<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">scbmt</journal-id><journal-title-group><journal-title xml:lang="ru">БИОМЕДИЦИНА</journal-title><trans-title-group xml:lang="en"><trans-title>Journal Biomed</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2074-5982</issn><issn pub-type="epub">2713-0428</issn><publisher><publisher-name>Scientific center of biomedical technologies of Federal Medical and Biological Agency</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.33647/2074-5982-21-4-96-100</article-id><article-id custom-type="elpub" pub-id-type="custom">scbmt-1804</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>РЕЛЕВАНТНОЕ И АЛЬТЕРНАТИВНОЕ БИОМОДЕЛИРОВАНИЕ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>RELEVANT AND ALTERNATIVE BIOMODELLING</subject></subj-group></article-categories><title-group><article-title>Биомоделирование воспалительно-амлоидного каскада как основы развития болезни Альцгеймера у старых мышей C57BL/6J</article-title><trans-title-group xml:lang="en"><trans-title>.Biomodeling the Inflammatory Amyloid Cascade as the Basis of Alzheimer's Disease in Old  C57BL/6J Mic</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Инокентьева</surname><given-names>В. И.</given-names></name><name name-style="western" xml:lang="en"><surname>Inokenteva</surname><given-names>V. I.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Инокентьева Виктория Игоревна</p><p>125315, Москва, ул. Балтийская, 8</p></bio><bio xml:lang="en"><p>Victoria I. Inokenteva</p><p>125315, Moscow, Baltiyskaya Str., 8</p></bio><email xlink:type="simple">inokenteva_vi@academpharm.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Грудень</surname><given-names>М. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Gruden</surname><given-names>M. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Грудень Марина Алексеевна, к.х.н.</p><p>125315, Москва, ул. Балтийская, 8</p></bio><bio xml:lang="en"><p>Marina A. Gruden, Cand. Sci. (Chem.)</p><p>125315, Moscow, Baltiyskaya Str., 8</p></bio><email xlink:type="simple">gruden_ma@academpharm.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Соловьева</surname><given-names>О. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Solovieva</surname><given-names>O. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Соловьева Ольга Александровна</p><p>125315, Москва, ул. Балтийская, 8</p></bio><bio xml:lang="en"><p>Olga A. Solovieva</p><p>125315, Moscow, Baltiyskaya Str., 8</p></bio><email xlink:type="simple">solovieva_oa@academpharm.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Михайлова</surname><given-names>Н. П.</given-names></name><name name-style="western" xml:lang="en"><surname>Mikhailova</surname><given-names>N. P.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Михайлова Наталия Павловна</p><p>125315, Москва, ул. Балтийская, 8</p></bio><bio xml:lang="en"><p>Nataliya P. Mikhailova</p><p>125315, Moscow, Baltiyskaya Str., 8</p></bio><email xlink:type="simple">mikhajlova_np@academpharm.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Ратмиров</surname><given-names>А. М.</given-names></name><name name-style="western" xml:lang="en"><surname>Ratmirov</surname><given-names>A. M.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Ратмиров Александр Максимович</p><p>125315, Москва, ул. Балтийская, 8</p></bio><bio xml:lang="en"><p>Alexander M. Ratmirov</p><p>125315, Moscow, Baltiyskaya Str., 8</p></bio><email xlink:type="simple">ratmirov_am@academpharm.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Сторожева</surname><given-names>З. И.</given-names></name><name name-style="western" xml:lang="en"><surname>Storozheva</surname><given-names>Z. I.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Сторожева Зинаида Ивановна, д.б.н.</p><p>125315, Москва, ул. Балтийская, 8</p></bio><bio xml:lang="en"><p>Zinaida I. Storozheva, Dr. Sci. (Biol.)