Maternal immune activation alters behavior in adult offspring, with subtle changes in the cortical transcriptome and epigenome.

Maternal immune activation during prenatal development, including treatment with the viral RNA mimic, polyriboinosinic-polyribocytidilic acid (poly IC), serves as a widely used animal model to induce behavioral deficits reminiscent of schizophrenia and related disease. Here, we report that massive cytokine activation after a single dose of poly IC in the prenatal period is associated with lasting working memory deficits in adult offspring. To explore whether dysregulated gene expression in cerebral cortex, contributes to cognitive dysfunction, we profiled the cortical transcriptome, and in addition, mapped the genome-wide distribution of trimethylated histone H3-lysine 4 (H3K4me3), an epigenetic mark sharply regulated at the 5' end of transcriptional units.

White matter neuron alterations in schizophrenia and related disorders.

Increased density and altered spatial distribution of subcortical white matter neurons (WMNs) represents one of the more well replicated cellular alterations found in schizophrenia and related disease. In many of the affected cases, the underlying genetic risk architecture for these WMN abnormalities remains unknown. Increased density of neurons immunoreactive for Microtubule-Associated Protein 2 (MAP2) and Neuronal Nuclear Antigen (NeuN) have been reported by independent studies, though there are negative reports as well; additionally, group differences in some of the studies appear to be driven by a small subset of cases.

Cingulate white matter neurons in schizophrenia and bipolar disorder.

Background: Increased neuronal density in prefrontal, parietal, and temporal white matter of schizophrenia subjects is thought to reflect disordered neurodevelopment; however, it is not known if this cellular alteration affects the cingulate cortex and whether similar changes exist in bipolar disorder.

Method: Eighty-two postmortem specimens (bipolar 15, schizophrenia 22, control 45) were included in this clinical study. Densities for two neuronal markers, neuron-specific nuclear protein (NeuN) and neuregulin 1 alpha (NRG), were determined in white matter up to 2.

Amygdalar GABAergic-rich neural grafts attenuate anxiety-like behavior in rats.

Transplantation experiments have shown that neurologic deficits may be reversed by engrafting fresh tissue or engineered cells within dysfunctional neural circuitry. In experimental and clinical settings, this approach has provided insights into the pathology and treatment of neurologic diseases, primarily movement disorders. The present experiments were designed to investigate whether a similar strategy is feasible as a method to investigate, and perhaps repair, circuitry integral to emotional disorders.

DNA methylation changes in schizophrenia and bipolar disorder.

The etiology of the major psychotic disorders, including schizophrenia and bipolar disorder, remains poorly understood. Postmortem brain studies have revealed altered expression of multiple mRNAs, affecting neurotransmission, metabolism, myelination and other functions. Epigenetic mechanisms could be involved, because for a limited number of genes, the alterations of mRNA levels have been linked to inverse DNA methylation changes at sites of the corresponding promoters.

DNA methylation in the human cerebral cortex is dynamically regulated throughout the life span and involves differentiated neurons.

The role of DNA cytosine methylation, an epigenetic regulator of chromatin structure and function, during normal and pathological brain development and aging remains unclear. Here, we examined by MethyLight PCR the DNA methylation status at 50 loci, encompassing primarily 5' CpG islands of genes related to CNS growth and development, in temporal neocortex of 125 subjects ranging in age from 17 weeks of gestation to 104 years old. Two psychiatric disease cohorts--defined by chronic neurodegeneration (Alzheimer's) or lack thereof (schizophrenia)--were included.

Diminished serotonergic innervation of adult medial prefrontal cortex after 6-OHDA lesions in the newborn rat.

The development of the serotonergic (5HT) and dopaminergic (DA) systems may contribute to the onset of psychotic disorders during late adolescence and early adulthood. Previous studies in our laboratory have suggested that these systems may compete for functional territory on neurons during development, as lesions of the serotonergic system at postnatal day 5 (P5) result in an increase in the density of dopaminergic fibers in rat medial prefrontal cortex (mPFC). In the present study, the dopaminergic system of P5 rats was lesioned with intracisternal injections of 6-hydroxydopamine (6-OHDA).

Coagulation abnormalities in patients with single-ventricle physiology precede the Fontan procedure.

Objective: Thromboembolic events in patients who have undergone the Fontan operation have been reported to be as high as 20% to 33%. A hypercoagulable state with deficiencies in proteins C and S has been implicated. Using age-matched control subjects, we evaluated whether an altered coagulation state is present earlier in the course of staged single-ventricle repair.