Dopamine and serotonin levels following prenatal viral infection in mouse--implications for psychiatric disorders such as schizophrenia and autism.

Prenatal viral infection has been associated with neurodevelopmental disorders such as schizophrenia and autism. It has previously been demonstrated that viral infection causes deleterious effects on brain structure and function in mouse offspring following late first trimester (E9) and middle-late second trimester (E18) administration of influenza virus. Neurochemical analysis following infection on E18 using this model has revealed significantly altered levels of serotonin, 5-hydroxyindoleacetic acid, and taurine, but not dopamine. In order to monitor these different patterns of monoamine expression in exposed offspring in more detail and to see if there are changes in the dopamine system at another time point, pregnant C57BL6J mice were infected with a sublethal dose of human influenza virus or sham-infected using vehicle solution on E16. Male offspring of the infected mice were collected at P0, P14, and P56, their brains removed and cerebellum dissected and flash frozen. Dopamine and serotonin levels were then measured using HPLC-ED technique. When compared to controls, there was a significant decrease in serotonin levels in the cerebella of offspring of virally exposed mice at P14. No differences in levels of dopamine were observed in exposed and control mice, although there was a significant decrease in dopamine at P14 and P56 when compared to P0. The present study shows that the serotonergic system is disrupted following prenatal viral infection, potentially modelling disruptions that occur in patients with schizophrenia and autism.

Microglial activation in a neuroinflammational animal model of schizophrenia--a pilot study.

Inflammatory and immunological processes interfering with brain development are discussed as one cause of schizophrenia. Various signs of overactivation of the immune system were often found in this disease. Based on post-mortem analysis showing an increased number of activated microglial cells in patients with schizophrenia, it can be hypothesized that these cells contribute to disease pathogenesis and may actively be involved in gray matter loss observed in such patients. In the present study, PolyI:C incubation of pregnant dams was used as animal model of schizophrenia, and the number and shape of microglia were assessed in the offspring in the early phase of this disease, using fluorescence immunostaining (Iba1). Descendants of mice exposed to PolyI:C at embryonic day 9 showed higher number of microglial cells in the hippocampus and striatum, but not in the frontal cortex at postnatal day 30, which is similarly to adolescence in man, as compared to those exposed to saline. Furthermore, offspring microglia from PolyI:C treated mothers were morphologically characterized by a reduced arborization indicative for a status of higher activation compared to the offspring microglia from vehicle treated mice. This study supports the hypothesis that maternal infection during embryogenesis contributes to microglial activation in the offspring, which may therefore represent a contributing factor to the pathogenesis of schizophrenia and underlines the need for new pharmacological treatment options in this regard.

Loudness dependence of auditory evoked potentials as indicator of central serotonergic neurotransmission: simultaneous electrophysiological recordings and in vivo microdialysis in the rat primary auditory cortex.

Serotonin released in synapsis is one of the key neurotransmitters in psychiatry and psychopharmacology. The loudness dependence of auditory evoked potentials (LDAEP) has been proposed as a marker for central serotonergic neurotransmission. Several findings in animals and humans support this hypothesis. However, the in vivo measurement of cortical extracellular serotonin levels has never been performed simultaneously with the recording of auditory evoked potentials. The interrelationship between low cortical serotonergic activity and strong LDAEP is yet to be proven. The auditory evoked potentials were recorded in the epidura above the primary auditory cortex of male Wistar rats whereas extracellular serotonin levels in the primary auditory cortex were measured by in vivo microdialysis before and after i.p. application of the selective serotonin reuptake inhibitor citalopram. At baseline, the correlation of coefficients between the LDAEP, especially of the N1 component, and extracellular serotonin levels in the primary auditory cortex was negative. The increase of serotonin levels after citalopram application was significantly related to a decrease of LDAEP of the N1 component (r=-0.86, p=0.003). These data support the view that the LDAEP is closely modulated by cortical serotonergic activity. Thus, the LDAEP might serve as an inversely related marker of synaptically released serotonin in the CNS.