Taar1 modulates neuronal and glial density in the neocortex following spinal cord injury

Мұқаба

Дәйексөз келтіру

Толық мәтін

Ашық рұқсат Ашық рұқсат
Рұқсат жабық Рұқсат берілді
Рұқсат жабық Тек жазылушылар үшін

Аннотация

Spinal cord injury (SCI) initiates a complex cascade of secondary pathological processes, including chronic neuroinflammation and neuroplastic remodeling both at the lesion site and in distant regions, such as the cerebral cortex. This study explores the role of trace amine-associated receptor 1 (TAAR1) in modulating neuroinflammatory responses in the somatosensory cortex following lateral spinal cord hemisection in wild-type mice and TAAR1-knockout (TAAR1-KO). Behavioral tests revealed no significant differences in sensorimotor recovery, suggesting a limited impact of TAAR1 on functional recovery. However, immunohistochemical analysis uncovered substantial alterations in glial reactivity. Specifically, TAAR1-KO mice exhibited a marked increase in GFAP⁺ astrocyte density within the granular and pyramidal cortical layers, indicating enhanced astrogliosis. At the same time, the number of pro-inflammatory S100β⁺ astrocytes remained unchanged, which emphasizes the selective effect of TAAR1 on distinct astrocyte subpopulations. Additionally, TAAR1-KO mice showed a reduction in the density of Iba-1⁺ microglial cells. Furthermore, a decline in pyramidal neuron counts was noted, potentially indicative of impaired survival. Crucially, these differences emerged only post-injury, as genotypes were indistinguishable under baseline conditions. The obtained data demonstrate the key role of TAAR1 in modulating the glial response and expand our understanding of the molecular mechanisms of neuroinflammation in SCI, opening new avenues for the development of TAAR1-targeted neuroprotective strategies.

Авторлар туралы

D. Kalinina

Sirius University of Science and Technology; St. Petersburg State University, Institute of Translational Biomedicine; Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences

Email: kalinina.ds@talantiuspeh.ru
Sirius Federal Territory, Russia; St. Petersburg, Russia; St. Petersburg, Russia

A. Chesnokov

Sirius University of Science and Technology

Sirius Federal Territory, Russia

E. Romanyuk

Sirius University of Science and Technology

Sirius Federal Territory, Russia

A. Buglinina

Sirius University of Science and Technology

Sirius Federal Territory, Russia

D. Khuzin

Sirius University of Science and Technology

Sirius Federal Territory, Russia

S. Milov

Sirius University of Science and Technology

Sirius Federal Territory, Russia

S. Konavalova

Sirius University of Science and Technology

Sirius Federal Territory, Russia

P. Shkorbatova

St. Petersburg State University, Institute of Translational Biomedicine; Pavlov Institute of Physiology, Russian Academy of Sciences

St. Petersburg, Russia; St. Petersburg, Russia

N. Pavlova

Pavlov Institute of Physiology, Russian Academy of Sciences

St. Petersburg, Russia

A. Belskaya

St. Petersburg State University, Institute of Translational Biomedicine

St. Petersburg, Russia

R. Gainetdinov

St. Petersburg State University, Institute of Translational Biomedicine

St. Petersburg, Russia

P. Musienko

Pavlov Institute of Physiology, Russian Academy of Sciences; Life Improvement by Future Technologies (LIFT) Center; Federal Center for Brain and Neurotechnologies

