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Current Alzheimer Research

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ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

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Research Article

Amisulpride Decreases Tau Protein Hyperphosphorylation in the Brain of OXYS Rats

Author(s): Camilla A. Molobekova, Elena M. Kondaurova, Tatiana V. Ilchibaeva, Alexander Ya. Rodnyy*, Natalia A. Stefanova, Nataliya G. Kolosova and Vladimir S. Naumenko*

Volume 20, Issue 7, 2023

Published on: 11 September, 2023

Page: [496 - 505] Pages: 10

DOI: 10.2174/1567205020666230828144651

Price: $65

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Abstract

Aim: In this study, OXYS rats of three ages (1, 3, and 6 months), a proven model of Alzheimer’s disease (AD), at various stages of disease progression were used to thoroughly study the effects of amisulpride on behavior and tau protein phosphorylation.

Background: With the growing number of patients with AD, the problem of finding a cure is very acute. Neurodegeneration in AD has various causes, one of which is hyperphosphorylation of tau protein.

Objective: This study aimed to investigate whether amisulpride would affect pathological tau phosphorylation in AD.

Methods: We assessed the influence of chronic administration of amisulpride (3 weeks, 3 mg/kg per day, intraperitoneally)-a 5-HT7 receptor inverse agonist-on behavior and tau hyperphosphorylation in OXYS rats (at ages of 1, 3, and 6 months).

Results: Chronic administration of amisulpride dramatically decreased tau phosphorylation in the frontal cortex and hippocampus of 3-month-old OXYS rats. Additionally, in 1- and 3-month-old rats’ hippocampi, amisulpride diminished the mRNA level of the Cdk5 gene encoding one of the main tau kinases involved in the 5-HT7 receptor-induced effect on tau phosphorylation.

Conclusion: Thus, We found that chronic administration of amisulpride could reduce pathological tau hyperphosphorylation while reducing anxiety. We propose amisulpride to have therapeutic potential against AD and that it can be the most effective in the early stages of the disease.

