Effect of a purine derivative containing selenium to improve memory decline and anxiety through modulation of the cholinergic system and Na+/K+-ATPase in an Alzheimer’s disease model

Pinz, Mikaela Peglow; Vogt, Ane Gabriela; da Costa Rodrigues, Karline; dos Reis, Angélica Schiavom; Duarte, Luis Fernando Barbosa; Fronza, Mariana Gallio; Domingues, William Borges; Blodorn, Eduardo Bierhaus; Alves, Diego; Campos, Vinicius Farias; Savegnago, Lucielli; Wilhelm, Ethel Antunes; Luchese, Cristiane

doi:10.1007/s11011-021-00703-w

Original Article
Published: 02 March 2021

Effect of a purine derivative containing selenium to improve memory decline and anxiety through modulation of the cholinergic system and Na⁺/K⁺-ATPase in an Alzheimer’s disease model

Mikaela Peglow Pinz¹,
Ane Gabriela Vogt¹,
Karline da Costa Rodrigues¹,
Angélica Schiavom dos Reis¹,
Luis Fernando Barbosa Duarte²,
Mariana Gallio Fronza⁴,
William Borges Domingues³,
Eduardo Bierhaus Blodorn³,
Diego Alves²,
Vinicius Farias Campos³,
Lucielli Savegnago⁴,
Ethel Antunes Wilhelm¹^na1 &
Cristiane Luchese ORCID: orcid.org/0000-0001-6001-0532¹^na1

Metabolic Brain Disease volume 36, pages 871–888 (2021)Cite this article

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Abstract

Alzheimer’s disease (AD) is a worldwide problem, and there are currently no treatments that can stop this disease. To investigate the binding affinity of 6-((4-fluorophenyl) selanyl)-9H-purine (FSP) with acetylcholinesterase (AChE), to verify the effects of FSP in an AD model in mice and to evaluate the toxicological potential of this compound in mice. The binding affinity of FSP with AChE was investigated by molecular docking analyses. The AD model was induced by streptozotocin (STZ) in Swiss mice after FSP treatment (1 mg/kg, intragastrically (i.g.)), 1st-10th day of the experimental protocol. Anxiety was evaluated in an elevated plus maze test, and memory impairment was evaluated in the Y-maze, object recognition and step-down inhibitory avoidance tasks. The cholinergic system was investigated based on by looking at expression and activity of AChE and expression of choline acetyltransferase (ChAT). We evaluated expression and activity of Na⁺/K⁺-ATPase. For toxicological analysis, animals received FSP (300 mg/kg, i.g.) and aspartate aminotransferase, alanine aminotransferase activities were determined in plasma and δ-aminolevulinate dehydratase activity in brain and liver. FSP interacts with residues of the AChE active site. FSP mitigated the induction of anxiety and memory impairment caused by STZ. FSP protected cholinergic system dysfunction and reduction of activity and expression of Na⁺/K⁺-ATPase. FSP did not modify toxicological parameters evaluated and did not cause the death of mice. FSP protected against anxiety, learning and memory impairment with involvement of the cholinergic system and Na⁺/K⁺-ATPase in these actions.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