Email: pol-spb@mail.ru
St. Petersburg, Russia; Moscow, Russia; Moscow, Russia

Әдебиет тізімі

  1. Ahuja CS, Wilson JR, Nori S, Kotter MRN, Druschel C, Curt A, Fehlings MG (2017) Traumatic spinal cord injury. Nat Rev Dis Primers 3: 17018. https://doi.org/10.1038/nrdp.2017.18
  2. Sun X, Jones ZB, Chen X, Zhou L, So K-F, Ren Y (2016) Multiple organ dysfunction and systemic inflammation after spinal cord injury: А complex relationship. J Neuroinflammat 13. https://doi.org/10.1186/s12974-016-0736-y
  3. Arevalo-Martin A, Grassner L, Garcia-Ovejero D, Paniagua-Torija B, Barroso-Garcia G, Arandilla AG, Mach O, Turrero A, Vargas E, Alcobendas M, Rosell C, Alcaraz MA, Ceruelo S, Casado R, Talavera F, Palazón R, Sanchez-Blanco N, Maier D, Esclarin A, Molina-Holgado E (2018) Elevated Autoantibodies in Subacute Human Spinal Cord Injury Are Naturally Occurring Antibodies. Front Immunol 9: 2365. https://doi.org/10.3389/fimmu.2018.02365
  4. Sterner RC, Sterner RM (2023) Immune response following traumatic spinal cord injury: Pathophysiology and therapies. Front Immunol 13. https://doi.org/10.3389/fimmu.2022.1084101
  5. Rowe CJ, Nwaolu U, Martin L, Huang BJ, Mang J, Salinas D, Schlaff CD, Ghenbot S, Lansford JL, Potter BK, Schobel SA, Gann ER, Davis TA (2024) Systemic inflammation following traumatic injury and its impact on neuroinflammatory gene expression in the rodent brain. J Neuroinflammat 21. https://doi.org/10.1186/s12974-024-03205-5
  6. Frith C, Dolan R (1996) The role of the prefrontal cortex in higher cognitive functions. Cognitiv Brain Res 5: 175–181. https://doi.org/10.1016/S0926-6410(96)00054-7
  7. Krishnan VS, Shin SS, Belegu V, Celnik P, Reimers M, Smith KR, Pelled G (2019) Multimodal Evaluation of TMS – Induced Somatosensory Plasticity and Behavioral Recovery in Rats With Contusion Spinal Cord Injury. Front Neurosci 13387. https://doi.org/10.3389/fnins.2019.00387
  8. Ghosh A, Peduzzi S, Snyder M, Schneider R, Starkey M, Schwab ME (2012) Heterogeneous Spine Loss in Layer 5 Cortical Neurons after Spinal Cord Injury. Cerebral Cortex 22: 1309–1317. https://doi.org/10.1093/cercor/bhr191
  9. Nagendran T, Larsen RS, Bigler RL, Frost SB, Philpot BD, Nudo RJ, Taylor AM (2017) Distal axotomy enhances retrograde presynaptic excitability onto injured pyramidal neurons via trans-synaptic signaling. Nat Commun 8: 625. https://doi.org/10.1038/s41467-017-00652-y
  10. Barron KD, Dentinger MP, Popp AJ, Mankes R (1988) Neurons of Layer Vb of Rat Sensorimotor Cortex Atrophy But Do Not Die After Thoracic Cord Transection. J Neuropathol Exp Neurol 47: 62–74. https://doi.org/10.1097/00005072-198801000-00008
  11. Moro V, Beccherle M, Scandola M, Aglioti SM (2023) Massive body-brain disconnection consequent to spinal cord injuries drives profound changes in higher-order cognitive and emotional functions: A PRISMA scoping review. Neurosci Biobehavl Rev 154: 105395. https://doi.org/10.1016/j.neubiorev.2023.105395
  12. David S, Kroner A (2011) Repertoire of microglial and macrophage responses after spinal cord injury. Nat Rev Neurosci 12: 388–399. https://doi.org/10.1038/nrn3053
  13. Gainetdinov RR, Hoener MC, Berry MD (2018) Trace Amines and Their Receptors. Pharmacol Rev 70: 549–620. https://doi.org/10.1124/pr.117.015305
  14. Espinoza S, Lignani G, Caffino L, Maggi S, Sukhanov I, Leo D, Mus L, Emanuele M, Ronzitti G, Harmeier A, Medrihan L, Sotnikova TD, Chieregatti E, Hoener MC, Benfenati F, Tucci V, Fumagalli F, Gainetdinov RR (2015) TAAR1 Modulates Cortical Glutamate NMDA Receptor Function. Neuropsychopharmacology 40: 2217–2227. https://doi.org/10.1038/npp.2015.65
  15. Harrison M, O’Brien A, Adams L, Cowin G, Ruitenberg MJ, Sengul G, Watson C (2013) Vertebral landmarks for the identification of spinal cord segments in the mouse. NeuroImage 68: 22–29. https://doi.org/10.1016/j.neuroimage.2012.11.048
  16. Endo T, Spenger C, Tominaga T, Brene S, Olson L (2007) Cortical sensory map rearrangement after spinal cord injury: fMRI responses linked to Nogo signalling. Brain 130: 2951–2961. https://doi.org/10.1093/brain/awm237
