Glutathione Deficit Affects the Integrity and Function of the Fimbria/Fornix and Anterior Commissure in Mice: Relevance for Schizophrenia

Abstract Background: Structural anomalies of white matter are found in various brain regions of patients with schizophrenia and bipolar and other psychiatric disorders, but the causes at the cellular and molecular levels remain unclear. Oxidative stress and redox dysregulation have been proposed to play a role in the pathophysiology of several psychiatric conditions, but their anatomical and functional consequences are poorly understood. The aim of this study was to investigate white matter throughout the brain in a preclinical model of redox dysregulation. Methods: In a mouse model with impaired glutathione synthesis (Gclm KO), a state-of-the-art multimodal magnetic resonance protocol at high field (14.1 T) was used to assess longitudinally the white matter structure, prefrontal neurochemical profile, and ventricular volume. Electrophysiological recordings in the abnormal white matter tracts identified by diffusion tensor imaging were performed to characterize the functional consequences of fractional anisotropy alterations. Results: Structural alterations observed at peri-pubertal age and adulthood in Gclm KO mice were restricted to the anterior commissure and fornix-fimbria. Reduced fractional anisotropy in the anterior commissure (-7.5%±1.9, P<.01) and fornix-fimbria (-4.5%±1.3, P<.05) were accompanied by reduced conduction velocity in fast-conducting fibers of the posterior limb of the anterior commissure (-14.3%±5.1, P<.05) and slow-conducting fibers of the fornix-fimbria (-8.6%±2.6, P<.05). Ventricular enlargement was found at peri-puberty (+25%±8 P<.05) but not in adult Gclm KO mice. Conclusions: Glutathione deficit in Gclm KO mice affects ventricular size and the integrity of the fornix-fimbria and anterior commissure. This suggests that redox dysregulation could contribute during neurodevelopment to the impaired white matter and ventricle enlargement observed in schizophrenia and other psychiatric disorders

Growth and Production of Litter-Associated Bacteria

Bacterial secondary production (BSP) can be a significant fraction of total microbial production associated with decomposing litter in aquatic environments. Quantifying production rates is hence important for addressing many ecological questions. This chapter describes a method for estimating rates of bacterial production and growth rates by measuring the incorporation of [3H]leucine into bacterial protein. Decomposing plant litter is incubated with [3H]leucine for a given time, typically 30 min. Leucine incorporation is stopped by adding trichloroacetic acid and the resulting precipitated protein is extracted, successively washed, and collected on a membrane filter. The partially purified protein adhering to the filter and residual litter are combined, and the protein is dissolved in hot alkaline solution and radioassayed. Bacterial production is calculated as the amount of bacterial biomass produced per gram of plant litter dry mass, ash-free dry mass or carbon per unit time, or per stream, marsh or soil surface area if the amount of litter per square metre is known. In conjunction with estimates of bacterial biomass, BSP also allows calculating bacterial growth rate as another key variable describing bacterial population dynamics on decomposing litter