title: Reduced neuronal proliferation by proconvulsant drugs in the developing zebrafish brain.
abstract: Seizures have been reported to modify neural development in the immature brain. In this study, we attempted to determine whether pentylenetetrazol (a GABAergic receptor antagonist, PTZ)-induced seizures influence cell proliferation in zebrafish larvae (5 and 15 days of post-fertilization), using bromodeoxyuridine (BrdU) to label dividing cells. In the brains of 5 dpf larvae, PTZ treatment significantly reduced the number of BrdU-labeled cells in the telencephalic area (pallium and subpallium), diencephalic area (thalamus and preoptic area), medial tectal proliferation zone, and medial cerebellar proliferation zone to 52.4%, 62.9%, 47.2%, and 54.0% of the controls, respectively. In contrast, we noted no reductions in the number of BrdU-labeled cells in the brains of the 15 dpf larvae. The double-label of BrdU and Hu, a neuronal marker, demonstrated that the majority of newborn cells showed the neuronal phenotype. Similarly, kainic acid (200 microM), a glutamatergic receptor agonist, significantly reduced the number of BrdU-labeled cells in the telencephalic area, diencephalic area, and medial tectal proliferation zone to 51.4%, 61.9%, and 40.4% of the controls, respectively. Physostigmine (500 microM), an acetylcholinesterase inhibitor, also reduced the number of BrdU-labeled cells in the telencephalic area, diencephalic area, medial tectal proliferation zone, and medial cerebellar proliferation zone to 52.8%, 35.9%, 30.5%, and 39.8% of the controls, respectively. All of these drugs resulted in electrographic seizures in the larval brain when perfused directly through artificial cerebrospinal fluid. These results indicated that seizures result in a massive reduction in cell proliferation in wide-ranging areas of the developing brain.
authors.affiliation: Department of Biological Sciences, Inha University, Inchon, Republic of Korea.
authors.forename: Yeon-Hwa
authors.initials: YH
authors.lastname: Kim
authors.forename: Yunkyoung
authors.initials: Y
authors.lastname: Lee
authors.forename: Keumju
authors.initials: K
authors.lastname: Lee
authors.forename: Taehee
authors.initials: T
authors.lastname: Lee
authors.forename: Yong-Jung
authors.initials: YJ
authors.lastname: Kim
authors.forename: Chang-Joong
authors.initials: CJ
authors.lastname: Lee
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D003292:Convulsants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D051959:ELAV Proteins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D007608:Kainic Acid / Q000494:pharmacology; D007814:Larva; D009474:Neurons / Q000187:drug effects*; D010433:Pentylenetetrazole / Q000494:pharmacology; D010830:Physostigmine / Q000494:pharmacology; D015027:Zebrafish
chemical_list: D003292:Convulsants; D051959:ELAV Proteins; D010830:Physostigmine; D001973:Bromodeoxyuridine; D007608:Kainic Acid; D010433:Pentylenetetrazole