Type

Journal Article

Authors

Ciaran M Regan
David von Schack
Robert H Ring
William T O'Connor
Karen L Marquis
Menelas N Pangalos
Desmond G Higgins
Sean K Mulvany
Zoe A Hughes
Caitlin M Wantuch
and 18 others

Subjects

Biochemistry

Topics
physiology computational biology rats synapses transcription factors animals motor activity stress psychological cerebral cortex metabolism ultrastructure gene expression regulation dna reverse transcriptase polymerase chain reaction rna complementary microdialysis behavior animal psychology genetics chemistry rats wistar oligonucleotide array sequence analysis multigene family rna male biosynthesis social isolation

Temporal dysregulation of cortical gene expression in the isolation reared Wistar rat. (2010)

Abstract The critical sequence of molecular, neurotransmission and synaptic disruptions that underpin the emergence of psychiatric disorders like schizophrenia remain to be established with progress only likely using animal models that capture key features of such disorders. We have related the emergence of behavioural, neurochemical and synapse ultrastructure deficits to transcriptional dysregulation in the medial prefrontal cortex of Wistar rats reared in isolation. Isolation reared animals developed sensorimotor deficits at postnatal day 60 which persisted into adulthood. Analysis of gene expression prior to the emergence of the sensorimotor deficits revealed a significant disruption in transcriptional control, notably of immediate early and interferon-associated genes. At postnatal day 60 many gene transcripts relating particularly to GABA transmission and synapse structure, for example Gabra4, Nsf, Syn2 and Dlgh1, transiently increased expression. A subsequent decrease in genes such as Gria2 and Dlgh2 at postnatal day 80 suggested deficits in glutamatergic transmission and synapse integrity, respectively. Microdialysis studies revealed decreased extracellular glutamate suggesting a state of hypofrontality while ultrastructural analysis showed total and perforated synapse complement in layer III to be significantly reduced in the prefrontal cortex of postnatal day 80 isolated animals. These studies provide a molecular framework to understand the developmental emergence of the structural and behavioural characteristics that may in part define psychiatric illness.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

Ciaran M Regan, David von Schack, Robert H Ring, William T O'Connor, Karen L Marquis, Menelas N Pangalos, Desmond G Higgins, Sean K Mulvany, Zoe A Hughes, Caitlin M Wantuch and 18 others

Experts in our system

1
Desmond G Higgins
University College Dublin
Total Publications: 76