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Alterations in microglial metabolism have been proposed to contribute to AD-related inflammatory responses and reduced A\u03b2 clearance, suggesting that thiamine-dependent pathways may be relevant in this context. Thiamine pyrophosphate (TPP), the active form of vitamin B1, is essential for glucose metabolism and mitochondrial function; however, its association with microglial changes in AD remains unclear. In this study, 9-month-old female triple-transgenic AD (3xTg-AD) mice and non-transgenic controls (NoTg) received TPP (2.0 mg\/mL) or saline as a vehicle for six weeks via osmotic pumps. Nesting, a hippocampus-dependent behavioral test, as well analyses of A\u03b2 burden, microglial morphology, and the expression of genes related to metabolic and immune pathways were evaluated. Differences in nesting behavior between experimental groups were observed, but TPP treatment was not associated with an evident change in 3xTg-AD mice. In the subiculum and CA1 regions of the hippocampus of female 3xTg-AD mice exposed to TPP, a lower A\u03b2 burden was observed, and morphological variations in microglia were detected in both groups (3xTg-AD and NoTg). Additionally, in the brain of the TPP-treated group, some changes in mRNA gene expression were recorded. Together, these findings describe hippocampal microglial and amyloid profiles following TPP treatment in 3xTg-AD mice and provide a basis for further investigation of thiamine-dependent pathways in AD-related neuroinflammatory contexts.<\/jats:p>","DOI":"10.3390\/ijms27115022","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T12:45:08Z","timestamp":1780404308000},"page":"5022","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Hippocampal, Microglial, Morphological, and Amyloid Profiles Following Thiamine Pyrophosphate Treatment in 3xTg-AD Mice"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0515-722X","authenticated-orcid":false,"given":"Nelly Jovana","family":"Past\u00e9n-Castrej\u00f3n","sequence":"first","affiliation":[{"name":"Laboratorio de Endocrinolog\u00eda y Nutrici\u00f3n, Facultad de Medicina, Centro de Investigaci\u00f3n Biom\u00e9dica Avanzada de la Universidad Aut\u00f3noma de Quer\u00e9taro, Santiago de Quer\u00e9taro 76140, Mexico"},{"name":"Departamento de Neurobiolog\u00eda del Desarrollo y Neurofisiolog\u00eda, Instituto de Neurobiolog\u00eda-UNAM Campus Juriquilla, Boulevard Juriquilla 3001, Quer\u00e9taro 76230, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7529-8476","authenticated-orcid":false,"given":"Humberto","family":"Mart\u00ednez-Orozco","sequence":"additional","affiliation":[{"name":"Departamento de Neurobiolog\u00eda del Desarrollo y Neurofisiolog\u00eda, Instituto de Neurobiolog\u00eda-UNAM Campus Juriquilla, Boulevard Juriquilla 3001, Quer\u00e9taro 76230, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria Yareli","family":"Guti\u00e9rrez-Silerio","sequence":"additional","affiliation":[{"name":"Laboratorio de Endocrinolog\u00eda y Nutrici\u00f3n, Facultad de Medicina, Centro de Investigaci\u00f3n Biom\u00e9dica Avanzada de la Universidad Aut\u00f3noma de Quer\u00e9taro, Santiago de Quer\u00e9taro 76140, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hebert Luis","family":"Hern\u00e1ndez-Montiel","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurobiolog\u00eda y Bioingenier\u00eda Celular, Facultad de Ciencias Naturales de la Universidad Aut\u00f3noma de Quer\u00e9taro, Quer\u00e9taro 76230, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3570-9255","authenticated-orcid":false,"given":"Juan Pablo","family":"Maya-Arteaga","sequence":"additional","affiliation":[{"name":"Departamento de Neurobiolog\u00eda del Desarrollo y Neurofisiolog\u00eda, Instituto de Neurobiolog\u00eda-UNAM Campus Juriquilla, Boulevard Juriquilla 3001, Quer\u00e9taro 76230, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Israel","family":"Poblano-Paez","sequence":"additional","affiliation":[{"name":"Departamento de Neurobiolog\u00eda del Desarrollo y Neurofisiolog\u00eda, Instituto de Neurobiolog\u00eda-UNAM Campus Juriquilla, Boulevard Juriquilla 3001, Quer\u00e9taro 76230, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7483-0555","authenticated-orcid":false,"given":"Pablo","family":"Garc\u00eda-Sol\u00eds","sequence":"additional","affiliation":[{"name":"Laboratorio de Endocrinolog\u00eda y Nutrici\u00f3n, Facultad de Medicina, Centro de Investigaci\u00f3n Biom\u00e9dica Avanzada de la Universidad Aut\u00f3noma de Quer\u00e9taro, Santiago de Quer\u00e9taro 76140, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3354-2717","authenticated-orcid":false,"given":"Sof\u00eda Yolanda","family":"D\u00edaz-Miranda","sequence":"additional","affiliation":[{"name":"Departamento de Neurobiolog\u00eda del Desarrollo y Neurofisiolog\u00eda, Instituto de Neurobiolog\u00eda-UNAM Campus Juriquilla, Boulevard Juriquilla 3001, Quer\u00e9taro 76230, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"ref_1","unstructured":"(2025, August 15). 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