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[1]
Bondi, M.W.; Edmonds, E.C.; Salmon, D.P. Alzheimer’s Disease: Past, Present, and Future. J. Int. Neuropsychol. Soc., 2017, 23(9-10), 818-831.
[http://dx.doi.org/10.1017/S135561771700100X] [PMID: 29198280]
[2]
Breijyeh, Z.; Karaman, R. Comprehensive review on Alzheimer’s disease: Causes and treatment. Molecules, 2020, 25(24), 5789.
[http://dx.doi.org/10.3390/molecules25245789] [PMID: 33302541]
[3]
Avila, J.; Lucas, J.J.; Pérez, M.; Hernández, F. Role of tau protein in both physiological and pathological conditions. Physiol. Rev., 2004, 84(2), 361-384.
[http://dx.doi.org/10.1152/physrev.00024.2003] [PMID: 15044677]
[4]
Jouanne, M.; Rault, S.; Voisin-Chiret, A.S. Tau protein aggregation in Alzheimer’s disease: An attractive target for the development of novel therapeutic agents. Eur. J. Med. Chem., 2017, 139, 153-167.
[http://dx.doi.org/10.1016/j.ejmech.2017.07.070] [PMID: 28800454]
[5]
Martin, L.; Latypova, X.; Wilson, C.M.; Magnaudeix, A.; Perrin, M.L.; Terro, F. Tau protein phosphatases in Alzheimer’s disease: The leading role of PP2A. Ageing Res. Rev., 2013, 12(1), 39-49.
[http://dx.doi.org/10.1016/j.arr.2012.06.008] [PMID: 22771380]
[6]
Wang, Y.; Mandelkow, E. Tau in physiology and pathology. Nat. Rev. Neurosci., 2016, 17(1), 22-35.
[http://dx.doi.org/10.1038/nrn.2015.1] [PMID: 26631930]
[7]
Labus, J.; Röhrs, K.F.; Ackmann, J.; Varbanov, H.; Müller, F.E.; Jia, S.; Jahreis, K.; Vollbrecht, A.L.; Butzlaff, M.; Schill, Y.; Guseva, D.; Böhm, K.; Kaushik, R.; Bijata, M.; Marin, P.; Chaumont-Dubel, S.; Zeug, A.; Dityatev, A.; Ponimaskin, E. Amelioration of Tau pathology and memory deficits by targeting 5-HT7 receptor. Prog. Neurobiol., 2021, 197, 101900.
[http://dx.doi.org/10.1016/j.pneurobio.2020.101900] [PMID: 32841723]
[8]
Ballard, C.; Waite, J. The effectiveness of atypical antipsychotics for the treatment of aggression and psychosis in Alzheimer’s disease. Cochrane Database Syst. Rev., 2006, (1), CD003476.
[PMID: 16437455]
[9]
Mauri, M.; Mancioli, A.; Rebecchi, V.; Corbetta, S.; Colombo, C.; Bono, G. Amisulpride in the treatment of behavioural disturbances among patients with moderate to severe Alzheimer’s disease. Acta Neurol. Scand., 2006, 114(2), 97-101.
[http://dx.doi.org/10.1111/j.1600-0404.2006.00660.x] [PMID: 16867031]
[10]
Urban, A.; Cubała, W. Therapeutic drug monitoring of atypical antipsychotics. Psychiatr. Pol., 2017, 51(6), 1059-1077.
[http://dx.doi.org/10.12740/PP/65307] [PMID: 29432503]
[11]
Kucwaj-Brysz, K.; Baltrukevich, H.; Czarnota, K.; Handzlik, J. Chemical update on the potential for serotonin 5-HT6 and 5-HT7 receptor agents in the treatment of Alzheimer’s disease. Bioorg. Med. Chem. Lett., 2021, 49, 128275.
[http://dx.doi.org/10.1016/j.bmcl.2021.128275] [PMID: 34311086]
[12]
Jahreis, K.; Brüge, A.; Borsdorf, S.; Müller, F.E.; Sun, W.; Jia, S.; Kang, D.M.; Boesen, N.; Shin, S.; Lim, S.; Koroleva, A.; Satała, G.; Bojarski, A.J.; Rakuša, E.; Fink, A.; Doblhammer-Reiter, G.; Kim, Y.K.; Dityatev, A.; Ponimaskin, E.; Labus, J. Amisulpride as a potential disease-modifying drug in the treatment of tauopathies. Alzheimers Dement., 2023, 2023, 13090.
[http://dx.doi.org/10.1002/alz.13090] [PMID: 37218673]
[13]
Stefanova, N.; Kozhevnikova, O.; Vitovtov, A.; Maksimova, K.; Logvinov, S.; Rudnitskaya, E.; Korbolina, E.; Muraleva, N.; Kolosova, N. Senescence-accelerated OXYS rats: A model of age-related cognitive decline with relevance to abnormalities in Alzheimer disease. Cell Cycle, 2014, 13(6), 898-909.
[http://dx.doi.org/10.4161/cc.28255] [PMID: 24552807]
[14]
Gulyaeva, N.V.; Bobkova, N.V.; Kolosova, N.G.; Samokhin, A.N.; Stepanichev, M.Y.; Stefanova, N.A. Molecular and cellular mechanisms of sporadic Alzheimer’s disease: Studies on rodent models in vivo. Biochemistry (Mosc.), 2017, 82(10), 1088-1102.
[http://dx.doi.org/10.1134/S0006297917100029] [PMID: 29037130]
[15]
Stefanova, N.A.; Muraleva, N.A.; Korbolina, E.E.; Kiseleva, E.; Maksimova, K.Y.; Kolosova, N.G. Amyloid accumulation is a late event in sporadic Alzheimer’s disease-like pathology in nontransgenic rats. Oncotarget, 2015, 6(3), 1396-1413.
[http://dx.doi.org/10.18632/oncotarget.2751] [PMID: 25595891]
[16]
