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In this study, we investigate the effects of prolonged hyperglycemia on the motoneurons of the ventral horn of the spinal cord, a lesser-studied area of the nervous system, with a focus on alterations in the Kynurenine Pathway (KP) as potential factors contributing to the induction, progression, and\/or chronicity of diabetic neuropathy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>KP metabolites were identified and assessed by immunohistochemistry in cross-sections of the lumbar spinal cord of type 2 diabetes (T2D) streptozotocin-induced (STZ) adult Sprague-Dawley rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Neuropathy, hyperglycemia, and gait alterations were associated to myelin loss in the spinal cord. KP metabolites were identified in glia, motoneuron, and non-motoneuron. The KP induction, as evidenced by enhanced L-kynurenine (L-KYN) fluorescence, appears to be associated with increased levels of interferon-gamma (IFN-\u03b3) and tumor necrosis factor-alpha (TNF-\u03b1). Notable differences in fluorescence merging of L-KYN with IFN-\u03b3 and TNF-\u03b1, of Quinolinic acid (QUIN) with 3-Hydroxykynurenine (3-HK), and of QUIN with advanced glycation end products (AGEs) were observed in the T2D group, contrasting with the control (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u2009.05). Additionally, in ventral horn cells, AGEs emerged as an added pro-inflammatory factor.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>The KP is activated during diabetic neuropathy, and it displays divergent metabolic profiles in glia, motoneuron, and non-motoneuron, which differ from the controls. Their presence also evolves with time, indicating the dynamic nature of the process.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/11786469251372797","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T08:41:42Z","timestamp":1759135302000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Neuroactive Kynurenine Metabolite Alterations Unveil Novel Association to Locomotor Deterioration in Diabetic Neuropathy"],"prefix":"10.1177","volume":"18","author":[{"given":"Alejandra","family":"Perez-Alvarez","sequence":"first","affiliation":[{"name":"Proteomics Unit, Center of Structural Biology and Biophysics and Biochemistry Center, Instituto Venezolano de Investigaciones Cient\u00edficas (IVIC) Caracas, San Antonio de Los Altos, Miranda, Venezuela"},{"name":"Histology Service, Biophysics and Biochemistry Center, Instituto Venezolano de Investigaciones Cientificas (IVIC) Caracas, San Antonio de Los Altos, Miranda, Venezuela"},{"name":"Centro de Biof\u00edsica y Neurociencia, Facultad de Ciencias de la Salud, Universidad de Carabobo, Valencia, Venezuela"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor","family":"Salazar","sequence":"additional","affiliation":[{"name":"Histology Service, Biophysics and Biochemistry Center, Instituto Venezolano de Investigaciones Cientificas (IVIC) Caracas, San Antonio de Los Altos, Miranda, Venezuela"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gustavo","family":"Bruges","sequence":"additional","affiliation":[{"name":"Department of Basic Science, Universidad Autonoma de Bucaramanga, Santander, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Vonasek","sequence":"additional","affiliation":[{"name":"Proteomics Unit, Center of Structural Biology and Biophysics and Biochemistry Center, Instituto Venezolano de Investigaciones Cient\u00edficas (IVIC) Caracas, San Antonio de Los Altos, Miranda, Venezuela"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0077-0318","authenticated-orcid":false,"given":"Antonio","family":"Eblen-Zajjur","sequence":"additional","affiliation":[{"name":"Translational Neuroscience Lab, Instituto de Ciencias Biom\u00e9dicas, Universidad Aut\u00f3noma de Chile, Santiago, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,9,29]]},"reference":[{"key":"e_1_3_2_2_2","volume-title":"IDF Diabetes Atlas","author":"IDF","year":"2022","unstructured":"IDF. 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