</p><p>125315, Moscow, Baltiyskaya Str., 8</p></bio><email xlink:type="simple">storozheva_zi@academpharm.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГБНУ «Федеральный исследовательский центр оригинальных и перспективных биомедицинских и фармацевтических технологий»</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2025</year></pub-date><pub-date pub-type="epub"><day>18</day><month>12</month><year>2025</year></pub-date><volume>21</volume><issue>4</issue><fpage>96</fpage><lpage>100</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Инокентьева В.И., Грудень М.А., Соловьева О.А., Михайлова Н.П., Ратмиров А.М., Сторожева З.И., 2025</copyright-statement><copyright-year>2025</copyright-year><copyright-holder xml:lang="ru">Инокентьева В.И., Грудень М.А., Соловьева О.А., Михайлова Н.П., Ратмиров А.М., Сторожева З.И.</copyright-holder><copyright-holder xml:lang="en">Inokenteva V.I., Gruden M.A., Solovieva O.A., Mikhailova N.P., Ratmirov A.M., Storozheva Z.I.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://journal.scbmt.ru/jour/article/view/1804">https://journal.scbmt.ru/jour/article/view/1804</self-uri><abstract><p>В данной работе было изучено влияние хронического интраназального введения олигомеров провоспалительного белка S100A9, индуцирующих воспалительно-амилоидный каскад, у 24-месячных мышей C57BL/6J на формирование и сохранность долговременной пространственной памяти, экспрессию гена Th, а также содержание и обмен дофамина в гиппокампе, фронтальной коре и мозжечке. Обнаружено нарушение долговременной памяти в 3-й и 4-й дни обучения и в сеансе тестирования в водном лабиринте Морриса у опытных животных по сравнению с контролем. Экспрессия Th статистически значимо повышалась в мозжечке, а содержание дофамина достоверно снижалось в гиппокампе. Таким образом, хроническое интраназальное введение олигомеров S100A9 старым животным способствует формированию патологических симптомов, подобных болезни Альцгеймера, и может рассматриваться в качестве разрабатываемой модели этого заболевания.</p></abstract><trans-abstract xml:lang="en"><p>In this work, the effect of chronic intranasal administration of S100A9 proinflammatory protein oligomers, inducing the inflammatory-amyloid cascade, in 24-month-old C57BL/6J mice on the formation and preservation of long-term spatial memory, Th gene expression, as well as dopamine content and metabolism in the hippocampus, frontal cortex, and cerebellum was studied. Compared to the control, experimental animals showed an impairment of the long-term memory on days 3 and 4 of training and testing session in a Morris water maze. Th expression increased significantly in the cerebellum, while dopamine levels decreased significantly in the hippocampus. Thus, chronic intranasal administration of S100A9 oligomers to old animals contributes to the formation of pathological symptoms similar to Alzheimer's disease, thus showing potential as a model of this disease.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>биомоделирование</kwd><kwd>олигомеры S100A9</kwd><kwd>пространственная память</kwd><kwd>ген Th</kwd><kwd>дофамин</kwd><kwd>болезнь Альцгеймера</kwd></kwd-group><kwd-group xml:lang="en"><kwd>biomodeling</kwd><kwd>S100A9 oligomers</kwd><kwd>spatial memory</kwd><kwd>Th gene</kwd><kwd>dopamine</kwd><kwd>Alzheimer's disease</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">в рамках Госзадания</funding-statement><funding-statement xml:lang="en">under State assignment.</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Coleman P.D., Delvaux E., Kordower J.H., Boehringer A., Huseby C.J. Massive changes in gene expression and their cause(s) can be a unifying principle in the pa- thobiology of Alzheimer's disease. Alzheimers Dement. 2025;21(2):e14555. DOI: 10.1002/alz.14555.