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What have we learned from the streptozotocin-induced animal model of sporadic Alzheimer’s disease, about the therapeutic strategies in Alzheimer’s research

  • Dementias - Review article
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Abstract

Experimental models that faithfully mimic the developmental pathology of sporadic Alzheimer’s disease (sAD) in humans are important for testing the novel therapeutic approaches in sAD treatment. Widely used transgenic mice AD models have provided valuable insights into the molecular mechanisms underlying the memory decline but, due to the particular β-amyloid-related gene manipulation, they resemble the familial but not the sporadic AD form, and are, therefore, inappropriate for this purpose. In line with the recent findings of sAD being recognised as an insulin resistant brains state (IRBS), a new, non-transgenic, animal model has been proposed as a representative model of sAD, developed by intracerebroventricular application of the betacytotoxic drug streptozotocin (STZ-icv). The STZ-icv-treated animals (mostly rats and mice) develop IRBS associated with memory impairment and progressive cholinergic deficits, glucose hypometabolism, oxidative stress and neurodegeneration that share many features in common with sAD in humans. The therapeutic strategies (acetylcholinesterase inhibitors, antioxidants and many other drugs) that have been tested until now on the STZ-icv animal model have been reviewed and the comparability of the drugs’ efficacy in this non-transgenic sAD model and the results from clinical trials on sAD patients, evaluated.

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References

  • 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  PubMed  CAS  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

  • Akasofu S, Kimura M, Kosasa T, Sawada K, Ogura H (2008) Study of neuroprotection of donepezil, a therapy for Alzheimer's disease. Chem Biol Interact 175:222–226

    Google Scholar 

  • Arrieta-Cruz I, Wang J, Pavlides C, Pasinetti GM (2010) Carvedilol reestablishes long-term potentiation in a mouse model of Alzheimer’s disease. J Alzheimers Dis 21:649–654

    PubMed  CAS  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

  • Baum L, Ng A (2004) Curcumin interaction with copper and iron suggests one possible mechanism of action in Alzheimer’s disease animal models. J Alzheimers Dis 6:367–377

    PubMed  CAS  Google Scholar 

  • Bi H, Sze CI (2002) N-methyl-D-aspartate receptor subunit NR2A and NR2B messenger RNA levels are altered in the hippocampus and entorhinal cortex in Alzheimer's disease. J Neurol Sci 200:11–18

    Google Scholar 

  • Birks J, Grimley Evans J (2009) Ginkgo biloba for cognitive impairment and dementia. Cochrane Database Syst Rev 21:CD003120

    Google Scholar 

  • Blokland A, Jolles J (1993) Spatial learning deficit and reduced hippocampal ChAT activity in rats after an ICV injection of streptozotocin. Pharmacol Biochem Behav 44:491–494

    Article  PubMed  CAS  Google Scholar 

  • Blokland A, Jolles J (1994) Behavioral and biochemical effects of an ICV injection of streptozotocin in old Lewis rats. Pharmacol Biochem Behav 47:833–837

    Article  PubMed  CAS  Google Scholar 

  • Blondel O, Portha B (1989) Early appearance of in vivo insulin resistance in adult streptozotocin-injected rats. Diabete Metab 15:382–387

    PubMed  CAS  Google Scholar 

  • Boimel M, Grigoriadis N, Lourbopoulos A, Touloumi O, Rosenmann D, Abramsky O, Rosenmann H (2009) Statins reduce the neurofibrillary tangle burden in a mouse model of tauopathy. J Neuropathol Exp Neurol 68:314–325

    Article  PubMed  CAS  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

  • Borroni B, Grassi M, Agosti C, Costanzi C, Archetti S, Franzoni S, Caltagirone C, Di Luca M, Caimi L, Padovani A (2006) Genetic correlates of behavioral endophenotypes in Alzheimer disease: role of COMT, 5-HTTLPR and APOE polymorphisms. Neurobiol Aging 27:1595–1603

    Article  PubMed  CAS  Google Scholar 

  • Bosco D, Fava A, Plastino M, Montalcini T, Pujia A (2011) Possible implications of insulin resistance and glucose metabolism in Alzheimer’s disease pathogenesis. J Cell Mol Med 15:1807–1821

    Article  PubMed  CAS  Google Scholar 

  • Braida D, Paladini E, Griffini P, Lamperti M, Maggi A, Sala M (1996) An inverted U-shaped curve for heptylphysostigmine on radial maze performance in rats: comparison with other cholinesterase inhibitors. Eur J Pharmacol 302:13–20

    Article  PubMed  CAS  Google Scholar 

  • Breitner JC, Baker LD, Montine TJ, Meinert CL, Lyketsos CG, Ashe KH, Brandt J, Craft S, Evans DE, Green RC, Ismail MS, Martin BK, Mullan MJ, Sabbagh M, Tariot PN (2011) ADAPT Research Group. Extended results of the Alzheimer’s disease anti-inflammatory prevention trial. Alzheimers Dement 7:402–411

    Article  PubMed  Google Scholar 

  • Carroll JC, Rosario ER, Chang L, Stanczyk FZ, Oddo S, LaFerla FM, Pike CJ (2007) Progesterone and estrogen regulate Alzheimer-like neuropathology in female 3xTg-AD mice. J Neurosci 27:13357–133365

