Neuroprotective effect of extracellular vesicles obtained from human glial derivatives on the model of glutamate excitotoxicity

Cover Page

Cite item

Full Text

Abstract

Relevance. Modern research in the field of biomedicine leads to the development of therapeutic drugs based on extracellular vesicles, which are defined as sources of production, as well as targeted modification. In the presented work, for the first time, transcriptome profiling of primary culture of cortical neurons under the influence of extracellular vesicles obtained from glial cells during glutamate excitotoxicity was carried out in order to determine differentially expressed genes. Materials and Methods. Extracellular vesicles were obtained from the conditioned medium of human glial progenitor cells using ultracentrifugation. Model of glutamate excitotoxicity, distributed on the first cultured cortical neurons of cells (P0) with the addition of 100 μM glutamate. Sequencing of prepared libraries of electronic technologies on the NextSeq 1000 platform (Illumina, USA) using the NextSeq 1000/2000 P2 (200 cycles) v3 reagent kit supplemented with 2 % Phix (Illumina) as an internal control. The criterion for statistical innovation of gene expression change between officially recognized FDR< 0.05. Results and Discussion. Transcriptome analysis showed that the addition of extracellular vesicles during glutamate excitotoxicity leads to increased expression of 190 genes and decreased expression of 309 genes (p value < 0.05 and |FC|< 1.5). Gene analysis using the Gene Onthology database showed that genes with increased expression are consistently classified by biological processes. The most represented were: regeneration, reorganization of the extracellular matrix and cytoskeleton, maintenance of homeostasis, activation of the PI3K-Akt pathway and response to cellular stress. Genes with reduced expression were consistently classified into groups: calcium transport, regulation of neuronal processes, apoptosis, glutathergic synapse. These data can indicate that. Extracellular vesicles trigger survival processes in nerve cells when exposed to glutamate and inhibit pathways associated with the entry of substances and glutamate into the cell. Conclusions. Extracellular vesicles enhance the expression of genes with survival and inhibit genes, resulting in calcium transport and apoptosis. The results of the study show the promise of using extracellular vesicles of glial origin as a basis for developing new therapeutic approaches to individual neurological diseases.

About the authors

Margarita O. Shedenkova

Research Centre for Medical Genetics

Author for correspondence.
Email: margarita.shedenkova@gmail.com
ORCID iD: 0000-0001-7415-1520
SPIN-code: 3390-4201
Moscow, Russian Federation

Anastasiia A. Gurianova

Institute for System Programming, Russian Academy of Sciences

Email: margarita.shedenkova@gmail.com
ORCID iD: 0000-0002-6589-2164
Moscow, Russian Federation

Anastasia K. Sudina

Research Centre for Medical Genetics

Email: margarita.shedenkova@gmail.com
ORCID iD: 0000-0003-3531-7684
SPIN-code: 5225-7878
Moscow, Russian Federation

Egor P. Guguchin

Institute for System Programming, Russian Academy of Sciences

Email: margarita.shedenkova@gmail.com
ORCID iD: 0000-0001-7885-9892
Moscow, Russian Federation

Evgeny A. Karpulevich

Institute for System Programming, Russian Academy of Sciences

Email: margarita.shedenkova@gmail.com
ORCID iD: 0000-0002-6771-2163
SPIN-code: 8064-2794
Moscow, Russian Federation

Timur Kh. Fatkhudinov

Avtsyn Research Institute of Human Morphology of FSBSI «Petrovsky National Research Centre of Surgery»

Email: margarita.shedenkova@gmail.com
ORCID iD: 0000-0002-6498-5764
SPIN-code: 7919-8430
Moscow, Russian Federation

Dmitry V. Goldstein

Research Centre for Medical Genetics

Email: margarita.shedenkova@gmail.com
ORCID iD: 0000-0003-2438-1605
SPIN-code: 7714-9099
Moscow, Russian Federation

Diana I. Salikhova

Research Centre for Medical Genetics

Email: margarita.shedenkova@gmail.com
ORCID iD: 0000-0001-7842-7635
SPIN-code: 1436-5027
Moscow, Russian Federation

