Gene expression changes in prefrontal cortex of isolation reared animals: molecular mapping of emergence of schizophrenia-like behaviours
Judith
P.
Ter Horst1*,
Andrew
W.
Cassidy1,
Christine
Li2,
Laura
M.
Connole1,
Niamh
C.
O'Sullivan1,
Jennifer
S.
Loscher1,
Nanette
Rombach1,
Sean
K.
Mulvany1,
Mene
N.
Pangalos3,
Karen
L.
Marquis3,
Rob
H.
Ring3,
David
Von Schack2,
Ciaran
M.
Regan1 and
Keith
J.
Murphy1
-
1
University College Dublin, Applied Neurotherapeutics Research Group, UCD School of Biomolecular and Biomedical Science, Ireland
-
2
Wyeth Research, Biological Technologies, United States
-
3
Wyeth Research, Discovery Neuroscience, United States
Schizophrenia is a devastating disease affecting around 1% of the population worldwide associated with multiple symptoms, namely positive, negative and cognitive deficits. Studies of the aetiology of schizophrenia suggest genetic risk interacts with environmental insults, such as second trimester influenza infection or traumatic childhood events, to impinge on cortical development. Most molecular changes associated with the disorder were identified by post-mortem studies on brain tissue from patients in their forties yet schizophrenia emerges in the mid to early teenage years. Thus, at present, an understanding of the molecular dysregulation that underpins schizophrenia emergence can only come from the study of accurate animal models of the disease. Here, we have employed isolation rearing of male Wistar rats housed singly from weaning (postnatal day (P) 25). We have shown that isolated animals show emergence of abnormalities in sensorimotor gating as measured by prepulse inhibition (PPI) with normal appearance at P30 and P40 but defective behaviour at P60 and P80, in close accord with emergence of similar deficits in schizophrenic patients. In this study, medial prefrontal cortex was dissected from isolated animals and social-housed controls at the postnatal ages, P30, P40, P60 and P80 and isolation rearing-induced gene expression alterations evaluated by Affymetrix microarray analysis. A total of 2,255 transcripts were found to be differentially expressed (1.5-fold change; p<0.01) in isolation reared animals across all ages studied. Of particular interest, a substantial number of genes involved in GABAergic and glutamatergic neurotransmission and synaptic function were dysregulated at P40 and P60 (including Gabra4, Nsf and Syn2). These studies provide insight into the earliest molecular dysregulations that may underpin emergence of schizophrenia-like behavioural deficits in the isolation rearing model.
Supported by SFI and Wyeth Discovery.
Conference:
41st European Brain and Behaviour Society Meeting, Rhodes Island, Greece, 13 Sep - 18 Sep, 2009.
Presentation Type:
Poster Presentation
Topic:
Poster presentations
Citation:
Ter Horst
JP,
Cassidy
AW,
Li
C,
Connole
LM,
O'Sullivan
NC,
Loscher
JS,
Rombach
N,
Mulvany
SK,
Pangalos
MN,
Marquis
KL,
Ring
RH,
Von Schack
D,
Regan
CM and
Murphy
KJ
(1900). Gene expression changes in prefrontal cortex of isolation reared animals: molecular mapping of emergence of schizophrenia-like behaviours.
Conference Abstract:
41st European Brain and Behaviour Society Meeting.
doi: 10.3389/conf.neuro.08.2009.09.173
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Received:
01 Jan 1900;
Published Online:
01 Jan 1900.
*
Correspondence:
Judith P Ter Horst, University College Dublin, Applied Neurotherapeutics Research Group, UCD School of Biomolecular and Biomedical Science, Dublin, Ireland, j.terhorst@lacdr.leidenuniv.nl