    Article  PubMed  CAS  Google Scholar 

  • Castellani RJ, Moreira PI, Liu G, Dobson J, Perry G, Smith MA, Zhu X (2007) Iron: the redox-active center of oxidative stress in Alzheimer disease. Neurochem Res 32:1640–1645

    Article  PubMed  CAS  Google Scholar 

  • Castellani RJ, Moreira PI, Perry G, Zhu X (2012) The role of iron as a mediator of oxidative stress in Alzheimer disease. BioFactors 38:133–138

    Article  PubMed  CAS  Google Scholar 

  • Chen S, Liu AR, An FM, Yao WB, Gao XD (2011) Amelioration of neurodegenerative changes in cellular and rat models of diabetes-related Alzheimer’s disease by exendin-4. Age (Dordr) Sep 8 [Epub ahead of print]. doi:10.1007/s11357-011-9303-8

  • Connor B, Young D, Yan Q, Faull RL, Synek B, Dragunow M (1997) Brain-derived neurotrophic factor is reduced in Alzheimer's disease. Brain Res Mol Brain Res 49:71–81

    Google Scholar 

  • Correia SC, Santos RX, Perry G, Zhu X, Moreira PI, Smith MA (2011) Insulin-resistant brain state: the culprit in sporadic Alzheimer’s disease? Ageing Res Rev 10:264–273

    Article  PubMed  CAS  Google Scholar 

  • Dalla Y, Singh N, Jaggi AS, Singh D, Ghulati P (2009) Potential of ezetimibe in memory deficits associated with dementia of Alzheimer’s type in mice. Indian J Pharmacol 41:262–267

    Article  PubMed  CAS  Google Scholar 

  • Dalla Y, Singh N, Jaggi AS, Singh D (2010) Memory restorative role of statins in experimental dementia: an evidence of their cholesterol dependent and independent actions. Pharmacol Rep 62:784–796

    PubMed  CAS  Google Scholar 

  • Danielyan L, Klein R, Hanson LR, Buadze M, Schwab M, Gleiter CH, Frey WH (2010) Protective effects of intranasal losartan in the APP/PS1 transgenic mouse model of Alzheimer disease. Rejuvenation Res 13:195–201

    Article  PubMed  CAS  Google Scholar 

  • de la Monte SM, Wands JR (2005) Review of insulin and insulin-like growth factor expression, signaling, and malfunction in the central nervous system: relevance to Alzheimer’s disease. J Alzheimers Dis 7:45–61

    PubMed  Google Scholar 

  • de la Monte SM, Tong M, Lester-Coll N, Plater M Jr, Wands JR (2006) Therapeutic rescue of neurodegeneration in experimental type 3 diabetes: relevance to Alzheimer’s disease. J Alzheimers Dis 10:89–109

    PubMed  Google Scholar 

  • Degerman Gunnarsson M, Kilander L, Basun H, Lannfelt L (2007) Reduction of phosphorylated tau during memantine treatment of Alzheimer’s disease. Dement Geriatr Cogn Disord 24:247–252

    Article  PubMed  CAS  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

  • Dhull DK, Bhateja D, Dhull RK, Padi SS (2012a) Differential role of cyclooxygenase isozymes on neuronal density in hippocampus CA1 region of intracerebroventricular streptozotocin treated rat brain. J Chem Neuroanat 43:48–51

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Diwu YC, Tian JZ, Shi J (2011) Effects of Chinese herbal medicine Yinsiwei compound on spatial learning and memory ability and the ultrastructure of hippocampal neurons in a rat model of sporadic Alzheimer disease. Zhong Xi Yi Jie He Xue Bao 9:209–215

    Article  PubMed  Google Scholar 

  • Dodart JC, Bales KR, Gannon KS, Greene SJ, DeMattos RB, Mathis C, DeLong CA, Wu S, Wu X, Holtzman DM, Paul SM (2002) Immunization reverses memory deficits without reducing brain Abeta burden in Alzheimer’s disease model. Nat Neurosci 5:452–457

    PubMed  CAS  Google Scholar 

  • Dong YF, Kataoka K, Tokutomi Y, Nako H, Nakamura T, Toyama K, Sueta D, Koibuchi N, Yamamoto E, Ogawa H, Kim-Mitsuyama S (2011) Perindopril, a centrally active angiotensin-convertingenzymeinhibitor, prevents cognitive impairment in mouse models of Alzheimer’s disease. FASEB J 25:2911–2920

    Article  PubMed  CAS  Google Scholar 

  • Dragicevic N, Copes N, O’Neal-Moffitt G, Jin J, Buzzeo R, Mamcarz M, Tan J, Cao C, Olcese JM, Arendash GW, Bradshaw PC (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  PubMed  CAS  Google Scholar 

  • Escribano L, Simón AM, Gimeno E, Cuadrado-Tejedor M, López de Maturana R, García-Osta A, Ricobaraza A, Pérez-Mediavilla A, Del Río J, Frechilla D (2010) Rosiglitazone rescues memory impairment in Alzheimer’s transgenic mice: mechanisms involving a reduced amyloid and tau pathology. Neuropsychopharmacology 35:1593–1604

    Article  PubMed  CAS  Google Scholar 

  • Forlenza OV, Diniz BS, Radanovic M, Santos FS, Talib LL, Gattaz WF (2011) Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial. Br J Psychiatry 198:351–356