References

  1. McEntee WJ, Crook TH. Glutamate: its role in learning, memory, and the aging brain. Psychopharmacology (Berl). 1993;111(4). doi: 10.1007/BF02253527
  2. Niswender CM, Conn PJ. Metabotropic glutamate receptors: Physiology, pharmacology, and disease. Annu Rev Pharmacol Toxicol. 2010;50. doi: 10.1146/annurev.pharmtox.011008.145533
  3. Lau A, Tymianski M. Glutamate receptors, neurotoxicity and neurodegeneration. Pflugers Arch. 2010;460(2). doi: 10.1007/s00424-010-0809-1
  4. Miladinovic T, Nashed MG, Singh G. Overview of glutamatergic dysregulation in central pathologies. Biomolecules. 2015;5(4). doi: 10.3390/biom5043112
  5. Kumar MA, Baba SK, Sadida HQ, Marzooqi S Al, Jerobin J, Altemani FH, Algehainy N, Alanazi MA, Abou-Samra AB, Kumar R, Al-Shabeeb Akil AS, Macha MA, Mir R, Bhat AA. Extracellular vesicles as tools and targets in therapy for diseases. Signal Transduct Target Ther. 2024;9(1). doi: 10.1038/s41392-024-01735-1
  6. Cecchin R, Troyer Z, Witwer K, Morris K V. Extracellular vesicles: The next generation in gene therapy delivery. Molecular Therapy. 2023;31(5). doi: 10.1016/j.ymthe.2023.01.021
  7. Salikhova D, Bukharova T, Cherkashova E, Namestnikova D, Leonov G, Nikitina M, Gubskiy I, Akopyan G, Elchaninov A, Midiber K, Bulatenco N, Mokrousova V, Makarov A, Yarygin K, Chekhonin V, Mikhaleva L, Fatkhudinov T, Goldshtein D. Therapeutic effects of hipsc-derived glial and neuronal progenitor cells-conditioned medium in experimental ischemic stroke in rats. Int J Mol Sci. 2021;22(9). doi: 10.3390/ijms22094694
  8. Turovsky EA, Golovicheva V V., Varlamova EG, Danilina TI, Goryunov K V., Shevtsova YA, Pevzner IB, Zorova LD, Babenko VA, Evtushenko EA, Zharikova AA, Khutornenko AA, Kovalchuk SI, Plotnikov EY, Zorov DB, Sukhikh GT, Silachev DN. Mesenchymal stromal cell-derived extracellular vesicles afford neuroprotection by modulating PI3K/AKT pathway and calcium oscillations. Int J Biol Sci. 2022;18(14). doi: 10.7150/ijbs.73747
  9. Bakaeva Z, Lizunova N, Tarzhanov I, Boyarkin D, Petrichuk S, Pinelis V, Fisenko A, Tuzikov A, Sharipov R, Surin A. Lipopolysaccharide From E. coli Increases Glutamate-Induced Disturbances of Calcium Homeostasis, the Functional State of Mitochondria, and the Death of Cultured Cortical Neurons. Front Mol Neurosci. 2022;14. doi: 10.3389/fnmol.2021.811171
  10. Andrews S, others. FastQC: a quality control tool for high throughput sequence data. 2010. Https://WwwBioinformaticsBabrahamAcUk/Projects/Fastqc/. Published online 2019.
  11. Bolger AM, Lohse M, Usadel B. Trimmo1. Bolger AM, Lohse M, Usadel B. Trimmomatic: A flexible trimmer for Illumina sequence data. Bioinformatics. 2014;30(15):2114-2120. doi: 10.1093/bioinformatics/btu170matic: A flexible trimmer for Illumina sequence data. Bioinformatics. 2014;30(15).
  12. Patro R, Duggal G, Love MI, Irizarry RA, Kingsford C. Salmon provides fast and bias-aware quantification of transcript expression. Nat Methods. 2017;14(4). doi: 10.1038/nmeth.4197
