Evidence map›Paper›PMID 41035962›Full record

ArticleInternational journal of tryptophan research : IJTR2025

Neuroactive Kynurenine Metabolite Alterations Unveil Novel Association to Locomotor Deterioration in Diabetic Neuropathy.

Alejandra Perez-Alvarez, Victor Salazar, Gustavo Bruges, Eva Vonasek, Antonio Eblen-Zajjur

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Article in International journal of tryptophan research : IJTR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

5 authors.

Alejandra Perez-AlvarezProteomics Unit, Center of Structural Biology and Biophysics and Biochemistry Center, Instituto Venezolano de Investigaciones Científicas (IVIC) Caracas, San Antonio de Los Altos, Miranda, Venezuela.
Victor SalazarHistology Service, Biophysics and Biochemistry Center, Instituto Venezolano de Investigaciones Cientificas (IVIC) Caracas, San Antonio de Los Altos, Miranda, Venezuela.
Gustavo BrugesDepartment of Basic Science, Universidad Autonoma de Bucaramanga, Santander, Colombia.
Eva VonasekProteomics Unit, Center of Structural Biology and Biophysics and Biochemistry Center, Instituto Venezolano de Investigaciones Científicas (IVIC) Caracas, San Antonio de Los Altos, Miranda, Venezuela.
Antonio Eblen-ZajjurTranslational Neuroscience Lab, Instituto de Ciencias Biomédicas, Universidad Autónoma de Chile, Santiago, Chile.ORCID https://orcid.org/0000-0002-0077-0318

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: The effect of prolonged hyperglycemia on the sensory pathway of the nervous system has been the focus of numerous diabetes studies that aim at understanding the pathophysiology of the underlying inflammatory condition and neuropathy. 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. Methods: 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. Results: 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-γ) and tumor necrosis factor-alpha (TNF-α). Notable differences in fluorescence merging of L-KYN with IFN-γ and TNF-α, 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 ( Conclusions: 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.

Indexed as

AGESand TNF-αdiabetic neuropathyIFN-γkynurenine pathway

Identifiers

PMID41035962
PMCPMC12480792

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