Skip to main content

Advertisement

Log in

Tannic Acid Ameliorates STZ-Induced Alzheimer’s Disease-Like Impairment of Memory, Neuroinflammation, Neuronal Death and Modulates Akt Expression

  • Original Article
  • Published:
Neurotoxicity Research Aims and scope Submit manuscript

Abstract

Tannic acid (TA) is a hydrolysable glycosidic polyphenol polymer of gallic acid, which possesses neuroprotective properties. The aim of this study was to evaluate the effect of TA treatment on cognitive performance and neurochemical changes in an experimental model of sporadic dementia of Alzheimer’s type (SDAT) induced by intracerebroventricular (ICV) injection of streptozotocin (STZ) and to explore the potential cellular and molecular mechanisms underlying these effects. Adult male rats were divided into four groups: control, TA, STZ, and TA + STZ. Animals from TA and TA + STZ groups were treated with TA (30 mg/kg) daily, by gavage, for 21 days; others groups received water (1 mL/kg). Subsequently, an ICV injection of STZ (3 mg/kg) was administered into the lateral ventricles of animals from STZ and TA + STZ groups, while other groups received citrate buffer. Cognitive deficits (short-term memory), neuronal survival, neuroinflammation as well as expression of SNAP-25, Akt, and pAkt were evaluated in the cerebral cortex. TA treatment protected against the impairment of memory in STZ-induced SDAT. STZ promoted an increase in neuronal death and the levels of proinflammatory cytokines (IL-6 and TNF-α) and a decrease in Akt and pAkt expression; TA was able to restore these changes. Neither STZ nor TA altered SNAP-25 expression or the levels of IL-12 and IL-4 in the cerebral cortex. Our study highlights that treatment with TA prevents memory deficits and reestablishes Akt and pAkt expression, protecting against neuronal death and neuroinflammation in STZ-induced SDAT in rats.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Adeli S, Zahmatkesh M, Ansari Dezfouli M (2019) Simvastatin attenuates hippocampal MMP-9 expression in the streptozotocin-induced cognitive impairment. Iran Biomed J 23:262–271

    PubMed  PubMed Central  Google Scholar 

  • Ahmed T, Javed S, Javed S, Tariq A, Šamec D, Tejada S, Nabavi SF, Braidy N, Nabavi SM (2017) Resveratrol and Alzheimer’s disease: mechanistic insights. Mol Neurobiol 54:2622–2635

    CAS  PubMed  Google Scholar 

  • Alam Q, Alam MZ, Mushtaq G, Damanhouri GA, Rasool M, Kamal MA, Haque A (2016) Inflammatory process in Alzheimer's and Parkinson’s diseases: central role of cytokines. Curr Pharm Des 22:541–548

    CAS  PubMed  Google Scholar 

  • Anand R, Gill KD, Mahdi AA (2014) Therapeutics of Alzheimer’s disease: past, present and future. Neuropharmacol 76:27–50

    CAS  Google Scholar 

  • Bassani TB, Turnes JM, Moura ELR, Bonato JM, Cóppola-Segovia V, Zanata SM, Oliveira RMMW, Vital MABF (2017) Effects of curcumin on short-term spatial and recognition memory, adult neurogenesis and neuroinflammation in a streptozotocin-induced rat model of dementia of Alzheimer’s type. Behav Brain Res 29:41–54

    Google Scholar 

  • Berté TE, Dalmagro AP, Zimath PL, Gonçalves AE, Meyre-Silva C, Bürger C, Weber CJ, Dos Santos DA, Cechinel-Filho V, de Souza MM (2018) Taraxerol as a possible therapeutic agent on memory impairments and Alzheimer’s disease: effects against scopolamine and streptozotocin-induced cognitive dysfunctions. Steroids 132:5–11

    PubMed  Google Scholar 

  • Brunet A, Datta SR, Greenberg ME (2001) Transcription-dependent and -independent control of neuronal survival by the PI3K-Akt signaling pathway. Curr Opin Neurobiol 11:297–305

    CAS  PubMed  Google Scholar 

  • Canto-de-Souza L, Mattioli R (2016) The consolidation of inhibitory avoidance memory in mice depends on the intensity of the aversive stimulus: the involvement of the amygdala, dorsal hippocampus and medial prefrontal cortex. Neurobiol Learn Mem 130:44–51

