A comparison of the synaptic proteome in human chronic schizophrenia and rat ketamine psychosis suggest that prohibitin is involved in the synaptic pathology of schizophrenia

Smalla, Karl‐Heinz; Mikhaylova, Marina; Sahin, Jale; Bernstein, Hans‐Gert; Bogerts, Bernhard; Schmitt, Andrea; Schors, Roel C. van der; Smit, August B.; Li, Ka Wan; Gundelfinger, Eckart D.; Kreutz, Michael R.

doi:10.1038/mp.2008.60

Cited by 51 publications

(34 citation statements)

References 89 publications

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“…Synaptic structural and ultrastructural changes, altered expression of presynaptic proteins, reduction of dendritic spine density, fewer synaptic vesicles and shrinkage of axon boutons have been reported in several brain regions (Eastwood and Harrison, 1995, Perrone Bizzozero et al, 1996, Uranova et al, 1996, Glantz and Lewis, 1997, Garey et al, 1998, Harrison, 1999, Glantz and Lewis, 2000, Mirnics et al, 2000, Rosoklija et al, 2000, Prabakaran et al, 2004, Clark et al, 2006, Camargo et al, 2007, Le-Niculescu et al, 2007, Sweet et al, 2007, Pennington et al, 2008, Smalla et al, 2008, Sweet et al, 2009, Chan et al, 2010, Chu and Liu, 2010, English et al, 2011). Importantly, synaptic abnormalities have been detected in the entorhinal and perirhinal cortices, regions where CSPG changes were also found (Eastwood and Harrison, 1995, Arnold, 1997, Harrison, 1999, Hemby et al, 2002, Law et al, 2004, Beneyto et al, 2007, Pantazopoulos et al, 2010).…”

Section: Ecm Functions Bear Direct Relevance To the Pathophysiologmentioning

confidence: 98%

Extracellular matrix abnormalities in schizophrenia

2012

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Emerging evidence points to the involvement of the brain extracellular matrix (ECM) in the pathophysiology of schizophrenia (SZ). Abnormalities affecting several ECM components, including Reelin and chondroitin sulfate proteoglycans (CSPGs), have been described in subjects with this disease. Solid evidence supports the involvement of Reelin, an ECM glycoprotein involved in corticogenesis, synaptic functions and glutamate NMDA receptor regulation, expressed prevalently in distinct populations of GABAergic neurons, which secrete it into the ECM. Marked changes of Reelin expression in SZ have typically been reported in association with GABA-related abnormalities in subjects with SZ and bipolar disorder. Recent findings from our group point to substantial abnormalities affecting CSPGs, a main ECM component, in the amygdala and entorhinal cortex of subjects with schizophrenia, but not bipolar disorder. Striking increases of glial cells expressing CSPGs were accompanied by reductions of perineuronal nets, CSPG- and Reelin-enriched ECM aggregates enveloping distinct neuronal populations. CSPGs developmental and adult functions, including neuronal migration, axon guidance, synaptic and neurotransmission regulation are highly relevant to the pathophysiology of SZ. Together with reports of anomalies affecting several other ECM components, these findings point to the ECM as a key component of the pathology of SZ. We propose that ECM abnormalities may contribute to several aspects of the pathophysiology of this disease, including disrupted connectivity and neuronal migration, synaptic anomalies and altered GABAergic, glutamatergic and dopaminergic neurotransmission.

