1-40, Abeta1-42, tau202, tau396 and tau404 after intracerebroventricular injection of streptozotocin in rats]. Di 1 jun yi da xue xue bao = Acad J First Med Coll PLA 25:168–170, 173

    CAS  Google Scholar 

  84. Martin L, Magnaudeix A, Esclaire F, Yardin C, Terro F (2009) Inhibition of glycogen synthase kinase-3beta downregulates total tau proteins in cultured neurons and its reversal by the blockade of protein phosphatase-2A. Brain Res 1252:66–75

    Article  CAS  PubMed  Google Scholar 

  85. Blennow K, de Leon MJ, Zetterberg H (2006) Alzheimer's disease. Lancet 368:387–403

    Article  CAS  PubMed  Google Scholar 

  86. Sharma M, Gupta YK (2003) Effect of alpha lipoic acid on intracerebroventricular streptozotocin model of cognitive impairment in rats. Eur Neuropsychopharmacol 13:241–247

    Article  CAS  PubMed  Google Scholar 

  87. Montgomery SA, Thal LJ, Amrein R (2003) Meta-analysis of double blind randomized controlled clinical trials of acetyl-L-carnitine versus placebo in the treatment of mild cognitive impairment and mild Alzheimer's disease. Int Clin Psychopharmacol 18:61–71

    Article  PubMed  Google Scholar 

  88. Bonda DJ, Wang X, Perry G, Nunomura A, Tabaton M, Zhu X, Smith MA (2010) Oxidative stress in Alzheimer disease: a possibility for prevention. Neuropharmacology 59:290–294

    Article  CAS  PubMed  Google Scholar 

  89. Galasko DR, Peskind E, Clark CM, Quinn JF, Ringman JM, Jicha GA, Cotman C, Cottrell B et al (2012) Antioxidants for Alzheimer disease: a randomized clinical trial with cerebrospinal fluid biomarker measures. Arch Neurol 69:836–841

    Article  PubMed  PubMed Central  Google Scholar 

  90. Wollmer MA, Streffer JR, Tsolaki M, Grimaldi LM, Lutjohann D, Thal D, von Bergmann K, Nitsch RM et al (2003) Genetic association of acyl-coenzyme A: cholesterol acyltransferase with cerebrospinal fluid cholesterol levels, brain amyloid load, and risk for Alzheimer's disease. Mol Psychiatry 8:635–638

    Article  CAS  PubMed  Google Scholar 

  91. Ishrat T, Khan MB, Hoda MN, Yousuf S, Ahmad M, Ansari MA, Ahmad AS, Islam F (2006) Coenzyme Q10 modulates cognitive impairment against intracerebroventricular injection of streptozotocin in rats. Behav Brain Res 171:9–16

    Article  CAS  PubMed  Google Scholar 

  92. Misra S, Tiwari V, Kuhad A, Chopra K (2011) Modulation of nitrergic pathway by sesamol prevents cognitive deficits and associated biochemical alterations in intracerebroventricular streptozotocin administered rats. Eur J Pharmacol 659:177–186

    Article  CAS  PubMed  Google Scholar 

  93. Khan MB, Hoda MN, Ishrat T, Ahmad S, Moshahid Khan M, Ahmad A, Yusuf S, Islam F (2012) Neuroprotective efficacy of Nardostachys jatamansi and crocetin in conjunction with selenium in cognitive impairment. Neurol Sci 33:1011–1020

    Article  PubMed  Google Scholar 

  94. Tiwari V, Kuhad A, Bishnoi M, Chopra K (2009) Chronic treatment with tocotrienol, an isoform of vitamin E, prevents intracerebroventricular streptozotocin-induced cognitive impairment and oxidative-nitrosative stress in rats. Pharmacol Biochem Behav 93:183–189

    Article  CAS  PubMed  Google Scholar 

  95. Vingtdeux V, Dreses-Werringloer U, Zhao H, Davies P, Marambaud P (2008) Therapeutic potential of resveratrol in Alzheimer's disease. BMC Neurosci 9(Suppl 2):S6

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  96. Riviere C, Richard T, Quentin L, Krisa S, Merillon JM, Monti JP (2007) Inhibitory activity of stilbenes on Alzheimer's beta-amyloid fibrils in vitro. Bioorg Med Chem 15:1160–1167

