{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T14:42:51Z","timestamp":1792852971533,"version":"4.5.0"},"reference-count":82,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T00:00:00Z","timestamp":1682553600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T00:00:00Z","timestamp":1682553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Malaysian government"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Infection with the protozoan\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    induces changes in neurotransmission, neuroinflammation, and behavior, yet it remains elusive how these changes come about. In this study we investigated how norepinephrine levels are altered by infection. TINEV (Toxoplasma-induced neuronal extracellular vesicles) isolated from infected noradrenergic cells down-regulated dopamine \u00df-hydroxylase (\n                    <jats:italic>DBH<\/jats:italic>\n                    ) gene expression in human and rodent cells. Here we report that intracerebral injection of TINEVs into the brain is sufficient to induce\n                    <jats:italic>DBH<\/jats:italic>\n                    down-regulation and distrupt catecholaminergic signalling. Further, TINEV treatment induced hypermethylation upstream of the DBH gene. An antisense lncRNA to\n                    <jats:italic>DBH<\/jats:italic>\n                    was found in purified TINEV preparations. Paracrine signalling to induce transcriptional gene silencing and DNA methylation may be a common mode to regulate neurologic function.\n                  <\/jats:p>","DOI":"10.1038\/s41598-023-34074-2","type":"journal-article","created":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T13:02:42Z","timestamp":1682600562000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Infection-induced extracellular vesicles evoke neuronal transcriptional and epigenetic changes"],"prefix":"10.1038","volume":"13","author":[{"given":"Ellen","family":"Tedford","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norhidayah Binti","family":"Badya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conor","family":"Laing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nozomi","family":"Asaoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuji","family":"Kaneko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice Maria","family":"Filippi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenn Alan","family":"McConkey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,4,27]]},"reference":[{"key":"34074_CR1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.59384","author":"D Smith","year":"2021","unstructured":"Smith, D. et al. Toxoplasma TgATG9 is critical for autophagy and long-term persistence in tissue cyst. Elife https:\/\/doi.org\/10.7554\/eLife.59384 (2021).","journal-title":"Elife"},{"issue":"1","key":"34074_CR2","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1186\/1471-2164-15-806","volume":"15","author":"KJ Pittman","year":"2014","unstructured":"Pittman, K. J., Aliota, M. T. & Knoll, L. J. Dual transcriptional profiling of mice and Toxoplasma gondii during acute and chronic infection. BMC Genom. 15(1), 806\u2013811 (2014).","journal-title":"BMC Genom."},{"issue":"2","key":"34074_CR3","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1016\/j.celrep.2019.12.019","volume":"30","author":"M Boillat","year":"2020","unstructured":"Boillat, M. et al. Neuroinflammation-associated aspecific manipulation of mouse predator fear by Toxoplasma gondii. Cell Rep. 30(2), 320-334.e6 (2020).","journal-title":"Cell Rep."},{"issue":"1","key":"34074_CR4","first-page":"96","volume":"7","author":"HM Ng\u00f4","year":"2017","unstructured":"Ng\u00f4, H. M. et al. Toxoplasma modulates signature pathways of human epilepsy. Neurodegener. Cancer Sci. Rep. 7(1), 96\u2013114 (2017).","journal-title":"Neurodegener. Cancer Sci. Rep."},{"issue":"3","key":"34074_CR5","doi-asserted-by":"publisher","first-page":"16001","DOI":"10.1038\/nmicrobiol.2016.1","volume":"1","author":"C Konradt","year":"2016","unstructured":"Konradt, C. et al. Endothelial cells are a replicative niche for entry of Toxoplasma gondii to the central nervous system. Nat. Microbiol. 1(3), 16001 (2016).","journal-title":"Nat. Microbiol."