Neuron type-selective effects of activin on development of the hippocampus.
Activin is a member of the transforming growth factor-beta superfamily and affects the viability of hippocampal neurons during postnatal neurogenesis. We used primary hippocampal neuron to study the actions of activin on developing neurons. Continuous treatment of hippocampal cultures with activin suppressed the emergence of GAD67(+) neurons, which are a subtype of GABAergic interneurons, and increased the percentage of Prox1(+) neurons, which are dentate granule cells. The effects of activin were abolished by co-treatment with follistatin, which is a direct inhibitor of activin. In contrast, follistatin treatment alone increased the percentage of GAD67(+) neurons and decreased the percentage of Prox1(+) neurons. These results indicate that changes in activin signaling during postnatal neural development alter the composition of the neural circuitry and suggest that alterations in the ratio of excitatory to inhibitory neurons may be responsible for changes in the spontaneous and evoked-reactivity of these neurons to other neural inputs.
Mitsubishi Kagaku Institute of Life Sciences, MITILS, Tokyo, Japan.
Mariko
M
Sekiguchi
Fumihiko
F
Hayashi
Kunihiro
K
Tsuchida
Kaoru
K
Inokuchi
D030301:Activin Receptors, Type II / Q000378:metabolism; D028341:Activins / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D018891:Dentate Gyrus / Q000254:growth & development / Q000502:physiology; D038681:Follistatin / Q000378:metabolism / Q000494:pharmacology; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006624:Hippocampus / Q000254:growth & development* / Q000502:physiology*; D018398:Homeodomain Proteins / Q000378:metabolism; D007395:Interneurons / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism; D017966:Pyramidal Cells / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism; D000098551:Prospero-Related Homeobox 1 Protein
D004268:DNA-Binding Proteins; D038681:Follistatin; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein; D028341:Activins; D005680:gamma-Aminobutyric Acid; D030301:Activin Receptors, Type II; C425585:activin receptor type II-A; C425584:activin receptor type II-B; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1