Developmental lead exposure impairs contextual fear conditioning and reduces adult hippocampal neurogenesis in the rat brain.
The effects of developmental lead exposure on the emotional reactivity, contextual fear conditioning and neurogenesis in the dentate gyrus of 60-80 days-old rats were studied. Wistar rat pups were exposed to 0.2% lead acetate via their dams' drinking water from postnatal day (PND) 1 to PND 21 and directly via drinking water from weaning until PND 30. At PND 60 and 80 the level of anxiety and contextual fear conditioning were studied, respectively. At PND 80 all animals received injections of BrdU to determine the effects of Pb on the generation of new cells in the dentate gyrus of hippocampus and on their survival and differentiation patterns. The results of the present study demonstrate that developmental lead exposure induces persistent increase in the level of anxiety and inhibition of contextual fear conditioning. Developmental lead exposure reduced generation of new cells in the dentate gyrus and altered the pattern of differentiation of BrdU-positive cells into mature neurons. A lower proportion of BrdU-positive cells co-expressed with the marker for mature neurons, calbindin. In contrast, the proportions of young not fully differentiated neurons and proportions of astroglial cells, generated from newly born cells, were increased in lead-exposed animals. Our results demonstrate that developmental lead exposure induces persistent inhibition of neurogenesis and alters the pattern of differentiation of newly born cells in the dentate gyrus of rat hippocampus, which could, at least partly, contribute to behavioral and cognitive impairments observed in adulthood.
Jaako-Movits
Külli
K
Department of Pharmacology, University of Tartu, 19 Ravila Street, 51014 Tartu, Estonia.
Zharkovsky
Tamara
T
Romantchik
Olga
O
Jurgenson
Monika
M
Merisalu
Eda
E
Heidmets
Lenne-Triin
LT
Zharkovsky
Alexander
A
D000818:Animals; D001007:Anxiety / Q000523:psychology; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D003072:Cognition Disorders / Q000139:chemically induced / Q000523:psychology; D003213:Conditioning, Psychological / Q000187:drug effects*; D004644:Emotions / Q000187:drug effects; D005239:Fear / Q000187:drug effects* / Q000523:psychology*; D005452:Fluoresceins; D005456:Fluorescent Dyes; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development*; D007150:Immunohistochemistry; D007855:Lead Poisoning / Q000523:psychology*; D018613:Microscopy, Confocal; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D009930:Organic Chemicals; D051381:Rats; D017208:Rats, Wistar
D005452:Fluoresceins; D005456:Fluorescent Dyes; D009930:Organic Chemicals; C435731:fluoro jade; D001973:Bromodeoxyuridine