Schizophrenia Research Forum - A Catalyst for Creative Thinking


Vuillermot S, Weber L, Feldon J, Meyer U. A longitudinal examination of the neurodevelopmental impact of prenatal immune activation in mice reveals primary defects in dopaminergic development relevant to schizophrenia. J Neurosci. 2010 Jan 27 ; 30(4):1270-87. Pubmed Abstract

Comments on News and Primary Papers


Primary Papers: A longitudinal examination of the neurodevelopmental impact of prenatal immune activation in mice reveals primary defects in dopaminergic development relevant to schizophrenia.

Comment by:  Mikhail Pletnikov
Submitted 1 March 2010
Posted 1 March 2010

Vuillermot et al. have published a new study that evaluates the effects of early prenatal immune stimulation with Poly I:C on development of the dopaminergic system and dopamine-related behaviors in juvenile and adult mice. They found that prenatal immune activation at early/middle gestation in mice produced age-dependent dopamine abnormalities. New important findings are the effects of immune activation on the fetal dopamine system, suggesting that adverse environmental factors can affect prenatal development of the dopamine system. This report advances our understanding of the potential targets and mechanisms whereby immune stimulation contributes to adult psychopathology. The report is in good agreement with prior studies of dopamine alterations during postnatal development and adulthood in rats and mice (Zuckerman, 2003; Romero, 2008; Winter et al., 2008).

Another interesting result of the study is that, even though the effects of Poly I:C seem relatively moderate, they were able to impact on dopamine-related brain functions and behaviors. These data are in line with the notion that even subtle changes during early neurodevelopment may lead to long-lasting consequences in adulthood.

It has been suggested that maternal infection during pregnancy may affect brain maturation to contribute to the pathogenesis of mental illnesses (Brown and Derkits, 2010). Given the complexity of etiology and pathogenic mechanisms of major mental diseases, a promising direction for future research with this and similar approaches can include combinations of prenatal and early postnatal immune challenges in mice and rats with genetically manipulated neurodevelopmental and/or immunological genes to explore the underlying mechanisms of gene-environment and neuroimmune interactions in psychiatric illnesses (Ayhan, 2010).

References:

Zuckerman L, Rehavi M, Nachman R, Weiner I. Immune activation during pregnancy in rats leads to a postpubertal emergence of disrupted latent inhibition, dopaminergic hyperfunction, and altered limbic morphology in the offspring: a novel neurodevelopmental model of schizophrenia. Neuropsychopharmacology. 2003;28:177889. Abstract

Romero E, Guaza C, Castellano B, Borrell J. Ontogeny of sensorimotor gating and immune impairment induced by prenatal immune challenge in rats: implications for the etiopathology of schizophrenia. Mol Psychiatry. 2008 Apr 15. Abstract

Winter C, Reutiman TJ, Folsom TD, Sohr R, Wolf RJ, Juckel G, Fatemi SH. Dopamine and serotonin levels following prenatal viral infection in mouse--implications for psychiatric disorders such as schizophrenia and autism. Eur Neuropsychopharmacol. 2008 Oct;18(10):712-6. Abstract

Brown AS, Derkits EJ. Prenatal infection and schizophrenia: a review of epidemiologic and translational studies. Am J Psychiatry. 2010 Feb 1. Abstract

Ayhan Y, Sawa A, Ross CA, Pletnikov MV. Animal models of gene-environment interactions in schizophrenia. Behav Brain Res. 2009 Dec 7;204(2):274-81. Abstract

View all comments by Mikhail Pletnikov