References

Abdalla FH, Cardoso AMH, Pereira LB et al (2013) Neuroprotective effect of quercetin in ectoenzymes and acetylcholinesterase activities in cerebral cortex synaptosomes of cadmium-exposed rats. Mol Cell Biochem 381:1–8. https://doi.org/10.1007/s11010-013-1659-x
CAS Article PubMed Google Scholar
Abeijon P, Garcia-Mera X, Caamano O, Yanez M, Lopez-Castro E, Romero-Duran F, Gonzalez-Diaz H (2017) Multi-target Mining of Alzheimer Disease Proteome with Hansch’s QSBR-perturbation theory and experimental-theoretic study of new Thiophene Isosters of Rasagiline. Curr Drug Targets 18:511–521. https://doi.org/10.2174/1389450116666151102095243
CAS Article PubMed Google Scholar
Agnieszka D, Wilkaniec A, Wroczyński P, Agata A (2016) Selenium in the therapy of neurological diseases. Where is it going? Curr Neuropharmacol 14:282–299. https://doi.org/10.2174/1570159X14666151223100011
Article 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. https://doi.org/10.1016/j.cbi.2008.04.045
CAS Article PubMed Google Scholar
Ali TB, Schleret TR, Reilly BM, Chen WY, Abagyan R (2015) Adverse effects of cholinesterase inhibitors in dementia, according to the pharmacovigilance databases of the United-States and Canada. PLoS One 10:1–10. https://doi.org/10.1371/journal.pone.0144337
CAS Article Google Scholar
Ambure P, Roy K (2017) CADD modeling of multi-target drugs against Alzheimer’s disease. Curr Drug Targets 18:522–533. https://doi.org/10.2174/138945011666615090710
CAS Article PubMed Google Scholar
Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254. https://doi.org/10.1016/j.cj.2017.04.003
CAS Article PubMed Google Scholar
Brand Y, Levano S, Radojevic V, Naldi AM, Setz C, Ryan AF, Pak K, Hemmings BA, Bodmer D (2015) All Akt isoforms (Akt1, Akt2, Akt3) are involved in normal hearing, but only Akt2 and Akt3 are involved in auditory hair cell survival in the mammalian inner ear. PLoS One 10:1–13. https://doi.org/10.1371/journal.pone.0121599
CAS Article Google Scholar
Brookmeyer R, Abdalla N, Kawas CH, Corrada MM (2018) Forecasting the prevalence of pre-clinical and clinical alzheimer’s disease in the United States. Alzheimers Dement 14:121–129. https://doi.org/10.1016/j.physbeh.2017.03.040
CAS Article PubMed Google Scholar
Bruckert G, Vivien D, Docagne F, Roussel BD (2016) Normalization of reverse transcription quantitative PCR data during ageing in distinct cerebral structures. Mol Neurobiol 53:1540–1550. https://doi.org/10.1007/s12035-015-9114-5
CAS Article PubMed Google Scholar
Carageorgiou H, Sideris AC, Messari I et al (2008) The effects of rivastigmine plus selegiline on brain acetylcholinesterase, (Na+, K+)-, Mg2+-ATPase activities, antioxidant status, and learning performance of aged rats. Neuropsychiatr Dis Treat 4:687–699. https://doi.org/10.2147/ndt.s3272
CAS Article PubMed PubMed Central Google Scholar
Chen Y, Tian Z, Liang Z, Sun S, Dai CL, Lee MH, LaFerla FM, Grundke-Iqbal I, Iqbal K, Liu F, Gong CX (2012) Brain gene expression of a sporadic (icv-STZ mouse) and a familial mouse model (3xTg-AD mouse) of Alzheimer’s disease. PLoS One 7:1–12. https://doi.org/10.1371/journal.pone.0051432
CAS Article Google Scholar
De Ferrari GV, Canales MAC, Shin I et al (2001) A structural motif of acetylcholinesterase that promotes amyloid β-peptide fibril formation. Biochemistry 40:10447–10457. https://doi.org/10.1021/bi0101392
CAS Article PubMed Google Scholar
Dickey CA, Gordon MN, Wilcock DM, Herber DL, Freeman MJ, Morgan D (2005) Dysregulation of Na+/K+ ATPase by amyloid in APP+PS1 transgenic mice. BMC Neurosci 6:1–11. https://doi.org/10.1186/1471-2202-6-7
CAS Article Google Scholar
