Effects of Two Commonly Found Strains of Influenza A Virus on Developing Dopaminergic Neurons, in Relation to the Pathophysiology of Schizophrenia

Abstract

Influenza virus (InfV) infection during pregnancy is a known risk factor for neurodevelopment abnormalities in the offspring, including the risk of schizophrenia, and has been shown to result in an abnormal behavioral phenotype in mice. However, previous reports have concentrated on neuroadapted influenza strains, whereas increased schizophrenia risk is associated with common respiratory InfV. In addition, no specific mechanism has been proposed for the actions of maternal infection on the developing brain that could account for schizophrenia risk. We identified two common isolates from the community with antigenic configurations H3N2 and H1N1 and compared their effects on developing brain with a mouse modified-strain A/WSN/33 specifically on the developing of dopaminergic neurons. We found that H1N1 InfV have high affinity for dopaminergic neurons in vitro, leading to nuclear factor kappa B activation and apoptosis. Furthermore, prenatal infection of mothers with the same strains results in loss of dopaminergic neurons in the offspring, and in an abnormal behavioral phenotype. We propose that the well-known contribution of InfV to risk of schizophrenia during development may involve a similar specific mechanism and discuss evidence from the literature in relation to this hypothesis.

Sex and laterality differences in parkinsonian impairment and transcranial ultrasound in never-treated schizophrenics and their first degree relatives in an Andean population

“…Interestingly, obstetric complications associated with parkinsonism in schizophrenia (Peralta and Cuesta, 2011) may be influenced by sex (Lane et al, 1996). Midbrain dopamine neurons are known to play a role in the development of sexual dimorphism in the brain and have been shown to be particularly susceptible to environmental insults (de Erausquin et al, 2003;Dorsey et al, 2006;Landreau et al, 2012). Specifically, dopaminergic neurons in the mesocortical projections are more numerous (Kritzer and Creutz, 2008), and have been shown to be more resistant to cytotoxic insults in females than in males (Bourque et al, 2009).…”

Schizophrenia and Influenza at the Centenary of the 1918-1919 Spanish Influenza Pandemic: Mechanisms of Psychosis Risk

“…MIA may lead straightforwardly to damage to the foetal brain during the early stages of neurodevelopment (82), but may also provide entry into a deviant trajectory of neural development which predisposes offspring to behavioral deficits depending on the intensity of the infection and when in gestation it occurs [early vs. late-and potentially as late as the lactation stage (88)]. MIA-associated abnormalities have been described, sometimes inconsistently, for multiple brain cell types, all of which are implicated across psychiatric disorders from postmortem data and genetic studies to a greater or lesser extent: Schwann cells (89), astrocytes and microglia (90,91), hippocampal GABAergic cells (92,93), dopaminergic neurons (94), and parvalbumin interneurons (95,96).…”

Moderate and severe perinatal asphyxia induces differential effects on cocaine sensitization in adult rats

“…As it was mentioned in the introduction, PA is a known risk factor to develop attention deficit hyperactivity disorder (ADHD) and schizophrenia (Cannon et al, 2002;Lewis and Murray, 1987;van Handel et al, 2007). This could be due to the fact that PA produces a dopaminergic system dysregulation (Boksa and El-Khodor, 2003), which in turn has been proposed as one of the neurobiological abnormalities underlying both psychiatric disorders (Del Campo et al, 2011;Howes and Kapur, 2009;Landreau et al, 2012). Moreover, ADHD and schizophrenia are very frequently comorbid with substance abuse (Arias et al, 2008;Gudjonsson et al, 2012;Ringen et al, 2008) and all drugs of abuse cause common effects on the mesolimbic dopamine pathway (Nestler, 2005b).…”