Tyumentsev, M.A.; Stefanova, N.A.; Muraleva, N.A.; Rumyantseva, Y.V.; Kiseleva, E.; Vavilin, V.A.; Kolosova, N.G. Mitochondrial dysfunction as a predictor and driver of Alzheimer’s disease-like pathology in OXYS rats. J. Alzheimers Dis., 2018, 63(3), 1075-1088.
[http://dx.doi.org/10.3233/JAD-180065] [PMID: 29710722]
[17]
Kulikov, A.V.; Naumenko, V.S.; Voronova, I.P.; Tikhonova, M.A.; Popova, N.K. Quantitative RT-PCR assay of 5-HT1A and 5-HT2A serotonin receptor mRNAs using genomic DNA as an external standard. J. Neurosci. Methods, 2005, 141(1), 97-101.
[http://dx.doi.org/10.1016/j.jneumeth.2004.06.005] [PMID: 15585293]
[18]
Naumenko, V.S.; Kulikov, A.V. Quantitative assay of 5-HT(1A) serotonin receptor gene expression in the brain. Mol. Biol. (Mosk.), 2006, 40(1), 37-44.
[PMID: 16523690]
[19]
Naumenko, V.S.; Osipova, D.V.; Kostina, E.V.; Kulikov, A.V. Utilization of a two-standard system in real-time PCR for quantification of gene expression in the brain. J. Neurosci. Methods, 2008, 170(2), 197-203.
[http://dx.doi.org/10.1016/j.jneumeth.2008.01.008] [PMID: 18308402]
[20]
Hsu, D.; Marshall, G.A. Primary and secondary prevention trials in Alzheimer disease: Looking back, moving forward. Curr. Alzheimer Res., 2017, 14(4), 426-440.
[http://dx.doi.org/10.2174/1567205013666160930112125] [PMID: 27697063]
[21]
Briggs, R.; Kennelly, S.P.; O’Neill, D. Drug treatments in Alzheimer’s disease. Clin. Med. (Lond.), 2016, 16(3), 247-253.
[http://dx.doi.org/10.7861/clinmedicine.16-3-247] [PMID: 27251914]
[22]
McKeage, K.; Plosker, G.L. Amisulpride. CNS Drugs, 2004, 18(13), 933-956.
[http://dx.doi.org/10.2165/00023210-200418130-00007] [PMID: 15521794]
[23]
Renner, U.; Zeug, A.; Woehler, A.; Niebert, M.; Dityatev, A.; Dityateva, G.; Gorinski, N.; Guseva, D.; Abdel-Galil, D.; Fröhlich, M.; Döring, F.; Wischmeyer, E.; Richter, D.W.; Neher, E.; Ponimaskin, E.G. Heterodimerization of serotonin receptors 5-HT1A and 5-HT7 differentially regulates receptor signalling and trafficking. J. Cell Sci., 2012, 125(Pt 10), jcs.101337.
[http://dx.doi.org/10.1242/jcs.101337] [PMID: 22357950]
[24]
Kondaurova, E.M.; Bazovkina, D.V.; Naumenko, V.S. [5-HT1A/5-HT7 receptor interplay: Chronic activation of 5-HT7 receptors decreases the functional activity of 5-HT1A receptor and its сontent in the mouse brain]. Mol. Biol. (Mosk.), 2017, 51(1), 157-165.
[PMID: 28251979]
[25]
de Bartolomeis, A.; Marmo, F.; Buonaguro, E.F.; Rossi, R.; Tomasetti, C.; Iasevoli, F. Imaging brain gene expression profiles by antipsychotics: Region-specific action of amisulpride on postsynaptic density transcripts compared to haloperidol. Eur. Neuropsychopharmacol., 2013, 23(11), 1516-1529.
[http://dx.doi.org/10.1016/j.euroneuro.2012.11.014] [PMID: 23357084]
[26]
Shukla, V.; Skuntz, S.; Pant, H.C. Deregulated Cdk5 activity is involved in inducing Alzheimer’s disease. Arch. Med. Res., 2012, 43(8), 655-662.
[http://dx.doi.org/10.1016/j.arcmed.2012.10.015] [PMID: 23142263]
[27]
Jeong, J.; Park, Y.U.; Kim, D.K.; Lee, S.; Kwak, Y.; Lee, S.A.; Lee, H.; Suh, Y.H.; Gho, Y.S.; Hwang, D.; Park, S.K. Cdk5 phosphorylates dopamine D2 receptor and attenuates downstream signaling. PLoS One, 2013, 8(12), e84482.
[http://dx.doi.org/10.1371/journal.pone.0084482] [PMID: 24391960]
[28]
Kumar, S.P.; Babu, P.P. Aberrant dopamine receptor signaling plays critical role in the impairment of striatal neurons in experimental cerebral malaria. Mol. Neurobiol., 2020, 57(12), 5069-5083.
[http://dx.doi.org/10.1007/s12035-020-02076-0] [PMID: 32833186]
[29]
Missale, C.; Nash, S.R.; Robinson, S.W.; Jaber, M.; Caron, M.G. Dopamine receptors: From structure to function. Physiol. Rev., 1998, 78(1), 189-225.
[http://dx.doi.org/10.1152/physrev.1998.78.1.189] [PMID: 9457173]
[30]
Shah, K.; Lahiri, D.K. Cdk5 activity in the brain – multiple paths of regulation. J. Cell Sci., 2014, 127(11), 2391-2400.
[http://dx.doi.org/10.1242/jcs.147553] [PMID: 24879856]
[31]
Nikiforuk, A.; Popik, P. Amisulpride promotes cognitive flexibility in rats: The role of 5-HT7 receptors. Behav. Brain Res., 2013, 248, 136-140.
[http://dx.doi.org/10.1016/j.bbr.2013.04.008] [PMID: 23603557]
[32]
Kolosova, N.G.; Vitovtov, A.O.; Muraleva, N.A.; Akulov, A.E.; Stefanova, N.A.; Blagosklonny, M.V. Rapamycin suppresses brain aging in senescence-accelerated OXYS rats. Aging, 2013, 5(6), 474-484.
[http://dx.doi.org/10.18632/aging.100573] [PMID: 23817674]

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