    Article  CAS  PubMed  Google Scholar 

  97. Sharma M, Gupta YK (2002) Chronic treatment with trans resveratrol prevents intracerebroventricular streptozotocin induced cognitive impairment and oxidative stress in rats. Life Sci 71:2489–2498

    Article  CAS  PubMed  Google Scholar 

  98. Baum L, Ng A (2004) Curcumin interaction with copper and iron suggests one possible mechanism of action in Alzheimer's disease animal models. J Alzheimer's Dis : JAD 6:367–377, discussion 443-369

    CAS  PubMed  Google Scholar 

  99. Ma QL, Yang F, Rosario ER, Ubeda OJ, Beech W, Gant DJ, Chen PP, Hudspeth B et al (2009) Beta-amyloid oligomers induce phosphorylation of tau and inactivation of insulin receptor substrate via c-Jun N-terminal kinase signaling: suppression by omega-3 fatty acids and curcumin. J Neurosci : Off J Soc Neurosci 29:9078–9089

    Article  CAS  Google Scholar 

  100. Sodhi RK, Singh N (2013) Defensive effect of lansoprazole in dementia of AD type in mice exposed to streptozotocin and cholesterol enriched diet. PLoS One 8:e70487

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Tota S, Awasthi H, Kamat PK, Nath C, Hanif K (2010) Protective effect of quercetin against intracerebral streptozotocin induced reduction in cerebral blood flow and impairment of memory in mice. Behav Brain Res 209:73–79

    Article  CAS  PubMed  Google Scholar 

  102. Tota S, Kamat PK, Shukla R, Nath C (2011) Improvement of brain energy metabolism and cholinergic functions contributes to the beneficial effects of silibinin against streptozotocin induced memory impairment. Behav Brain Res 221:207–215

    Article  CAS  PubMed  Google Scholar 

  103. Javed H, Khan MM, Ahmad A, Vaibhav K, Ahmad ME, Khan A, Ashafaq M, Islam F et al (2012) Rutin prevents cognitive impairments by ameliorating oxidative stress and neuroinflammation in rat model of sporadic dementia of Alzheimer type. Neuroscience 210:340–352

    Article  CAS  PubMed  Google Scholar 

  104. Wallen EP, Yochim JM (1975) An analysis of the pineal hydroxyindole-O-methyl transferase rhythm during the estrous cycle of the rat. Adv Exp Med Biol 54:79–84

    Article  CAS  PubMed  Google Scholar 

  105. Agrawal R, Tyagi E, Shukla R, Nath C (2009) A study of brain insulin receptors, AChE activity and oxidative stress in rat model of ICV STZ induced dementia. Neuropharmacology 56:779–787

    Article  CAS  PubMed  Google Scholar 

  106. Dragicevic N, Copes N, O'Neal-Moffitt G, Jin J, Buzzeo R, Mamcarz M, Tan J, Cao C et al (2011) Melatonin treatment restores mitochondrial function in Alzheimer's mice: a mitochondrial protective role of melatonin membrane receptor signaling. J Pineal Res 51:75–86

    Article  CAS  PubMed  Google Scholar 

  107. Kumar R, Jaggi AS, Singh N (2010) Effects of erythropoietin on memory deficits and brain oxidative stress in the mouse models of dementia. Korean J Physiol Pharmacol 14:345–352

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Sharma B, Singh N, Singh M, Jaggi AS (2008) Exploitation of HIV protease inhibitor Indinavir as a memory restorative agent in experimental dementia. Pharmacol Biochem Behav 89:535–545

    Article  CAS  PubMed  Google Scholar 

  109. Sharma V, Bala A, Deshmukh R, Bedi KL, Sharma PL (2012) Neuroprotective effect of RO-20-1724-a phosphodiesterase4 inhibitor against intracerebroventricular streptozotocin induced cognitive deficit and oxidative stress in rats. Pharmacol Biochem Behav 101:239–245

    Article  CAS  PubMed  Google Scholar 

  110. Birks J, Grimley Evans J (2009) Ginkgo biloba for cognitive impairment and dementia. The Cochrane database of systematic reviews CD003120

  111. Kupershmidt L, Amit T, Bar-Am O, Youdim MB, Weinreb O (2012) The novel multi-target iron chelating-radical scavenging compound M30 possesses beneficial effects on major hallmarks of Alzheimer's disease. Antioxid Redox Signal 17:860–877