Ding Y, Zhao J, Zhang X, Wang S, Viola KL, Chow FE, Zhang Y, Lippa C, Klein WL, Gong Y (2019) Amyloid Beta Oligomers Target to Extracellular and Intracellular Neuronal Synaptic Proteins in Alzheimer ’ s Disease 10:1–16. https://doi.org/10.3389/fneur.2019.01140
Dorszewska J, Prendecki M, Oczkowska A, Dezor M, Kozubski W (2016) Molecular basis of familial and sporadic Alzheimer’s disease. Curr Alzheimer Res 13:952–963. https://doi.org/10.2174/1567205013666160314150501
CAS Article PubMed Google Scholar
Duarte LFB, Oliveira RL, Rodrigues KC, Voss GT, Godoi B, Schumacher RF, Perin G, Wilhelm EA, Luchese C, Alves D (2017) Organoselenium compounds from purines: synthesis of 6-arylselanylpurines with antioxidant and anticholinesterase activities and memory improvement effect. Bioorganic Med Chem 25:6718–6723. https://doi.org/10.1016/j.bmc.2017.11.019
CAS Article Google Scholar
Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77
CAS Article Google Scholar
Ellman GL, Courtney KD, Andres V, Featherstone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95. https://doi.org/10.1016/0006-2952(61)90145-9
CAS Article PubMed Google Scholar
Fiske CH, Subbarow Y (1925) The colorimetric determination of phosphorus. J Biol Chem 66:375–400
CAS Article Google Scholar
Gibson GE, Blass JP (1976) Impaired synthesis of acetylcholine in brain accompanying mild hypoxia and hypoglycemia. J Neurochem 27:37–42. https://doi.org/10.1111/j.1471-4159.1976.tb01540.x
CAS Article PubMed Google Scholar
Grieb P (2016) Intracerebroventricular Streptozotocin injections as a model of Alzheimer’s disease: in search of a relevant mechanism. Mol Neurobiol 53:1741–1752. https://doi.org/10.1007/s12035-015-9132-3
CAS Article PubMed Google Scholar
Gu G, Zhang W, Li M, Ni J, Wang P (2015) Transplantation of NSC-derived cholinergic neuron-like cells improves cognitive function in APP/PS1 transgenic mice. Neuroscience 291:81–92. https://doi.org/10.1016/j.neuroscience.2015.01.073
CAS Article PubMed Google Scholar
Gupta S, Mohan CG (2014) Dual binding site and selective acetylcholinesterase inhibitors derived from integrated pharmacophore models and sequential virtual screening. Biomed Res Int 2014:1–21. https://doi.org/10.1155/2014/291214
CAS Article Google Scholar
Haley TJ, Mccormick WG (1957) Pharmacological effects produced by intracerebral injection of drugs in the conscious mouse. Br J Pharmacol Chemother 12:12–15. https://doi.org/10.1111/j.1476-5381.1957.tb01354.x
CAS Article PubMed PubMed Central Google Scholar
Hanwell MD, Curtis DE, Lonie DC et al (2012) Avogadro: an advanced semantic chemical editor, visualization, and analysis platform. J Cheminform 4:1–17
Article Google Scholar
He Q, Chen X, Wu T, Li L, Fei X (2019) Risk of dementia in long-term benzodiazepine users: evidence from a meta-analysis of observational studies. J Clin Neurol 15:9–19. https://doi.org/10.3988/jcn.2019.15.1.9
Article PubMed Google Scholar
Hou LN, Xu JR, Zhao QN, Gao XL, Cui YY, Xu J, Wang H, Chen HZ (2014) A new motif in the n-terminal of acetylcholinesterase triggers amyloid-β aggregation and deposition. CNS Neurosci Ther 20:59–66. https://doi.org/10.1111/cns.12161
CAS Article PubMed Google Scholar
Jack CRJ, Bennettb DA, Blennowc K et al (2018) NIA-AA research framework: toward a biological definition of Alzheimer’s disease. Alzheimers Dement 14:535–562. https://doi.org/10.1016/j.physbeh.2017.03.040
CAS Article PubMed PubMed Central Google Scholar
Jang C, Yadav DK, Subedi L, Venkatesan R, Venkanna A, Afzal S, Lee E, Yoo J, Ji E, Kim SY, Kim MH (2018) Identification of novel acetylcholinesterase inhibitors designed by pharmacophore-based virtual screening, molecular docking and bioassay. Sci Rep 8:1–21. https://doi.org/10.1038/s41598-018-33354-6
