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[P218]: Decreased dopamine D2 mRNA expression in rats with neonatal ventral hippocampus lesion after puberty
Author(s) -
AlAmin H.,
ElRawas R.,
Saadé N.,
Atweh S.,
Jaber M.
Publication year - 2006
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2006.09.278
Subject(s) - dopamine , hippocampus , art , medicine , biology , neuroscience
Organomercurial toxicants may contribute to disorders of the developing brain. These toxicants may act at multiple times, eliciting acute effects on neurogenesis that influence later ontogeny. While high dose mercury exposure causes gross defects, effects of lower levels not associated with deformities are less well defined, especially regarding precursor proliferation. After 24 h of exposure, MeHg 5 g/gbw reduced DNA synthesis by 24% in the hippocampus. This dose significantly reduced DNA synthesis after 6 h indicating rapid effects on cell cycle progression, raising the possibility of a G1-S block. In contrast, MeHg did not affect cerebellum, suggesting regional vulnerability. The reduction in DNA synthesis elicited by MeHg could be attributed to several processes including a block in G1/S transition, initiation of cell death or energy failure. To examine G1/S transition, we counted BrdU labeled cells in the hilus of the hippocampal dentate gyrus. Following MeHg exposure, BrdU positive cell number decreased by 35% at 8 h indicating that MeHg affects DNA synthesis by reducing S-phase entry. To assess possible cell death, we studied MeHg effects on caspase-3 levels: MeHg increased activated caspase-3 in hippocampus at 8 h, suggesting the toxicant induced programmed cell death. Moreover, we have shown that the reduction in cyclin E level could be attributable to its cleavage by caspase-3, reinforcing the importance of cell death in this model. We then studied the long-term effects of MeHg on hippocampal structure. We found a strong reduction in the cell number in the dentate gyrus of the hippocampus 2 weeks after MeHg injection. Recent analysis indicate that MeHg treated animals exhibit impairement in Morris watermaze visual learning test. This study provides new concepts concerning MeHg toxicity during development. In particular, MeHg alters neurogenesis by acutely inhibiting cell cycle progression and stimulating apoptosis, leading to long-term modifications of hippocampal structure (NIH ES11256, ES05022, EPA R82939101, FRM SPE2006).