Behaviour and hippocampus-specific changes in spiny mouse neonates after treatment of the mother with the viral-mimetic Poly I:C at mid-pregnancy

Udani Ratnayake, Tracey Anne Quinn, Margie Esmeralda Zakhem, Hayley Dickinson, David William Walker

Research output: Contribution to journalArticleResearchpeer-review

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Abstract

Epidemiological studies have suggested a link between prenatal exposure to bacterial or viral infections and subsequent development of mental disorders such as schizophrenia and autism. Animal models to study the prenatal origin of such outcomes of pregnancy have largely used conventional rodents which are immature at birth compared to the human neonate, and doses of the infective agent (i.e., lipopolysaccharide, Poly I:C) have been large enough to cause sickness behaviour in the mother. In this study we have used the precocial spiny mouse (Acomys cahirinus) whose offspring have completed organogenesis at birth, and a single subcutaneous injection of a low (0.5mg/kg) dose of polyriboinosinic-polyribocytidilic acid (Poly I:C) at mid gestation (20days, term is 39days). The treatment had no effect on maternal, fetal or neonatal survival, or postnatal growth of the offspring. However, offspring showed significant impairments in non-spatial memory and learning tasks, and motor activity. Brain histology examined at 1 and 100days of age revealed significant decreases in reelin, increased GFAP expression, and increased numbers of activated microglia, specifically in the hippocampus. This study provides evidence that a prenatal subclinical infection can have profound effects on brain development that are long-lasting.
Original languageEnglish
Pages (from-to)1288 - 1299
Number of pages12
JournalBrain, Behavior, and Immunity
Volume26
Issue number8
DOIs
Publication statusPublished - 2012

Cite this

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title = "Behaviour and hippocampus-specific changes in spiny mouse neonates after treatment of the mother with the viral-mimetic Poly I:C at mid-pregnancy",
abstract = "Epidemiological studies have suggested a link between prenatal exposure to bacterial or viral infections and subsequent development of mental disorders such as schizophrenia and autism. Animal models to study the prenatal origin of such outcomes of pregnancy have largely used conventional rodents which are immature at birth compared to the human neonate, and doses of the infective agent (i.e., lipopolysaccharide, Poly I:C) have been large enough to cause sickness behaviour in the mother. In this study we have used the precocial spiny mouse (Acomys cahirinus) whose offspring have completed organogenesis at birth, and a single subcutaneous injection of a low (0.5mg/kg) dose of polyriboinosinic-polyribocytidilic acid (Poly I:C) at mid gestation (20days, term is 39days). The treatment had no effect on maternal, fetal or neonatal survival, or postnatal growth of the offspring. However, offspring showed significant impairments in non-spatial memory and learning tasks, and motor activity. Brain histology examined at 1 and 100days of age revealed significant decreases in reelin, increased GFAP expression, and increased numbers of activated microglia, specifically in the hippocampus. This study provides evidence that a prenatal subclinical infection can have profound effects on brain development that are long-lasting.",
author = "Udani Ratnayake and Quinn, {Tracey Anne} and Zakhem, {Margie Esmeralda} and Hayley Dickinson and Walker, {David William}",
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Behaviour and hippocampus-specific changes in spiny mouse neonates after treatment of the mother with the viral-mimetic Poly I:C at mid-pregnancy. / Ratnayake, Udani; Quinn, Tracey Anne; Zakhem, Margie Esmeralda; Dickinson, Hayley; Walker, David William.

In: Brain, Behavior, and Immunity, Vol. 26, No. 8, 2012, p. 1288 - 1299.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Quinn, Tracey Anne

AU - Zakhem, Margie Esmeralda

AU - Dickinson, Hayley

AU - Walker, David William

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AB - Epidemiological studies have suggested a link between prenatal exposure to bacterial or viral infections and subsequent development of mental disorders such as schizophrenia and autism. Animal models to study the prenatal origin of such outcomes of pregnancy have largely used conventional rodents which are immature at birth compared to the human neonate, and doses of the infective agent (i.e., lipopolysaccharide, Poly I:C) have been large enough to cause sickness behaviour in the mother. In this study we have used the precocial spiny mouse (Acomys cahirinus) whose offspring have completed organogenesis at birth, and a single subcutaneous injection of a low (0.5mg/kg) dose of polyriboinosinic-polyribocytidilic acid (Poly I:C) at mid gestation (20days, term is 39days). The treatment had no effect on maternal, fetal or neonatal survival, or postnatal growth of the offspring. However, offspring showed significant impairments in non-spatial memory and learning tasks, and motor activity. Brain histology examined at 1 and 100days of age revealed significant decreases in reelin, increased GFAP expression, and increased numbers of activated microglia, specifically in the hippocampus. This study provides evidence that a prenatal subclinical infection can have profound effects on brain development that are long-lasting.

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