CAS Article Google Scholar
Johansson M, Stomrud E, Lindberg O, Westman E, Johansson PM, van Westen D, Mattsson N, Hansson O (2019) Apathy and anxiety are early markers of Alzheimer’s disease. Neurobiol Aging 85:74–82. https://doi.org/10.1016/j.neurobiolaging.2019.10.008
CAS Article PubMed Google Scholar
Johnson G, Moore S (2006) The peripheral anionic site of Acetylcholinesterase: structure, functions and potential role in rational drug design. Curr Pharm Des 12:217–225. https://doi.org/10.2174/138161206775193127
CAS Article PubMed Google Scholar
Lakunina VA, Petrushanko IY, Burnysheva KM, Mitkevich VA, Makarov AA (2017) Alzheimer’s disease Aβ42peptide induces an increase in Na,K-ATPase glutathionylation. Dokl Biochem Biophys 473:114–117. https://doi.org/10.1134/S1607672917020077
CAS Article PubMed Google Scholar
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method. Methods 25:402–408. https://doi.org/10.1006/meth.2001.1262
CAS Article PubMed PubMed Central Google Scholar
MacKay EM, MacKay LL (1927) The concentration of urea in the blood of Normal individuals 1. J Clin Invest 4:295–306. https://doi.org/10.1172/jci100124
CAS Article PubMed PubMed Central Google Scholar
Mangialasche F, Solomon A, Winblad B, Mecocci P, Kivipelto M (2010) Alzheimer’s disease: clinical trials and drug development. Lancet Neurol 9:702–716. https://doi.org/10.1016/S1474-4422(10)70119-8
CAS Article PubMed Google Scholar
Marks DR, Tucker K, Cavallin MA, Mast TG, Fadool DA (2009) Awake intranasal insulin delivery modifies protein complexes and alters memory, anxiety, and olfactory behaviors. J Neurosci 29:6734–6751. https://doi.org/10.1523/JNEUROSCI.1350-09.2009
CAS Article PubMed PubMed Central Google Scholar
Martini F, Rosa SG, Klann IP, Fulco BCW, Carvalho FB, Rahmeier FL, Fernandes MC, Nogueira CW (2019) A multifunctional compound ebselen reverses memory impairment, apoptosis and oxidative stress in a mouse model of sporadic Alzheimer’s disease. J Psychiatr Res 109:107–117. https://doi.org/10.1016/j.jpsychires.2018.11.021
Article PubMed Google Scholar
Mehta D, Jackson R, Paul G, Shi J, Sabbagh M (2017) Why do trials for Alzheimer’s disease drugs keep failing? A discontinued drug perspective for 2010-2015. Expert Opin Investig Drugs 26:735–739. https://doi.org/10.1080/13543784.2017.1323868
CAS Article PubMed PubMed Central Google Scholar
Mokrani EH, Bensegueni A, Chaput L, Beauvineau C, Djeghim H, Mouawad L (2019) Identification of new potent Acetylcholinesterase inhibitors using virtual screening and in vitro approaches. Mol Inform 38:1–11. https://doi.org/10.1002/minf.201800118
CAS Article Google Scholar
Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, Olson AJ (2009) AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J Comput Chem 30:2785–2791. https://doi.org/10.1002/jcc.21256.AutoDock4
CAS Article PubMed PubMed Central Google Scholar
Moseley AE, Williams MT, Schaefer TL, Bohanan CS, Neumann JC, Behbehani MM, Vorhees CV, Lingrel JB (2007) Deficiency in Na,K-ATPase α isoform genes alters spatial learning, motor activity, and anxiety in mice. J Neurosci 27:616–626. https://doi.org/10.1523/JNEUROSCI.4464-06.2007, Deficiency in Na,K-ATPase Isoform Genes Alters Spatial Learning, Motor Activity, and Anxiety in Mice
National Research Council (1996) Guide for the care and use of laboratory animals. The National Academies Press, Washington (DC)
Google Scholar
Nogueira CW, Rocha JBT (2011) Toxicology and pharmacology of selenium : emphasis on synthetic organoselenium compounds. Arch Toxicol 85:1313–1359. https://doi.org/10.1007/s00204-011-0720-3