    Article  PubMed  Google Scholar 

  • Frölich L, Blum-Degen D, Bernstein HG, Engelsberger S, Humrich J, Laufer S, Muschner D, Thalheimer A, Turk A, Hoyer S, Zöchling R, Boissl KW, Jellinger K, Riederer P (1998) Brain insulin and insulin receptors in aging and sporadic Alzheimer’s disease. J Neural Transm 105:423–438

    Article  PubMed  Google Scholar 

  • Galasko DR, Peskind E, Clark CM, Quinn JF, Ringman JM, Jicha GA, Cotman C, Cottrell B, Montine TJ, Thomas RG, Aisen P (2012) Antioxidants for Alzheimer disease: a randomized clinical trial with cerebrospinal fluid biomarker measures. Arch Neurol 2012 Mar 19. [Epub ahead of print]. doi:10.1001/archneurol.2012.85

  • 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

    Article  PubMed  Google Scholar 

  • Ghosh AK, Brindisi M, Tang J (2012) Developing β-secretase inhibitors for treatment of Alzheimer’s disease. J Neurochem 120(Suppl 1):71–83

    Article  PubMed  CAS  Google Scholar 

  • Giorgino F, Chen JH, Smith RJ (1992) Changes in tyrosine phosphorylation of insulin receptors and a 170,000 molecular weight non-receptor protein in vivo in skeletal muscle of streptozotocin-induced diabetic rats: effects of insulin and glucose. Endocrinology 130:1433–1444

    Article  PubMed  CAS  Google Scholar 

  • Götz ME, Künig G, Riederer P, Youdim MB (1994) Oxidative stress: free radical production in neural degeneration. Pharmacol Ther 63:37–122

    Article  PubMed  Google Scholar 

  • Greenwald BS, Davis KL (1983) Experimental pharmacology of Alzheimer disease. Adv Neurol 38:87–102

    PubMed  CAS  Google Scholar 

  • Grünblatt E, Hoyer S, Riederer P (2004) Gene expression profile in streptozotocin rat model for sporadic Alzheimer’s disease. J Neural Transm 111:367–386

    Article  PubMed  CAS  Google Scholar 

  • Grünblatt 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 

  • Gutzmann H, Hadler D (1998) Sustained efficacy and safety of idebenone in the treatment of Alzheimer’s disease: update on a 2-year double-blind multicentre study. J Neural Transm Suppl 54:301–310

    PubMed  CAS  Google Scholar 

  • Hager K, Kenklies M, McAfoose J, Engel J, Münch G (2007) Alpha-lipoic acid as a new treatment option for Alzheimer’s disease—a 48 months follow-up analysis. J Neural Transm Suppl 72:189–193

    Article  PubMed  CAS  Google Scholar 

  • Hajjar IM, Keown M, Lewis P, Almor A (2008) Angiotensin converting enzyme inhibitors and cognitive and functional decline in patients with Alzheimer’s disease: an observational study. Am J Alzheimers Dis Other Demen 23:77–83

    Article  PubMed  Google Scholar 

  • Hampel H, Ewers M, Bürger K, Annas P, Mörtberg A, Bogstedt A, Frölich L, Schröder J, Schönknecht P, Riepe MW, Kraft I, Gasser T, Leyhe T, Möller HJ, Kurz A, Basun H (2009) Lithium trial in Alzheimer’s disease: a randomized, single-blind, placebo-controlled, multicenter 10-week study. J Clin Psychiatry 70:922–931

    Article  PubMed  CAS  Google Scholar 

  • Harrington C, Sawchak S, Chiang C, Davies J, Donovan C, Saunders AM, Irizarry M, Jeter B, Zvartau-Hind M, van Dyck CH, Gold M (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. Curr Alzheimer Res 8:592–606

    Article  PubMed  CAS  Google Scholar 

  • Hashimoto M, Kazui H, Matsumoto K, Nakano Y, Yasuda M, Mori E (2005) Does donepezil treatment slow the progression of hippocampal atrophy in patients with Alzheimer's disease? Am J Psychiatry 162:676–682

    Google Scholar 

  • Hellweg R, Nitsch R, Hock C, Jaksch M, Hoyer S (1992) Nerve growth factor and choline acetyltransferase activity levels in the rat brain following experimental impairment of cerebral glucose and energy metabolism. J Neurosci Res 31:479–486

    Article  PubMed  CAS  Google Scholar 

  • Heneka MT, Sastre M, Dumitrescu-Ozimek L, Hanke A, Dewachter I, Kuiperi C, O’Banion K, Klockgether T, Van Leuven F, Landreth GE (2005) Acute treatment with the PPARgamma agonist pioglitazone and ibuprofen reduces glial inflammation and Abeta1-42 levels in APPV717I transgenic mice. Brain 128:1442–1453

    Article  PubMed  Google Scholar 

  • Heo JH, Lee SR, Lee ST, Lee KM, Oh JH, Jang DP, Chang KT, Cho ZH (2011) Spatial distribution of glucose hypometabolism induced by intracerebroventricular streptozotocin in monkeys. J Alzheimers Dis 25:517–523

    PubMed  Google Scholar 

  • Holmes C, Boche D, Wilkinson D, Yadegarfar G, Hopkins V, Bayer A, Jones RW, Bullock R, Love S, Neal JW, Zotova E, Nicoll JA (2008) Long-term effects of Abeta42 immunisation in Alzheimer's disease: follow-up of a randomised, placebo-controlled phase I trial. Lancet 372:216–223