</mixed-citation><mixed-citation xml:lang="en">Coleman P.D., Delvaux E., Kordower J.H., Boehringer A., Huseby C.J. Massive changes in gene expression and their cause(s) can be a unifying principle in the pa- thobiology of Alzheimer's disease. Alzheimers Dement. 2025;21(2):e14555. DOI: 10.1002/alz.14555.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Dahl M.J., Kulesza A., Werkle-Bergner M., Mather M. Declining locus coeruleus-dopaminergic and noradrenergic modulation of long-term memory in aging and Alzheimer's disease. Neurosci. Biobehav. Rev. 2023;153:105358. DOI: 10.1016/j.neubiorev.2023.105358.</mixed-citation><mixed-citation xml:lang="en">Dahl M.J., Kulesza A., Werkle-Bergner M., Mather M. Declining locus coeruleus-dopaminergic and noradrenergic modulation of long-term memory in aging and Alzheimer's disease. Neurosci. Biobehav. Rev. 2023;153:105358. DOI: 10.1016/j.neubiorev.2023.105358.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Davydova T.V., Gruden M.A., Kudrin V.S., Narkevich V.B., Vetrile L.A., Zakharova I.A., Sewell R.D.E. Delayed Behavioral and Neurochemical Effects of Anti-Glutamate Antibodies in Aging C57BL/6 Mice. Bull. Exp. Biol. Med. 2021;171(1):19–22. DOI: 10.1007/s10517-021-05163-x.</mixed-citation><mixed-citation xml:lang="en">Davydova T.V., Gruden M.A., Kudrin V.S., Narkevich V.B., Vetrile L.A., Zakharova I.A., Sewell R.D.E. Delayed Behavioral and Neurochemical Effects of Anti-Glutamate Antibodies in Aging C57BL/6 Mice. Bull. Exp. Biol. Med. 2021;171(1):19–22. DOI: 10.1007/s10517-021-05163-x.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Dorszewska J., Prendecki M., Oczkowska A., Dezor M., Kozubski W. Molecular Basis of Familial and Sporadic Alzheimer's Disease. Curr. Alzheimer Res. 2016;13(9):952–963. DOI: 10.2174/1567205013666160314150501.</mixed-citation><mixed-citation xml:lang="en">Dorszewska J., Prendecki M., Oczkowska A., Dezor M., Kozubski W. Molecular Basis of Familial and Sporadic Alzheimer's Disease. Curr. Alzheimer Res. 2016;13(9):952–963. DOI: 10.2174/1567205013666160314150501.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Iashchishyn I.A., Gruden M.A., Moskalenko R.A., Davydova T.V., Wang C., Sewell R.D.E., Morozova- Roche L.A. Intranasally Administered S100A9 Amyloids Induced Cellular Stress, Amyloid Seeding, and Behavioral Impairment in Aged Mice. ACS Chem. Neurosci. 2018;9(6):1338–1348. DOI: 10.1021/acschemneuro.7b00512.</mixed-citation><mixed-citation xml:lang="en">Iashchishyn I.A., Gruden M.A., Moskalenko R.A., Davydova T.V., Wang C., Sewell R.D.E., Morozova- Roche L.A. Intranasally Administered S100A9 Amyloids Induced Cellular Stress, Amyloid Seeding, and Behavioral Impairment in Aged Mice. ACS Chem. Neurosci. 2018;9(6):1338–1348. DOI: 10.1021/acschemneuro.7b00512.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Livak K.J., Schmittgen T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402–408. DOI: 10.1006/meth.2001.1262.</mixed-citation><mixed-citation xml:lang="en">Livak K.J., Schmittgen T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402–408. DOI: 10.1006/meth.2001.1262.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Liu E., Zhang Y., Wang J.Z. Updates in Alzheimer's disease: from basic research to diagnosis and therapies. Transl. Neurodegener. 2024;13(1):45. DOI: 10.1186/s40035-024-00432-x.</mixed-citation><mixed-citation xml:lang="en">Liu E., Zhang Y., Wang J.Z. Updates in Alzheimer's disease: from basic research to diagnosis and therapies. Transl. Neurodegener. 2024;13(1):45. DOI: 10.1186/s40035-024-00432-x.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Puzzo D., Gulisano W., Palmeri A., Arancio O. Rodent models for Alzheimer's disease drug discovery. Expert Opin. Drug Discov. 2015;10(7):703–711. DOI: 10.1517/17460441.2015.1041913.</mixed-citation><mixed-citation xml:lang="en">Puzzo D., Gulisano W., Palmeri A., Arancio O. Rodent models for Alzheimer's disease drug discovery. Expert Opin. Drug Discov. 