Cognitive and social behaviour deficits at adulthood in female rat offspring of Poly I:C treated rat dams, a developmental model for schizophrenia
Ben Grayson, Victoria Fasolino, Michelle Edye, Joanna Oladipo, Nagi Idris, Michael Harte, Joanna C Neill
Manchester Pharmacy School, University of Manchester, Manchester, M13 9PT, UK
Introduction
Methods
Results
.
Conclusions
Social interaction
Sniffing
Avoidance Object exploration
Following
Novel object recognition
Based on the innate preference for novelty
Ve
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: C)
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A d o l e s c e n t f e m a l e : R e t e n t i o n
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A d u l t m a l e : R e t e n t i o n
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**
PND 41
PND 67
Veh
icle
Poly(
I:C
)0
5
10
15
Tim
e (s
)
p=0.056
Following
PND 39
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A v o i d i n g
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PND 66
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F o l l o w i n g
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A v o i d i n g
S D C D R e v 1 I D S R e v 2 E D S R e v 3
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P h a s e
Tr
ia
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to
cr
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* * *
P o l y I : C
V e h i c l e
~ ~ ~
~ ~ ~
Cohort: 1
PND 100
Cohort: 1
3h post poly I:C injection
Cohort: 2
3h post poly I:C injection
• Significant increase in IL-6
• Decrease in bodyweight
• Significant increase in IL-6
• Significant reduction in
body weight, placenta
weight & pup length.
• PolyI:C produces a trend toward a reduction
social behaviours in adolescent (PND 39) female
offspring.
• Enhanced reduction in social behaviours
following treatment with PolyI:C in adult (PND
66) in female offspring.
• PolyI:C treatment has no effect on novel object
recognition in adolescent (PND 41) male and
female offspring.
• PolyI:C treatment impairs novel object
recognition in adult (PND 67) female offspring.
• PolyI:C treatment significantly increases trials to
criterion in the EDS phase of the ASST in adult
(PND 100) female offspring.
PD100
set shift
Females
only
Reasoning and problem solving
Rat analogue of the ID/ED test in
CANTAB. Rewarded paradigm – 7
discriminations
Attentional Set-shifting:
ASST
Poly I:C (10 mg/kg, i.p.) administered to
Pregnant rats on GD 15.
Social Interaction Test Cohort: 1
Novel Object Recognition Test Cohort: 1
• Maternal Immune activation (mIA) by the administration of the viral-mimetic polyriboinosinic-polyribocytidylic acid (polyI:C) is a key model for
neurodevelopmental disorders (NDDs) such as schizophrenia (Knuesel et al, 2014).
• We have established that the most robust systemic inflammatory response to polyI:C is produced by an acute dose of 10 mg/kg, i.p. in rats of the Wistar strain
Aim
To investigate the physiological and behavioural consequences of mIA in male and female offspring at specific developmental time points.
Attentional set-shifting Task (ASST) Cohort: 1
We have developed a robust model of mIA in Wistar rats and used this to identify the longitudinal development of behavioural changes.
• PolyI:C (10 mg/kg,i.p.) at GD15 induced a variable but reproducible immune response (IL-6) in Wistar rats (cohort 1 & 2).
• At GD21 there were significant reductions in both male and female pup body weight, pup length and placenta weight (cohort 2). Placental weight reduction is a consistent finding.
• Significant behavioural deficits were not detectable during adolescence.
• Social behaviour deficits seemed to be emerging and a cognitive phenotype was clearly observed in adult females, particularly in the prefrontal cortical mediated ASST at the later
stage of PND 100.
Neurobiological mechanisms for the behavioural effects are currently being investigated.
Cohort: 2
GD21