CAS Article PubMed Google Scholar
Nørgaard A, Kjeldsen K, Clausen T (1981) Potassium depletion decreases the number of 3H-ouabain binding sites and the active Na-K transport in skeletal muscle. Nature 293:739–741. https://doi.org/10.1017/CBO9781107415324.004
Article PubMed Google Scholar
Oda Y (1999) Choline acetyltransferase: the structure, distribution and pathologic changes in the central nervous system. Pathol Int 49:921–937. https://doi.org/10.1046/j.1440-1827.1999.00977.x
CAS Article PubMed Google Scholar
Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358. https://doi.org/10.1016/0003-2697(79)90738-3
CAS Article PubMed Google Scholar
Panek D, Więckowska A, Wichur T, Bajda M, Godyń J, Jończyk J, Mika K, Janockova J, Soukup O, Knez D, Korabecny J, Gobec S, Malawska B (2017) Design, synthesis and biological evaluation of new phthalimide and saccharin derivatives with alicyclic amines targeting cholinesterases, beta-secretase and amyloid beta aggregation. Eur J Med Chem 125:676–695. https://doi.org/10.1016/j.ejmech.2016.09.078
CAS Article PubMed Google Scholar
Pellow S, Chopin P, File SE, Briley M (1985) Validation of open : closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods 14:149–167. https://doi.org/10.1016/0165-0270(85)90031-7
CAS Article PubMed Google Scholar
Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE (2004) UCSF Chimera - a visualization system for exploratory research and analysis. J Comput Chem 25:1605–1612. https://doi.org/10.1002/jcc.20084
CAS Article PubMed Google Scholar
Phiel CJ, Wilson CA, Lee VM, Klein PS (2003) GSK-3a regulates production of Alzheimer’s disease amyloid-b peptides Christopher. Nature 423:435–438
CAS Article Google Scholar
Pinz MP, dos Reis AS, Vogt AG et al (2018) Current advances of pharmacological properties of 7-chloro-4-(phenylselanyl) quinoline: prevention of cognitive deficit and anxiety in Alzheimer’s disease model. Biomed Pharmacother 105. https://doi.org/10.1016/j.biopha.2018.06.049
Prati F, Cavalli A, Bolognesi ML (2016) Navigating the chemical space of multitarget-directed ligands: from hybrids to fragments in Alzheimer’s disease. Molecules 21:2–12. https://doi.org/10.3390/molecules21040466
CAS Article Google Scholar
Rani V, Deshmukh R, Jaswal P, Kumar P, Bariwal J (2016) Alzheimer’s disease: is this a brain specific diabetic condition? Physiol Behav 164:259–267. https://doi.org/10.1016/j.physbeh.2016.05.041
CAS Article PubMed Google Scholar
Ravelli KG, dos Rosário BA, Camarini R et al (2017) Intracerebroventricular Streptozotocin as a model of Alzheimer’s disease: neurochemical and behavioral characterization in mice. Neurotox Res 31:327–333. https://doi.org/10.1007/s12640-016-9684-7
CAS Article PubMed Google Scholar
Reitman S, Frankel S (1957) A colorimetric method for the determination of serum glutamic Oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol 28:56–63
CAS Article Google Scholar
Sakaguchi M, Koseki M, Wakamatsu M, Matsumura E (2006) Effects of systemic administration of β-casomorphin-5 on learning and memory in mice. Eur J Pharmacol 530:81–87. https://doi.org/10.1016/j.ejphar.2005.11.014
CAS Article PubMed Google Scholar
Sarter M, Bodewitz G, Stephens DN (1988) Attenuation of scopolamine-induced impairment of spontaneous alternation behaviour by antagonist but not inverse agonist and agonist β-carbolines. Psychopharmacology 94:491–495. https://doi.org/10.1007/BF00212843
CAS Article PubMed Google Scholar
Sassa S (1982) Delta-aminolevulinic acid dehydratase assay. Enzyme 28:133–145. https://doi.org/10.1159/000459097
