Emotion-induced retrograde amnesia varies as a function of noradrenergic-glucocorticoid activity

RATIONALE: Privileged episodic encoding of an aversive event often comes at a cost of neutral events flanking the aversive event, resulting in decreased episodic memory for these neutral events. This peri-emotional amnesia is amygdala-dependent and varies as a function of norepinephrine activity. However, less is known about the amnesiogenic potential of cortisol. OBJECTIVE: We used a strategy of pharmacologically potentiating cortisol and norepinephrine activity to probe the putative neurochemical substrates of peri-emotional amnesia. MATERIALS AND METHODS: Fifty-four healthy individuals participated in a randomized double-blind placebo-controlled study. Within the experimental context of an established peri-emotional amnesia paradigm, we tested the amnesiogenic potential of hydrocortisone (30 mg p.o.) in the presence or absence of the norepinephrine-reuptake inhibitor reboxetine (4 mg p.o.). RESULTS: Under dual challenge conditions, we observed a linear dose-response relationship in the magnitude and duration of emotion-induced retrograde amnesia. CONCLUSIONS: Our results are consistent with a phenotypic expression of retrograde amnesia varying as a function of norepinephrine and cortisol coactivation during episodic encoding of aversive events. Our study demonstrates that the adverse cognitive and behavioral sequelae of aversive emotion can be experimentally modeled by a pharmacological manipulation of its putative neurochemical substrates

Fungal iron availability during deep seated candidiasis is defined by a complex interplay involving systemic and local events

Peer reviewedPublisher PD

Bio-imaging of metals in a mouse model of Alzheimer's disease by laser ablation inductively coupled plasma mass spectrometry

Quantitative mass spectrometry imaging (MSI) of metals in biological tissue sections by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) using matrix-matched laboratory standards has been established previously. Here an improved calibration strategy is proposed, correcting for variable section thickness by normalization of sample and standard ion intensities to the average 13C+ ion signal of all ablated sample and standard material, respectively. Altered metal metabolism is known in Alzheimer's disease of which amyloid precursor protein (APP) transgenic mice are a popular model. Quantitative distribution analysis of Fe, Zn, Cu and Mn in horizontal brain sections of 45 week old Tg2576 transgenic mice showed a 22% decrease of Cu and changes of Fe, Zn and Mn of −1%, −7% and −17%. Local evaluation across a set of anatomically defined regions of interest showed an increased circum-ventricular to parenchyma ratio of Cu pointing to a higher Cu efflux and a heterogeneous pattern of Fe changes pointing to clearance of Fe at the sites of early pathology. Congruencies to synchrotron X-ray fluorescence data on distinct types of APP mice are discussed. MSI by LA-ICP-MS thus proved as a valuable and versatile tool for studying the cerebral metallo-architecture and the validation of animal models

Trace metal imaging with high spatial resolution: Applications in biomedicine

New generations of analytical techniques for imaging of metals are pushing hitherto boundaries of spatial resolution and quantitative analysis in biology. Because of this, the application of these imaging techniques described herein to the study of the organization and dynamics of metal cations and metal-containing biomolecules in biological cell and tissue is becoming an important issue in biomedical research. In the current review, three common metal imaging techniques in biomedical research are introduced, including synchrotron X-ray fluorescence (SXRF) microscopy, secondary ion mass spectrometry (SIMS), and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). These are exemplified by a demonstration of the dopamine-Fe complexes, by assessment of boron distribution in a boron neutron capture therapy cell model, by mapping Cu and Zn in human brain cancer and a rat brain tumor model, and by the analysis of metal topography within neuromelanin. These studies have provided solid evidence that demonstrates that the sensitivity, spatial resolution, specificity, and quantification ability of metal imaging techniques is suitable and highly desirable for biomedical research. Moreover, these novel studies on the nanometre scale (e.g., of individual single cells or cell organelles) will lead to a better understanding of metal processes in cells and tissues

Element imaging in formalin fixed slices of human mesencephalon

The scarcity of native frozen pathological and healthy human brain tissue is actually one of the major bottlenecks concerning the investigation of neuropsychiatric diseases. Therefore it is of some interest to make formalin fixed tissue specimens accessible to mass spectrometric analytical techniques. Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and matrix matched standards were employed to generate quantitative element maps of human mesencephalon slices that had been stored in formalin for more than 10 years of a single subject. The characteristic distribution patterns of Cu and Zn were completely blunted but Fe was clearly enriched in the substantia nigra (SN) - especially in the matrix of the pars compacta - and the nucleus ruber (NR) at concentrations of 179 mu g g(-1), 231 mu g g(-1) and 187 mu g g(-1) (wet weight), respectively, very similar to literature values obtained from homogenates of fresh tissue. Mn and Ca congruently reflected the distribution of melanised SN neurons. Interestingly, the distribution of Pb was congruent to that of Fe reaching 0.8 mu g g(-1) in the SN, 1.1 mu g g(-1) in the matrix and 0.9 mu g g(-1) in the NR. Images of C and P reflected the gray matter-white matter partition of the tissue. These results suggest that a meaningful quantitative assessment of Fe, Mn and Pb is possible in tissue samples which have previously been stored in buffered formalin solution. (C) 2011 Elsevier B.V. All rights reserved

Mass spectrometry imaging (MSI) of metals in mouse spinal cord by laser ablation ICP-MS

Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been developed as a powerful MS imaging (MSI) tool for the direct investigation of element distributions in biological tissues. Here, this technique was adapted for the analysis of native mouse spinal cord cryosections of 3.1 mm × 1.7 mm by implementing a new conventional ablation system (NWR-213) and improving the spatial resolution from 120 μm to 65 μm in routine mode. Element images of the spinal cord are provided for the first time and the metalloarchitecture was established using a multimodal atlas approach. Furthermore, the spatial distribution of Rb was mapped for the first time in biological tissue. Metal concentrations were quantified using matrix-matched laboratory standards and normalization of the respective ion intensities to the average (13)C ion intensity of standards and samples as a surrogate of slice thickness. The "butterfly" shape of the central spinal grey matter was visualized in positive contrast by the distributions of Fe, Mn, Cu and Zn and in negative contrast by C and P. Mg, Na, K, S and Rb showed a more homogenous distribution. The concentrations averaged throughout grey matter and white matter were 8 and 4 μg g(-1) of Fe, 3 and 2 μg g(-1) of Cu, 8 and 5 μg g(-1) of Zn, 0.4 and 0.2 μg g(-1) of Mn. The carbon concentration in white matter exceeded that of grey matter by a factor of 1.44. Zn and Cu at 9 and 4 μg g(-1), respectively, were particularly enriched in the laminae I and II, in line with the high synaptic and cellular density there. Surprisingly Zn but not Cu was enriched in the central channel. Rb occurred at 0.3 μg g(-1) with a distribution pattern congruent to that of K. The coefficients of variation were 6%, 5%, 8% and 10% for Fe, Cu, Zn and Mn, respectively, throughout three different animals measured on different days. These MSI analyses of healthy wild type spinal cords demonstrate the suitability of the established techniques for investigating diseased or transgenic states in future imaging studies