},{"issue":"5","key":"34074_CR6","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1080\/00034983.1980.11687376","volume":"74","author":"WM Hutchison","year":"1980","unstructured":"Hutchison, W. M., Aitken, P. P. & Wells, B. W. P. Chronic toxoplasma infections and motor performance in the mouse. Ann. Trop. Med. Parasitol. 74(5), 507\u2013510 (1980).","journal-title":"Ann. Trop. Med. Parasitol."},{"issue":"10","key":"34074_CR7","doi-asserted-by":"publisher","first-page":"2861","DOI":"10.1128\/IAI.00217-16","volume":"84","author":"F Ihara","year":"2016","unstructured":"Ihara, F. et al. Toxoplasma gondii infection in mice impairs long-term fear memory consolidation through dysfunction of the cortex and amygdala. Infect. Immun. 84(10), 2861\u20132870 (2016).","journal-title":"Infect. Immun."},{"issue":"6","key":"34074_CR8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.ppat.1005643","volume":"12","author":"CN David","year":"2016","unstructured":"David, C. N. et al. GLT-1-dependent disruption of CNS glutamate homeostasis and neuronal function by the protozoan parasite Toxoplasma gondii. PLoS Pathog. 12(6), 1\u201311 (2016).","journal-title":"PLoS Pathog."},{"issue":"6","key":"34074_CR9","doi-asserted-by":"publisher","first-page":"e01428-15","DOI":"10.1128\/mBio.01428-15","volume":"6","author":"JM Brooks","year":"2015","unstructured":"Brooks, J. M. et al. Toxoplasma gondii infections alter GABAergic synapses and signaling in the central nervous system. MBio 6(6), e01428-15 (2015).","journal-title":"MBio"},{"issue":"10","key":"34074_CR10","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1128\/IAI.00398-18","volume":"86","author":"Y Li","year":"2018","unstructured":"Li, Y. et al. Chronic Toxoplasma gondii infection induces anti-N-methyl-D-aspartate receptor autoantibodies and associated behavioral changes and neuropathology. Infect. Immun. 86(10), 25. https:\/\/doi.org\/10.1128\/IAI.00398-18 (2018).","journal-title":"Infect. Immun."},{"issue":"2","key":"34074_CR11","first-page":"567","volume":"87","author":"I Alsaady","year":"2018","unstructured":"Alsaady, I. et al. Downregulation of the central noradrenergic system by Toxoplasma gondii infection. Infect. Immun. 87(2), 567\u2013598 (2018).","journal-title":"Infect. Immun."},{"issue":"4","key":"34074_CR12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0035516","volume":"7","author":"F Haroon","year":"2012","unstructured":"Haroon, F. et al. Toxoplasma gondii actively inhibits neuronal function in chronically infected mice. PLoS ONE 7(4), 1\u201316 (2012).","journal-title":"PLoS ONE"},{"issue":"2","key":"34074_CR13","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1080\/00034983.1985.11811902","volume":"79","author":"HH Stibbs","year":"1985","unstructured":"Stibbs, H. H. Changes in brain concentrations of catecholamines and indoleamines in Toxoplasma gondii infected mice. Ann. Trop. Med. Parasitol 79(2), 153\u2013157 (1985).","journal-title":"Ann. Trop. Med. Parasitol"},{"issue":"2","key":"34074_CR14","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1017\/S003118200007774X","volume":"109","author":"JP Webster","year":"1994","unstructured":"Webster, J. P., Brunton, C. F. & MacDonald, D. W. Effect of Toxoplasma gondii upon neophobic behaviour in wild brown rats, Rattus norvegicus. Parasitology 109(2), 37\u201343 (1994).","journal-title":"Parasitology"},{"issue":"1452","key":"34074_CR15","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1098\/rspb.2000.1182","volume":"267","author":"M Berdoy","year":"2000","unstructured":"Berdoy, M., Webster, J. P. & Macdonald, D. W. Fatal attraction in rats infected with Toxoplasma gondii. Proc. R. Soc. B Biol. Sci. 267(1452), 1591\u20131594 (2000).","journal-title":"Proc. R. Soc. B Biol. Sci."},{"issue":"15","key":"34074_CR16","doi-asserted-by":"publisher","first-page":"6442","DOI":"10.1073\/pnas.0608310104","volume":"104","author":"A Vyas","year":"2007","unstructured":"Vyas, A., Kim, S.-K., Giacomini, N., Boothroyd, J. C. & Sapolsky, R. M. Behavioral changes induced by Toxoplasma infection of rodents are highly specific to aversion of cat odors. Proc. Natl. Acad. Sci. USA 104(15), 6442\u20136447 (2007).