    Google Scholar 

  • Hong L, Koelsch G, Lin X, Wu S, Terzyan S, Ghosh AK, Zhang XC, Tang J (2000) Structure if the protease domain of memapsin 2 (beta-secretase) complexed with inhibitor. Science 290:150–153

    Article  PubMed  CAS  Google Scholar 

  • Hou Y, Zhou L, Yang QD, Du XP, Li M, Yuan M, Zhou ZW (2012) Changes in hippocampal synapses and learning-memory abilities in a streptozotocin-treated rat model and intervention by using fasudil hydrochloride. Neuroscience 200:120–129

    Article  PubMed  CAS  Google Scholar 

  • Hoyer S (1998) Is sporadic Alzheimer disease the brain type of non-insulin dependent diabetes mellitus? A challenging hypothesis. J Neural Transm 105:415–422

    Article  PubMed  CAS  Google Scholar 

  • Hoyer S (2004) Glucose metabolism and insulin receptor signal transduction in Alzheimer disease. Eur J Pharmacol 490:115–125

    Article  PubMed  CAS  Google Scholar 

  • 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 72:195–202

    Article  PubMed  CAS  Google Scholar 

  • Hoyer S, Riederer P (2007) Alzheimer disease–no target for statin treatment. A mini review. Neurochem Res 32:695–706

    Article  PubMed  CAS  Google Scholar 

  • Hoyer S, Lannert H, Nöldner M, Chatterjee SS (1999) Damaged neuronal energy metabolism and behavior are improved by Ginkgo biloba extract (EGb 761). J Neural Transm 106:1171–1188

    Article  PubMed  CAS  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

  • Ishrat T, Hoda MN, Khan MB, Yousuf S, Ahmad M, Khan MM, Ahmad A, Islam F (2009a) 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  PubMed  CAS  Google Scholar 

  • Ishrat T, Parveen K, Hoda MN, Khan MB, Yousuf S, Ansari MA, Saleem S, Islam F (2009b) Effects of pycnogenol and vitamin E on cognitive deficits and oxidative damage induced by intracerebroventricular streptozotocin in rats. Behav Pharmacol 20:567–575

    Article  PubMed  CAS  Google Scholar 

  • Ishrat T, Parveen K, Khan MM, Khuwaja G, Khan MB, Yousuf S, Ahmad A, Shrivastav P, Islam F (2009c) 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  PubMed  CAS  Google Scholar 

  • Isik AT, Celik T, Ulusoy G, Ongoru O, Elibol B, Doruk H, Bozoglu E, Kayir H, Mas MR, Akman S (2009) Curcumin ameliorates impaired insulin/IGF signalling and memory deficit in a streptozotocin-treated rat model. Age (Dordr) 31:39–49

    Article  CAS  Google Scholar 

  • Jantzen PT, Connor KE, DiCarlo G, Wenk GL, Wallace JL, Rojiani AM, Coppola D, Morgan D, Gordon MN (2002) Microglial activation and beta-amyloid deposit reduction caused by a nitric oxide-releasing nonsteroidal anti-inflammatory drug in amyloid precursor protein plus presenilin-1 transgenic mice. J Neurosci 22:2246–2254

    PubMed  CAS  Google Scholar 

  • Jaturapatporn D, Isaac MG, McCleery J, Tabet N (2012) Aspirin, steroidal and non-steroidal anti-inflammatory drugs for the treatment of Alzheimer’s disease. Cochrane Database Syst Rev 2:CD006378

    PubMed  Google Scholar 

  • Javed H, Khan MM, Ahmad A, Vaibhav K, Ahmad ME, Khan A, Ashafaq M, Islam F, Siddiqui MS, Safhi MM, Islam F (2012) Rutin prevents cognitive impairments by ameliorating oxidative stress and neuroinflammation in rat model of sporadic dementia of Alzheimer type. Neuroscience [Epub ahead of print]. doi:10.1016/j.neuroscience.2012.02.046

  • Jee YS, Ko IG, Sung YH, Lee JW, Kim YS, Kim SE, Kim BK, Seo JH, Shin MS, Lee HH, Cho HJ, Kim CJ (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  PubMed  CAS  Google Scholar 

  • Jiménez-Jiménez FJ, de Bustos F, Molina JA, Benito-León J, Tallón-Barranco A, Gasalla T, Ortí-Pareja M, Guillamón F, Rubio JC, Arenas J, Enríquez-de-Salamanca R (1997) Cerebrospinal fluid levels of alpha-tocopherol (vitamin E) in Alzheimer’s disease. J Neural Transm 104:703–710

    Article  PubMed  Google Scholar 

  • Kadowaki T, Kasuga M, Akanuma Y, Ezaki O, Takaku F (1984) Decreased autophosphorylation of the insulin receptor-kinase in streptozotocin-diabetic rats. J Biol Chem 259:14208–142016

    PubMed  CAS  Google Scholar 

  • Kaur B, Singh N, Jaggi AS (2009) Exploring mechanism of pioglitazone-induced memory restorative effect in experimental dementia. Fundam Clin Pharmacol 23:557–566

    Article  PubMed  CAS  Google Scholar 

  • Kontush K, Schekatolina S (2004) Vitamin E in neurodegenerative disorders: Alzheimer’s disease. Ann N Y Acad Sci 1031:249–262