    CAS  PubMed  Google Scholar 

  • Cauwenberghe CV, Broeckhoven CV, Sleegers K (2016) The genetic landscape of Alzheimer disease: clinical implications and perspectives. Genet Med 18:421–430

    PubMed  Google Scholar 

  • Cevik B, Solmaz V, Yigitturk G, Cavusoğlu T, Peker G, Erbas O (2017) Neuroprotective effects of erythropoietin on Alzheimer’s dementia model in rats. Adv Clin Exp Med 26:23–29

    PubMed  Google Scholar 

  • Chen Z, Zhong C (2014) Oxidative stress in Alzheimer’s disease. Neurosci Bull 30:271–281

    CAS  PubMed  PubMed Central  Google Scholar 

  • Choi DY, Lee YJ, Hong JT, Lee HJ (2012) Antioxidant properties of natural polyphenols and their therapeutic potentials for Alzheimer’s disease. Brain Res Bull 87:144–153

    CAS  PubMed  Google Scholar 

  • Clark LF, Kodadek T (2016) The immune system and neuroinflammation as potential sources of blood-based biomarkers for Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. ACS Chem Neurosci 18:520–527

    Google Scholar 

  • DemirÖzkay Ü, Can ÖD, Sağlık BN, Turan N (2017) A benzothiazole/piperazine derivative with acetylcholinesterase inhibitory activity: improvement in streptozotocin induced cognitive deficits in rats. Pharmacol Rep 69:1349–1356

    Google Scholar 

  • Deng Y, Li B, Liu Y, Iqbal K, Grundke-Iqbal I, Gong CX (2009) Dysregulation of insulin signaling, glucose transporters, OGlcNAcylation, and phosphorylation of tau and neurofilaments in the brain: implication for Alzheimer’s disease. Am J Pathol 175:2089–2098

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dinarello CA (2007) Historical insights into cytokines. Eur J Immunol 37:34–45

    Google Scholar 

  • Duarte JM, Carvalho RA, Cunha RA, Gruetter R (2009) Caffeine consumption attenuates neurochemical modifications in the hippocampus of streptozotocin-induced diabetic rats. J Neurochem 111:368–379

    CAS  PubMed  Google Scholar 

  • Filippi-Chiela EC, Thome MP, Bueno e Silva MM, Pelegrini AL, Ledur PF, Garicoche B, Zamin LL, Lenz G (2013) Resveratrol abrogates the temozolomide-induced G2 arrest leading to mitotic catastrophe and reinforces the temozolomide-induced senescence in glioma cells. BMC Cancer 13:147–160

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gerzson MFB, Pacheco SM, Soares MSP, Bona NP, Oliveira PS, Azambuja JH, da Costa P, Gutierres JM, Carvalho FB, Morsch VM, Spanevello RM, Stefanello FS (2019) Effects of tannic acid in streptozotocin-induced sporadic Alzheimer’s disease: insights into memory, redox status, Na+, K+-ATPase and acetylcholinesterase activity. Arch Physiol Biochem. https://doi.org/10.1080/13813455.2019.1673430

  • Grieb P (2016) Intracerebroventricular streptozotocin injections as a model of Alzheimer’s disease: in search of a relevant mechanism. Mol Neurobiol 53:1741–1752

    CAS  PubMed  Google Scholar 

  • Gutierres JM, Carvalho FB, Schetinger MRC, Marisco P, Agostinho P, Rodrigues M, Rubin MA, Schmatz R, Da Silva CR, Cognato GP, Farias JG, Signor C, Morsch VM, Mazzanti CM, Bogo M, Bonan CD, Spanevello R (2014) Anthocyanins restore behavioral and biochemical changes caused by streptozotocin-induced sporadic dementia of Alzheimer's type. Life Sci 96:7–17

    CAS  PubMed  Google Scholar 

  • Hoyer S (2004a) Causes and consequences of disturbances of cerebral glucose metabolism in sporadic Alzheimer disease: therapeutic implications. Adv Exp Med Biol 541:135–152