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"issue":"1","key":"34074_CR17","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1007\/BF00927085","volume":"61","author":"P-A Witting","year":"1979","unstructured":"Witting, P.-A. Learning capacity and memory of normal and Toxoplasma-infected laboratory rats and mice. Z. Parasitenkd. 61(1), 29\u201351 (1979).","journal-title":"Z. Parasitenkd."},{"key":"34074_CR18","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.bbi.2013.11.019","volume":"36","author":"PD Gajewski","year":"2014","unstructured":"Gajewski, P. D., Falkenstein, M., Hengstler, J. G. & Golka, K. Toxoplasma gondii impairs memory in infected seniors. Brain Behav. Immun. 36, 193\u2013199 (2014).","journal-title":"Brain Behav. Immun."},{"issue":"1","key":"34074_CR19","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.parint.2014.09.002","volume":"64","author":"BP Daniels","year":"2015","unstructured":"Daniels, B. P., Sestito, S. R. & Rouse, S. T. An expanded task battery in the Morris water maze reveals effects of Toxoplasma gondii infection on learning and memory in rats. Parasitol. Int. 64(1), 5\u201312 (2015).","journal-title":"Parasitol. Int."},{"issue":"2","key":"34074_CR20","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1007\/s10096-018-3427-z","volume":"38","author":"D Samoj\u0142owicz","year":"2019","unstructured":"Samoj\u0142owicz, D. et al. Presence of Toxoplasma gondii infection in brain as a potential cause of risky behavior: A report of 102 autopsy cases. Eur. J. Clin. Microbiol. Infect. Dis. 38(2), 305\u2013317 (2019).","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"issue":"1","key":"34074_CR21","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/1471-2334-2-11","volume":"2","author":"J Flegr","year":"2002","unstructured":"Flegr, J., Havl\u00edcek, J., Kodym, P., Mal\u00fd, M. & Smahel, Z. Increased risk of traffic accidents in subjects with latent toxoplasmosis: A retrospective case-control study. BMC Infect. Dis. 2(1), 11 (2002).","journal-title":"BMC Infect. Dis."},{"issue":"1","key":"34074_CR22","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1002\/mds.870080119","volume":"8","author":"A Nath","year":"1993","unstructured":"Nath, A., Hobson, D. E. & Russell, A. Movement disorders with cerebral toxoplasmosis and AIDS. Mov. Disord. 8(1), 107\u2013112 (1993).","journal-title":"Mov. Disord."},{"key":"34074_CR23","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/j.bbi.2019.01.026","volume":"79","author":"KS Burgdorf","year":"2019","unstructured":"Burgdorf, K. S. et al. Large-scale study of Toxoplasma and Cytomegalovirus shows an association between infection and serious psychiatric disorders. Brain Behav. Immun. 79, 152\u2013158 (2019).","journal-title":"Brain Behav. Immun."},{"issue":"34","key":"34074_CR24","doi-asserted-by":"publisher","first-page":"13804","DOI":"10.1073\/pnas.0702753104","volume":"104","author":"KS Rommelfanger","year":"2007","unstructured":"Rommelfanger, K. S. et al. Norepinephrine loss produces more profound motor deficits than MPTP treatment in mice. Proc. Natl. Acad. Sci. USA 104(34), 13804\u201313809 (2007).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"issue":"2","key":"34074_CR25","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.bbr.2005.02.005","volume":"161","author":"MD Marino","year":"2005","unstructured":"Marino, M. D., Bourd\u00e9lat-Parks, B. N., Cameron Liles, L. & Weinshenker, D. Genetic reduction of noradrenergic function alters social memory and reduces aggression in mice. Behav. Brain Res. 161(2), 197\u2013203 (2005).","journal-title":"Behav. Brain Res."},{"issue":"11","key":"34074_CR26","doi-asserted-by":"publisher","first-page":"1782","DOI":"10.1038\/s41593-019-0514-0","volume":"22","author":"RD Stowell","year":"2019","unstructured":"Stowell, R. D. et al. Noradrenergic signaling in the wakeful state inhibits microglial surveillance and synaptic plasticity in the mouse visual cortex. Nat. Neurosci. 22(11), 1782\u20131792 (2019).","journal-title":"Nat. Neurosci."},{"issue":"11","key":"34074_CR27","doi-asserted-by":"publisher","first-page":"1771","DOI":"10.1038\/s41593-019-0511-3","volume":"22","author":"YU Liu","year":"2019","unstructured":"Liu, Y. U. et al. Neuronal network activity controls microglial process surveillance in awake mice via norepinephrine signaling. Nat. Neurosci. 