  17. Wrigley PJ, Gustin SM, Macey PM, Nash PG, Gandevia SC, Macefield VG, Siddall PJ, Henderson LA (2009) Anatomical Changes in Human Motor Cortex and Motor Pathways following Complete Thoracic Spinal Cord Injury. Cerebral Cortex 19: 224–232. https://doi.org/10.1093/cercor/bhn072
  18. Maldonado-Bouchard S, Peters K, Woller SA, Madahian B, Faghihi U, Patel S, Bake S, Hook MA (2016) Inflammation is increased with anxiety- and depression-like signs in a rat model of spinal cord injury. Brain, Behavior, and Immunity 51: 176–195. https://doi.org/10.1016/j.bbi.2015.08.009
  19. Wu J, Stoica BA, Luo T, Sabirzhanov B, Zhao Z, Guanciale K, Nayar SK, Foss CA, Pomper MG, Faden AI (2014) Isolated spinal cord contusion in rats induces chronic brain neuroinflammation, neurodegeneration, and cognitive impairment: Involvement of cell cycle activation. Cell Cycle 13: 2446–2458. https://doi.org/10.4161/cc.29420
  20. Babusyte A, Kotthoff M, Fiedler J, Krautwurst D (2013) Biogenic amines activate blood leukocytes via trace amine-associated receptors TAAR1 and TAAR2. J Leukocyte Biol 93: 387–394. https://doi.org/10.1189/jlb.0912433
  21. Barnes DA, Galloway DA, Hoener MC, Berry MD, Moore CS (2021) TAAR1 Expression in Human Macrophages and Brain Tissue: A Potential Novel Facet of MS Neuroinflammation. IJMS 22: 11576. https://doi.org/10.3390/ijms222111576
  22. Polini B, Ricardi C, Bertolini A, Carnicelli V, Rutigliano G, Saponaro F, Zucchi R, Chiellini G (2023) T1AM/TAAR1 System Reduces Inflammatory Response and β-Amyloid Toxicity in Human Microglial HMC3 Cell Line. IJMS 24: 11569. https://doi.org/10.3390/ijms241411569
  23. Cisneros IE, Ghorpade A (2014) Methamphetamine and HIV-1-induced neurotoxicity: Role of trace amine associated receptor 1 cAMP signaling in astrocytes. Neuropharmacology 85: 499–507. https://doi.org/10.1016/j.neuropharm.2014.06.011
  24. Zhang M-X, Hong H, Shi Y, Huang W-Y, Xia Y-M, Tan L-L, Zhao W-J, Qiao C-M, Wu J, Zhao L-P, Huang S-B, Jia X-B, Shen Y-Q, Cui C (2024) A Pilot Study on a Possible Mechanism behind Olfactory Dysfunction in Parkinson’s Disease: The Association of TAAR1 Downregulation with Neuronal Loss and Inflammation along Olfactory Pathway. Brain Sci 14: 300. https://doi.org/10.3390/brainsci14040300
  25. Sun M, Zhang Y, Zhang X-Q, Zhang Y, Wang X-D, Li J-T, Si T-M, Su Y-A (2024) Dopamine D1 receptor in medial prefrontal cortex mediates the effects of TAAR1 activation on chronic stress-induced cognitive and social deficits. Neuropsychopharmacology 49: 1341–1351. https://doi.org/10.1038/s41386-024-01866-7
  26. Andersen G, Krautwurst D (2016) Trace Amine-Associated Receptors in the Cellular Immune System. In: Trace Amines and Neurological Disorders. Elsevier. 97–105. https://doi.org/10.1016/B978-0-12-803603-7.00007-0
  27. Guerra-Gomes S, Sousa N, Pinto L, Oliveira JF (2018) Functional Roles of Astrocyte Calcium Elevations: From Synapses to Behavior. Front Cell Neurosci 11: 427. https://doi.org/10.3389/fncel.2017.00427
  28. Lee H-G, Wheeler MA, Quintana FJ (2022) Function and therapeutic value of astrocytes in neurological diseases. Nat Rev Drug Discov 21: 339–358. https://doi.org/10.1038/s41573-022-00390-x
  29. Hart CG, Karimi-Abdolrezaee S (2021) Recent insights on astrocyte mechanisms in CNS homeostasis, pathology, and repair. J Neurosci Res 99: 2427–2462. https://doi.org/10.1002/jnr.24922
  30. Hol EM, Pekny M (2015) Glial fibrillary acidic protein (GFAP) and the astrocyte intermediate filament system in diseases of the central nervous system. Curr Opin Cell Biol 32: 121–130. https://doi.org/10.1016/j.ceb.2015.02.004
  31. Wu J, Zhao Z, Sabirzhanov B, Stoica BA, Kumar A, Luo T, Skovira J, Faden AI (2014) Spinal Cord Injury Causes Brain Inflammation Associated with Cognitive and Affective Changes: Role of Cell Cycle Pathways. J Neurosci 34: 10989–11006. https://doi.org/10.1523/JNEUROSCI.5110-13.2014
  32. Liu T, Zuo H, Ma D, Song D, Zhao Y, Cheng O (2023) Cerebrospinal fluid GFAP is a predictive biomarker for conversion to dementia and Alzheimer’s disease-associated biomarkers alterations among de novo Parkinson’s disease patients: А prospective cohort study. J Neuroinflammat 20: 167. https://doi.org/10.1186/s12974-023-02843-5
