Mirjam I Schubert

Publications (3)13.07 Total impact

• Article: Novel cage stress alters remote contextual fear extinction and regional T2 magnetic resonance relaxation times in TASTPM mice overexpressing amyloid.

  Ivan Rattray, Alain Pitiot, James Lowe, Dorothee P Auer, Sarah-Jane Lima, Mirjam I Schubert, Malcolm J W Prior, Charles A Marsden, Fernando Pérez Diaz, David A Kendall, Marie-Christine Pardon
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  ABSTRACT: We have previously shown that repeated exposure to mild novel cage stress prevents the onset of recent contextual fear memory deficits and attenuated amyloid deposition in the TASTPM mouse model of Alzheimer's disease. Here, we extended this investigation to remote contextual fear memory and extinction. TASTPM and wild-type mice acquired contextual fear at 4 months of age. Retention and extinction of contextual fear were assessed at 5.5 months prior to in vivo MRI assessment of regional T2 relaxation times and brain volumes followed by immunostaining to determine amyloid plaque load. Remote contextual fear memory was preserved in TASTPM mice regardless of the stress condition. Stress impaired extinction in wild-type mice but facilitated this process in TASTPM mice. Genotype-dependent effects of stress were observed on regional T2 times which were prolonged in the subiculum and thalamus of stressed TASTPM, possibly reflecting reduced amyloid pathology. Amyloid plaque load was particularly decreased in the retrosplenial cortex of stressed TASTPM mice, which also showed an overall reduction in the number of diffuse plaques. These findings support the hypothesis that repeated mild levels of stress induced by novel activities can delay the progression of pathological changes relevant to Alzheimer's disease.
  Journal of Alzheimer's disease: JAD 04/2010; 20(4):1049-68. · 3.74 Impact Factor
• Article: The glutamatergic system and its relation to the clinical effect of therapeutic-sleep deprivation in depression - an MR spectroscopy study.

  Harald Murck, Mirjam I Schubert, Dagmar Schmid, Petra Schüssler, Axel Steiger, Dorothee P Auer
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  ABSTRACT: Rapid improvement of depressive symptoms occurs after the administration of the NMDA antagonist ketamine. Ketamine administration is accompanied by an increase in GLX (sum-peak of glutamate, glutamine (GLN) and GABA) and GLN in the brain, as measured by magnetic-resonance (MR) spectroscopy. In healthy subjects, we observed an increase in GLX and GLN levels after total sleep deprivation (TSD), which has a rapid antidepressant effects. We examined, if an increase in GLX or GLN is related to the therapeutic effect of TSD. We examined 13 patients with major depression by means of proton MR spectroscopy (field strength: 1.5T) before and after 24h of TSD. Two anatomical areas (dorsolateral prefrontal cortex (DLPC) and parieto-occipital cortex (POC)) were studied. In the DLPC TSD did not change GLX or its elements, whereas the total creatine and choline signal increased marginally. No change could be observed in the POC. For further exploration we took gender and the presence of vegetative characteristics of melancholic depression into account, i.e. the presence of early morning awakening, appetite and weight loss was taken into account, to define vegetative melancholia (VM). TSD led to an increase in GLX and GLN in the DLPC only of male patients. In patients with VM an increase in GLN occurred in this area. The low field strength limits the accuracy for GLX and GLN estimates. Despite the exploratory nature of the study, it nevertheless supports earlier data on the importance of glutamatergic neurotransmission and furthermore of gender and/or vegetative features in depression.
  Journal of Psychiatric Research 07/2008; 43(3):175-80. · 4.66 Impact Factor
• Article: Effects of altered corticosteroid milieu on rat hippocampal neurochemistry and structure--an in vivo magnetic resonance spectroscopy and imaging study.

  Mirjam I Schubert, Raffael Kalisch, Ioannis Sotiropoulos, Caterina Catania, Nuno Sousa, Osborne F X Almeida, Dorothee P Auer
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  ABSTRACT: Altered corticosteroid milieu induces changes in hippocampal volume, neuronal structure, neurochemistry and cognitive function in humans and rodents. This in vivo magnetic resonance spectroscopy (1H MRS) and imaging (MRI) study investigated whether long-term alterations of the corticosteroid milieu cause: (i) metabolic and/or (ii) structural changes of the rat hippocampus. Therefore, hypocortisolism was induced by adrenalectomy (ADX), normocortisolism by ADX with low-dose corticosterone replacement, and hypercortisolism by ADX and high-dose dexamethasone treatment (for 11 weeks, respectively). All groups including a control group (n=23) were studied by in vivo 1H MRS and MR volumetry. Effects of treatment on normalized hippocampal metabolites and volumes were tested for significance using one-factorial multivariate analysis of variance (MANOVA). Hypercortisolemic rats revealed significantly elevated glutamate. Hypocortisolemic rats showed significantly decreased myo-inositol ratio levels, and were associated with significantly reduced normalized hippocampal volumes. Our findings suggest chronic hypercortisolism to be associated with glutamate-mediated excitotoxicity in the absence of volumetric abnormalities. In contrast, hypocortisolism appears to be associated with neurodegenerative processes, altered astrocytic metabolism but preserved neuronal density.
  Journal of Psychiatric Research 02/2008; 42(11):902-12. · 4.66 Impact Factor