    Article  PubMed  CAS  Google Scholar 

  • Kornhuber J, Bormann J, Retz W, Hübers M, Riederer P (1989) Memantine displaces [3H]MK-801 at therapeutic concentrations in postmortem human frontal cortex. Eur J Pharmacol 166:589–590

    Article  PubMed  CAS  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

  • Kupershmidt L, Weinreb O, Amit T, Mandel S, Bar-Am O, Youdim MB (2011) Novel molecular targets of the neuroprotective/neurorescue multimodal iron chelating drug M30 in the mouse brain. Neuroscience 189:345–358

    Article  PubMed  CAS  Google Scholar 

  • Kupershmidt L, Amit T, Bar-Am O, Youdim MB, Weinreb O (2012a) The novel multi-target iron chelating-radical scavenging compound M30 possesses beneficial effects on major Hallmarks of Alzheimer’s disease. antioxid redox signal. [Epub ahead of print]. doi:10.1089/ars.2011.4279

  • Kupershmidt L, Amit T, Bar-Am O, Youdim MB, Weinreb O (2012b) Neuroprotection by the multitarget iron chelator M30 on age-related alterations in mice. Mech Ageing Dev. [Epub ahead of print]. doi:10.1016/j.mad.2012.03.001

  • Lannert H, Hoyer S (1998) Intracerebroventricular administration of streptozotocin causes long-term diminutions in learning and memory abilities and in cerebral energy metabolism in adult rats. Behav Neurosci 112:1199–1208

    Article  PubMed  CAS  Google Scholar 

  • Lannert H, Wirtz P, Schuhmann V, Galmbacher R (1998) Effects of Estradiol (-17beta) on learning, memory and cerebral energy metabolism in male rats after intracerebroventricular administration of streptozotocin. J Neural Transm 105:1045–1063

    Article  PubMed  CAS  Google Scholar 

  • 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 Alzheimers Dis 9:13–33

    PubMed  CAS  Google Scholar 

  • Levin-Allerhand JA, Lominska CE, Wang J, Smith JD (2002) 17Alpha-estradiol and 17beta-estradiol treatments are effective in lowering cerebral amyloid-beta levels in AbetaPPSWE transgenic mice. J Alzheimers Dis 4:449–457

    PubMed  CAS  Google Scholar 

  • Li L, Zhang ZF, Holscher C, Gao C, Jiang YH, Liu YZ (2012) (Val8) glucagon-like peptide-1 prevents tau hyperphosphorylation, impairment of spatial learning and ultra-structural cellular damage induced by streptozotocin in rat brains. Eur J Pharmacol 674:280–286

    Article  PubMed  CAS  Google Scholar 

  • Löffler T, Lee SK, Nöldner M, Chatterjee SS, Hoyer S, Schliebs R (2001) Effect of Ginkgo biloba extract (EGb761) on glucose metabolism-related markers in streptozotocin-damaged rat brain. J Neural Transm 108:1457–1474

    Article  PubMed  Google Scholar 

  • Ma QL, Yang F, Rosario ER, Ubeda OJ, Beech W, Gant DJ, Chen PP, Hudspeth B, Chen C, Zhao Y, Vinters HV, Frautschy SA, Cole GM (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 29:9078–9089

    Article  PubMed  CAS  Google Scholar 

  • Mayer G, Nitsch R, Hoyer S (1990) Effects of changes in peripheral and cerebral glucose metabolism on locomotor activity, learning and memory in adult male rats. Brain Res 532:95–100

    Article  PubMed  CAS  Google Scholar 

  • McGeer PL, McGeer EG (2007) NSAIDs and Alzheimer disease: epidemiological, animal model and clinical studies. Neurobiol Aging 28:639–647

    Article  PubMed  CAS  Google Scholar 

  • Medina M, Avila J (2010) Glycogen synthase kinase-3 (GSK-3) inhibitors for the treatment of Alzheimer’s disease. Curr Pharm Des 16:2790–2798

    Article  PubMed  CAS  Google Scholar 

  • Melnikova T, Savonenko A, Wang Q, Liang X, Hand T, Wu L, Kaufmann WE, Vehmas A, Andreasson KI (2006) Cycloxygenase-2 activity promotes cognitive deficits but not increased amyloid burden in a model. Neuroscience 141:1149–1162

    Article  PubMed  CAS  Google Scholar 

  • Minkeviciene R, Banerjee P, Tanila H (2004) Memantine improves spatial learning in a transgenic mouse model of Alzheimer’s disease. J Pharmacol Exp Ther 311:677–682

    Article  PubMed  CAS  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

  • 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 

  • Muller AP, Zimmer ER, Kalinine E, Haas CB, Oses JP, Martimbianco de Assis A, Galina A, Souza DO, Portela LV (2012) Physical exercise exacerbates memory deficits induced by intracerebroventricular STZ but improves insulin regulation of H2O2 production in mice synaptosomes. J Alzheimers Dis. [Epub ahead of print]. doi:10.3233/JAD-2012-112066

  • Mulnard RA, Cotman CW, Kawas C, van Dyck CH, Sano M, Doody R, Koss E, Pfeiffer E, Jin S, Gamst A, Grundman M, Thomas R, Thal LJ (2000) Estrogen replacement therapy for treatment of mild to moderate Alzheimer disease: a randomized controlled trial. Alzheimer’s Disease Cooperative Study. JAMA 283:1007–1015