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Khalili-Fomeshi M, Azizi MG, Esmaeili MR, Gol M, Kazemi S, Ashrafpour M, Moghadamnia AA, Hosseinzadeh S (2018) Piperine restores streptozotocin-induced cognitive impairments: insights into oxidative balance in cerebrospinal fluid and hippocampus. Behav Brain Res 30:131–138

    Google Scholar 

  • Knezovic A, Osmanovic-Barilar J, Curlin M, Hof PR, Simic G, Riederer P, Salkovic-Petrisic M (2015) Staging of cognitive deficits and neuropathological and ultrastructural changes in streptozotocin-induced rat model of Alzheimer’s disease. J Neural Transm 122:577–592

    CAS  PubMed  Google Scholar 

  • Kumar A, Ekavali AS (2015) A review on Alzheimer’s disease pathophysiology and its management: an update. Pharmacol Rep 67:195–203

    CAS  PubMed  Google Scholar 

  • 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 112:199–208

    Google Scholar 

  • Liu Y, Liu F, Grundke-Iqbal I, Iqbal K, Gong CX (2011) Deficient brain insulin signalling pathway in Alzheimer’s disease and diabetes. J Pathol 225:54–62

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 265–275

  • Mahajan K, Mahajan NP (2012) PI3K-independent AKT activation in cancers: a treasure trove for novel therapeutics. J Cell Physiol 227:3178–3184

    CAS  PubMed  PubMed Central  Google Scholar 

  • Manning BD, Toker A (2017) AKT/PKB signaling: navigating the network. Cell 169:381–405

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mattioli R, Francioso A, d’Erme, Trovato M, Mancini P, Piacentini L, Casale AM, Wessjohann L, Gazzino R, Costantino P, Mosca L (2019) Anti-inflammatory activity of a Polyphenolic extract from Arabidopsis thaliana in in vitro and in vivo models of Alzheimer’s disease. Int J Mol Sci 20:708–727

    CAS  PubMed Central  Google Scholar 

  • Mayeux R, Stern Y (2012) Epidemiology of Alzheimer disease. Cold Spring Harb Perspect Med 2:1–18

    Google Scholar 

  • Mori T, Rezai-Zadeh K, Koyama N, Arendash G, Yamaguchi H, Kakuda N, Horikoshi-Sakuraba Y, Tan J, Town T (2012) Tannic acid is a natural β-secretase inhibitor that prevents cognitive impairment and mitigates Alzheimer-like pathology in transgenic mice. J Biol Chem 287:6912–6927

    CAS  PubMed  PubMed Central  Google Scholar 

  • Moseley AE, Lieske SP, Wetzel RK, James PF, He S, Shelly DA (2003) The Na, K-ATPase alpha 2 isoform is expressed in neurons, and its absence disrupts neuronal activity in new born mice. J Biol Chem 278:5317–5324

    CAS  PubMed  Google Scholar 

  • Moseley AE, Williams MT, Schaefer TL, Bohanan CS, Neumann JC, Behbehani MM (2007) Deficiency in Na, K-ATPase alpha isoform genes alters spatial learning, motor activity, and anxiety in mice. J Neurosci 27:616–626

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nakayama D, Yamasaki Y, Matsuki N, Nomura H (2013) Post-retrieval late process contributes to persistence of reactivated fear memory. Learn Mem 20:307–310

    PubMed  Google Scholar 

  • Noor A, Zahid S (2016) A review of the role of synaptosomal-associated protein 25 (SNAP- 25) in neurological disorders. Int J Neurosci 127:805–811

    PubMed  Google Scholar 

  • Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates. Academic Press, San Diego

    Google Scholar 

  • Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP (2013) The global prevalence of dementia: a systematic review and meta-analysis. Alzheimers Dement 9:63–75

    PubMed  Google Scholar 

  • Robbins TW (2005) Chemistry of the mind: neurochemical modulation of prefrontal cortical function. J Comp Neurol 493:140–146

    CAS  PubMed  Google Scholar 

  • Rubin MA, Boemo RL, Jurach A, Rojas DB, Zanolla GR, Obregon AD (2000) Intrahippocampal spermidine administration improves inhibitory avoidance performance in rats. Behav Pharmacol 11:57–61

