ANDREA SCHMITT
Projetos de Pesquisa
Unidades Organizacionais
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina
4 resultados
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- Structural synaptic elements are differentially regulated in superior temporal cortex of schizophrenia patients(2012) SCHMITT, Andrea; LEONARDI-ESSMANN, Fernando; DURRENBERGER, Pascal F.; WICHERT, Sven P.; SPANAGEL, Rainer; ARZBERGER, Thomas; KRETZSCHMAR, Hans; ZINK, Mathias; HERRERA-MARSCHITZ, Mario; REYNOLDS, Richard; ROSSNER, Moritz J.; FALKAI, Peter; GEBICKE-HAERTER, Peter J.Inaccurate wiring and synaptic pathology appear to be major hallmarks of schizophrenia. A variety of gene products involved in synaptic neurotransmission and receptor signaling are differentially expressed in brains of schizophrenia patients. However, synaptic pathology may also develop by improper expression of intra- and extra-cellular structural elements weakening synaptic stability. Therefore, we have investigated transcription of these elements in the left superior temporal gyrus of 10 schizophrenia patients and 10 healthy controls by genome-wide microarrays (Illumina). Fourteen up-regulated and 22 downregulated genes encoding structural elements were chosen from the lists of differentially regulated genes for further qRT-PCR analysis. Almost all genes confirmed by this method were downregulated. Their gene products belonged to vesicle-associated proteins, that is, synaptotagmin 6 and syntaxin 12, to cytoskeletal proteins, like myosin 6, pleckstrin, or to proteins of the extracellular matrix, such as collagens, or laminin C3. Our results underline the pivotal roles of structural genes that control formation and stabilization of pre- and post-synaptic elements or influence axon guidance in schizophrenia. The glial origin of collagen or laminin highlights the close interrelationship between neurons and glial cells in establishment and maintenance of synaptic strength and plasticity. It is hypothesized that abnormal expression of these and related genes has a major impact on the pathophysiology of schizophrenia.
- Differential expression of HINT1 in schizophrenia brain tissue(2012) VARADARAJULU, Jeeva; SCHMITT, Andrea; FALKAI, Peter; ALSAIF, Murtada; TURCK, Christoph W.; MARTINS-DE-SOUZA, DanielRecent findings in the literature suggest a relation between histidine triad nucleotide-binding protein-1 (HINT1) and psychiatric disorders such as major depression, anxiety, and schizophrenia, although its physiological roles are not completely comprehended. Using Western blot, we compared HINT1 protein expression in the postmortem dorsolateral prefrontal cortex and thalamus of schizophrenia patients and healthy controls for contributing to elucidate the role of HINT1 in schizophrenia pathophysiology. HINT1 was found to be downregulated in the dorsolateral prefrontal cortex and upregulated in the thalamus. Our results combined to previous studies in human samples and preclinical models support the notion that HINT1 must be more explored as a potential target for psychiatric disorders.
conferenceObject PROTEOME ANALYSES OF POST-MORTEMBRAIN TISSUE FROM PATIENTS WITH SCHIZOPHRENIA SUGGEST DYSFUNCTION OF OLIGODENDROCYTES AND ASTROCYTES AND POTENTIAL BIOMARKER CANDIDATES?(2012) MARTINS-DE-SOUZA, Daniel; MACCARRONE, Giuseppina; SCHMITT, Andrea; FALKAI, Peter; DIAS-NETO, Emmanuel; GATTAZ, Wagner F.; TURCK, Chris W.- Decreased Reelin Expression in the Left Prefrontal Cortex (BA9) in Chronic Schizophrenia Patients(2012) HABL, Gregor; SCHMITT, Andrea; ZINK, Mathias; WILMSDORFF, Martina von; YEGANEH-DOOST, Peyman; JATZKO, Alexander; SCHNEIDER-AXMANN, Thomas; BAUER, Manfred; FALKAI, PeterBackground: Reelin is under epigenetic control and has been reported to be decreased in cortical regions in schizophrenia. Methods: To establish if expression of reelin is altered in specific cortical, hippocampal or thalamic regions of schizophrenia patients, we measured gene expression of reelin in a postmortem study of elderly patients with schizophrenia and non-affected controls in both hemispheres differentiating between gray and white matter. We compared cerebral postmortem samples (dorsolateral prefrontal cortex BA9 and BA46, superior temporal cortex BA22, entorhinal cortex BA28, sensoric cortex BA1-3, hippocampus, CA4, mediodorsal nucleus of the thalamus) from 12 schizophrenia patients with 13 normal subjects investigating gene expression of reelin in the gray and white matter of both hemispheres by in situ-hybridization. Results: The left prefrontal area (BA9) of schizophrenia patients revealed a decreased expression of reelin-mRNA of 29.1% in the white (p = 0.022) and 13.6% in the gray matter (p = 0.007) compared to the control group. None of the other regions examined showed any statistically significant differences. Conclusion: Since reelin is responsible for migration and synapse formation, the decreased gene expression of reelin in the left prefrontal area of schizophrenia patients points to neurodevelopmental deficits in neuronal migration and synaptic plasticity. However, our study group was small, and results should be verified using larger samples.