  33. Liddelow SA, Guttenplan KA, Clarke LE, Bennett FC, Bohlen CJ, Schirmer L, Bennett ML, Münch AE, Chung W-S, Peterson TC, Wilton DK, Frouin A, Napier BA, Panicker N, Kumar M, Buckwalter MS, Rowitch DH, Dawson VL, Dawson TM, Stevens B, Barres BA (2017) Neurotoxic reactive astrocytes are induced by activated microglia. Nature 541: 481–487. https://doi.org/10.1038/nature21029
  34. Ito M, Komai K, Mise-Omata S, Iizuka-Koga M, Noguchi Y, Kondo T, Sakai R, Matsuo K, Nakayama T, Yoshie O, Nakatsukasa H, Chikuma S, Shichita T, Yoshimura A (2019) Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery. Nature 565: 246–250. https://doi.org/10.1038/s41586-018-0824-5
  35. Sebek M, Gillie G, Autio D, Solt V, Le L, Martinetti L, Bonekamp K (2024) A Morphologically Distinct Subclass of Somatostatin-expressing Interneurons in the Somatosensory Cortex are Strongly Recruited by Input from the Motor Cortex. Physiology 39. https://doi.org/10.1152/physiol.2024.39.s1.690
  36. Freund P, Curt A, Friston K, Thompson A (2013) Tracking changes following spinal cord injury: insights from neuroimaging. Neuroscientist 19: 116–128. https://doi.org/10.1177/1073858412449192
  37. Nardone R, Höller Y, Sebastianelli L, Versace V, Saltuari L, Brigo F, Lochner P, Trinka E (2018) Cortical morphometric changes after spinal cord injury. Brain Res Bull 137: 107–119. https://doi.org/10.1016/j.brainresbull.2017.11.013
  38. Takata Y, Yamanaka H, Nakagawa H, Takada M (2023) Morphological changes of large layer V pyramidal neurons in cortical motor-related areas after spinal cord injury in macaque monkeys. Sci Rep 13: 82. https://doi.org/10.1038/s41598-022-26931-3
  39. Michetti F, Clementi ME, Di Liddo R, Valeriani F, Ria F, Rende M, Di Sante G, Romano Spica V (2023) The S100B Protein: A Multifaceted Pathogenic Factor More Than a Biomarker. IJMS 24: 9605. https://doi.org/10.3390/ijms24119605
  40. Zhang Z, Ma Z, Zou W, Guo H, Liu M, Ma Y, Zhang L (2019) The Appropriate Marker for Astrocytes: Comparing the Distribution and Expression of Three Astrocytic Markers in Different Mouse Cerebral Regions. BioMed Res Int 2019: 9605265. https://doi.org/10.1155/2019/9605265
  41. Tatsumi K, Isonishi A, Yamasaki M, Kawabe Y, Morita-Takemura S, Nakahara K, Terada Y, Shinjo T, Okuda H, Tanaka T, Wanaka A (2018) Olig2-Lineage Astrocytes: A Distinct Subtype of Astrocytes That Differs from GFAP Astrocytes. Front Neuroanat 12: 8. https://doi.org/10.3389/fnana.2018.00008
  42. Du J, Yi M, Zhou F, He W, Yang A, Qiu M, Huang H (2021) S100B is selectively expressed by gray matter protoplasmic astrocytes and myelinating oligodendrocytes in the developing CNS. Mol Brain 14: 154. https://doi.org/10.1186/s13041-021-00865-9
  43. Janigro D, Mondello S, Posti JP, Unden J (2022) GFAP and S100B: What You Always Wanted to Know and Never Dared to Ask. Front Neurol 13: 835597. https://doi.org/10.3389/fneur.2022.835597
  44. Batiuk MY, Martirosyan A, Wahis J, De Vin F, Marneffe C, Kusserow C, Koeppen J, Viana JF, Oliveira JF, Voet T, Ponting CP, Belgard TG, Holt MG (2020) Identification of region-specific astrocyte subtypes at single cell resolution. Nat Commun 11: 1220. https://doi.org/10.1038/s41467-019-14198-8
  45. Pfau SJ, Langen UH, Fisher TM, Prakash I, Nagpurwala F, Lozoya RA, Lee W-CA, Wu Z, Gu C (2024) Characteristics of blood–brain barrier heterogeneity between brain regions revealed by profiling vascular and perivascular cells. Nat Neurosci 27: 1892–1903. https://doi.org/10.1038/s41593-024-01743-y
  46. Hu X, Zhang Y, Wang L, Ding J, Li M, Li H, Wu L, Zeng Z, Xia H (2022) Microglial activation in the motor cortex mediated NLRP3-related neuroinflammation and neuronal damage following spinal cord injury. Front Cell Neurosci 16: 956079. https://doi.org/10.3389/fncel.2022.956079
  47. Pottorf TS, Rotterman TM, McCallum WM, Haley-Johnson ZA, Alvarez FJ (2022) The Role of Microglia in Neuroinflammation of the Spinal Cord after Peripheral Nerve Injury. Cells 11: 2083. https://doi.org/10.3390/cells11132083