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Section: Ecm Functions Bear Direct Relevance To the Pathophysiologmentioning

confidence: 98%

Extracellular matrix abnormalities in schizophrenia

2012

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“…In postmortem parietal cortex samples of schizophrenia, bipolar disorder and unipolar depression of medicated and nonmedicated patients, a decrease in mitochondrial attachment of HK1 was found, which may lead to impairment in energy metabolism by increasing oxidative stress, and also alterations in brain growth and development [29]. ALDOC has so far been described as a brain-specific isozyme involved in fructose metabolism, and it also plays a role as a zinc-activated ribonuclease to neurofilament light polypeptide (NF-L) mRNA [30,31]. ENO2, also known as neuron-specific enolase, has been extensively used as a marker for nervous tissue damage, especially in meningitis.…”

Section: Glycolysis Pathway and Oxidative Stressmentioning

confidence: 98%

Proteomic Characterization of the Brain and Cerebrospinal Fluid of Schizophrenia Patients

Café-Mendes

Gattaz

Schmitt

et al. 2014

Advances in Biological Psychiatry

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As a multifactorial mental disorder, schizophrenia presents a complex combination of genetic, neurodevelopmental and environmental components. These lead to difficulties in comprehending the molecular basis of schizophrenia as well as in identifying biomarkers. These issues can be tackled by proteomics, which has been used increasingly along with genetics and other '-omics' approaches. In the present chapter, we explore some advances in proteomic studies involving brain tissue and cerebrospinal fluid collected from schizophrenic patients. We demonstrate that proteomic findings have been confirmed by other approaches, and added new information about the role of synaptic connectivity, oxidative stress, glucose metabolism and cytoskeletal alterations as core features of the disease pathophysiology. Integrative systems analysis including proteomics is a valid strategy for understanding the molecular basis of schizophrenia and may indicate the way to future clinical applications. SchizophreniaSchizophrenia is a severe mental disorder with a lifetime prevalence of 0.3-0.7% and presenting a heterogeneous range of symptoms [1]. It is a multifactorial disorder composed of a number of etiological factors of small effect that may be triggered by environmental components [2]. The causes of schizophrenia are strongly determined by genetics, but also by other factors such as epistatic (interaction between two or more genes controlling a single phenotype) and environmental ones (epigenetics). This is supported by the fact that 90% of individuals who develop schizophrenia have no history of schizophrenic parents or relatives. This conclusion does not exclude the heritable factor of schizophrenia, which is high (up to 80%), but reinforces the fact that environmental factors influence the onset/development of the disease [3]. Although interactions occur and are responsible for the establishment of the Martins-de-Souza D (ed): Proteomics and Metabolomics in Psychiatry.

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“…The majority of studies that compared the proteome of synapses were performed on human brain disease states (12,40,72,73,76,78,(123)(124)(125)(126) and despite significant methodological progress in recent years the resulting picture is still not representative. Apart from the problem of tissue preservation and preparation the limitations of conventional proteomic analysis lead to a situation where in several studies very different proteins where shown to be up-and downregulated in the same brain region and disease state.…”

Section: Figmentioning

confidence: 99%

Proteomics of the Synapse – A Quantitative Approach to Neuronal Plasticity

Dieterich

Kreutz

2016

Molecular & Cellular Proteomics

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The advances in mass spectrometry based proteomics in the past 15 years have contributed to a deeper appreciation of protein networks and the composition of functional synaptic protein complexes. However, research on protein dynamics underlying core mechanisms of synaptic plasticity in brain lag far behind. In this review, we provide a synopsis on proteomic research addressing various aspects of synaptic function. We discuss the major topics in the study of protein dynamics of the chemical synapse and the limitations of current methodology. We highlight recent developments and the future importance of multidimensional proteomics and metabolic labeling. Finally, emphasis is given on the conceptual framework of modern proteomics and its current shortcomings in the quest to gain a deeper understanding of synaptic plasticity. Molecular & Cellular Proteomics

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A comparison of the synaptic proteome in human chronic schizophrenia and rat ketamine psychosis suggest that prohibitin is involved in the synaptic pathology of schizophrenia

Cited by 51 publications

References 89 publications

Extracellular matrix abnormalities in schizophrenia

Extracellular matrix abnormalities in schizophrenia

Proteomic Characterization of the Brain and Cerebrospinal Fluid of Schizophrenia Patients

Proteomics of the Synapse – A Quantitative Approach to Neuronal Plasticity

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