    Article  CAS  PubMed  Google Scholar 

  112. Melnikova T, Savonenko A, Wang Q, Liang X, Hand T, Wu L, Kaufmann WE, Vehmas A et al (2006) Cycloxygenase-2 activity promotes cognitive deficits but not increased amyloid burden in a model of Alzheimer's disease in a sex-dimorphic pattern. Neuroscience 141:1149–1162

    Article  CAS  PubMed  Google Scholar 

  113. Dhull DK, Jindal A, Dhull RK, Aggarwal S, Bhateja D, Padi SS (2012) Neuroprotective effect of cyclooxygenase inhibitors in ICV-STZ induced sporadic Alzheimer's disease in rats. J Mol Neurosci : MN 46:223–235

    Article  CAS  PubMed  Google Scholar 

  114. Yan Q, Zhang J, Liu H, Babu-Khan S, Vassar R, Biere AL, Citron M, Landreth G (2003) Anti-inflammatory drug therapy alters beta-amyloid processing and deposition in an animal model of Alzheimer's disease. J Neurosci : Off J Soc Neurosci 23:7504–7509

    CAS  Google Scholar 

  115. Heneka MT, Sastre M, Dumitrescu-Ozimek L, Hanke A, Dewachter I, Kuiperi C, O'Banion K, Klockgether T et al (2005) Acute treatment with the PPARgamma agonist pioglitazone and ibuprofen reduces glial inflammation and Abeta1-42 levels in APPV717I transgenic mice. Brain : J Neurol 128:1442–1453

    Article  Google Scholar 

  116. Geldmacher DS, Fritsch T, McClendon MJ, Landreth G (2011) A randomized pilot clinical trial of the safety of pioglitazone in treatment of patients with Alzheimer disease. Arch Neurol 68:45–50

    PubMed  Google Scholar 

  117. Ponce-Lopez T, Liy-Salmeron G, Hong E, Meneses A (2011) Lithium, phenserine, memantine and pioglitazone reverse memory deficit and restore phospho-GSK3beta decreased in hippocampus in intracerebroventricular streptozotocin induced memory deficit model. Brain Res 1426:73–85

    Article  CAS  PubMed  Google Scholar 

  118. Pathan AR, Viswanad B, Sonkusare SK, Ramarao P (2006) Chronic administration of pioglitazone attenuates intracerebroventricular streptozotocin induced-memory impairment in rats. Life Sci 79:2209–2216

    Article  CAS  PubMed  Google Scholar 

  119. Harrington C, Sawchak S, Chiang C, Davies J, Donovan C, Saunders AM, Irizarry M, Jeter B et al (2011) Rosiglitazone does not improve cognition or global function when used as adjunctive therapy to AChE inhibitors in mild-to-moderate Alzheimer's disease: two phase 3 studies. Current Alzheimer research 8:592–606

    Article  CAS  PubMed  Google Scholar 

  120. Tzimopoulou S, Cunningham VJ, Nichols TE, Searle G, Bird NP, Mistry P, Dixon IJ, Hallett WA et al (2010) A multi-center randomized proof-of-concept clinical trial applying [(1)(8)F]FDG-PET for evaluation of metabolic therapy with rosiglitazone XR in mild to moderate Alzheimer's disease. J Alzheimer's Dis : JAD 22:1241–1256

    CAS  PubMed  Google Scholar 

  121. Rinwa P, Kaur B, Jaggi AS, Singh N (2010) Involvement of PPAR-gamma in curcumin-mediated beneficial effects in experimental dementia. Naunyn Schmiedeberg's Arch Pharmacol 381:529–539

    Article  CAS  Google Scholar 

  122. Sonkusare S, Srinivasan K, Kaul C, Ramarao P (2005) Effect of donepezil and lercanidipine on memory impairment induced by intracerebroventricular streptozotocin in rats. Life Sci 77:1–14

    Article  CAS  PubMed  Google Scholar 

  123. Cutuli D, De Bartolo P, Caporali P, Tartaglione AM, Oddi D, D'Amato FR, Nobili A, D'Amelio M et al (2013) Neuroprotective effects of donepezil against cholinergic depletion. Alzheimers Res Ther 5:50

