{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T19:34:13Z","timestamp":1792956853616,"version":"4.5.0"},"reference-count":48,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    This study investigated the molecular and histopathological mechanism(s) contributing to fluoride induced neurotoxicity in male and female rats, focusing on dysregulation of cholinergic, neurotrophic, glutamatergic pathways and the accompanying structural alterations in the brain tissue. Forty male and female rats were administered sodium fluoride in water at concentrations (ppm) of 0.5 (control), 50 (low), 150 (medium), and 300 (high dose) for 90 days. The mRNA expression levels of cholinergic markers (acetylcholinesterase\u2010\n                    <jats:italic>AChE<\/jats:italic>\n                    , butyrylcholinesterase\u2010\n                    <jats:italic>BChE<\/jats:italic>\n                    ), the brain derived neurotrophic factor (\n                    <jats:italic>BDNF<\/jats:italic>\n                    ) and the metabotropic glutamate receptor 5 (\n                    <jats:italic>mGluR5<\/jats:italic>\n                    ) were quantified using RT\u2010qPCR, and histopathological alterations of different regions of brain was assessed by hematoxylin and eosin (H&amp;E) staining. Chronic NaF exposure resulted dose\u2010dependent neurodegenerative changes in the hippocampal CA1, CA3, and dentate gyrus (DG) regions, characterized by neuronal shrinkage, pyknosis, vacuolization, and spongiosis. The histopathological lesions were more pronounced in male rats than in females. Chronic fluoride exposure also resulted in a dose\u2010dependent decrease of blood AChE (1.09\u22120.604\u2009mU\/mL) and BChE (0.575\u22120.311\u2009mU\/mL) activities in both genders. Furthermore, chronic NaF exposure significantly down\u2010regulated the expression of\n                    <jats:italic>AChE<\/jats:italic>\n                    ,\n                    <jats:italic>BDNF<\/jats:italic>\n                    , and\n                    <jats:italic>mGluR5<\/jats:italic>\n                    in fluoride\u2010treated groups compared to controls. These findings demonstrate that prolonged NaF exposure disrupts cholinergic, neurotrophic, and glutamatergic signaling pathways, thereby contributing to neurotoxicity and potential neurodegeneration. Collectively, this mechanistic evidence underlines the importance of public health to monitor environmental fluoride exposure and highlight the potential for therapeutic strategies targeting cholinergic, neurotrophic and glutamatergic pathways to mitigate fluoride\u2010induced neuronal injury.\n                  <\/jats:p>","DOI":"10.1002\/jbt.71095","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T08:51:30Z","timestamp":1788771090000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanistic Insights Into Cholinergic, Neurotrophic, and Glutamatergic Pathways in Fluoride Neurotoxicity"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5494-5312","authenticated-orcid":false,"given":"Ashiru","family":"Dahiru","sequence":"first","affiliation":[{"name":"Department of Biosciences COMSATS University Islamabad Islamabad Pakistan"},{"name":"Department of Veterinary Physiology and Biochemistry Usmanu Danfodiyo University Sokoto Sokoto Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4732-1680","authenticated-orcid":false,"given":"Ismat","family":"Nawaz","sequence":"additional","affiliation":[{"name":"Department of Biosciences COMSATS University Islamabad Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7965-4178","authenticated-orcid":false,"given":"Syeda Kiran","family":"Riaz","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology Shaheed Zulfiqar Ali Bhutto Medical University Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6695-8698","authenticated-orcid":false,"given":"Nazneen","family":"Bangash","sequence":"additional","affiliation":[{"name":"Department of Biosciences COMSATS University Islamabad Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Tayyab","sequence":"additional","affiliation":[{"name":"Department of Biosciences COMSATS University Islamabad Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1395-6960","authenticated-orcid":false,"given":"Summaya Sohail","family":"Chaudry","sequence":"additional","affiliation":[{"name":"Pakistan Institute of Medical Science Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Jadoon","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Biosciences COMSATS University Islamabad Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyu","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Urban Environment Chinese Academy of Sciences Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed Ali Musstjab Akber Shah","family":"Eqani","sequence":"additional","affiliation":[{"name":"Department of Biosciences COMSATS University Islamabad Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"e_1_2_10_2_1","first-page":"48","volume-title":"Monographs in Oral Science","author":"Zohoori F. 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