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

  title={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},
  author={Lee Zuckerman and Moshe Rehavi and Rachel Nachman and Ina Weiner},
Prenatal exposure to infection is associated with increased liability to schizophrenia, and it is believed that such an association is mediated by the maternal immune response, in particular, the proinflammatory cytokines released by the maternal immune system, which may disrupt fetal brain development. Impaired capacity to ignore irrelevant stimuli is one of the central deficits in schizophrenia, and is manifested, among others, in loss of latent inhibition (LI), a phenomenon whereby repeated… 
Late Prenatal Immune Activation in Mice Leads to Behavioral and Neurochemical Abnormalities Relevant to the Negative Symptoms of Schizophrenia
The constellation of behavioral and neurochemical abnormalities emerging after late prenatal Poly-I:C exposure in mice leads us to conclude that this immune-based experimental model provides a powerful neurodevelopmental animal model especially for (but not limited to) the negative symptoms of schizophrenia.
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These results confirm that maternal immune activation severely impairs dopamine system and that the polyriboinosinic-polyribocytidilic acid model can be considered a proper animal model of a psychiatric condition that fulfills a multidimensional set of validity criteria predictive of a human pathology.
Dysregulation of kisspeptin and neurogenesis at adolescence link inborn immune deficits to the late onset of abnormal sensorimotor gating in congenital psychological disorders
The results suggest that a form of congenital immune deficiency may be a key factor that determines manifestation of developmental neuropsychological disorders with onset only at early adulthood.
Maternal immune activation produces neonatal excitability defects in offspring hippocampal neurons from pregnant rats treated with poly I:C
C cultured pyramidal-like hippocampal neurons prepared from neonatal (P0-P2) offspring of pregnant rats injected with poly I:C exhibited significantly lower intrinsic excitability and stronger spike frequency adaptation, compared to saline, suggesting that MIA-induced alterations could occur earlier at neonatal/early postnatal stages.


Postpubertal Emergence of Hyperresponsiveness to Stress and to Amphetamine after Neonatal Excitotoxic Hippocampal Damage: A Potential Animal Model of Schizophrenia
It is demonstrated that in rats with neonatally induced excitotoxic VH lesions, behavioral indices consistent with increased mesolimbic DA responsivity to stressful and to pharmacologic stimuli emerge only in early adulthood.
Immunopathology and Viral Reactivation: A General Theory of Schizophrenia
A theory is proposed that explains a broad range of clinical manifestations in schizophrenia by postulating defective alpha-interferon (alFN) regulation resulting in excessive effect is postulated to cause schizophrenia.
Gender-dependent differences in latent inhibition following prenatal stress and corticosterone administration
Schizophrenia and viral infection during neurodevelopment: a focus on mechanisms
  • B. Pearce
  • Psychology, Medicine
    Molecular Psychiatry
  • 2001
Consideration is given to a new hypothesis that some cases of schizophrenia could be instigated by a viral infection that disrupts developing inhibitory circuits, consequently unleashing glutamatergic neurotransmission leading to selective excitotoxicity, and a degenerative disease course.
Defective corticogenesis and reduction in Reelin immunoreactivity in cortex and hippocampus of prenatally infected neonatal mice
Prenatally-infected murine brains from postnatal day 0 showed significant reductions in reelin-positive cell counts in layer I of neocortex and other cortical and hippocampal layers when compared to controls and prenatal viral infection caused decreases in neocortical and hippocampusal thickness.
Infection and autoimmunity as etiologic factors in schizophrenia: a review and reappraisal.
  • D. Kirch
  • Medicine, Psychology
    Schizophrenia bulletin
  • 1993
No research evidence to date irrefutably indicates an infectious or autoimmune etiologic process in schizophrenia, and it is probably unreasonable, however, to view schizophrenia as having a single cause.
Schizophrenia: genetics and the maternal immune response to viral infection.
It is proposed that prenatal exposure to influenza induces maternal antibodies which then cross-react with proteins in the developing foetal brain, becomingfoetal autoantibodies, the biological substrate for a proportion of adult schizophrenia.