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  124. Saxena G, Patro IK, Nath C (2011) ICV STZ induced impairment in memory and neuronal mitochondrial function: a protective role of nicotinic receptor. Behav Brain Res 224:50–57

    Article  CAS  PubMed  Google Scholar 

  125. Kusari J, Zhou S, Padillo E, Clarke KG, Gil DW (2007) Effect of memantine on neuroretinal function and retinal vascular changes of streptozotocin-induced diabetic rats. Invest Ophthalmol Vis Sci 48:5152–5159

    Article  PubMed  Google Scholar 

  126. Nayebi AM, Pourrabi S, Hossini S (2014) Testosterone ameliorates streptozotocin-induced memory impairment in male rats. Acta Pharmacol Sin 35:752–757

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Pachauri SD, Verma PR, Dwivedi AK, Tota S, Khandelwal K, Saxena JK, Nath C (2013) Ameliorative effect of Noni fruit extract on streptozotocin-induced memory impairment in mice. Behav Pharmacol 24:307–319

    Article  CAS  PubMed  Google Scholar 

  128. Biasibetti R, Tramontina AC, Costa AP, Dutra MF, Quincozes-Santos A, Nardin P, Bernardi CL, Wartchow KM et al (2013) Green tea (-)epigallocatechin-3-gallate reverses oxidative stress and reduces acetylcholinesterase activity in a streptozotocin-induced model of dementia. Behav Brain Res 236:186–193

    Article  CAS  PubMed  Google Scholar 

  129. da Costa AV, Calabria LK, Furtado FB, de Gouveia NM, Oliveira RJ, de Oliveira VN, Beletti ME, Espindola FS (2013) Neuroprotective effects of Pouteria ramiflora (Mart.) Radlk (Sapotaceae) extract on the brains of rats with streptozotocin-induced diabetes. Metab Brain Dis 28:411–419

    Article  PubMed  Google Scholar 

  130. Mushtaq N, Schmatz R, Pereira LB, Ahmad M, Stefanello N, Vieira JM, Abdalla F, Rodrigues MV et al (2014) Rosmarinic acid prevents lipid peroxidation and increase in acetylcholinesterase activity in brain of streptozotocin-induced diabetic rats. Cell Biochem Funct 32:287–293

    Article  CAS  PubMed  Google Scholar 

  131. Tota S, Nath C, Najmi AK, Shukla R, Hanif K (2012) Inhibition of central angiotensin converting enzyme ameliorates scopolamine induced memory impairment in mice: role of cholinergic neurotransmission, cerebral blood flow and brain energy metabolism. Behav Brain Res 232:66–76

    Article  CAS  PubMed  Google Scholar 

  132. Agrawal R, Tyagi E, Shukla R, Nath C (2011) Insulin receptor signaling in rat hippocampus: a study in STZ (ICV) induced memory deficit model. Eur Neuropsychopharmacol 21:261–273

    Article  CAS  PubMed  Google Scholar 

  133. Saxena G, Singh SP, Pal R, Singh S, Pratap R, Nath C (2007) Gugulipid, an extract of Commiphora whighitii with lipid-lowering properties, has protective effects against streptozotocin-induced memory deficits in mice. Pharmacol Biochem Behav 86:797–805

    Article  CAS  PubMed  Google Scholar 

  134. Singh B, Sharma B, Jaggi AS, Singh N (2013) Attenuating effect of lisinopril and telmisartan in intracerebroventricular streptozotocin induced experimental dementia of Alzheimer's disease type: possible involvement of PPAR-gamma agonistic property. J Renin-Angiotensin-Aldosterone Syst : JRAAS 14:124–136

    Article  CAS  PubMed  Google Scholar 

  135. Lakshmanan AP, Watanabe K, Thandavarayan RA, Sari FR, Harima M, Giridharan VV, Soetikno V, Kodama M et al (2011) Telmisartan attenuates oxidative stress and renal fibrosis in streptozotocin induced diabetic mice with the alteration of angiotensin-(1-7) mas receptor expression associated with its PPAR-gamma agonist action. Free Radic Res 45:575–584

    Article  CAS  PubMed  Google Scholar 

  136. Sodhi RK, Singh N (2014) Liver X receptor agonist T0901317 reduces neuropathological changes and improves memory in mouse models of experimental dementia. Eur J Pharmacol 732:50–59

