Neurodegeneration and production of the new cells in the dentate gyrus of juvenile rat hippocampus after a single administration of ethanol.
Administration of ethanol during brain development induces widespread neuronal loss in various structures of the brain. Here, we show that a single administration of ethanol given during the early postnatal period can induce not only neuronal death, but also an increase in proliferation of the progenitor cells in the dentate gyrus of hippocampal formation in rats. Ethanol (1.5 or 3 g/kg, i.p.) administered to 10-day-old rats induced massive neuronal degeneration as evidenced by TUNEL assay in the dentate gyrus. The neuronal death induced by a high dose of ethanol (3 g/kg) was accompanied by an enhanced proliferation of the progenitor cells labeled by bromodeoxyuridine (BrdU, 50 mg/kg, i.p.) in dentate gyrus. One and 3 weeks following ethanol or saline administration, ethanol-treated rats still had significantly more BrdU-labeled cells than control animals. In ethanol-treated rats, a higher proportion of newly born cells acquired the phenotype of immature postmitotic neurons whereas the final differentiation into calbindin-expressing granule cells remained unchanged. The proportion of astroglial cells was also increased in ethanol-treated rats. Thus, ethanol given in high doses not only induces neurodegeneration but also initiates the process of neuro- and gliogenesis, which might be responsible for the neuronal and glial reorganization of the dentate gyrus.
Zharkovsky
Tamara
T
Department of Pharmacology, University of Tartu, 19 Ravila Street, 51014 Tartu, Estonia.
Kaasik
Allen
A
Jaako
Külli
K
Zharkovsky
Alexander
A
D000818:Animals; D000831:Animals, Newborn; D001973:Bromodeoxyuridine / Q000493:pharmacokinetics; D002452:Cell Count; D002455:Cell Division; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D053938:DNA Fragmentation / Q000187:drug effects; D018891:Dentate Gyrus / Q000187:drug effects* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D006624:Hippocampus / Q000473:pathology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling / Q000379:methods; D009410:Nerve Degeneration / Q000139:chemically induced; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration / Q000187:drug effects*; D012794:Sialic Acids / Q000378:metabolism
D002492:Central Nervous System Depressants; D039842:Neural Cell Adhesion Molecule L1; D011838:Radiation-Sensitizing Agents; D012794:Sialic Acids; C103469:polysialyl neural cell adhesion molecule; D000431:Ethanol; D001973:Bromodeoxyuridine