Chronic lead exposure reduces doublecortin-expressing immature neurons in young adult guinea pig cerebral cortex.
BACKGROUND
Chronic lead (Pb) poisoning remains an environmental risk especially for the pediatric population, and it may affect brain development. Immature neurons expressing doublecortin (DCX+) exist around cortical layer II in various mammals, including adult guinea pigs and humans. Using young adult guinea pigs as an experimental model, the present study explored if chronic Pb exposure affects cortical DCX + immature neurons and those around the subventricular and subgranular zones (SVZ, SGZ).


RESULTS
Two month-old guinea pigs were treated with 0.2% lead acetate in drinking water for 2, 4 and 6 months. Blood Pb levels in these animals reached 10.27 ± 0.62, 16.25 ± 0.78 and 19.03 ± 0.86 μg/dL at the above time points, respectively, relative to ~3 μg/dL in vehicle controls. The density of DCX + neurons was significantly reduced around cortical layer II, SVZ and SGZ in Pb-treated animals surviving 4 and 6 months relative to controls. Bromodeoxyuridine (BrdU) pulse-chasing studies failed to find cellular colocalization of this DNA synthesis indicator in DCX + cells around layer II in Pb-treated and control animals. These cortical immature neurons were not found to coexist with active caspase-3 or Fluoro-Jade C labeling.


CONCLUSIONS
Chronic Pb exposure can lead to significant reduction in the number of the immature neurons around cortical layer II and in the conventional neurogenic sites in young adult guinea pigs. No direct evidence could be identified to link the reduced cortical DCX expression with alteration in local neurogenesis or neuronal death.
Department of Anatomy and Neurobiology, Central South University School of Basic Medical Sciences, Changsha, Hunan, China.
JuFang
J
Huang
Kai
K
Huang
Lei
L
Shang
Hui
H
Wang
Mengqi
M
Zhang
Chun-Ling
CL
Fan
Dan
D
Chen
Xiaoxin
X
Yan
Kun
K
Xiong
D000367:Age Factors; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects; D002552:Cerebral Ventricles / Q000166:cytology / Q000378:metabolism; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D015536:Down-Regulation / Q000187:drug effects*; D005452:Fluoresceins / Q000378:metabolism; D006168:Guinea Pigs; D007854:Lead / Q000097:blood / Q000494:pharmacology*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D058953:Neural Stem Cells / Q000187:drug effects* / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D013997:Time Factors
C000714328:DCX protein, human; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005452:Fluoresceins; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; C534582:fluoro-jade C; D007854:Lead; D053148:Caspase 3; D001973:Bromodeoxyuridine