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

Neurotoxicology. 2016 Sep;56:150-158. doi: 10.1016/j.neuro.2016.07.013. Epub 2016 Aug 1.


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.

Keywords: Apoptosis; BDNF; Lead exposure; Lipid peroxide; Neurotoxicity; PSD-95; SNAP-25; TNFα; TrkB; VAChT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Brain / drug effects
  • Brain / growth & development*
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cytochromes c / metabolism
  • Cytokines / metabolism
  • Female
  • Humans
  • Inflammation / chemically induced*
  • Lead / toxicity*
  • Lipid Peroxidation / drug effects
  • Male
  • Mammary Glands, Human / drug effects
  • Mammary Glands, Human / metabolism
  • Membrane Proteins / metabolism
  • Oxidative Stress / drug effects*
  • Pregnancy
  • Prenatal Exposure Delayed Effects* / chemically induced
  • Prenatal Exposure Delayed Effects* / pathology
  • Prenatal Exposure Delayed Effects* / physiopathology
  • Rats
  • Rats, Wistar
  • Up-Regulation / drug effects*


  • Brain-Derived Neurotrophic Factor
  • Cytokines
  • Membrane Proteins
  • Lead
  • Cytochromes c