{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T23:56:56Z","timestamp":1792540616562,"version":"4.5.0"},"reference-count":148,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lead (Pb) disrupts mitochondrial function, but its impact on the mitochondrial dynamics and biogenesis during early brain development remains insufficiently understood. This study aimed to investigate the effects of pre- and neonatal Pb exposure on the processes involved in mitochondrial network formation in the brains of rat offspring, simulating environmental exposure. We quantified mRNA expression (qRT-PCR) and protein levels (ELISA) of key mitochondrial fusion (Mfn1, Mfn2, Opa1), fission (Drp1, Fis1) regulators, as well as biogenesis markers (PGC-1\u03b1, TFAM, NRF1) in the hippocampus, forebrain cortex, and cerebellum of rats exposed to Pb. Mitochondrial ultrastructure was evaluated using transmission electron microscopy (TEM), and the expression of mitochondrial electron transport chain (ETC) genes was analysed (qRT-PCR). Furthermore, to examine the involvement of the cGAS\u2013STING pathway in Pb-induced neuroinflammation, we measured the expression of ISGs (qRT-PCR), TBK1 phosphorylation (Western blot), and 2\u2032,3\u2032-cGAMP synthesis (ELISA). Our results showed that Pb exposure markedly reduced PGC-1\u03b1 and region-specific NRF1 levels, broadly supressed fusion proteins (Mfn1, Mfn2, Opa1), increased Fis1, and depleted Drp1. ETC gene expression (mtNd1, mtCyb and mtCo1) were upregulated in a brain-structure-dependent manner. These molecular changes were accompanied by pronounced mitochondrial morphological abnormalities. Despite upregulation of Mx1, Ifi44, and Sting1, along with synthesis of 2\u20323\u2032-cGAMP, TBK1 activation was not detected. All these findings demonstrate that early-life Pb exposure, even low-dose, disrupts mitochondrial biogenesis and the fusion\u2013fission machinery, thus impairs brain energy homeostasis, and implicates mitochondria as central mediators of Pb-induced neuroinflammation and neurodevelopmental toxicity.<\/jats:p>","DOI":"10.3390\/ijms262411907","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T14:22:40Z","timestamp":1765376560000},"page":"11907","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Disturbances in Mitochondrial Network, Biogenesis, and Mitochondria-Mediated Inflammatory Responses in Selected Brain Structures of Rats Exposed to Lead (Pb) During Prenatal and Neonatal Development"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4301-6195","authenticated-orcid":false,"given":"Miko\u0142aj","family":"Chlubek","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Powsta\u0144c\u00f3w Wlkp. 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9777-1378","authenticated-orcid":false,"given":"Magdalena","family":"G\u0105ssowska-Dobrowolska","sequence":"additional","affiliation":[{"name":"Department of Cellular Signalling, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6933-7643","authenticated-orcid":false,"given":"Agnieszka","family":"Kolasa","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Pomeranian Medical University, Powsta\u0144c\u00f3w Wlkp. 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3869-5077","authenticated-orcid":false,"given":"Maciej","family":"Tarnowski","sequence":"additional","affiliation":[{"name":"Department of Physiology in Health Sciences, Pomeranian Medical University, \u017bo\u0142nierska 54, 70-210 Szczecin, Poland"},{"name":"Institute of Physical Culture Sciences, University of Szczecin, 70-240 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8147-6419","authenticated-orcid":false,"given":"Patrycja","family":"Tomasiak","sequence":"additional","affiliation":[{"name":"Institute of Physical Culture Sciences, University of Szczecin, 70-240 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0687-9717","authenticated-orcid":false,"given":"Agnieszka","family":"Maruszewska","sequence":"additional","affiliation":[{"name":"Institute of Biology, University of Szczecin, W\u0105ska 13, 71-415 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6381-566X","authenticated-orcid":false,"given":"Katarzyna","family":"Barczak","sequence":"additional","affiliation":[{"name":"Department of Endodontic Surgery, Pomeranian Medical University, Powsta\u0144c\u00f3w Wlkp. 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9187-8895","authenticated-orcid":false,"given":"Irena","family":"Baranowska-Bosiacka","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Powsta\u0144c\u00f3w Wlkp. 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"840547","DOI":"10.1155\/2014\/840547","article-title":"Pb Neurotoxicity: Neuropsychological Effects of Lead Toxicity","volume":"2014","author":"Mason","year":"2014","journal-title":"BioMed Res. 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