    CAS  PubMed  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 72:217–233

    CAS  Google Scholar 

  • Salkovic-Petrisic M, Knezovic A, Hoyer S, Riederer P (2013) 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

    CAS  PubMed  Google Scholar 

  • Scheltens P, Blennow K, Breteler MMB, Strooper B, Frisoni GB, Salloway S, Van der Flier WM (2016) Alzheimer’s disease. Lancet 388:505–517

    CAS  PubMed  Google Scholar 

  • Schifilliti D, Santamaria B, Rosa G, Nino GD, Mandal PK, Fodale V (2010) Cholinergic central system, Alzheimer's disease, and anaesthetics liaison: a vicious circle? J Alzheimers Dis 22:35–41

    PubMed  Google Scholar 

  • Serrano J, Puupponen-Pimiä R, Dauer A, Aura AM, Saura-Calixto F (2009) Tannins: current knowledge of food sources, intake, bioavailability and biological effects. Mol Nutr Food Res 53:310–329

    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

    CAS  PubMed  Google Scholar 

  • Sheng C, Xu P, Kexin K, Deng D, Zhang C, Wang Z (2017) Icariin attenuates synaptic and cognitive deficits in an A훽1–42-induced rat model of Alzheimer’s disease. Biomed Res Int 2017:1–12

    Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Shingo AS, Kanabayashi T, Murase T, Kito S (2013) Intracerebroventricular administration of an insulin analogue recovers STZ-induced cognitive decline in rats. Behav Brain Res 241:105–111

    CAS  PubMed  Google Scholar 

  • Spagnuolo C, Napolitano M, Tedesco I, Moccia S, Milito A, Russo GL (2016) Neuroprotective role of natural polyphenols. Curr Top Med Chem 16:1943–1950

    CAS  PubMed  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

    CAS  PubMed  Google Scholar 

  • Tiwari SK, Seth B, Agarwal S, Yadav A, Karmakar M, Gupta SK, Choubey V, Sharma A, Chaturvedi RK (2015) Ethosuximide induces hippocampal neurogenesis and reverses cognitive deficits in amyloid-beta toxin induced Alzheimer’s rat model via PI3K/Akt/Wnt/beta-catenin pathway. J Biol Chem 290:28540–28558

    CAS  PubMed  PubMed Central  Google Scholar 

  • Vianna MR, Szapiro G, McGaugh JL, Medina JH, Izquierdo I (2001) Retrieval of memory for fear-motivated training initiates extinction requiring protein synthesis in the rat hippocampus. Proc Natl Acad Sci U S A 98:12251–12254

    CAS  PubMed  PubMed Central  Google Scholar 

  • Walsh RN, Cummins RA (1976) The open-field test: a critical review. Psychol Bull 83:482–504

    CAS  PubMed  Google Scholar 

  • Wang WY, Tan MS, Yu JT, Tan L (2015) Role of pro-inflammatory cytokines released from microglia in Alzheimer's disease. Ann Transl Med 3:136–151

    PubMed  PubMed Central  Google Scholar 

  • Welinder C, Ekblad L (2011) Coomassie staining as loading control in Western blot analysis. J Proteome Res 10:1416–1419

    CAS  PubMed  Google Scholar 

  • Wu Y, Zhong L, Yu Z, Qi J (2019) Anti-neuroinflammatory effects of tannic acid against lipopolysaccharide-induced BV2 microglial cells via inhibition of NF-κB activation. Drug Dev Res 80:262–268

    CAS  PubMed  Google Scholar 

Download references

Funding

The Brazilian research funding agencies FAPERGS, CNPq, CAPES (Finance code 001) supported this study.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Roselia M. Spanevello or Francieli M. Stefanello.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gerzson, M.F.B., Bona, N.P., Soares, M.S.P. et al. Tannic Acid Ameliorates STZ-Induced Alzheimer’s Disease-Like Impairment of Memory, Neuroinflammation, Neuronal Death and Modulates Akt Expression. Neurotox Res 37, 1009–1017 (2020). https://doi.org/10.1007/s12640-020-00167-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12640-020-00167-3

Keywords

Navigation