    Article  PubMed  CAS  Google Scholar 

  • Nc Li, Lee A, Whitmer RA, Kivipelto M, Lawler E, Kazis LE, Wolozin B (2010) Use of angiotensin receptor blockers and risk of dementia in a predominantly male population: prospective cohort analysis. BMJ 340:b5465. doi:10.1136/bmj.b5465

    Article  Google Scholar 

  • Nicolakakis N, Aboulkassim T, Ongali B, Lecrux C, Fernandes P, Rosa-Neto P, Tong XK, Hamel E (2008) Complete rescue of cerebrovascular function in aged Alzheimer’s disease transgenic mice by antioxidants and pioglitazone, a peroxisome proliferator-activated receptor gamma agonist. J Neurosci 28:9287–9296

    Article  PubMed  CAS  Google Scholar 

  • Nitsch R, Hoyer S (1991) Local action of the diabetogenic drug, streptozotocin, on glucose and energy metabolism in rat brain cortex. Neurosci Lett 128:199–202

    Article  PubMed  CAS  Google Scholar 

  • Nunan J, Small DH (2000) Regulation of APP cleavage by alpha-, beta- and gamma-secretases. FEBS Lett 483:6–10

    Article  PubMed  CAS  Google Scholar 

  • Oddo S, Vasilevko V, Caccamo A, Kitazawa M, Cribbs DH, LaFerla FM (2006) Reduction of soluble Abeta and tau, but not soluble Abeta alone, ameliorates cognitive decline in transgenic mice with plaques and tangles. J Biol Chem 281:39413–39423

    Article  PubMed  CAS  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

  • Pedersen WA, McMillan PJ, Kulstad JJ, Leverenz JB, Craft S, Haynatzki GR (2006) Rosiglitazone attenuates learning and memory deficits in Tg2576 Alzheimer mice. Exp Neurol 199:265–273

    Article  PubMed  CAS  Google Scholar 

  • Peskind ER, Tsuang DW, Bonner LT, Pascualy M, Riekse RG, Snowden MB, Thomas R, Raskind MA (2005) Propranolol for disruptive behaviors in nursing home residents with probable or possible Alzheimer disease: a placebo-controlled study. Alzheimer Dis Assoc Disord 19:23–28

    Article  PubMed  CAS  Google Scholar 

  • Pinton S, da Rocha JT, Zeni G, Nogueira CW (2010) Organoselenium improves memory decline in mice: involvement of acetylcholinesterase activity. Neurosci Lett 472:56–60

    Article  PubMed  CAS  Google Scholar 

  • Pinton S, da Rocha JT, Gai BM, Prigol M, da Rosa LV, Nogueira CW (2011) Neuroprotector effect of p,p′-methoxyl-diphenyl diselenide in a model of sporadic dementia of Alzheimer’s type in mice: contribution of antioxidant mechanism. Cell Biochem Funct 29:235–243

    Article  PubMed  CAS  Google Scholar 

  • Plaschke K, Hoyer S (1993) Action of the diabetogenic drug streptozotocin on glycolytic and glycogenolytic metabolism in adult rat brain cortex and hippocampus. Int J Dev Neurosci 11:477–483

    Google Scholar 

  • Ponce-Lopez T, Liy-Salmeron G, Hong E, Meneses A (2011) Lithium, phenserine, memantine and pioglitazone reverse memory deficit and restore phospho-GSK3β decreased in hippocampus in intracerebroventricular streptozotocin induced memory deficit model. Brain Res 1426:73–85

    Article  PubMed  CAS  Google Scholar 

  • Prakash AK, Kumar A (2009) Effect of chronic treatment of carvedilol on oxidative stress in an intracerebroventricular streptozotocin induced model of dementia in rats. J Pharm Pharmacol 61:1665–1672

    Article  PubMed  Google Scholar 

  • Prickaerts J, Blokland A, Honig W, Meng F, Jolles J (1995) Spatial discrimination learning and choline acetyltransferase activity in streptozotocin-treated rats: effects of chronic treatment with acetyl-l-carnitine. Brain Res 674:142–146

    Article  PubMed  CAS  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

  • Reitz C (2012) Alzheimer’s disease and the amyloid cascade hypothesis: a critical review. Int J Alzheimers Dis 2012:369808

    PubMed  Google Scholar 

  • Richter H, Ambrée O, Lewejohann L, Herring A, Keyvani K, Paulus W, Palme R, Touma C, Schäbitz WR, Sachser N (2008) Wheel-running in a transgenic mouse model of Alzheimer’s disease: protection or symptom? Behav Brain Res 190:74–84

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Riviere C, Richard T, Vitrac X, Merillon JM, Valls J, Monti JP (2008) New polyphenols active on beta-amyloid aggregation. Bioorg Med Chem Lett 18:828–831

    Article  PubMed  CAS  Google Scholar 

  • Rodrigues L, Biasibetti R, Swarowsky A, Leite MC, Quincozes-Santos A, Quilfeldt JA, Achaval M, Gonçalves CA (2009) Hippocampal alterations in rats submitted to streptozotocin-induced dementia model are prevented by aminoguanidine. J Alzheimers Dis 17:193–202