22(11), 1771\u20131781 (2019).","journal-title":"Nat. Neurosci."},{"key":"34074_CR28","doi-asserted-by":"crossref","unstructured":"Laing, C., Blanchard, N., & McConkey GA. Noradrenergic Signaling-neuroinflammation cross-talk regulates Toxoplasma gondii-induced behavioral changes. Trends Immunol. 2020 (in press).","DOI":"10.1016\/j.it.2020.10.001"},{"issue":"5","key":"34074_CR29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0156255","volume":"11","author":"JP Dubey","year":"2016","unstructured":"Dubey, J. P. et al. Experimental toxoplasmosis in rats induced orally with eleven strains of Toxoplasma gondii of seven genotypes: Tissue tropism, tissue cyst size, neural lesions, tissue cyst rupture without reactivation, and ocular lesions. PLoS ONE 11(5), 1\u201315 (2016).","journal-title":"PLoS ONE"},{"issue":"1","key":"34074_CR30","doi-asserted-by":"publisher","first-page":"24","DOI":"10.15252\/embr.201439363","volume":"16","author":"JS Schorey","year":"2015","unstructured":"Schorey, J. S., Cheng, Y., Singh, P. P. & Smith, V. L. Exosomes and other extracellular vesicles in host-pathogen interactions. EMBO Rep. 16(1), 24\u201343 (2015).","journal-title":"EMBO Rep."},{"issue":"1","key":"34074_CR31","doi-asserted-by":"publisher","first-page":"25040","DOI":"10.3402\/jev.v3.25040","volume":"3","author":"A Marcilla","year":"2014","unstructured":"Marcilla, A. et al. Extracellular vesicles in parasitic diseases. J. Extracell Vesicles 3(1), 25040 (2014).","journal-title":"J. Extracell Vesicles"},{"issue":"1","key":"34074_CR32","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1038\/s41398-019-0459-9","volume":"9","author":"S Saeedi","year":"2019","unstructured":"Saeedi, S., Israel, S., Nagy, C. & Turecki, G. The emerging role of exosomes in mental disorders. Transl. Psychiatry 9(1), 122 (2019).","journal-title":"Transl. Psychiatry"},{"issue":"6478","key":"34074_CR33","first-page":"69","volume":"367","author":"R Kalluri","year":"2020","unstructured":"Kalluri, R. & LeBleu, V. S. The biology, function, and biomedical applications of exosomes. Science (1979) 367(6478), 69\u201377 (2020).","journal-title":"Science (1979)"},{"issue":"1","key":"34074_CR34","doi-asserted-by":"publisher","first-page":"1535750","DOI":"10.1080\/20013078.2018.1535750","volume":"7","author":"C Th\u00e9ry","year":"2018","unstructured":"Th\u00e9ry, C. et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J. Extracell Vesicles 7(1), 1535750 (2018).","journal-title":"J. Extracell Vesicles"},{"issue":"2","key":"34074_CR35","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1111\/jnc.14893","volume":"152","author":"E Gonzalez-Lopez","year":"2020","unstructured":"Gonzalez-Lopez, E. & Vrana, K. E. Dopamine beta-hydroxylase and its genetic variants in human health and disease. J. Neurochem. 152(2), 157\u2013181 (2020).","journal-title":"J. Neurochem."},{"issue":"7","key":"34074_CR36","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1371\/journal.ppat.1002825","volume":"8","author":"AA Koshy","year":"2012","unstructured":"Koshy, A. A. et al. Toxoplasma co-opts host cells it does not invade. PLoS Pathog. 8(7), 10\u201328 (2012).","journal-title":"PLoS Pathog."},{"issue":"6","key":"34074_CR37","doi-asserted-by":"publisher","first-page":"1164","DOI":"10.1038\/mt.2014.29","volume":"22","author":"S Saayman","year":"2014","unstructured":"Saayman, S. et al. An HIV-encoded antisense long noncoding RNA epigenetically regulates viral transcription. Mol. Ther. 22(6), 1164\u20131175 (2014).","journal-title":"Mol. Ther."},{"issue":"13","key":"34074_CR38","doi-asserted-by":"publisher","first-page":"1923","DOI":"10.1016\/j.febslet.2013.04.045","volume":"587","author":"A Sinning","year":"2013","unstructured":"Sinning, A. & H\u00fcbner, C. A. Minireview: pH and synaptic transmission. FEBS Lett. 587(13), 1923\u20131928 (2013).","journal-title":"FEBS Lett."},{"issue":"8","key":"34074_CR39","doi-asserted-by":"publisher","first-page":"3334","DOI":"10.1128\/IAI.00605-15","volume":"83","author":"GA McConkey","year":"2015","unstructured":"McConkey, G. A., Peers, C. & Prandovszky, E. Reproducing increased dopamine with infection to evaluate the role of parasite-encoded tyrosine hydroxylase activity. Infect. Immun. 