Decreased adhesiveness and altered cellular distribution of fibronectin in fibroblasts from schizophrenic patients

Mahadik, Sahebarao P.; Mukherjee, Sukdeb; Wakade, Chandramohan; Laev, Heljo; Reddy, Ravinder; Schnur, David B.

doi:10.1016/0165-1781(94)90097-3

Cited by 25 publications

(16 citation statements)

References 44 publications

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“…This hypothesis is in line with earlier work showing decreased adhesiveness and lower fibronectin levels in fibroblasts from patients with schizophrenia. 66 Immunoassays on serum from schizophrenia patients highlighted matrix metalloproteinases as part of the molecular signature associated with symptom severity and short time to relapse. 67 It is worth mentioning that our assay was not designed to study the extracellular compartment, and these results deserve further validation.…”

Section: Discussionmentioning

confidence: 99%

Impaired Metabolic Reactivity to Oxidative Stress in Early Psychosis Patients

Fournier¹,

Ferrari

Baumann

et al. 2014

Schizophrenia Bulletin

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Because increasing evidence point to the convergence of environmental and genetic risk factors to drive redox dysregulation in schizophrenia, we aim to clarify whether the metabolic anomalies associated with early psychosis reflect an adaptation to oxidative stress. Metabolomic profiling was performed to characterize the response to oxidative stress in fibroblasts from control individuals (n = 20) and early psychosis patients (n = 30), and in all, 282 metabolites were identified. In addition to the expected redox/ antioxidant response, oxidative stress induced a decrease of lysolipid levels in fibroblasts from healthy controls that were largely muted in fibroblasts from patients. Most notably, fibroblasts from patients showed disrupted extracellular matrix-and arginine-related metabolism after oxidative stress, indicating impairments beyond the redox system. Plasma membrane and extracellular matrix, 2 regulators of neuronal activity and plasticity, appeared as particularly susceptible to oxidative stress and thus provide novel mechanistic insights for pathophysiological understanding of early stages of psychosis. Statistically, antipsychotic medication at the time of biopsy was not accounting for these anomalies in the metabolism of patients' fibroblasts, indicating that they might be intrinsic to the disease. Although these results are preliminary and should be confirmed in a larger group of patients, they nevertheless indicate that the metabolic signature of reactivity to oxidative stress may provide reliable early markers of psychosis. Developing protective measures aimed at normalizing the disrupted pathways should prevent the pathological consequences of environmental stressors.

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Section: Discussionmentioning

confidence: 99%

Impaired Metabolic Reactivity to Oxidative Stress in Early Psychosis Patients

Fournier¹,

Ferrari

Baumann

et al. 2014

Schizophrenia Bulletin

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“…Fibronectin is a high molecular weight ECM glycoprotein that binds to integrin receptors and plays important roles in neuro- and synaptogenesis. Dysregulation of fibronectin may result in neurodevelopmental abnormalities related to the pathogenesis of Sz [58, 59]. In contrast, a study showed no significant association of fibronectin with Sz [60].…”

Section: Changes In Brain Ecm In Neurodegenerative Conditionsmentioning

confidence: 99%

Extracellular matrix proteomics in schizophrenia and Alzheimer’s disease

Sethi

Zaia

2016

Anal Bioanal Chem

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Brain extracellular matrix (ECM) is a highly organized system that consists of collagens, non-collagenous proteins, glycoproteins, hyaluronan and proteoglycans (PGs). Recognized physiological roles of ECM include developmental regulation, tissue homeostasis, cell migration, proliferation, differentiation, neuronal plasticity, and neurite outgrowth. Aberrant ECM structure is associated with brain neurodegenerative conditions. This review focuses on two neurodegenerative conditions, schizophrenia (Sz) and Alzheimer's disease (AD), and summarizes recent findings of altered ECM components, including PGs, glycosaminoglycans (GAGs), proteins and glycoproteins, and proteins and genes related to other brain components. The scope includes immunohistochemical, genomics, transcriptomics, proteomics and glycomics studies, and a critical assessment of current state of proteomics studies for neurodegenerative disorders. The intent is to summarize the ECM molecular alterations associated with neurodegenerative pathophysiology.

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“…There have been several studies undertaken on fibroblasts obtained from schizophrenic patients: decreased tyrosine transport, 5 abnormal growth, 6 , 7 lower plasma membrane phospholipid fatty acid and cholesterol distribution, 8 , 9 decreased adhesiveness and lower distribution of fibronectin 10 have been reported.…”

Section: Introductionmentioning

confidence: 99%

Altered adhesion efficiency and fibronectin content in fibroblasts from schizophrenic patients

Miyamae

Nakamura

Kashiwagi

et al. 1998

Psychiatry Clin Neurosci

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Cultured ®broblasts from the cutaneous tissue of 16 schizophrenic patients were compared with 16 control cultured ®broblasts from the healthy subjects. The ®broblasts from the schizophrenic patients showed a decreased adhesion ef®ciency within 30 min after plating compared to that of the control subjects. However, after 90 min, there was no signi®cant difference between the groups, where more than 90% of the cells from both groups had adhesed to the plate. By immunohistochemistry and western blotting using the antibodies against integrin (VLA5), talin, vinculin, fodrin, vimentin, ankyrin, plectin, ®bronectin, and focal adhesion kinase (FAK), there was no signi®cant difference in localization and amount between the groups. The amount of ®bronectin released into the medium in which the ®broblast had already kept con¯uency showed no signi®cant difference between the groups. However, the ®bronectin content in cell lysate within 48 h after plating was signi®cantly lower in the schizophrenic group.

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Decreased adhesiveness and altered cellular distribution of fibronectin in fibroblasts from schizophrenic patients

Cited by 25 publications

References 44 publications

Impaired Metabolic Reactivity to Oxidative Stress in Early Psychosis Patients

Impaired Metabolic Reactivity to Oxidative Stress in Early Psychosis Patients

Extracellular matrix proteomics in schizophrenia and Alzheimer’s disease

Altered adhesion efficiency and fibronectin content in fibroblasts from schizophrenic patients

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