  13. Soneson C, Love MI, Robinson MD. Differential analyses for RNA-seq: transcript-level estimates improve gene-level inferences. F1000Res. 2015;4. doi: 10.12688/f1000research.7563.1
  14. Robinson MD, McCarthy DJ, Smyth GK. edgeR: A Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2009;26(1). doi: 10.1093/bioinformatics/btp616
  15. Mihelc EM, Siepe DH, Chakraborty A, Kalocsay M, Moiseenkova-Bell V. Exploring the role of TRPV2 in neuronal development. Biophys J. 2024;123(3). doi: 10.1016/j.bpj.2023.11.2380
  16. Kim TH, Lee HK, Seo IA, Bae HR, Suh DJ, Wu J, Rao Y, Hwang KG, Park HT. Netrin induces down-regulation of its receptor, Deleted in Colorectal Cancer, through the ubiquitin-proteasome pathway in the embryonic cortical neuron. J Neurochem. 2005;95(1). doi: 10.1111/j.1471-4159.2005.03314.x
  17. Wang J, Miao Y, Wicklein R, Sun Z, Wang J, Jude KM, Fernandes RA, Merrill SA, Wernig M, Garcia KC, Südhof TC. RTN4/NoGo-receptor binding to BAI adhesion-GPCRs regulates neuronal development. Cell. 2021;184(24). doi: 10.1016/j.cell.2021.10.016
  18. Gatto G, Dudanova I, Suetterlin P, Davies AM, Drescher U, Bixby JL, Klein R. Protein tyrosine phosphatase receptor type O inhibits trigeminal axon growth and branching by repressing TrkB and ret signaling. Ann Intern Med. 2013;158(6). doi: 10.1523/JNEUROSCI.4707-12.2013
  19. Kim M, Roesener AP, Mendonca PRF, Mastick GS. Robo1 and Robo2 have distinct roles in pioneer longitudinal axon guidance. Dev Biol. 2011;358(1). doi: 10.1016/j.ydbio.2011.07.025
  20. Zhao J, Cooper LT, Boyd AW, Bartlett PF. Decreased signalling of EphA4 improves functional performance and motor neuron survival in the SOD1G93A ALS mouse model. Sci Rep. 2018;8(1). doi: 10.1038/s41598-018-29845-1
  21. Yang H, Zhang M, Shi J, Zhou Y, Wan Z, Wang Y, Wan Y, Li J, Wang Z, Fei J. Brain-Specific SNAP‑25 Deletion Leads to Elevated Extracellular Glutamate Level and Schizophrenia-Like Behavior in Mice. Neural Plast. 2017;2017. doi: 10.1155/2017/4526417
  22. Schuster S, Rivalan M, Strauss U, Stoenica L, Trimbuch T, Rademacher N, Parthasarathy S, Lajkó D, Rosenmund C, Shoichet SA, Winter Y, Tarabykin V, Rosário M. NOMA-GAP/ARHGAP33 regulates synapse development and autistic-like behavior in the mouse. Mol Psychiatry. 2015;20(9). doi: 10.1038/mp.2015.42
  23. Feyder M, Karlsson RM, Mathur P, Lyman M, Bock R, Momenan R, Munasinghe J, Scattoni ML, Ihne J, Camp M, Graybeal C, Strathdee D, Begg A, Alvarez VA, Kirsch P, Rietschel M, Cichon S, Walter H, Meyer-Lindenberg A, Grant SGN, Holmes A. Association of mouse Dlg4 (PSD‑95) gene deletion and human DLG4 gene variation with phenotypes relevant to autism spectrum disorders and Williams’ syndrome. American Journal of Psychiatry. 2010;167(12). doi: 10.1176/appi.ajp.2010.10040484
  24. Tolve M, Ulusoy A, Patikas N, Islam KUS, Bodea GO, Öztürk E, Broske B, Mentani A, Wagener A, van Loo KMJ, Britsch S, Liu P, Khaled WT, Metzakopian E, Baader SL, Di Monte DA, Blaess S. The transcription factor BCL11A defines distinct subsets of midbrain dopaminergic neurons. Cell Rep. 2021;36(11). doi: 10.1016/j.celrep.2021.109697
