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THD is associated with dystonia and infantile parkinsonism with a broad and complex spectrum and variable response to\n                    <jats:sc>l<\/jats:sc>\n                    \u2010Dopa therapy. TH1\u2010p.R202H is a frequent THD variant that affects TH stability and activity. The\n                    <jats:italic>Th knock\u2010in<\/jats:italic>\n                    (\n                    <jats:italic>Th\u2010ki<\/jats:italic>\n                    ) mice with the equivalent mutation (\n                    <jats:italic>Th\u2010<\/jats:italic>\n                    p.R203H) present reduced TH and DA levels, biological and molecular alterations, different phosphorylation patterns and altered distribution of dopaminergic markers relative to wild\u2010type mice.\n                    <jats:italic>Th\u2010ki<\/jats:italic>\n                    mice displayed significantly reduced TH, especially in the striatum, but also in the cortex, olfactory bulb, cerebellum, substantia nigra, globus pallidus, and spinal cord, a decrease that is not associated with dopaminergic neuronal degeneration. No changes were observed in\n                    <jats:italic>Th<\/jats:italic>\n                    \u2010mRNA expression, and the decreased level of TH in the concrete brain areas in\n                    <jats:italic>Th\u2010ki<\/jats:italic>\n                    mice appears to be due to defective TH protein axonal transport. Moreover, we characterized the development of dopaminergic neurons in the substantia nigra and neuronal plasticity in various brain regions. Our results indicated that alterations in TH expression within specific striatal GABAergic interneurons due to TH deficiency may potentially disrupt the balance of inhibitory neurotransmission in the striatum. Overall, our findings demonstrate that TH deficiency disrupts striatal inhibitory circuitry and triggers compensatory neuronal plasticity, without causing neuronal degeneration.\n                  <\/jats:p>","DOI":"10.1002\/jimd.70169","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T03:25:44Z","timestamp":1774322744000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Tyrosine Hydroxylase Deficiency Impairs\n                    <scp>TH<\/scp>\n                    Axonal Transport, Brain Function, and Neuronal Plasticity"],"prefix":"10.1002","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8736-0329","authenticated-orcid":false,"given":"Tie\u2010Jun Sten","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Clinical Dentistry, Faculty of Medicine and Dentistry University of Bergen  Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6745-7318","authenticated-orcid":false,"given":"Kunwar","family":"Jung\u2010KC","sequence":"additional","affiliation":[{"name":"Department of Biomedicine University of Bergen  Bergen Norway"},{"name":"K.G. Jebsen Center for Translational Research in Parkinson's Disease University of Bergen  Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6395-7625","authenticated-orcid":false,"given":"Gong\u2010Wei","family":"Lyu","sequence":"additional","affiliation":[{"name":"Department of Neurology 1st Affiliated Hospital of Harbin Medical University  Harbin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0768-0777","authenticated-orcid":false,"given":"Liang","family":"Han","sequence":"additional","affiliation":[{"name":"School\/Hospital of Stomatology Lanzhou University  Lanzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Ying","sequence":"additional","affiliation":[{"name":"Department of Biomedicine University of Bergen  Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5001-086X","authenticated-orcid":false,"given":"Beat","family":"Th\u00f6ny","sequence":"additional","affiliation":[{"name":"Division of Metabolism and Children's Research Center University Children's Hospital Zurich  Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1643-6506","authenticated-orcid":false,"given":"Aurora","family":"Martinez","sequence":"additional","affiliation":[{"name":"Department of Biomedicine University of Bergen  Bergen Norway"},{"name":"K.G. Jebsen Center for Translational Research in Parkinson's Disease University of Bergen  Bergen Norway"},{"name":"Neuro\u2010SysMed, Department of Neurology Haukeland University Hospital  Bergen 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