    Article  CAS  PubMed  Google Scholar 

  137. Song J, Hur BE, Bokara KK, Yang W, Cho HJ, Park KA, Lee WT, Lee KM et al (2014) Agmatine improves cognitive dysfunction and prevents cell death in a streptozotocin-induced Alzheimer rat model. Yonsei Med J 55:689–699

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Mansouri MT, Naghizadeh B, Ghorbanzadeh B, Farbood Y, Sarkaki A, Bavarsad K (2013) Gallic acid prevents memory deficits and oxidative stress induced by intracerebroventricular injection of streptozotocin in rats. Pharmacol Biochem Behav 111:90–96

    Article  CAS  PubMed  Google Scholar 

  139. Javed H, Khan MM, Khan A, Vaibhav K, Ahmad A, Khuwaja G, Ahmed ME, Raza SS et al (2011) S-allyl cysteine attenuates oxidative stress associated cognitive impairment and neurodegeneration in mouse model of streptozotocin-induced experimental dementia of Alzheimer's type. Brain Res 1389:133–142

    Article  CAS  PubMed  Google Scholar 

  140. Khan MB, Khan MM, Khan A, Ahmed ME, Ishrat T, Tabassum R, Vaibhav K, Ahmad A et al (2012) Naringenin ameliorates Alzheimer's disease (AD)-type neurodegeneration with cognitive impairment (AD-TNDCI) caused by the intracerebroventricular-streptozotocin in rat model. Neurochem Int 61:1081–1093

    Article  CAS  PubMed  Google Scholar 

  141. Sachdeva S, Flora SJ (2014) Efficacy of some antioxidants supplementation in reducing oxidative stress post sodium tungstate exposure in male wistar rats. J Trace Elem Med Biol 28:233–239

    Article  CAS  PubMed  Google Scholar 

  142. Javed H, Khan A, Vaibhav K, Moshahid Khan M, Ahmad A, Ejaz Ahmad M, Ahmad A, Tabassum R et al (2013) Taurine ameliorates neurobehavioral, neurochemical and immunohistochemical changes in sporadic dementia of Alzheimer's type (SDAT) caused by intracerebroventricular streptozotocin in rats. Neurol Sci 34:2181–2192

    Article  PubMed  Google Scholar 

  143. Liu P, Zou L, Jiao Q, Chi T, Ji X, Qi Y, Xu Q, Wang L (2013) Xanthoceraside attenuates learning and memory deficits via improving insulin signaling in STZ-induced AD rats. Neurosci Lett 543:115–120

    Article  CAS  PubMed  Google Scholar 

  144. Naghizadeh B, Mansouri MT, Ghorbanzadeh B, Farbood Y, Sarkaki A (2013) Protective effects of oral crocin against intracerebroventricular streptozotocin-induced spatial memory deficit and oxidative stress in rats. Phytomedicine 20:537–542

    Article  CAS  PubMed  Google Scholar 

  145. Khalili M, Hamzeh F (2010) Effects of active constituents of Crocus sativus L., crocin on streptozocin-induced model of sporadic Alzheimer's disease in male rats. Iran Biomed J 14:59–65

    CAS  PubMed  PubMed Central  Google Scholar 

  146. Veerendra Kumar MH, Gupta YK (2003) Effect of Centella asiatica on cognition and oxidative stress in an intracerebroventricular streptozotocin model of Alzheimer's disease in rats. Clin Exp Pharmacol Physiol 30:336–342

    Article  CAS  PubMed  Google Scholar 

  147. Khan MB, Ahmad M, Ahmad S, Ishrat T, Vaibhav K, Khuwaja G, Islam F (2015) Bacopa monniera ameliorates cognitive impairment and neurodegeneration induced by intracerebroventricular-streptozotocin in rat: behavioral, biochemical, immunohistochemical and histopathological evidences. Metab Brain Dis 30:115–127

    Article  CAS  PubMed  Google Scholar 

  148. Unsal C, Oran M, Albayrak Y, Aktas C, Erboga M, Topcu B, Uygur R, Tulubas F, Yanartas O, Ates O, Ozen OA (2013) Neuroprotective effect of ebselen against intracerebroventricular streptozotocin-induced neuronal apoptosis and oxidative stress in rats. Toxicol Ind Health