  25. Chen B, Wang L, Li X, Shi Z, Duan J, Wei JA, Li C, Pang C, Wang D, Zhang K, Chen H, Na W, Zhang L, So KF, Zhou L, Jiang B, Yuan TF, Qu Y. Celsr2 regulates NMDA receptors and dendritic homeostasis in dorsal CA1 to enable social memory. Mol Psychiatry. 2024;29(6). doi: 10.1038/s41380-022-01664‑x
  26. del Puerto A, Lopez-Fonseca C, Simón-García A, Martí-Prado B, Barrios-Muñoz AL, Pose-Utrilla J, López-Menéndez C, Alcover-Sanchez B, Cesca F, Schiavo G, Campanero MR, Fariñas I, Iglesias T, Porlan E. Kidins220 sets the threshold for survival of neural stem cells and progenitors to sustain adult neurogenesis. Cell Death Dis. 2023;14(8). doi: 10.1038/s41419-023-05995-7
  27. Chang T, Zhang M, Zhu J, Wang H, Li C cong, Wu K, Zhang Z ru, Jiang Y hong, Wang F, Wang H tian, Wang XC, Liu Y. Simulated vestibular spatial disorientation mouse model under coupled rotation revealing potential involvement of Slc17a6. iScience. 2023;26(12). doi: 10.1016/j.isci.2023.108498
  28. Shen W, Kilander MBC, Bridi MS, Frei JA, Niescier RF, Huang S, Lin YC. Tomosyn regulates the small RhoA GTPase to control the dendritic stability of neurons and the surface expression of AMPA receptors. J Neurosci Res. 2020;98(6). doi: 10.1002/jnr.24608
  29. Harper CB, Mancini GMS, van Slegtenhorst M, Cousin MA. Altered synaptobrevin-II trafficking in neurons expressing a synaptophysin mutation associated with a severe neurodevelopmental disorder. Neurobiol Dis. 2017;108. doi: 10.1016/j.nbd.2017.08.021
  30. Feig LA. Regulation of neuronal function by Ras-GRF exchange factors. Genes Cancer. 2011;2(3). doi: 10.1177/1947601911408077
  31. Itoh M, Okuno H, Yamada D, Yamashita M, Abe M, Natsume R, Kaizuka T, Sakimura K, Hoshino M, Mishina M, Wada K, Sekiguchi M, Hayashi T. Perturbed expression pattern of the immediate early gene Arc in the dentate gyrus of GluA1 C-terminal palmitoylation-deficient mice. Neuropsychopharmacol Rep. 2019;39(1). doi: 10.1002/npr2.12044
  32. Ragnarsson L, Zhang Z, Das SS, Tran P, Andersson Å, des Portes V, Desmettre Altuzarra C, Remerand G, Labalme A, Chatron N, Sanlaville D, Lesca G, Anggono V, Vetter I, Keramidas A. GRIN1 variants associated with neurodevelopmental disorders reveal channel gating pathomechanisms. Epilepsia. 2023;64(12). doi: 10.1111/epi.17776
  33. Piechota M, Skupio U, Borczyk M, Ziółkowska B, Gołda S, Szumiec Ł, Szklarczyk-Smolana K, Bilecki W, Rodriguez Parkitna JM, Korostyński M. Glucocorticoid-Regulated Kinase CAMKIγ in the Central Amygdala Controls Anxiety-like Behavior in Mice. Int J Mol Sci. 2022;23(20). doi: 10.3390/ijms232012328
  34. Mohanan AG, Gunasekaran S, Jacob RS, Omkumar R V. Role of Ca2+/Calmodulin-Dependent Protein Kinase Type II in Mediating Function and Dysfunction at Glutamatergic Synapses. Front Mol Neurosci. 2022;15. doi: 10.3389/fnmol.2022.855752
  35. Simon R, Wiegreffe C, Britsch S. Bcl11 Transcription Factors Regulate Cortical Development and Function. Front Mol Neurosci. 2020;13. doi: 10.3389/fnmol.2020.00051
