CHRONIC FLUORIDE EXPOSURE DISRUPTS BRAIN EXTRACELLULAR MATRIX AND INDUCES NEUROTOXICITY IN RATS Authors: Ashiru Dahiru, Zunaira Fatima, Ismat Nawaz, Syeda Kiran Riaz, Muhammad Abbas, Mustafa Nawaz Shafqat, Muhammad Jadoon Khan, Armaghana Qamar Khan, Syed Ali Musstjab Akber Shah Eqani Journal: Journal of Animal and Plant Sciences (JAPS) ISSN: 1018-7081 (Print), 2309-8694 (Online) Volume: 36 Issue: 6 Year: 2026 DOI: https://doi.org/10.36899/JAPS.2026.6.0152 URL: https://doi.org/https://doi.org/10.36899/JAPS.2026.6.0152 Publisher: Pakistan Agricultural Scientists Forum Abstract:

Fluoride is widely distributed in the environment, and excessive exposure has been associated with adverse effects in humans and animals. However, its effects on extracellular matrix (ECM) remodeling and collagen-related molecular pathways in the brain remain inadequately characterized. This study investigated the effects of different doses of sodium fluoride on the expression of ECM and collagen-related genes, and histopathological alterations in rat brain tissues. The findings are expected to provide baseline evidence for understanding ECM and collagen-associated alterations in fluoride-induced neurotoxicity. Using complete randomized design, forty Sprague-Dawley rats (20 males and 20 females) were allocated to four groups (n = 10/group; 5 males and 5 females) and exposed to 0.5 ppm (control), 50, 150, and 300 ppm NaF in drinking water for 90 days. Masson’s trichrome staining of brain tissues was performed to assess collagen deposition and tissue remodeling, while the expressions of COL1A1, COL1A2, and MMP9 were quantified using RT-qPCR. Masson’s trichrome staining revealed collagen deposition and extracellular matrix remodeling, accompanied by structural alterations, particularly in brain tissues exposed to higher NaF doses. Chronic NaF exposure was associated with dose-dependent downregulation (p≤0.05) of COL1A1 expression (0.69-, and 0.47-fold at 150, and 300 ppm, respectively), compared with the control. COL1A2 expression was also downregulated, particularly in male rats (p≤0.05), with expression levels of 0.39-, 0.85-, and 0.57-fold, respectively. MMP9 expression showed a decreasing trend (p>0.05) with increasing NaF exposure in both sexes. These findings suggest that chronic NaF exposure is associated with alterations in brain ECM-related gene expression and tissue architecture. The observed changes provide baseline evidence for further investigation of ECM remodeling and its potential involvement in fluoride-induced neurotoxicity.

Keywords: Fluoride, Extracellular matrix remodeling, Collagen, Neurotoxicity, COL1A1, COL1A2, MMP9