2015;10(7):703–711. DOI: 10.1517/17460441.2015.1041913.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Sukhareva E.V., Kalinina T.S., Bulygina V.V., Dygalo N.N. Tyrosine hydroxylase of the brain and its regulation by glucocorticoids. Vavilov Journal of Genetics and Breeding. 2016;20(2):212–219. DOI: 10.18699/VJ16.156.</mixed-citation><mixed-citation xml:lang="en">Sukhareva E.V., Kalinina T.S., Bulygina V.V., Dygalo N.N. Tyrosine hydroxylase of the brain and its regulation by glucocorticoids. Vavilov Journal of Genetics and Breeding. 2016;20(2):212–219. DOI: 10.18699/VJ16.156.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Szot P., Leverenz J.B., Peskind E.R., Kiyasu E., Rohde K., Miller M.A., Raskind M.A. Tyrosine hydroxylase and norepinephrine transporter mRNA expression in the locus coeruleus in Alzheimer's disease. Brain Res. Mol. Brain Res. 2000;84(1–2):135–140. DOI: 10.1016/s0169-328x(00)00168-6.</mixed-citation><mixed-citation xml:lang="en">Szot P., Leverenz J.B., Peskind E.R., Kiyasu E., Rohde K., Miller M.A., Raskind M.A. Tyrosine hydroxylase and norepinephrine transporter mRNA expression in the locus coeruleus in Alzheimer's disease. Brain Res. Mol. Brain Res. 2000;84(1–2):135–140. DOI: 10.1016/s0169-328x(00)00168-6.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Szot P., White S.S., Greenup J.L., Leverenz J.B., Peskind E.R., Raskind M.A. Compensatory changes in the noradrenergic nervous system in the locus ceruleus and hippocampus of postmortem subjects with Alzheimer's disease and dementia with Lewy bodies. J. Neurosci. 2006;26(2):467–478. DOI: 10.1523/JNEUROSCI.4265-05.2006.</mixed-citation><mixed-citation xml:lang="en">Szot P., White S.S., Greenup J.L., Leverenz J.B., Peskind E.R., Raskind M.A. Compensatory changes in the noradrenergic nervous system in the locus ceruleus and hippocampus of postmortem subjects with Alzheimer's disease and dementia with Lewy bodies. J. Neurosci. 2006;26(2):467–478. DOI: 10.1523/JNEUROSCI.4265-05.2006.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Vorhees CV, Williams MT. Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat. Protoc. 2006;1(2):848–858. DOI: 10.1038/nprot.2006.116.</mixed-citation><mixed-citation xml:lang="en">Vorhees CV, Williams MT. Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat. Protoc. 2006;1(2):848–858. DOI: 10.1038/nprot.2006.116.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Wang C., Klechikov A.G., Gharibyan A.L., Wärmländer S.K., Jarvet J., Zhao L., Jia X., Narayana V.K., Shankar S.K., Olofsson A., Brännström T., Mu Y., Gräslund A., Morozova-Roche L.A. The role of pro-inflammatory S100A9 in Alzheimer's disease amyloid-neuroinflammatory cascade. Acta. Neuropathol. 2014;127(4):507–522. DOI: 10.1007/s00401-013-1208-4.</mixed-citation><mixed-citation xml:lang="en">Wang C., Klechikov A.G., Gharibyan A.L., Wärmländer S.K., Jarvet J., Zhao L., Jia X., Narayana V.K., Shankar S.K., Olofsson A., Brännström T., Mu Y., Gräslund A., Morozova-Roche L.A. The role of pro-inflammatory S100A9 in Alzheimer's disease amyloid-neuroinflammatory cascade. Acta. Neuropathol. 2014;127(4):507–522. DOI: 10.1007/s00401-013-1208-4.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Watamura N., Kakiya N., Fujioka R., Kamano N., Takahashi M., Nilsson P., Saito T., Iwata N., Fujisawa S., Saido T.C. The dopaminergic system promotes neprilysin-mediated degradation of amyloid-β in the brain. Sci. Signal. 2024;17(848):eadk1822. DOI: 10.1126/scisignal.adk1822.</mixed-citation><mixed-citation xml:lang="en">Watamura N., Kakiya N., Fujioka R., Kamano N., Takahashi M., Nilsson P., Saito T., Iwata N., Fujisawa S., Saido T.C. The dopaminergic system promotes neprilysin-mediated degradation of amyloid-β in the brain. Sci. Signal. 2024;17(848):eadk1822. DOI: 10.1126/scisignal.adk1822.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