  36. Li H, Liu B, Lian L, Zhou J, Xiang S, Zhai Y, Chen Y, Ma X, Wu W, Hou L. High dose expression of heme oxigenase‑1 induces retinal degeneration through ER stress-related DDIT3. Mol Neurodegener. 2021;16(1). doi: 10.1186/s13024-021-00437-4
  37. Gadient RA, Lein P, Higgins D, Patterson PH. Effect of leukemia inhibitory factor (LIF) on the morphology and survival of cultured hippocampal neurons and glial cells. Brain Res. 1998;798(1-2). doi: 10.1016/S0006-8993(98)00236-4
  38. Joo JY, Schaukowitch K, Farbiak L, Kilaru G, Kim TK. Stimulus-specific combinatorial functionality of neuronal c-fos enhancers. Nat Neurosci. 2015;19(1). doi: 10.1038/nn.4170
  39. Huang X, Zhang W, Yang N, Zhang Y, Qin T, Ruan H, et al. Identification of HSP90B1 in pan-cancer hallmarks to aid development of a potential therapeutic target. Mol Cancer. 2024;23(1). doi: 10.1186/s12943-023-01920‑w
  40. Huang M, Wang J, Liu W, Zhou H. Advances in the role of the GADD45 family in neurodevelopmental, neurodegenerative, and neuropsychiatric disorders. Front Neurosci. 2024;18. doi: 10.3389/fnins.2024.1349409
  41. Labonté B, Jeong YH, Parise E, Issler O, Fatma M, Engmann O, Cho KA, Neve R, Nestler EJ, Koo JW. Gadd45b mediates depressive-like role through DNA demethylation. Sci Rep. 2019;9(1). doi: 10.1038/s41598-019-40844-8
  42. Levings DC, Pathak SS, Yang YM, Slattery M. Limited expression of Nrf2 in neurons across the central nervous system. Redox Biol. 2023;65. doi: 10.1016/j.redox.2023.102830
  43. Lytrivi M, Senée V, Salpea P, Fantuzzi F, Philippi A, Abdulkarim B, Sawatani T, Marín-Cañas S, Pachera N, Degavre A, Singh P, Derbois C, Lechner D, Ladrière L, Igoillo-Esteve M, Cosentino C, Marselli L, Deleuze JF, Marchetti P, Eizirik DL, Nicolino M, Chaussenot A, Julier C, Cnop M. DNAJC3 deficiency induces β-cell mitochondrial apoptosis and causes syndromic young-onset diabetes. Eur J Endocrinol. 2021;184(3). doi: 10.1530/EJE‑20-0636
  44. Kang L, Wang D, Shen T, Liu X, Dai B, Zhou D, Shen H, Gong J, Li G, Hu Y, Wang P, Mi X, Zhang Y, Tan X. PDIA4 confers resistance to ferroptosis via induction of ATF4/SLC7A11 in renal cell carcinoma. Cell Death Dis. 2023;14(3). doi: 10.1038/s41419-023-05719‑x
  45. Ousingsawat J, Wanitchakool P, Kmit A, Romao AM, Jantarajit W, Schreiber R, Kunzelmann K. Anoctamin 6 mediates effects essential for innate immunity downstream of P2X7 receptors in macrophages. Nat Commun. 2015;6. doi: 10.1038/ncomms7245
  46. Xia Q, Li X, Zhou H, Zheng L, Shi J. S100A11 protects against neuronal cell apoptosis induced by cerebral ischemia via inhibiting the nuclear translocation of annexin A1 article. Cell Death Dis. 2018;9(6). doi: 10.1038/s41419-018-0686-7
  47. Knierim E, Hirata H, Wolf NI, Morales-Gonzalez S, Schottmann G, Tanaka Y, Rudnik-Schöneborn S, Orgeur M, Zerres K, Vogt S, Van Riesen A, Gill E, Seifert F, Zwirner A, Kirschner J, Goebel HH, Hübner C, Stricker S, Meierhofer D, Stenzel W, Schuelke M. Mutations in Subunits of the Activating Signal Cointegrator 1 Complex Are Associated with Prenatal Spinal Muscular Atrophy and Congenital Bone Fractures. Am J Hum Genet. 2016;98(3). doi: 10.1016/j.ajhg.2016.01.006