83(8), 3334\u20133335 (2015).","journal-title":"Infect. Immun."},{"key":"34074_CR40","unstructured":"Tedford E. Thesis. Neurophysiological changes during chronic Toxoplasma gondii infection. 2019."},{"issue":"1\u20132","key":"34074_CR41","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.brainres.2004.04.033","volume":"1015","author":"T Maeda","year":"2004","unstructured":"Maeda, T. et al. Electrophysiological characteristic of corticoaccumbens synapses in rat mesolimbic system reconstructed using organotypic slice cultures. Brain Res. 1015(1\u20132), 34\u201340 (2004).","journal-title":"Brain Res."},{"issue":"24","key":"34074_CR42","doi-asserted-by":"publisher","first-page":"6114","DOI":"10.1111\/mec.12888","volume":"23","author":"SA Hari Dass","year":"2014","unstructured":"Hari Dass, S. A. & Vyas, A. Toxoplasma gondii infection reduces predator aversion in rats through epigenetic modulation in the host medial amygdala. Mol. Ecol. 23(24), 6114\u20136122 (2014).","journal-title":"Mol. Ecol."},{"issue":"3","key":"34074_CR43","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1128\/EC.00448-07","volume":"7","author":"M Gissot","year":"2008","unstructured":"Gissot, M., Choi, S.-W., Thompson, R. F., Greally, J. M. & Kim, K. Toxoplasma gondii and Cryptosporidium parvum lack detectable DNA cytosine methylation. Eukaryot. Cell 7(3), 537\u2013540 (2008).","journal-title":"Eukaryot. Cell"},{"issue":"32","key":"34074_CR44","doi-asserted-by":"publisher","first-page":"16086","DOI":"10.1073\/pnas.1902513116","volume":"116","author":"P Sharma","year":"2019","unstructured":"Sharma, P. et al. Exosomes regulate neurogenesis and circuit assembly. Proc. Natl. Acad. Sci. 116(32), 16086\u201316094 (2019).","journal-title":"Proc. Natl. Acad. Sci."},{"issue":"1652","key":"34074_CR45","doi-asserted-by":"publisher","first-page":"20130507","DOI":"10.1098\/rstb.2013.0507","volume":"369","author":"TC Roberts","year":"2014","unstructured":"Roberts, T. C., Morris, K. V. & Wood, M. J. A. The role of long non-coding RNAs in neurodevelopment, brain function and neurological disease. Philos. Trans. R. Soc. B Biol. Sci. 369(1652), 20130507 (2014).","journal-title":"Philos. Trans. R. Soc. B Biol. Sci."},{"issue":"14","key":"34074_CR46","doi-asserted-by":"publisher","first-page":"6505","DOI":"10.1093\/nar\/gkw139","volume":"44","author":"MS Weinberg","year":"2016","unstructured":"Weinberg, M. S. & Morris, K. V. Transcriptional gene silencing in humans. Nucleic Acids Res. 44(14), 6505\u20136517 (2016).","journal-title":"Nucleic Acids Res."},{"issue":"1","key":"34074_CR47","doi-asserted-by":"publisher","first-page":"17","DOI":"10.3390\/ncrna5010017","volume":"5","author":"J Fernandes","year":"2019","unstructured":"Fernandes, J., Acu\u00f1a, S., Aoki, J., Floeter-Winter, L. & Muxel, S. Long non-coding RNAs in the regulation of gene expression: Physiology and disease. Noncoding RNA 5(1), 17 (2019).","journal-title":"Noncoding RNA"},{"issue":"7861","key":"34074_CR48","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1038\/s41586-021-03556-6","volume":"594","author":"R Simone","year":"2021","unstructured":"Simone, R. et al. MIR-NATs repress MAPT translation and aid proteostasis in neurodegeneration. Nature 594(7861), 117\u2013123 (2021).","journal-title":"Nature"},{"issue":"1","key":"34074_CR49","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.ncrna.2016.06.001","volume":"1","author":"C Hewson","year":"2016","unstructured":"Hewson, C., Capraro, D., Burdach, J., Whitaker, N. & Morris, K. V. Extracellular vesicle associated long non-coding RNAs functionally enhance cell viability. Noncoding RNA Res. 1(1), 3\u201311 (2016).","journal-title":"Noncoding RNA Res."},{"key":"34074_CR50","doi-asserted-by":"publisher","DOI":"10.1186\/S13059-020-02145-6","author":"N Huang","year":"2020","unstructured":"Huang, N. et al. Natural display of nuclear-encoded RNA on the cell surface and its impact on cell interaction. Genome Biol. https:\/\/doi.org\/10.1186\/S13059-020-02145-6 (2020).","journal-title":"Genome Biol."