Disc1 Variation Leads to Specific Alterations in Adult Neurogenesis

Jayanth S Chandran, Ilias Kazanis, Steven J Clapcote, Fumiaki Ogawa, J Kirsty Millar, David J Porteous, Charles Ffrench-Constant

Research output: Contribution to journalArticlepeer-review

Abstract

Disrupted in schizophrenia 1 (DISC1) is a risk factor for a spectrum of neuropsychiatric illnesses including schizophrenia, bipolar disorder, and major depressive disorder. Here we use two missense Disc1 mouse mutants, described previously with distinct behavioural phenotypes, to demonstrate that Disc1 variation exerts differing effects on the formation of newly generated neurons in the adult hippocampus. Disc1 mice carrying a homozygous Q31L mutation, and displaying depressive-like phenotypes, have fewer proliferating cells while Disc1 mice with a homozygous L100P mutation that induces schizophrenia-like phenotypes, show changes in the generation, placement and maturation of newly generated neurons in the hippocampal dentate gyrus. Our results demonstrate Disc1 allele specific effects in the adult hippocampus, and suggest that the divergence in behavioural phenotypes may in part stem from changes in specific cell populations in the brain.

Original languageEnglish
Pages (from-to)e108088
JournalPLoS ONE
Volume9
Issue number10
Early online date1 Oct 2014
DOIs
Publication statusPublished - 1 Oct 2014

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