  48. Marqués-Torrejón MÁ, Porlan E, Banito A, Gómez-Ibarlucea E, Lopez-Contreras AJ, Fernández-Capetillo Ó, Vidal A, Gil J, Torres J, Fariñas I. Cyclin-dependent kinase inhibitor p21 controls adult neural stem cell expansion by regulating Sox2 gene expression. Cell Stem Cell. 2013;12(1). doi: 10.1016/j.stem.2012.12.001
  49. Ting AK, Chen Y, Wen L, Yin DM, Shen C, Tao Y, Liu X, Xiong WC, Mei L. Neuregulin 1 promotes excitatory synapse development and function in GABAergic interneurons. Journal of Neuroscience. 2011;31(1). doi: 10.1523/JNEUROSCI.2538-10.2011
  50. Escobedo N, Contreras O, Muñoz R, Farías M, Carrasco H, Hill C, Tran U, Pryor SE, Wessely O, Copp AJ, Larraín J. Syndecan 4 interacts genetically with Vangl2 to regulate neural tube closure and planar cell polarity. Development (Cambridge). 2013;140(14). doi: 10.1242/dev.091173
  51. Fowke TM, Karunasinghe RN, Bai JZ, Jordan S, Gunn AJ, Dean JM. Hyaluronan synthesis by developing cortical neurons in vitro. Sci Rep. 2017;7. doi: 10.1038/srep44135
  52. Zhu J, Xian Q, Hou X, Wong KF, Zhu T, Chen Z, He D, Kala S, Murugappan S, Jing J, Wu Y, Zhao X, Li D, Guo J, Qiu Z, Sun L. The mechanosensitive ion channel Piezo1 contributes to ultrasound neuromodulation. Proc Natl Acad Sci U S A. 2023;120(118). doi: 10.1073/pnas.2300291120
  53. Huang T, Fu G, Gao J, Zhang Y, Cai W, Wu S, Jia S, Xia S, Bachmann T, Bekker A, Tao YX. Fgr contributes to hemorrhage-induced thalamic pain by activating NF-κB/ ERK1/2 pathways. JCI Insight. 2020;5(20). doi: 10.1172/jci.insight.139987
  54. Wang A, Zhang H, Li X, Zhao Y. Annexin A1 in the nervous and ocular systems. Neural Regen Res. 2024;19(3). doi: 10.4103/1673-5374.380882
  55. Zheng SL, Li ZY, Song J, Liu JM, Miao CY. Metrnl: A secreted protein with new emerging functions. Acta Pharmacol Sin. 2016;37(5). doi: 10.1038/aps.2016.9
  56. Iwanicka J, Balcerzyk-Matić A, Iwanicki T, Mizia-Stec K, Bańka P, Filipecki A, Gawron K, Jarosz A, Nowak T, Krauze J, Niemiec P. The Association of ADAMTS7 Gene Polymorphisms with the Risk of Coronary Artery Disease Occurrence and Cardiovascular Survival in the Polish Population: A Case-Control and a Prospective Cohort Study. Int J Mol Sci. 2024;25(4). doi: 10.3390/ijms25042274
  57. Pagnamenta AT, Kaiyrzhanov R, Zou Y, Da’as SI, Maroofian R, Donkervoort S, Dominik N, Lauffer M, Ferla MP, Orioli A, et al. An ancestral 10‑bp repeat expansion in VWA1 causes recessive hereditary motor neuropathy. Brain. 2021;144(2). doi: 10.1093/brain/awaa420
  58. Konietzny A, Bär J, Mikhaylova M. Dendritic actin cytoskeleton: Structure, functions, and regulations. Front Cell Neurosci. 2017;11. doi: 10.3389/fncel.2017.00147
  59. Uzor NE, Scheihing DM, Kim GS, Moruno-Manchon JF, Zhu L, Reynolds CR, Stephenson JM, Holmes A, McCullough LD, Tsvetkov AS. Aging lowers PEX5 levels in cortical neurons in male and female mouse brains. Molecular and Cellular Neuroscience. 2020;107. doi: 10.1016/j.mcn.2020.103536
  60. Mohammadzadeh P, Amberg GC. AXL/Gas6 signaling mechanisms in the hypothalamic-pituitary-gonadal axis. Front Endocrinol (Lausanne). 2023;14. doi: 10.3389/fendo.2023.1212104