    PubMed  CAS  Google Scholar 

  • Rodrigues L, Dutra MF, Ilha J, Biasibetti R, Quincozes-Santos A, Leite MC, Marcuzzo S, Achaval M, Gonçalves CA (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  PubMed  CAS  Google Scholar 

  • Salkovic-Petrisic M, Hoyer S (2007) Central insulin resistance as a trigger for sporadic Alzheimer-like pathology: an experimental approach. J Neural Transm Suppl 72:217–233

    Article  PubMed  CAS  Google Scholar 

  • Salkovic-Petrisic M, Tribl F, Schmidt M, Hoyer S, Riederer P (2006) Alzheimer-like changes in protein kinase B and glycogen synthase kinase-3 in rat frontal cortex and hippocampus after damage to the insulin signalling pathway. J Neurochem 96:1005–1015

    Article  PubMed  CAS  Google Scholar 

  • Salkovic-Petrisic M, Osmanovic J, Grünblatt E, Riederer P, Hoyer S (2009) Modeling sporadic Alzheimer’s disease: the insulin resistant brain state generates multiple long-term morphobiological abnormalities including hyperphosphorylated tau protein and amyloid-beta. J Alzheimers Dis 18:729–750

    PubMed  CAS  Google Scholar 

  • Salkovic-Petrisic M, Osmanovic-Barilar J, Brückner 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  PubMed  CAS  Google Scholar 

  • Salkovic-Petrisic M, Hoyer S, Riederer P (2012) Experimental approach to Alzheimer disease (in print)

  • Sato T, Hanyu H, Hirao K, Kanetaka H, Sakurai H, Iwamoto T (2011) Efficacy of PPAR-γ agonist pioglitazone in mild Alzheimer disease. Neurobiol Aging 32:1626–1633

    Article  PubMed  CAS  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

  • Shepardson NE, Shankar GM, Selkoe DJ (2011a) Cholesterol level and statin use in Alzheimer disease: I. Review of epidemiological and preclinical studies. Arch Neurol 68:1239–1244

    Article  PubMed  Google Scholar 

  • Shepardson NE, Shankar GM, Selkoe DJ (2011b) Cholesterol level and statin use in Alzheimer disease: II. Review of human trials and recommendations. Arch Neurol 68:1385–1392

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

  • Shonesy BC, Thiruchelvam K, Parameshwaran K, Rahman EA, Karuppagounder SS, Huggins KW, Pinkert CA, Amin R, Dhanasekaran M, Suppiramaniam V (2012) Central insulin resistance and synaptic dysfunction in intracerebroventricular-streptozotocin injected rodents. Neurobiol Aging 33:430.e5–430.e18

    Google Scholar 

  • Shumaker SA, Legault C, Rapp SR, Thal L, Wallace RB, Ockene JK, Hendrix SL, Jones BN 3rd, Assaf AR, Jackson RD, Kotchen JM, Wassertheil-Smoller S, Wactawski-Wende J, WHIMS Investigators (2003) Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women’s Health Initiative Memory Study: a randomized controlled trial. JAMA 289:2651–2662

    Article  PubMed  CAS  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

  • Stackman RW, Eckenstein F, Frei B, Kulhanek D, Nowlin J, Quinn JF (2003) Prevention of age-related spatial memory deficits in a transgenic mouse model of Alzheimer’s disease by chronic Ginkgo biloba treatment. Exp Neurol 184:510–520

    Article  PubMed  Google Scholar 

  • Steen E, Terry BM, Rivera EJ, Cannon JL, Neely TR, Tavares R, Xu XJ, Wands JR, de la Monte SM (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 7:63–80

    CAS  Google Scholar 

  • Szkudelski T (2001) The mechanism of alloxan and streptozotocin action in B cell of the rat pancreas. Physiol Res 50:537–546

    PubMed  CAS  Google Scholar 

  • Takeda S, Sato N, Rakugi H, Morishita R (2011) Molecular mechanisms linking diabetes mellitus and Alzheimer disease: beta-amyloid peptide, insulin signaling, and neuronal function. Mol BioSyst 7:1822–1827

    Article  PubMed  CAS  Google Scholar 

  • Tang J, Ghosh A (2011) Treating transgenic Alzheimer mice with a β-secretase inhibitor, what have we learned? Aging (Albany NY) 3:14–16

    CAS  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

  • Thal LJ, Grundman M, Berg J, Ernstrom K, Margolin R, Pfeiffer E, Weiner MF, Zamrini E, Thomas RG (2003) Idebenone treatment fails to slow cognitive decline in Alzheimer’s disease. Neurology 61:1498–1502

    Article  PubMed  CAS  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

  • Toledo EM, Inestrosa NC (2010) Activation of Wnt signaling by lithium and rosiglitazone reduced spatial memory impairment and neurodegeneration in brains of an APPswe/PSEN1DeltaE9 mouse model of Alzheimer’s disease. Mol Psychiatry 15:272–285

    Article  PubMed  CAS  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

  • Tota S, Kamat PK, Saxena G, Hanif K, Najmi AK, Nath C (2012) Central angiotensin converting enzyme facilitates memory impairment in intracerebroventricular streptozotocin treated rats. BehavBrain Res 226:317–330

    CAS  Google Scholar 

  • Tramontina AC, Wartchow KM, Rodrigues L, Biasibetti R, Quincozes-Santos A, Bobermin L, Tramontina F, Gonçalves CA (2011) The neuroprotective effect of two statins: simvastatin and pravastatin on a streptozotocin-induced model of Alzheimer’s disease in rats. J Neural Transm 118:1641–1649