},{"issue":"8","key":"34074_CR51","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1002\/2211-5463.12092","volume":"6","author":"EB Harrison","year":"2016","unstructured":"Harrison, E. B. et al. Traumatic brain injury increases levels of miR-21 in extracellular vesicles: Implications for neuroinflammation. FEBS Open Bio 6(8), 835\u2013846 (2016).","journal-title":"FEBS Open Bio"},{"issue":"9","key":"34074_CR52","doi-asserted-by":"publisher","first-page":"2984","DOI":"10.1093\/nar\/gkp127","volume":"37","author":"PG Hawkins","year":"2009","unstructured":"Hawkins, P. G., Santoso, S., Adams, C., Anest, V. & Morris, K. V. Promoter targeted small RNAs induce long-term transcriptional gene silencing in human cells. Nucleic Acids Res. 37(9), 2984\u20132995 (2009).","journal-title":"Nucleic Acids Res."},{"issue":"1","key":"34074_CR53","doi-asserted-by":"publisher","first-page":"247","DOI":"10.3402\/jev.v3.24722","volume":"3","author":"M Chivet","year":"2014","unstructured":"Chivet, M. et al. Exosomes secreted by cortical neurons upon glutamatergic synapse activation specifically interact with neurons. J. Extracell Vesicles 3(1), 247\u2013252 (2014).","journal-title":"J. Extracell Vesicles"},{"issue":"7801","key":"34074_CR54","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1038\/s41586-020-2105-3","volume":"580","author":"Y Yin","year":"2020","unstructured":"Yin, Y. et al. U1 snRNP regulates chromatin retention of noncoding RNAs. Nature 580(7801), 147\u2013150 (2020).","journal-title":"Nature"},{"issue":"25","key":"34074_CR55","first-page":"25","volume":"11","author":"C Rodr\u00edguez-L\u00f3pez","year":"2017","unstructured":"Rodr\u00edguez-L\u00f3pez, C., Clasc\u00e1, F. & Prensa, L. The mesoaccumbens pathway: A retrograde labeling and single-cell axon tracing analysis in the mouse. Front. Neuroanat. 11(25), 25\u201331 (2017).","journal-title":"Front. Neuroanat."},{"issue":"4","key":"34074_CR56","doi-asserted-by":"publisher","first-page":"2237","DOI":"10.4049\/jimmunol.175.4.2237","volume":"175","author":"I Potolicchio","year":"2005","unstructured":"Potolicchio, I. et al. Proteomic analysis of microglia-derived exosomes: Metabolic role of the aminopeptidase CD13 in neuropeptide catabolism. J. Immunol. 175(4), 2237\u20132243 (2005).","journal-title":"J. Immunol."},{"issue":"11","key":"34074_CR57","doi-asserted-by":"publisher","first-page":"1446","DOI":"10.1002\/prca.200700522","volume":"1","author":"E-M Kramer-Albers","year":"2007","unstructured":"Kramer-Albers, E.-M. et al. Oligodendrocytes secrete exosomes containing major myelin and stress-protective proteins: Trophic support for axons?. Proteomics Clin. Appl. 1(11), 1446\u20131461 (2007).","journal-title":"Proteomics Clin. Appl."},{"issue":"32","key":"34074_CR58","doi-asserted-by":"publisher","first-page":"16086","DOI":"10.1073\/pnas.1902513116","volume":"116","author":"P Sharma","year":"2019","unstructured":"Sharma, P. et al. Exosomes regulate neurogenesis and circuit assembly. Proc. Natl. Acad. Sci. USA 116(32), 16086\u201316094 (2019).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"issue":"1","key":"34074_CR59","doi-asserted-by":"publisher","first-page":"15017","DOI":"10.1038\/s41598-018-33274-5","volume":"8","author":"KL Menard","year":"2018","unstructured":"Menard, K. L., Haskins, B. E., Colombo, A. P. & Denkers, E. Y. Toxoplasma gondii manipulates expression of host long noncoding RNA during intracellular infection. Sci. Rep. 8(1), 15017 (2018).","journal-title":"Sci. Rep."},{"issue":"1","key":"34074_CR60","doi-asserted-by":"publisher","first-page":"22484","DOI":"10.3402\/jev.v2i0.22484","volume":"2","author":"SM Pope","year":"2013","unstructured":"Pope, S. M. & L\u00e4sser, C. Toxoplasma gondii infection of fibroblasts causes the production of exosome-like vesicles containing a unique array of mRNA and miRNA transcripts compared to serum starvation. J. Extracell Vesicles 2(1), 22484 (2013).","journal-title":"J. Extracell Vesicles"},{"issue":"1","key":"34074_CR61","doi-asserted-by":"publisher","first-page":"1541708","DOI":"10.1080\/20013078.2018.1541708","volume":"7","author":"B P\u00e9rez-Cabezas","year":"2018","unstructured":"P\u00e9rez-Cabezas, B. et al. More than just exosomes: Distinct Leishmania infantum extracellular products potentiate the establishment of infection. J. Extracell Vesicles 7(1), 1541708 (2018).","journal-title":"J. Extracell Vesicles"},{"issue":"1","key":"34074_CR62","doi-asserted-by":"publisher","first-page":"28734","DOI":"10.3402\/jev.v4.28734","volume":"4","author":"PM Nogueira","year":"2015","unstructured":"Nogueira, P. M. et al. Vesicles from different Trypanosoma cruzi strains trigger differential innate and chronic immune responses. J. Extracell Vesicles 4(1), 28734 (2015).","journal-title":"J. Extracell Vesicles"},{"issue":"1","key":"34074_CR63","doi-asserted-by":"publisher","first-page":"2761","DOI":"10.1038\/s41467-020-16337-y","volume":"11","author":"H Toda","year":"2020","unstructured":"Toda, H. et al. Plasma-derived extracellular vesicles from Plasmodium vivax patients signal spleen fibroblasts via NF-kB facilitating parasite cytoadherence. Nat. Commun. 11(1), 2761 (2020).","journal-title":"Nat. Commun."},{"key":"34074_CR64","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens9010021","author":"SI Mbagwu","year":"2019","unstructured":"Mbagwu, S. I., Lannes, N., Walch, M., Filgueira, L. & Mantel, P.-Y. Human microglia respond to malaria-induced extracellular vesicles. Pathogens https:\/\/doi.org\/10.3390\/pathogens9010021 (2019).","journal-title":"Pathogens"},{"issue":"6","key":"34074_CR65","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1016\/j.neuron.2021.01.007","volume":"109","author":"AA Vilcaes","year":"2021","unstructured":"Vilcaes, A. A., Chanaday, N. L. & Kavalali, E. T. Interneuronal exchange and functional integration of synaptobrevin via extracellular vesicles. Neuron 109(6), 971-983.e5 (2021).","journal-title":"Neuron"},{"issue":"42","key":"34074_CR66","doi-asserted-by":"publisher","first-page":"8239","DOI":"10.1523\/JNEUROSCI.1164-19.2019","volume":"39","author":"DJ Chandler","year":"2019","unstructured":"Chandler, D. J. et al. Redefining noradrenergic neuromodulation of behavior: Impacts of a modular locus coeruleus architecture. J. Neurosci. 39(42), 8239\u20138249 (2019).","journal-title":"J. Neurosci."},{"issue":"7620","key":"34074_CR67","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nature19325","volume":"537","author":"T Takeuchi","year":"2016","unstructured":"Takeuchi, T. et al. Locus coeruleus and dopaminergic consolidation of everyday memory. Nature 537(7620), 357\u2013362 (2016).","journal-title":"Nature"},{"issue":"9","key":"34074_CR68","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0023866","volume":"6","author":"E Prandovszky","year":"2011","unstructured":"Prandovszky, E. et al. The neurotropic parasite Toxoplasma gondii increases dopamine metabolism. PLoS ONE 6(9), 1\u201323 (2011).","journal-title":"PLoS ONE"},{"key":"34074_CR69","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00381-19","author":"J Martynowicz","year":"2019","unstructured":"Martynowicz, J., Augusto, L., Wek, R. C., Boehm, S. L. & Sullivan, W. J. Guanabenz reverses a key behavioral change caused by latent toxoplasmosis in mice by reducing neuroinflammation. MBio https:\/\/doi.org\/10.1128\/mBio.00381-19 (2019).","journal-title":"MBio"},{"issue":"1","key":"34074_CR70","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1128\/AAC.47.1.309-316.2003","volume":"47","author":"M-J Gubbels","year":"2003","unstructured":"Gubbels, M.-J., Li, C. & Striepen, B. High-throughput growth assay for Toxoplasma gondii using yellow fluorescent protein. Antimicrob. Agents Chemother. 47(1), 309\u2013316 (2003).","journal-title":"Antimicrob. Agents Chemother."},{"issue":"9","key":"34074_CR71","doi-asserted-by":"publisher","first-page":"1193","DOI":"10.1128\/EC.00297-10","volume":"10","author":"BA Fox","year":"2011","unstructured":"Fox, B. A. et al. Type II Toxoplasma gondii KU80 knockout strains enable functional analysis of genes required for cyst development and latent infection. Eukaryot Cell 10(9), 1193\u20131206 (2011).","journal-title":"Eukaryot Cell"},{"issue":"4","key":"34074_CR72","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1016\/S0306-4522(01)00150-6","volume":"104","author":"RA Dielenberg","year":"2001","unstructured":"Dielenberg, R. A., Hunt, G. E. & McGregor, I. S. When a rat smells a cat: The distribution of Fos immunoreactivity in rat brain following exposure to a predatory odor. Neuroscience 104(4), 1085\u20131097 (2001).","journal-title":"Neuroscience"},{"issue":"10","key":"34074_CR73","doi-asserted-by":"publisher","first-page":"2301","DOI":"10.1016\/j.celrep.2017.02.035","volume":"18","author":"BM Filippi","year":"2017","unstructured":"Filippi, B. M. et al. Dynamin-related protein 1-dependent mitochondrial fission changes in the dorsal vagal complex regulate insulin action. Cell Rep. 18(10), 2301\u20132309 (2017).","journal-title":"Cell Rep."},{"issue":"20","key":"34074_CR74","first-page":"1","volume":"9","author":"A Matevossian","year":"2008","unstructured":"Matevossian, A. & Akbarian, S. Neuronal nuclei isolation from human postmortem brain tissue. J. Vis. Exp. 9(20), 1\u201321 (2008).","journal-title":"J. Vis. Exp."},{"issue":"1","key":"34074_CR75","doi-asserted-by":"publisher","first-page":"17319","DOI":"10.1038\/srep17319","volume":"5","author":"MA Livshits","year":"2015","unstructured":"Livshits, M. A. et al. Isolation of exosomes by differential centrifugation: Theoretical analysis of a commonly used protocol. Sci. Rep. 5(1), 17319 (2015).","journal-title":"Sci. Rep."},{"issue":"3","key":"34074_CR76","first-page":"1","volume":"11","author":"RP Alexander","year":"2016","unstructured":"Alexander, R. P., Chiou, N.-T. & Ansel, K. M. Improved exosome isolation by sucrose gradient fractionation of ultracentrifuged crude exosome pellets. Protoc. Exch. 11(3), 1\u20139 (2016).","journal-title":"Protoc. Exch."},{"issue":"19","key":"34074_CR77","doi-asserted-by":"publisher","first-page":"6631","DOI":"10.1039\/C5AN00688K","volume":"140","author":"Y Wu","year":"2015","unstructured":"Wu, Y., Deng, W. & Klinke, D. J. II. Exosomes: improved methods to characterize their morphology, RNA content, and surface protein biomarkers. Analyst 140(19), 6631\u20136642 (2015).","journal-title":"Analyst"},{"issue":"1","key":"34074_CR78","first-page":"44","volume":"6","author":"J Sambrook","year":"2006","unstructured":"Sambrook, J. & Russell, D. W. Purification of nucleic acids by extraction with phenol:chloroform. CSH Protoc. 6(1), 44\u201355 (2006).","journal-title":"CSH Protoc."},{"issue":"8","key":"34074_CR79","doi-asserted-by":"publisher","first-page":"1198","DOI":"10.1038\/nprot.2015.076","volume":"10","author":"TC Roberts","year":"2015","unstructured":"Roberts, T. C. et al. Quantification of nascent transcription by bromouridine immunocapture nuclear run-on RT-qPCR. Nat. Protoc. 10(8), 1198\u20131211 (2015).","journal-title":"Nat. Protoc."},{"issue":"1","key":"34074_CR80","doi-asserted-by":"publisher","first-page":"3221","DOI":"10.1002\/0471143030.cb0322s30","volume":"30","author":"C Th\u00e9ry","year":"2006","unstructured":"Th\u00e9ry, C., Amigorena, S., Raposo, G. & Clayton, A. Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr. Protoc. Cell Biol. 30(1), 3221\u20133229 (2006).","journal-title":"Curr. Protoc. Cell Biol."},{"key":"34074_CR81","volume-title":"The Rat Brain in Stereotaxic Coordinates","author":"G Paxinos","year":"2009","unstructured":"Paxinos, G. & Watson, C. The Rat Brain in Stereotaxic Coordinates (Academic Press, 2009)."},{"issue":"Web Server issu","key":"34074_CR82","doi-asserted-by":"publisher","first-page":"W70","DOI":"10.1093\/nar\/gkn188","volume":"36","author":"AR Gruber","year":"2008","unstructured":"Gruber, A. R., Lorenz, R., Bernhart, S. H., Neub\u00f6ck, R. & Hofacker, I. L. The Vienna RNA websuite. Nucleic Acids Res. 36(Web Server issue), W70\u2013W74 (2008).","journal-title":"Nucleic Acids Res."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-34074-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-34074-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-34074-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T13:03:35Z","timestamp":1682600615000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-34074-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,27]]},"references-count":82,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["34074"],"URL":"https:\/\/doi.org\/10.1038\/s41598-023-34074-2","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-2370968\/v1","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,27]]},"assertion":[{"value":"12 December 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 April 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 April 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"6913"}}