Environmental lead exposure during early life alters granule cell neurogenesis and morphology in the hippocampus of young adult rats

T. Verina, Charles A Rohde, T. R. Guilarte

Research output: Contribution to journalArticle

Abstract

Exposure to environmentally relevant levels of lead (Pb2+) during early life produces deficits in hippocampal synaptic plasticity in the form of long-term potentiation (LTP) and spatial learning in young adult rats [Nihei MK, Desmond NL, McGlothan JL, Kuhlmann AC, Guilarte TR (2000) N-methyl-D-aspartate receptor subunit changes are associated with lead-induced deficits of long-term potentiation and spatial learning. Neuroscience 99:233-242; Guilarte TR, Toscano CD, McGlothan JL, Weaver SA (2003) Environmental enrichment reverses cognitive and molecular deficits induced by developmental lead exposure. Ann Neurol 53:50-56]. Other evidence suggests that the performance of rats in the Morris water maze spatial learning tasks is associated with the level of granule cell neurogenesis in the dentate gyrus (DG) [Drapeau E, Mayo W, Aurousseau C, Le Moal M, Piazza P-V, Abrous DN (2003) Spatial memory performance of aged rats in the water maze predicts level of hippocampal neurogenesis. Proc Natl Acad Sci U S A 100:14385-14390]. In this study, we examined whether continuous exposure to environmentally relevant levels of Pb2+ during early life altered granule cell neurogenesis and morphology in the rat hippocampus. Control and Pb2+-exposed rats received bromodeoxyuridine (BrdU) injections (100 mg/kg; i.p.) for five consecutive days starting at postnatal day 45 and were killed either 1 day or 4 weeks after the last injection. The total number of newborn cells in the DG of Pb2+-exposed rats was significantly decreased (13%; P2+-exposed rats was significantly decreased by 22.7% (P2+ exposure on cellular fate. In Pb2+-exposed rats, immature granule cells immunolabeled with doublecortin (DCX) displayed aberrant dendritic morphology. That is, the overall length-density of the DCX-positive apical dendrites in the outer portion of the DG molecular layer was significantly reduced up to 36% in the suprapyramidal blade only. We also found that the area of Timm's-positive staining representative of the mossy fibers terminal fields in the CA3 stratum oriens (SO) was reduced by 26% in Pb2+-exposed rats. These findings demonstrate that exposure to environmentally relevant levels of Pb2+ during early life alters granule cell neurogenesis and morphology in the rat hippocampus. They provide a cellular and morphological basis for the deficits in synaptic plasticity and spatial learning documented in Pb2+-exposed animals.

Original languageEnglish (US)
Pages (from-to)1037-1047
Number of pages11
JournalNeuroscience
Volume145
Issue number3
DOIs
StatePublished - Mar 30 2007

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Neurogenesis
Environmental Exposure
Young Adult
Hippocampus
Dentate Gyrus
Neuronal Plasticity
Long-Term Potentiation
Lead
Maze Learning
Injections
Water
Bromodeoxyuridine
Neurosciences
Dendrites
N-Methyl-D-Aspartate Receptors
Cell Count
Newborn Infant
Staining and Labeling
Spatial Learning

Keywords

  • granule cell
  • hippocampus
  • morphology
  • neurogenesis
  • neurotoxicity
  • Pb

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Environmental lead exposure during early life alters granule cell neurogenesis and morphology in the hippocampus of young adult rats. / Verina, T.; Rohde, Charles A; Guilarte, T. R.

In: Neuroscience, Vol. 145, No. 3, 30.03.2007, p. 1037-1047.

Research output: Contribution to journalArticle

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