    Article  PubMed  CAS  Google Scholar 

  • Tzimopoulou S, Cunningham VJ, Nichols TE, Searle G, Bird NP, Mistry P, Dixon IJ, Hallett WA, Whitcher B, Brown AP, Zvartau-Hind M, Lotay N, Lai RY, Castiglia M, Jeter B, Matthews JC, Chen K, Bandy D, Reiman EM, Gold M, Rabiner EA, Matthews PM (2010) A multi-center randomized proof-of-concept clinical trial applying [18F]FDG-PET for evaluation of metabolic therapy with rosiglitazone XR in mild to moderate Alzheimer’s disease. J Alzheimers Dis 22:1241–1256

    PubMed  CAS  Google Scholar 

  • Van Dam D, De Deyn PP (2006) Cognitive evaluation of disease-modifying efficacy of galantamine and memantine in the APP23 model. Eur Neuropsychopharmacol 16:59–69

    Article  PubMed  CAS  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Wang J, Ho L, Zhao Z, Seror I, Humala N, Dickstein DL, Thiyagarajan M, Percival SS, Talcott ST, Pasinetti GM (2006) Moderate consumption of Cabernet Sauvignon attenuates Abeta neuropathology in a mouse model of Alzheimer’s disease. FASEB J 20:2313–2320

    Article  PubMed  CAS  Google Scholar 

  • Wang YJ, Thomas P, Zhong JH, Bi FF, Kosaraju S, Pollard A, Fenech M, Zhou XF (2009) Consumption of grape seed extract prevents amyloid-beta deposition and attenuates inflammation in brain of an Alzheimer’s disease mouse. Neurotox Res 15:3–14

    Article  PubMed  CAS  Google Scholar 

  • Weinstock M, Kirschbaum-Slager N, Lazarovici P, Bejar C, Youdim MB, Shoham S (2001) Neuroprotective effects of novel cholinesterase inhibitors derived from rasagiline as potential anti-Alzheimer drugs. Ann N Y Acad Sci 939:148–161

    Article  PubMed  CAS  Google Scholar 

  • Weyer G, Babej-Dölle RM, Hadler D, Hofmann S, Herrmann WM (1997) A controlled study of 2 doses of idebenone in the treatment of Alzheimer’s disease. Neuropsychobiology 36:73–82

    Article  PubMed  CAS  Google Scholar 

  • Wollen KA (2010) Alzheimer’s disease: the pros and cons of pharmaceutical, nutritional, botanical, and stimulatory therapies, with a discussion of treatment strategies from the perspective of patients and practitioners. Altern Med Rev 15:223–244

    PubMed  Google Scholar 

  • 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 23:7504–7509

    PubMed  CAS  Google Scholar 

  • Youdim MB (2012) M30, a brain permeable multi target neurorestorative drug in post nigrostriatal dopamine neuron lesion of parkinsonism animal models. Parkinsonism Relat Disord 18:S151–S154

    Article  PubMed  Google Scholar 

  • Youdim MB, Fridkin M, Zheng H (2005) Bifunctional drug derivatives of MAO-B inhibitor rasagiline and iron chelator VK-28 as a more effective approach to treatment of brain ageing and ageing neurodegenerative diseases. Mech Ageing Dev 126:317–326

    Article  PubMed  CAS  Google Scholar 

  • Zahs KR, Ashe KH (2010) Too much good news’—are Alzheimer mouse models trying to tell us how to prevent, not cure, Alzheimer’s disease? Trends Neurosci 33:381–389

    Article  PubMed  CAS  Google Scholar 

  • Zhang X, Heng X, Li T, Li L, Yang D, Zhang X, Du Y, Doody RS, Le W (2011) Long-term treatment with lithium alleviates memory deficits and reduces amyloid-β production in an aged Alzheimer’s disease transgenic mouse model. J Alzheimers Dis 24:739–749

    PubMed  CAS  Google Scholar 

  • Zhu X, Su B, Wang X, Smith MA, Perry G (2007) Causes of oxidative stress in Alzheimer disease. Cell Mol Life Sci 64:2202–2210

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

Supported by the Croatian Ministry of Science, Education and Sport (project No. 108-1080003-0020), Deutscher Akademischer Austausch Dienst (project 2012) and Unity through Knowledge Fund (UKF project 10/64). The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pharmacology and Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Salata 11, HR 10000, Zagreb, Croatia

    Melita Salkovic-Petrisic & Ana Knezovic

  2. Department of Pathology, University Clinic, University of Heidelberg, Im Neuenheimer Feld 220/221, 69120, Heidelberg, Germany

    Siegfried Hoyer

  3. Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital, Würzburg, Fuechsleinstr. 15, 97080, Würzburg, Germany

    Peter Riederer

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  1. Melita Salkovic-Petrisic
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  2. Ana Knezovic
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  3. Siegfried Hoyer
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Correspondence to Melita Salkovic-Petrisic.

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Salkovic-Petrisic, M., Knezovic, A., Hoyer, S. et al. What have we learned from the streptozotocin-induced animal model of sporadic Alzheimer’s disease, about the therapeutic strategies in Alzheimer’s research. J Neural Transm 120, 233–252 (2013). https://doi.org/10.1007/s00702-012-0877-9

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