  48. Espinoza S, Salahpour A, Masri B, Sotnikova TD, Messa M, Barak LS, Caron MG, Gainetdinov RR (2011) Functional Interaction between Trace Amine-Associated Receptor 1 and Dopamine D2 Receptor. Mol Pharmacol 80: 416–425. https://doi.org/10.1124/mol.111.073304
  49. Wang Y, Lv H, Cui Q, Tu P, Jiang Y, Zeng K (2020) Isosibiricin inhibits microglial activation by targeting the dopamine D1/D2 receptor-dependent NLRP3/caspase-1 inflammasome pathway. Acta Pharmacol Sin 41: 173–180. https://doi.org/10.1038/s41401-019-0296-7
  50. Pike AF, Longhena F, Faustini G, Van Eik J-M, Gombert I, Herrebout MAC, Fayed MMHE, Sandre M, Varanita T, Teunissen CE, Hoozemans JJM, Bellucci A, Veerhuis R, Bubacco L (2022) Dopamine signaling modulates microglial NLRP3 inflammasome activation: implications for Parkinson’s disease. J Neuroinflammat 19: 50. https://doi.org/10.1186/s12974-022-02410-4
  51. Andoh M, Koyama R (2021) Microglia regulate synaptic development and plasticity. Development Neurobiol 81: 568–590. https://doi.org/10.1002/dneu.22814
  52. Naka A, Veit J, Shababo B, Chance RK, Risso D, Stafford D, Snyder B, Egladyous A, Chu D, Sridharan S, Mossing DP, Paninski L, Ngai J, Adesnik H (2019) Complementary networks of cortical somatostatin interneurons enforce layer specific control. eLife 8: e43696. https://doi.org/10.7554/elife.43696
  53. Sillerud LO, Yang Y, Yang LY, Duval KB, Thompson J, Yang Y (2020) Longitudinal monitoring of microglial/macrophage activation in ischemic rat brain using Iba-1-specific nanoparticle-enhanced magnetic resonance imaging. J Cereb Blood Flow Metab 40: S117–S133. https://doi.org/10.1177/0271678x20953913
  54. Wu D, Miyamoto O, Shibuya S, Okada M, Igawa H, Janjua NA, Norimatsu H, Itano T (2005) Different expression of macrophages and microglia in rat spinal cord contusion injury model at morphological and regional levels. Acta Med Okayama 59(4): 121–127. https://doi.org/10.18926/AMO/31950
  55. Nielson JL, Sears-Kraxberger I, Strong MK, Wong JK, Willenberg R, Steward O (2010) Unexpected Survival of Neurons of Origin of the Pyramidal Tract after Spinal Cord Injury. J Neurosci 30: 11516–11528. https://doi.org/10.1523/JNEUROSCI.1433-10.2010
  56. Nielson JL, Strong MK, Steward O (2011) A reassessment of whether cortical motor neurons die following spinal cord injury. J Comparat Neurol 519: 2852–2869. https://doi.org/10.1002/cne.22661
  57. Chai W, Chen J-Y, Zhang K-X, Zhao J-J (2021) Synaptic remodeling in mouse motor cortex after spinal cord injury. Neural Regen Res 16: 744. https://doi.org/10.4103/1673-5374.295346
  58. Solstrand Dahlberg L, Becerra L, Borsook D, Linnman C (2018) Brain changes after spinal cord injury, a quantitative meta-analysis and review. Neurosci Biobehav Rev 90: 272–293. https://doi.org/10.1016/j.neubiorev.2018.04.018
  59. Feng Z, Min L, Chen H, Deng W, Tan M, Liu H, Hou J (2021) Iron overload in the motor cortex induces neuronal ferroptosis following spinal cord injury. Redox Biol 43. https://doi.org/10.1016/j.redox.2021.101984
  60. Nakhjiri E, Roqanian S, Zangbar HS, Seyedi Vafaee M, Mohammadnejad D, Ahmadian S, Zamanzadeh S, Ehsani E, Shahabi P, Shahpasand K (2022) Spinal Cord Injury Causes Prominent Tau Pathology Associated with Brain Post-Injury Sequela. Mol Neurobiol 59: 4197–4208. https://doi.org/10.1007/s12035-022-02843-1
  61. Shi X, Swanson TL, Miner NB, Eshleman AJ, Janowsky A (2019) Activation of Trace Amine-Associated Receptor 1 Stimulates an Antiapoptotic Signal Cascade via Extracellular Signal-Regulated Kinase 1/2. Mol Pharmacol 96: 493–504. https://doi.org/10.1124/mol.119.116798
  62. Wu R, Liu J, Seaman R, Johnson B, Zhang Y, Li J-X (2021) The selective TAAR1 partial agonist RO5263397 promoted novelty recognition memory in mice. Psychopharmacology (Berl) 238: 3221–3228. https://doi.org/10.1007/s00213-021-05937-1
  63. Miner NB, Elmore JS, Baumann MH, Phillips TJ, Janowsky A (2017) Trace amine-associated receptor 1 regulation of methamphetamine-induced neurotoxicity. Neurotoxicology 63: 57–69. https://doi.org/10.1016/j.neuro.2017.09.006