CAS Article PubMed Google Scholar
Silverman HA, Dancho M, Regnier-Golanov A, Nasim M, Ochani M, Olofsson PS, Ahmed M, Miller EJ, Chavan SS, Golanov E, Metz CN, Tracey KJ, Pavlov VA (2014) Brain region-specific alterations in the gene expression of cytokines, immune cell markers and cholinergic system components during peripheral endotoxin-induced inflammation. Mol Med 20:601–611. https://doi.org/10.2119/molmed.2014.00147
Article Google Scholar
Stangherlin EC, Rocha JBT, Nogueira CW (2009) Diphenyl ditelluride impairs short-term memory and alters neurochemical parameters in young rats. Pharmacol Biochem Behav 91:430–435. https://doi.org/10.1016/j.pbb.2008.08.020
CAS Article PubMed Google Scholar
Takeuchi A, Reyes N, Artigas P, Gadsby DC (2008) The ion pathway through the opened Na+,K+-ATPase pump. Nature 456:413–416. https://doi.org/10.1038/nature07350
Article PubMed PubMed Central Google Scholar
Thomé GR, Oliveira VA, Chitolina RMS et al (2018) Selenothymidine protects against biochemical and behavioral alterations induced by ICV-STZ model of dementia in mice. Chem Biol Interact 294:135–143. https://doi.org/10.1016/j.cbi.2018.08.004
CAS Article PubMed Google Scholar
Trott O, Olson A (2010) Autodock vina: improving the speed and accuracy of docking. J Comput Chem 31:455–461. https://doi.org/10.1002/jcc.21334.AutoDock
CAS Article PubMed PubMed Central Google Scholar
Varikasuvu SR, Prasad VS, Kothapalli J, Munikumar M (2018) BRAIN selenium in Alzheimer ’ s disease ( BRAIN SEAD study ): a systematic review and meta-analysis. Biol Trace Elem Res 189:361–369
Article Google Scholar
Vér Á, Szántó I, Bányász T, Csermely P, Végh E, Somogyi J (1997) Changes in the expression of Na+/K+-ATPase isoenzymes in the left ventricle of diabetic rat hearts: effect of insulin treatment. Diabetologia 40:1255–1262
Article Google Scholar
Walsh RN, Cummins RA (1976) The open-field test: a critical review. Psychol Bull 83:482–504
CAS Article Google Scholar
Wang F, Cai B, Li KC, Hu XY, Lu YJ, Wang Q, Bao L, Zhang X (2015) FXYD2, a γ subunit of Na+,K+-ATPase, maintains persistent mechanical allodynia induced by inflammation. Cell Res 25:318–334. https://doi.org/10.1038/cr.2015.12
CAS Article PubMed PubMed Central Google Scholar
Wang H, Stewart T, Toledo JB et al (2018) A longitudinal study of total and phosphorylated α-synuclein with other biomarkers in cerebrospinal fluid of Alzheimer’s disease and mild cognitive impairment. J Alzheimers Dis 61:1541–1553. https://doi.org/10.3233/JAD-171013
CAS Article PubMed PubMed Central Google Scholar
Wiesner J, Kříz Z, Kuca K et al (2007) Acetylcholinesterases - the structural similarities and differences. J Enzyme Inhib Med Chem 22:417–424. https://doi.org/10.1080/14756360701421294
CAS Article PubMed Google Scholar
Yan J, Pang Y, Zhuang J, Lin H, Zhang Q, Han L, Ke P, Zhuang J, Huang X (2019) Selenepezil, a selenium-containing compound, exerts Neuroprotective effect via modulation of the Keap1-Nrf2-ARE pathway and attenuates Aβ-induced cognitive impairment in vivo. ACS Chem Neurosci 10:2903–2914. https://doi.org/10.1021/acschemneuro.9b00106
CAS Article PubMed Google Scholar
Zhang Y, Kua J, McCammon JA (2002) Role of the catalytic triad and oxyanion hole in acetylcholinesterase catalysis: an ab initio QM/MM study. J Am Chem Soc 124:10572–10577. https://doi.org/10.1021/ja020243m
CAS Article PubMed Google Scholar
Zhang LN, Sun YJ, Pan S, Li JX, Qu YE, Li Y, Wang YL, Gao ZB (2013) Na+-K+-ATPase, a potent neuroprotective modulator against Alzheimer disease. Fundam Clin Pharmacol 27:96–103. https://doi.org/10.1111/fcp.12000
CAS Article PubMed Google Scholar

