Abnormal growth of skin fibroblasts from schizophrenic patients

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

doi:10.1016/0165-1781(91)90066-x

Cited by 39 publications

(13 citation statements)

References 25 publications

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“…Only within 48 h after plating, the fibronectin content of schizophrenic fibroblasts showed a lower level than control subjects. Mahadik et al 10 also reported that slower initial growth, longer doubling time and abnormal morphology, such as random size, multipolarity and irregular orientation, were observed in cultures from schizophrenic patients 6 . 7 Our observations did not show these abnormalities.…”

Section: Discussionmentioning

confidence: 97%

“…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%

“…Lower magnesium levels and a signi®cant increase in N-CAM immunoreactivity and decrease in L1 antigen have also been demonstrated in the CSF of acute schizophrenic patients. 3,4 There have been several studies undertaken on ®broblasts 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 ®bronectin 10 have been reported.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Altered adhesion efficiency and fibronectin content in fibroblasts from schizophrenic patients

Miyamae

Nakamura

Kashiwagi

et al. 1998

Psychiatry Clin Neurosci

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“…For example, in fibroblasts from patients with schizophrenia, alterations in pathways involved in cell cycle regulation and RNA processing have been identified [34]. Moreover, alterations in growth, morphology, cell adhesion, apoptotic pathways, composition of phospholipid fatty acids in the plasma membrane and glutathione synthesis are reported [35-39]. Aberrant amino acid transport has been identified in fibroblast from patients with schizophrenia, bipolar disorder as well as autism [40-42].…”

Section: Discussionmentioning

confidence: 99%

Effects of pro-inflammatory cytokines on expression of kynurenine pathway enzymes in human dermal fibroblasts

et al. 2011

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BackgroundThe kynurenine pathway (KP) is the main route of tryptophan degradation in the human body and generates several neuroactive and immunomodulatory metabolites. Altered levels of KP-metabolites have been observed in neuropsychiatric and neurodegenerative disorders as well as in patients with affective disorders. The purpose of the present study was to investigate if skin derived human fibroblasts are useful for studies of expression of enzymes in the KP.MethodsFibroblast cultures were established from cutaneous biopsies taken from the arm of consenting volunteers. Such cultures were subsequently treated with interferon (IFN)-γ 200 U/ml and/or tumor necrosis factor (TNF)-α, 100 U/ml for 48 hours in serum-free medium. Levels of transcripts encoding different enzymes were determined by real-time PCR and levels of kynurenic acid (KYNA) were determined by HPLC.ResultsAt base-line all cultures harbored detectable levels of transcripts encoding KP enzymes, albeit with considerable variation across individuals. Following cytokine treatment, considerable changes in many of the transcripts investigated were observed. For example, increases in the abundance of transcripts encoding indoleamine 2,3-dioxygenase, kynureninase or 3-hydroxyanthranilic acid oxygenase and decreases in the levels of transcripts encoding tryptophan 2,3-dioxygenase, kynurenine aminotransferases or quinolinic acid phosphoribosyltransferase were observed following IFN-γ and TNF-α treatment. Finally, the fibroblast cultures released detectable levels of KYNA in the cell culture medium at base-line conditions, which were increased after IFN-γ, but not TNF-α, treatments.ConclusionsAll of the investigated genes encoding KP enzymes were expressed in human fibroblasts. Expression of many of these appeared to be regulated in response to cytokine treatment as previously reported for other cell types. Fibroblast cultures, thus, appear to be useful for studies of disease-related abnormalities in the kynurenine pathway of tryptophan degradation.

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“…There is some evidence that phospholipid metabolism in both brain and red cells may have been altered in schizophrenia. Cultured skin fibroblasts from schizophrenic patients have abnormal membrane properties as indicated by altered adhesiveness and growth characteristics [8] not observed by Gliddon et al [4].…”

Section: Discussionmentioning

confidence: 85%

Nitric Oxide, Free Radicals and Polyamines May Have a Role in the Membrane Pathology of Schizophrenia

Das

Ramchand²,

Gliddon³

et al. 1998

Neuropsychobiology

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Studies on skin fibroblasts in culture derived from schizophrenic and control subjects showed that polyamines are increased, nitrate levels are reduced and thiobarbituric acid reacting substances did not alter in cultured cells from schizophrenic patients compared to control subjects. Results seem to indicate some alteration in membrane functions in schizophrenia, which is susceptible to neuroleptic treatment. Significantly increased levels of polyamines in drug-treated schizophrenic cells indicates a possible role of polyamines in the activation of proposed hypofunctional NMDA subtype of glutamate receptor systems in schizophrenia.

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Abnormal growth of skin fibroblasts from schizophrenic patients

Cited by 39 publications

References 25 publications

Altered adhesion efficiency and fibronectin content in fibroblasts from schizophrenic patients

Altered adhesion efficiency and fibronectin content in fibroblasts from schizophrenic patients

Effects of pro-inflammatory cytokines on expression of kynurenine pathway enzymes in human dermal fibroblasts

Nitric Oxide, