{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T11:29:45Z","timestamp":1780918185161,"version":"3.54.1"},"reference-count":60,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T00:00:00Z","timestamp":1746403200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Africa Healthcare Development Fund","award":["R126666"],"award-info":[{"award-number":["R126666"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background: Parkinson\u2019s disorder (PD) affects around 1:500 individuals and is associated with enlarged ventricles and symptoms of normal pressure hydrocephalus (NPH). These features suggest disrupted cerebrospinal fluid (CSF) dynamics and folate metabolism. With L-DOPA treatment showing diminishing benefits over time, there is an urgent need to investigate upstream metabolic disruptions, including folate and tetrahydrobiopterin (BH4) pathways, in post-mortem CSF and brain tissue to understand their roles in PD pathogenesis. Methods: CSF and brain tissue from 20 PD patients (mean age 84 years; 55% male; disease duration 10\u201330 years) and 20 controls (mean age 82 years; 50% male) were analysed. Western and Dot Blots measured proteins and metabolites, spectroscopic assays assessed enzyme activities, BH4 and Neopterin levels were measured using ELISA, and levels of hydrogen peroxide, used as a proxy for reactive oxygen species, and calcium were quantified using horseradish peroxidase and flame photometry assays, respectively. ClinVar genetic data were analysed for variants in genes encoding key enzymes. Statistical significance was assessed using unpaired t-tests (p &lt; 0.05). Results: All enzymes were significantly reduced in PD compared to controls (p &lt; 0.01) except for methyltetrahydrofolate reductase (MTHFR), which was elevated (p &lt; 0.0001). Enzymes were functional in control but undetectable in PD CSF except tyrosine hydroxylase (TH). BH4 and Neopterin were elevated in PD CSF (p &lt; 0.0001, p &lt; 0.001) but significantly reduced (p &lt; 0.001) or unchanged in tissue. Peroxide was increased in both PD CSF (p &lt; 0.001) and tissue (p &lt; 0.0001) selectively inhibiting TH. Calcium was 40% higher in PD than controls (p &lt; 0.05). No pathogenic variants in enzyme genes were found in ClinVar data searches, suggesting the observed deficiencies are physiological. Conclusions: We identified significant disruptions in folate and BH4 pathways in PD, with enzyme deficiencies, oxidative stress and calcium dysregulation pointing to choroid plexus dysfunction. These findings highlight the choroid plexus and CSF as key players in cerebral metabolism and promote further exploration of these as therapeutic targets to address dopaminergic dysfunction and ventricular enlargement in PD.<\/jats:p>","DOI":"10.3390\/metabo15050307","type":"journal-article","created":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T21:42:09Z","timestamp":1746481329000},"page":"307","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Multiple Hits on Cerebral Folate, Tetrahydrobiopterin and Dopamine Metabolism in the Pathophysiology of Parkinson\u2019s Disorder: A Limited Study of Post-Mortem Human Brain Tissues"],"prefix":"10.3390","volume":"15","author":[{"given":"Dhruti Balakrishna","family":"Doddaballapur","sequence":"first","affiliation":[{"name":"Division of Neuroscience, School of Biological Sciences, Faculty of Biology, Medicine & Health, The University of Manchester, 3.540 Stopford Building, Oxford Road, Manchester M13 9PT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derren J.","family":"Heyes","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology, Faculty of Science & Engineering, The University of Manchester, 131 Princess Street, Manchester M1 7DN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1835-0143","authenticated-orcid":false,"given":"Jaleel A.","family":"Miyan","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, School of Biological Sciences, Faculty of Biology, Medicine & Health, The University of Manchester, 3.540 Stopford Building, Oxford Road, Manchester M13 9PT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"259","DOI":"10.31887\/DCNS.2004.6.3\/galexander","article-title":"Biology of Parkinson\u2019s disease: Pathogenesis and pathophysiology of a multisystem neurodegenerative disorder","volume":"6","author":"Alexander","year":"2004","journal-title":"Dialogues Clin. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Anwar, A., Saleem, S., Akhtar, A., Ashraf, S., and Ahmed, M.F. (2019). Juvenile Parkinson Disease. Cureus, 11.","DOI":"10.7759\/cureus.5409"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1097\/WCO.0000000000000443","article-title":"Autoimmune encephalitis in children: Clinical phenomenology, therapeutics, and emerging challenges","volume":"30","author":"Dale","year":"2017","journal-title":"Curr. Opin. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neures.2021.11.010","article-title":"Challenges for future theories of Parkinson pathophysiology","volume":"177","author":"Darbin","year":"2022","journal-title":"Neurosci. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1016\/j.neuron.2018.07.028","article-title":"A Cortical Pathogenic Theory of Parkinson\u2019s Disease","volume":"99","author":"Foffani","year":"2018","journal-title":"Neuron."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"McConnell, H., and Bianchine, J. (1994). CSF as a Reflection of Cerebral Metabolism. Cerebrospinal Fluid in Neurology and Psychiatry, Springer.","DOI":"10.1007\/978-1-4899-3372-0"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Kira, R., Ohga, S., Takada, H., Gondo, K., Mihara, F., and Hara, T. (2000). MR choroid plexus sign of iron overload. Neurology, 55.","DOI":"10.1212\/WNL.55.9.1340"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1111\/j.1600-0404.1989.tb03820.x","article-title":"Tetrahydrobiopterin and Parkinson\u2019s disease","volume":"79","author":"Dissing","year":"1989","journal-title":"Acta Neurol. Scand."},{"key":"ref_9","first-page":"591","article-title":"Tetrahydrobioterin (BH4) Pathway: From Metabolism to Neuropsychiatry","volume":"19","author":"Fanet","year":"2021","journal-title":"Curr. Neuropharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Hong, S., Lee, S., and Cho, S.-R. (2020). Juvenile Parkinsonism with PARK2 Gene Mutation Misdiagnosed as Dopa-responsive Dystonia: A Case Report. Brain Neurorehabil., 13.","DOI":"10.12786\/bn.2020.13.e14"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Youn, J., Todisco, M., Zappia, M., Pacchetti, C., and Fasano, A. (2022). Parkinsonism and cerebrospinal fluid disorders. J. Neurol. Sci., 433.","DOI":"10.1016\/j.jns.2021.120019"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5201","DOI":"10.1007\/s10072-022-06119-3","article-title":"Parkinsonism in idiopathic normal pressure hydrocephalus: Is it time for defining a clinical tetrad?","volume":"43","author":"Mostile","year":"2022","journal-title":"Neurol. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1007\/s00415-017-8598-5","article-title":"Parkinsonian symptoms in normal pressure hydrocephalus: A population-based study","volume":"264","author":"Molde","year":"2017","journal-title":"J. Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Davis, A., Gulyani, S., Manthripragada, L., Luciano, M., Moghekar, A., and Yasar, S. (2021). Evaluation of the effect comorbid Parkinson syndrome on normal pressure hydrocephalus assessment. Clin. Neurol. Neurosurg., 207.","DOI":"10.1016\/j.clineuro.2021.106810"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Feng, Y., Feng, Y., Gu, L., Liu, P., Cao, J., and Zhang, S. (2021). The Critical Role of Tetrahydrobiopterin (BH4) Metabolism in Modulating Radiosensitivity: BH4\/NOS Axis as an Angel or a Devil. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.720632"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1203\/00006450-199307000-00003","article-title":"Cerebrospinal fluid concentrations of pterins and metabolites of serotonin and dopamine in a pediatric reference population","volume":"34","author":"Hyland","year":"1993","journal-title":"Pediatr. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1160\/TH12-06-0424","article-title":"The role of tetrahydrobiopterin in inflammation and cardiovascular disease","volume":"108","author":"McNeill","year":"2012","journal-title":"Thromb. Haemost."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.coph.2011.10.019","article-title":"Analgesia by inhibiting tetrahydrobiopterin synthesis","volume":"12","author":"Costigan","year":"2012","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Ikeda, L., Capel, A.V., Doddaballapur, D., and Miyan, J. (2024). Accumulation of Cerebrospinal Fluid, Ventricular Enlargement, and Cerebral Folate Metabolic Errors Unify a Diverse Group of Neuropsychiatric Conditions Affecting Adult Neocortical Functions. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms251810205"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Spix, T., and Gittis, A. (2020). Debunking an old theory. eLife, 9.","DOI":"10.7554\/eLife.62694"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/BF02741387","article-title":"Tyrosine hydroxylase and Parkinson\u2019s disease","volume":"16","author":"Haavik","year":"1998","journal-title":"Mol. Neurobiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1111\/jnc.15432","article-title":"Enhanced tyrosine hydroxylase activity induces oxidative stress, causes accumulation of autotoxic catecholamine metabolites, and augments amphetamine effects in vivo","volume":"158","author":"Vecchio","year":"2021","journal-title":"J. Neurochem."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Blesa, J., Trigo-Damas, I., Quiroga-Varela, A., and Jackson-Lewis, V.R. (2015). Oxidative stress and Parkinson\u2019s disease. Front. Neuroanat., 9.","DOI":"10.3389\/fnana.2015.00091"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Hedges, D.M., Yorgason, J.T., Perez, A.W., Schilaty, N.D., Williams, B.M., Watt, R.K., and Steffensen, S.C. (2020). Spontaneous Formation of Melanin from Dopamine in the Presence of Iron. Antioxidants, 9.","DOI":"10.3390\/antiox9121285"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1016\/j.bbamcr.2012.03.004","article-title":"Ferroportin-mediated iron transport: Expression and regulation","volume":"1823","author":"Ward","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Praetorius, J., Blazer-Yost, B., and Damkier, H. (2020). The Significance of the Choroid Plexus for Cerebral Iron Homeostasis. Role of the Choroid Plexus in Health and Disease, Springer.","DOI":"10.1007\/978-1-0716-0536-3"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Lorenzo, S., Ferreira Francisco, D.M., Vos, R., van het Hof, B., Rijnsburger, M., Schroten, H., Ishikawa, H., Beaino, W., Bruggmann, R., and Kooij, G. (2020). Altered secretory and neuroprotective function of the choroid plexus in progressive multiple sclerosis. Acta Neuropathol. Commun., 8.","DOI":"10.1186\/s40478-020-00903-y"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Ma, L., Gholam Azad, M., Dharmasivam, M., Richardson, V., Quinn, R.J., Feng, Y., Pountney, D.L., Tonissen, K.F., Mellick, G.D., and Yanatori, I. (2021). Parkinson\u2019s disease: Alterations in iron and redox biology as a key to unlock therapeutic strategies. Redox Biol., 41.","DOI":"10.1016\/j.redox.2021.101896"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Lin, C.C., Ding, C.C., Sun, T., Wu, J., Chen, K.Y., Zhou, P., and Chi, J.T. (2021). The regulation of ferroptosis by MESH1 through the activation of the integrative stress response. Cell Death Dis., 12.","DOI":"10.1038\/s41419-021-04018-7"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1038\/s41388-023-02933-x","article-title":"DMT1-dependent endosome-mitochondria interactions regulate mitochondrial iron translocation and metastatic outgrowth","volume":"43","author":"Barra","year":"2024","journal-title":"Oncogene"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Hong, C.T., Huang, Y.H., Liu, H.Y., Chiou, H.-Y., Chan, L., and Chien, L.-N. (2016). Newly Diagnosed Anemia Increases Risk of Parkinson\u2019s disease: A Population-Based Cohort Study. Sci. Rep., 6.","DOI":"10.1038\/srep29651"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Bahar, E., Kim, H., and Yoon, H. (2016). ER Stress-Mediated Signaling: Action Potential and Ca(2+) as Key Players. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17091558"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1111\/j.1474-9726.2007.00275.x","article-title":"Calcium and neurodegeneration","volume":"6","author":"Mattson","year":"2007","journal-title":"Aging Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"13","DOI":"10.3389\/fphar.2012.00061","article-title":"Physiology and pathology of calcium signaling in the brain","volume":"3","author":"Kawamoto","year":"2012","journal-title":"Front. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Lautenschl\u00e4ger, J., Stephens, A.D., Fusco, G., Str\u00f6hl, F., Curry, N., Zacharopoulou, M., Michel, C.H., Laine, R., Nespovitaya, N., and Fantham, M. (2018). C-terminal calcium binding of \u03b1-synuclein modulates synaptic vesicle interaction. Nat. Commun., 9.","DOI":"10.1038\/s41467-018-03111-4"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1016\/j.cell.2007.11.028","article-title":"Calcium signaling","volume":"131","author":"Clapham","year":"2007","journal-title":"Cell"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1038\/cdd.2017.82","article-title":"BCL-2 family: Integrating stress responses at the ER to control cell demise","volume":"24","author":"Hetz","year":"2017","journal-title":"Cell Death Differ."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Landrum, M.J., Lee, M.J., Riley, G.R., Jang, W., Rubinstein, W.S., Church, D.M., and Maglott, D.R. (2014). ClinVar: Public archive of relationships among sequence variation and human phenotype. Nucleic Acids Res., 42.","DOI":"10.1093\/nar\/gkt1113"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.ymgme.2005.07.027","article-title":"Disorders of purine and pyrimidine metabolism","volume":"86","author":"Nyhan","year":"2005","journal-title":"Mol. Genet. Metab."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Fumagalli, M., Lecca, D., Abbracchio, M.P., and Ceruti, S. (2017). Pathophysiological Role of Purines and Pyrimidines in Neurodevelopment: Unveiling New Pharmacological Approaches to Congenital Brain Diseases. Exp. Pharmacol. Drug Discov., 8.","DOI":"10.3389\/fphar.2017.00941"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Weng, R., Shen, S., Tian, Y., Burton, C., Xu, X., Liu, Y., Chang, C., Bai, Y., and Liu, H. (2015). Metabolomics Approach Reveals Integrated Metabolic Network Associated with Serotonin Deficiency. Sci. Rep., 5.","DOI":"10.1038\/srep11864"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1093\/jnen\/59.7.561","article-title":"Choroid Plexus in the Central Nervous System: Biology and Physiopathology","volume":"59","author":"Strazielle","year":"2000","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1016\/j.neuron.2019.03.004","article-title":"Circuit Mechanisms of Parkinson\u2019s Disease","volume":"101","author":"McGregor","year":"2019","journal-title":"Neuron"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Stuart, S.D.F., and Villalobos, A.R. (2021). GSH and Zinc Supplementation Attenuate Cadmium-Induced Cellular Stress and Stimulation of Choline Uptake in Cultured Neonatal Rat Choroid Plexus Epithelia. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22168857"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"19221","DOI":"10.1074\/jbc.M112.402164","article-title":"Sepiapterin reductase mediates chemical redox cycling in lung epithelial cells","volume":"288","author":"Yang","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Calakos, N., and Caffall, Z.F. (2024). The integrated stress response pathway and neuromodulator signaling in the brain: Lessons learned from dystonia. J. Clin. Investig., 134.","DOI":"10.1172\/JCI177833"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"E6420","DOI":"10.1073\/pnas.1707661114","article-title":"Inhibition of the integrated stress response reverses cognitive deficits after traumatic brain injury","volume":"114","author":"Chou","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Ryoo, H.D. (2024). The integrated stress response in metabolic adaptation. J. Biol. Chem., 300.","DOI":"10.1016\/j.jbc.2024.107151"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1161\/CIRCULATIONAHA.120.053125","article-title":"Integrated Stress Response Couples Mitochondrial Protein Translation With Oxidative Stress Control","volume":"144","author":"Zhang","year":"2021","journal-title":"Circulation"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.15252\/embr.201642195","article-title":"The integrated stress response","volume":"17","author":"Koryga","year":"2016","journal-title":"EMBO Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"H331","DOI":"10.1152\/ajpheart.00007.2009","article-title":"Sepiapterin reductase regulation of endothelial tetrahydrobiopterin and nitric oxide bioavailability","volume":"297","author":"Gao","year":"2009","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1001\/archinte.159.12.1289","article-title":"Laboratory Diagnosis of Vitamin B12 and Folate Deficiency: A Guide for the Primary Care Physician","volume":"159","author":"Snow","year":"1999","journal-title":"Arch. Intern. Med."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Cai, H., Liu, G., Sun, L., and Ding, J. (2014). Aldehyde Dehydrogenase 1 making molecular inroads into the differential vulnerability of nigrostriatal dopaminergic neuron subtypes in Parkinson\u2019s disease. Transl. Neurodegener., 3.","DOI":"10.1186\/2047-9158-3-27"},{"key":"ref_54","first-page":"19","article-title":"Association of anemia with Parkinson\u2019s disease: A systematic review with meta-analysis of epidemiological studies","volume":"24","year":"2023","journal-title":"Rev. Mex. Neurociencia"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1006\/bbrc.1998.8072","article-title":"Modulation of Inducible Nitric Oxide Synthase mRNA Stability by Tetrahydrobiopterin in Vascular Smooth Muscle Cells","volume":"243","author":"Linscheid","year":"1998","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3786","DOI":"10.1016\/j.febslet.2015.10.002","article-title":"Dissecting the role of Engrailed in adult dopaminergic neurons\u2014Insights into Parkinson disease pathogenesis","volume":"589","author":"Rekaik","year":"2015","journal-title":"FEBS Lett."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"11930","DOI":"10.1523\/JNEUROSCI.0443-17.2017","article-title":"CK2 Oppositely Modulates l-DOPA-Induced Dyskinesia via Striatal Projection Neurons Expressing D1 or D2 Receptors","volume":"37","author":"Malave","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"107","DOI":"10.4103\/0019-5278.44690","article-title":"Neopterin: Biomarker of cell-mediated immunity and potent usage as biomarker in silicosis and other occupational diseases","volume":"12","author":"Pingle","year":"2008","journal-title":"Indian. J. Occup. Environ. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/B978-0-12-804279-3.00003-4","article-title":"Chapter 3\u2014More than a drainage fluid: The role of CSF in signaling in the brain and other effects on brain tissue","volume":"146","author":"Illes","year":"2018","journal-title":"Handb. Clin. Neurol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Ortenl\u00f6f, N., Vallius, S., Karlsson, H., Ekstr\u00f6m, C., Kristiansson, A., Holmqvist, B., Pankratova, S., Barton, N., Ley, D., and Gram, M. (2024). Choroid plexus extracellular vesicle transport of blood-borne insulin-like growth factor 1 to the hippocampus of the immature brain. PNAS Nexus, 3.","DOI":"10.1093\/pnasnexus\/pgae496"}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/15\/5\/307\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:27:14Z","timestamp":1760030834000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/15\/5\/307"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,5]]},"references-count":60,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["metabo15050307"],"URL":"https:\/\/doi.org\/10.3390\/metabo15050307","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,5]]}}}