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Acknowledgments

We are grateful for the financial support and scholarships from the Brazilian agencies Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (UNIVERSAL 408874/2016-3 and 429859/2018-0), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS) (PRONEM 16/2551-0000240-1, PRONUPEQ 16/2551-0000526-5 and PqG 17/2551-0001013-2 and 19/2551-0001745-6). CNPq is also acknowledged for the fellowships granted to C.L., D.A. and E.A.W., L.S., V.F.C. This study was funded in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível superior – Brasil (CAPES) - Finance Code 001.

Funding

This study received financial support and scholarships from the following Brazilian agencies: CNPq (UNIVERSAL 408874/2016–3 and 429859/2018–0), FAPERGS (PRONEM 16/2551–0000240-1, PRONUPEQ 16/2551–0000526-5 and PqG 17/2551–0001013-2 and 19/2551–0001745-6). CNPq is also acknowledged for the fellowships granted to C.L., D.A. and E.A.W., L.S., V.F.C. This study was also financed in part by the CAPES- Finance Code 001.

Author information

Ethel Antunes Wilhelm and Cristiane Luchese contributed equally to this work.

Affiliations

Programa de Pós-graduação em Bioquímica e Bioprospecção, Laboratório de Pesquisa em Farmacologia Bioquímica (LaFarBio), Grupo de Pesquisa em Neurobiotecnologia (GPN), Centro de Ciências Químicas, Farmacêuticas e de Alimentos (CCQFA), Universidade Federal de Pelotas (UFPel), Campus Capão do Leão, Pelotas, RS, CEP96010-900, Brazil
Mikaela Peglow Pinz, Ane Gabriela Vogt, Karline da Costa Rodrigues, Angélica Schiavom dos Reis, Ethel Antunes Wilhelm & Cristiane Luchese
Programa de Pós-Graduação em Química, Laboratório de Síntese Orgânica Limpa (LASOL), CCQFA, UFPel, Pelotas, RS, CEP 96010-900, Brazil
Luis Fernando Barbosa Duarte & Diego Alves
Programa de Pós-Graduação em Biotecnologia, Laboratório de Genômica Estrutural, Centro de Desenvolvimento Tecnológico (CDTec), UFPel, Pelotas, RS, CEP 96010-900, Brazil
William Borges Domingues, Eduardo Bierhaus Blodorn & Vinicius Farias Campos
Programa de Pós-Graduação em Biotecnologia, GPN, CDTec, UFPel, Pelotas, RS, CEP 96010-900, Brazil
Mariana Gallio Fronza & Lucielli Savegnago

Authors

Mikaela Peglow Pinz
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Ane Gabriela Vogt
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Karline da Costa Rodrigues
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Angélica Schiavom dos Reis
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Luis Fernando Barbosa Duarte
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Mariana Gallio Fronza
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William Borges Domingues
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Eduardo Bierhaus Blodorn
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Diego Alves
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Vinicius Farias Campos
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Lucielli Savegnago
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Ethel Antunes Wilhelm
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Cristiane Luchese
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Contributions

MPP: Conceptualization, Methodology, Formal analysis, Investigation, Writing - Original Draft. CL and EAW: Conceptualization, Verification, Resources, Writing - Review & Editing, Supervision, Project administration, Funding acquisition. LS, DA and VFC: Methodology, Formal analysis, Funding acquisition. AGV, KCR, ASR, EBB and LFBD: Methodology. MGF: Methodology, Formal analysis, Writing Original Draft. WBD: Methodology, Formal analysis.

Corresponding authors

Correspondence to Ethel Antunes Wilhelm or Cristiane Luchese.

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Animal care and all experimental procedures were conducted in compliance with the National Institute of Health Guide for the Care and Use of Laboratory Animals (NIH publications no. 80–23, revised in 1996) (National Research Council 1996) and in accordance with the Committee on Care and Use of Experimental Animal Resources, Federal University of Pelotas, Brazil (CEEA 1974/2016). All efforts were made to minimize the number of animals used and their suffering.

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Pinz, M.P., Vogt, A.G., da Costa Rodrigues, K. et al. Effect of a purine derivative containing selenium to improve memory decline and anxiety through modulation of the cholinergic system and Na⁺/K⁺-ATPase in an Alzheimer’s disease model. Metab Brain Dis 36, 871–888 (2021). https://doi.org/10.1007/s11011-021-00703-w

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Received: 20 September 2020
Accepted: 22 February 2021
Published: 02 March 2021
Issue Date: June 2021
DOI: https://doi.org/10.1007/s11011-021-00703-w

Keywords

Alzheimer’s disease
Anxiety
Cholinergic system
Na⁺/K⁺-ATPase
Organoselenium
Molecular docking