  61. Kolobynina KG, Solovyova V V., Levay K, Rizvanov AA, Slepak VZ. Emerging roles of the single EF-hand Ca2+ sensor tescalcin in the regulation of gene expression, cell growth and differentiation. J Cell Sci. 2016;129(19). doi: 10.1242/jcs.191486
  62. Wu LY, Song YJ, Zhang CL, Liu J. KV Channel-Interacting Proteins in the Neurological and Cardiovascular Systems: An Updated Review. Cells. 2023;12(14). doi: 10.3390/cells12141894
  63. Gotliv IL. FXYD5: Na + /K + -ATPase regulator in health and disease. Front Cell Dev Biol. 2016;4(MAR). doi: 10.3389/fcell.2016.00026
  64. Shen J, Shi D, Suzuki T, Xia Z, Zhang H, Araki K, Wakana S, Takeda N, Yamamura KI, Jin S, Li Z. Severe ocular phenotypes in Rbp4‑deficient mice in the C57BL/6 genetic background. Laboratory Investigation. 2016;96(6). doi: 10.1038/labinvest.2016.39
  65. Reichmann F, Holzer P. Neuropeptide Y: A stressful review. Neuropeptides. 2016;55. doi: 10.1016/j.npep.2015.09.008
  66. Rolando C, Erni A, Grison A, Beattie R, Engler A, Gokhale PJ, Milo M, Wegleiter T, Jessberger S, Taylor V. Multipotency of Adult Hippocampal NSCs In Vivo Is Restricted by Drosha/NFIB. Cell Stem Cell. 2016;19(5). doi: 10.1016/j.stem.2016.07.003
  67. Carvalho SDS, Moreau MM, Hien YE, Garcia M, Aubailly N, Henderson DJ, Studer V, Sans N, Thoumine O, Montcouquiol M. Vangl2 acts at the interface between actin and N-cadherin to modulate mammalian neuronal outgrowth. Elife. 2020;9. doi: 10.7554/eLife.51822
  68. Cukier HN, Duarte CL, Laverde-Paz MJ, Simon SA, Van Booven DJ, Miyares AT, Whitehead PL, Hamilton-Nelson KL, Adams LD, Carney RM, Cuccaro ML, Vance JM, Pericak-Vance MA, Griswold AJ, Dykxhoorn DM. An Alzheimer’s disease risk variant in TTC3 modifies the actin cytoskeleton organization and the PI3K-Akt signaling pathway in iPSC-derived forebrain neurons. Neurobiol Aging. 2023;131. doi: 10.1016/j.neurobiolaging.2023.07.007
  69. Strang KH, Golde TE, Giasson BI. MAPT mutations, tauopathy, and mechanisms of neurodegeneration. Laboratory Investigation. 2019;99(7). doi: 10.1038/s41374-019-0197‑x
  70. Sakabe I, Hu R, Jin L, Clarke R, Kasid UN. TMEM33: a new stress-inducible endoplasmic reticulum transmembrane protein and modulator of the unfolded protein response signaling. Breast Cancer Res Treat. 2015;153(2). doi: 10.1007/s10549-015-3536-7
  71. Łuczyńska K, Zhang Z, Pietras T, Zhang Y, Taniguchi H. NFE2L1/Nrf1 serves as a potential therapeutical target for neurodegenerative diseases. Redox Biol. 2024;69. doi: 10.1016/j.redox.2023.103003
  72. Santo EE, Paik J. FOXO in Neural Cells and Diseases of the Nervous System. In: Current Topics in Developmental Biology. Vol 127.; 2018. doi: 10.1016/bs.ctdb.2017.10.002
  73. Zhang Z, Zhao Y. Progress on the roles of MEF2C in neuropsychiatric diseases. Mol Brain. 2022;15(1). doi: 10.1186/s13041-021-00892-6
  74. Guo H, Bettella E, Marcogliese PC, Zhao R, Andrews JC, Nowakowski TJ, Gillentine MA, Hoekzema K, Wang T, Wu H, et al. Disruptive mutations in TANC2 define a neurodevelopmental syndrome associated with psychiatric disorders. Nat Commun. 2019;10(1). doi: 10.1038/s41467-019-12435-8