  149. Prakash A, Kalra JK, Kumar A (2015) Neuroprotective effect of N-acetyl cysteine against streptozotocin-induced memory dysfunction and oxidative damage in rats. J Basic Clin Physiol Pharmacol 26:13–23

    Article  CAS  PubMed  Google Scholar 

  150. Sharma B, Singh N, Singh M (2008) Modulation of celecoxib- and streptozotocin-induced experimental dementia of Alzheimer's disease by pitavastatin and donepezil. J Psychopharmacol 22:162–171

    Article  CAS  PubMed  Google Scholar 

  151. Mehla J, Pahuja M, Dethe SM, Agarwal A, Gupta YK (2012) Amelioration of intracerebroventricular streptozotocin induced cognitive impairment by Evolvulus alsinoides in rats: in vitro and in vivo evidence. Neurochem Int 61:1052–1064

    Article  CAS  PubMed  Google Scholar 

  152. Kumar A, Sharma S, Prashar A, Deshmukh R (2015) Effect of licofelone—a dual COX/5-LOX inhibitor in intracerebroventricular streptozotocin-induced behavioral and biochemical abnormalities in rats. J Mol Neurosci : MN 55:749–759

    Article  CAS  PubMed  Google Scholar 

  153. Jee YS, Ko IG, Sung YH, Lee JW, Kim YS, Kim SE, Kim BK, Seo JH et al (2008) Effects of treadmill exercise on memory and c-Fos expression in the hippocampus of the rats with intracerebroventricular injection of streptozotocin. Neurosci Lett 443:188–192

    Article  CAS  PubMed  Google Scholar 

  154. Rodrigues L, Dutra MF, Ilha J, Biasibetti R, Quincozes-Santos A, Leite MC, Marcuzzo S, Achaval M et al (2010) Treadmill training restores spatial cognitive deficits and neurochemical alterations in the hippocampus of rats submitted to an intracerebroventricular administration of streptozotocin. J Neural Transm 117:1295–1305

    Article  CAS  PubMed  Google Scholar 

  155. Khan MB, Hoda MN, Yousuf S, Ishrat T, Ahmad M, Ahmad AS, Alavi SH, Haque N et al (2006) Prevention of cognitive impairments and neurodegeneration by Khamira Abresham Hakim Arshad Wala. J Ethnopharmacol 108:68–73

    Article  PubMed  Google Scholar 

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Acknowledgments

This work was supported in part by the Council of Scientific and Industrial Research (CSIR), India, and financial support to Pradip Kumar Kamat from National Institute of Health, USA, is greatly acknowledged. We are thankful to Dr. Maneesh K. Gupta for the supports for drawing chemical structures (The Hebrew University, Jerusalem), Israel.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Anesthesiology, Center for Translational Research in Neurodegenerative Disease (CTRND), College of Medicin, University of Florida, Gainesville, FL, 32610, USA

    Pradip K. Kamat & Abdullah S. Ahmad

  2. Division of Physiology and Biophysics, School of Medicine, University of Louisville, Louisville, KY, 40202, USA

    Anuradha Kalani

  3. Division of Pharmacology, CSIR-Central drug Research Institute (CDRI), Lucknow, 226031, India

    Shivika Rai & Santosh Kumar Tota

  4. The Academy of Scientific & Innovative Research (AcSIR), New Delhi, 110025, India

    Shivika Rai

  5. McKnight Brain Institute, University of Florida, Gainesville, FL, 32610, USA

    Ashok Kumar

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  1. Pradip K. Kamat
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  2. Anuradha Kalani
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  3. Shivika Rai
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  4. Santosh Kumar Tota
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Correspondence to Pradip K. Kamat.

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Kamat, P.K., Kalani, A., Rai, S. et al. Streptozotocin Intracerebroventricular-Induced Neurotoxicity and Brain Insulin Resistance: a Therapeutic Intervention for Treatment of Sporadic Alzheimer’s Disease (sAD)-Like Pathology. Mol Neurobiol 53, 4548–4562 (2016). https://doi.org/10.1007/s12035-015-9384-y

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  • DOI: https://doi.org/10.1007/s12035-015-9384-y

Keywords

  • Streptozotocin
  • Insulin
  • Kinase
  • Neuroinflammation
  • Alzheimer’s disease