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Gamma-aminobutyric acid (GABA)-ergic disturbances are hallmark features of schizophrenia and other neuropsychiatric disorders and encompass multiple interneuronal cell types. Using bacterial artificial chromosome-driven, miRNA silencing technology we generated transgenic mouse lines that suppress glutamic acid decarboxylase 1 (GAD1) in either cholecystokinin (CCK)- or neuropeptide Y (NPY)-expressing interneurons. In situ lipidomic and proteomic analyses on brain tissue sections revealed distinct, brain region-specific profiles in each transgenic line. Behavioral analyses revealed that suppression of GAD1 in CCK+ interneurons resulted in locomotor and olfactory sensory changes, whereas suppression in NPY+ interneurons affected anxiety-related behaviors and social interaction. Both transgenic mouse lines had altered sensitivity to amphetamine albeit in opposite directions. Together, these data argue that reduced GAD1 expression leads to altered molecular and behavioral profiles in a cell type-dependent manner, and that these subpopulations of interneurons are strong and opposing modulators of dopamine system function. Furthermore, our findings also support the hypothesis that neuronal networks are differentially controlled by diverse inhibitory subnetworks. [ABSTRACT FROM AUTHOR]

A method involving the use of an energy-dispersive X-ray fluorescence spectrometer was developed for assaying total platinum concentrations in body fluids of patients treated with the antitumor drug cis-dichlorodiammineplatinum(II). Sample preparation by this procedure is simple, consisting in adding an internal standard (Zr) to 1 ml of biological fluid or tissue homogenate, pipetting 20 microliter of the sample onto a Mylar sample holder, and drying. This produces a thin-film sample, which effectively eliminates absorption enhancement effects due to other elements in the specimen. Standard addition studies were found to be linear in the concentration range of interest (0.1-10.0 micrograms/ml), with correlation coefficients exceeding 0.99. Minimum detection limits range from 0.10 to 0.25 micrograms Pt per ml, depending on the body fluid, which is adequate for routine patient monitoring after normal chemotherapeutic doses of cis-dichlorodiammineplatinum(II). In preliminary studies with mammalian liver, standard addition experiments were found to be linear and the minimum detection limit was found to be 1.4 micrograms/g dry weight. [ABSTRACT FROM AUTHOR]

An image is presented depicting the Hippocampal CA3 region triple-immunostaining in transgenic mice.