  75. Aabdien A, Sichlinger L, Borgel Z, Jones MR, Waston IA, Gatford NJF, Raval P, Tanangonan L, Powell TR, Duarte RRR, Srivastava DP. Schizophrenia risk proteins ZNF804A and NT5C2 interact in cortical neurons. European Journal of Neuroscience. 2024;59(8). doi: 10.1111/ejn.16254
  76. Hussain NK, Hsin H, Huganir RL, Sheng M. MINK and TNIK differentially act on Rap2‑mediated signal transduction to regulate neuronal structure and AMPA receptor function. Journal of Neuroscience. 2010;30(44). doi: 10.1523/JNEUROSCI.4124-10.2010
  77. Baumgärtel K, Green A, Hornberger D, Lapira J, Rex C, Wheeler DG, Peters M. PDE4D regulates Spine Plasticity and Memory in the Retrosplenial Cortex. Sci Rep. 2018;8(1). doi: 10.1038/s41598-018-22193-0
  78. Kritis AA, Stamoula EG, Paniskaki KA, Vavilis TD. Researching glutamate — induced cytotoxicity in different cell lines: A comparative/collective analysis/study. Front Cell Neurosci. 2015;9. doi: 10.3389/fncel.2015.00091
  79. Mahmoud S, Gharagozloo M, Simard C, Gris D. Astrocytes maintain glutamate homeostasis in the cns by controlling the balance between glutamate uptake and release. Cells. 2019;8(2). doi: 10.3390/cells8020184
  80. Proia P, Schiera G, Mineo M, Ingrassia AMR, Santoro G, Savettieri G, Di Liegro I. Astrocytes shed extracellular vesicles that contain fibroblast growth factor‑2 and vascular endothelial growth factor. Int J Mol Med. 2008;21(1). doi: 10.3892/ijmm.21.1.63
  81. Taylor AR, Robinson MB, Gifondorwa DJ, Tytell M, Milligan CE. Regulation of heat shock protein 70 release in astrocytes: Role of signaling kinases. Dev Neurobiol. 2007;67(13). doi: 10.1002/dneu.20559
  82. Montecchi T, Shaba E, De Tommaso D, Di Giuseppe F, Angelucci S, Bini L, Landi C, Baldari CT, Ulivieri C. Differential proteomic analysis of astrocytes and astrocytes-derived extracellular vesicles from control and rai knockout mice: insights into the mechanisms of neuroprotection. Int J Mol Sci. 2021;22(15). doi: 10.3390/ijms22157933
  83. Patel MR, Weaver AM. Astrocyte-derived small extracellular vesicles promote synapse formation via fibulin‑2‑mediated TGF-β signaling. Cell Rep. 2021;34(10). doi: 10.1016/j.celrep.2021.108829
  84. You Y, Borgmann K, Edara VV, Stacy S, Ghorpade A, Ikezu T. Activated human astrocyte-derived extracellular vesicles modulate neuronal uptake, differentiation and firing. J Extracell Vesicles. 2020;9(1). doi: 10.1080/20013078.2019.1706801
  85. Krishnan A, Areti A, Komirishetty P, Chandrasekhar A, Cheng C, Zochodne DW. Survival of compromised adult sensory neurons involves macrovesicular formation. Cell Death Discov. 2022;8(1). doi: 10.1038/s41420-022-01247-3
  86. Vaillant AR, Zanassi P, Walsh GS, Aumont A, Alonso A, Miller FD. Signaling mechanisms underlying reversible activity-dependent dendrite formation. Neuron. 2002;34(6). doi: 10.1016/S0896-6273(02)00717-1

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

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».