Қосымша файлдар

Қосымша файлдар
Әрекет
1. JATS XML
Жүктеу

© Russian Academy of Sciences, 2025

Согласие на обработку персональных данных с помощью сервиса «Яндекс.Метрика»

1. Я (далее – «Пользователь» или «Субъект персональных данных»), осуществляя использование сайта https://journals.rcsi.science/ (далее – «Сайт»), подтверждая свою полную дееспособность даю согласие на обработку персональных данных с использованием средств автоматизации Оператору - федеральному государственному бюджетному учреждению «Российский центр научной информации» (РЦНИ), далее – «Оператор», расположенному по адресу: 119991, г. Москва, Ленинский просп., д.32А, со следующими условиями.

2. Категории обрабатываемых данных: файлы «cookies» (куки-файлы). Файлы «cookie» – это небольшой текстовый файл, который веб-сервер может хранить в браузере Пользователя. Данные файлы веб-сервер загружает на устройство Пользователя при посещении им Сайта. При каждом следующем посещении Пользователем Сайта «cookie» файлы отправляются на Сайт Оператора. Данные файлы позволяют Сайту распознавать устройство Пользователя. Содержимое такого файла может как относиться, так и не относиться к персональным данным, в зависимости от того, содержит ли такой файл персональные данные или содержит обезличенные технические данные.

3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».