title: Maternal lead exposure decreases the levels of brain development and cognition-related proteins with concomitant upsurges of oxidative stress, inflammatory response and apoptosis in the offspring rats.
abstract: The presence of lead (Pb) in fetal brain may affect brain development-related proteins. We studied whether gestational/lactational Pb-exposure affects oxidative stress, proinflammatory response, apoptosis and levels of brain development/cognition-related proteins, including presynaptic synaptosome-associated protein-25 (SNAP-25), postsynaptic density protein-95 (PSD-95), brain-derived neurotropic factor (BDNF), tyrosine receptor-kinase protein B (TrkB) and vesicular acetylcholine transporter (VAChT) in the offspring. Female Wistar rats were randomly divided into control and Pb-exposed mother groups. The Pb-exposed rats received 0.1% (w/v) Pb acetate via drinking water during pregnancy and lactation. Milk and mammary glands were collected from lactating mothers to measure milk/mammary gland levels of lipid peroxide (LPO), as indicator of oxidative stress and proinflammatory TNF-α. Afterwards, the pups were sacrificed to determine brain levels of Pb, LPO, TNF-α, cytochrome C, SNAP-25, PSD-95, BDNF, TrkB and VAChT. The levels of LPO and TNF-α increased in the milk/mammary glands of the Pb-exposed mothers, concurrently with increases in the levels of Pb, LPO, TNF-α and cytochrome C and decreases in the levels of SNAP-25, PSD-95, BDNF, TrkB and VAChT in the brains of their offspring. Our results demonstrate that Pb-exposure during development reduces the brain levels of PSD-95 and SNAP-25 (synaptogenesis-markers), with concomitant upsurges of oxidative stress, TNF-α and apoptosis in the offspring. Furthermore, BDNF-TrkB proteins that comprehend memory-related brain cognitions and/or VAChT that comprises cholinergic-neuromotor activities might be impaired by Pb-exposure. These findings provide evidence of toxic effects of Pb on brain development, at least, partially by decreasing the levels of PSD-95, SNAP-25 and other cognition-related proteins.
authors: Laboratory of Alternative Medicine and Behavioral Neurosciences, Department of Biochemistry and Molecular Biology, Jahangirnagar University, Savar, Dhaka 1342, Bangladesh. Electronic address: shahdat@dhaka.net.
authors: Shahdat
authors: S
authors: Hossain
authors: Laboratory of Alternative Medicine and Behavioral Neurosciences, Department of Biochemistry and Molecular Biology, Jahangirnagar University, Savar, Dhaka 1342, Bangladesh.
authors: Sujan
authors: S
authors: Bhowmick
authors: Laboratory of Alternative Medicine and Behavioral Neurosciences, Department of Biochemistry and Molecular Biology, Jahangirnagar University, Savar, Dhaka 1342, Bangladesh.
authors: Sabrin
authors: S
authors: Jahan
authors: Laboratory of Alternative Medicine and Behavioral Neurosciences, Department of Biochemistry and Molecular Biology, Jahangirnagar University, Savar, Dhaka 1342, Bangladesh.
authors: Liza
authors: L
authors: Rozario
authors: Laboratory of Alternative Medicine and Behavioral Neurosciences, Department of Biochemistry and Molecular Biology, Jahangirnagar University, Savar, Dhaka 1342, Bangladesh.
authors: Marzan
authors: M
authors: Sarkar
authors: Laboratory of Alternative Medicine and Behavioral Neurosciences, Department of Biochemistry and Molecular Biology, Jahangirnagar University, Savar, Dhaka 1342, Bangladesh.
authors: Saiful
authors: S
authors: Islam
authors: Laboratory of Alternative Medicine and Behavioral Neurosciences, Department of Biochemistry and Molecular Biology, Jahangirnagar University, Savar, Dhaka 1342, Bangladesh.
authors: Mafroz Ahmed
authors: MA
authors: Basunia
authors: Laboratory of Alternative Medicine and Behavioral Neurosciences, Department of Biochemistry and Molecular Biology, Jahangirnagar University, Savar, Dhaka 1342, Bangladesh.
authors: Azizur
authors: A
authors: Rahman
authors: Manikganj Medical College, Manikganj, 1800, Dhaka, Bangladesh.
authors: Bazlul Karim
authors: BK
authors: Choudhury
authors: Laboratory of Alternative Medicine and Behavioral Neurosciences, Department of Biochemistry and Molecular Biology, Jahangirnagar University, Savar, Dhaka 1342, Bangladesh.
authors: Hussain
authors: H
authors: Shahjalal
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000254:growth & development*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation / Q000139:chemically induced*; D007854:Lead / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D042361:Mammary Glands, Human / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D016207:Cytokines; D008565:Membrane Proteins; D007854:Lead; D045304:Cytochromes c
keywords: Apoptosis; BDNF; Lead exposure; Lipid peroxide; Neurotoxicity; PSD-95; SNAP-25; TNFα; TrkB; VAChT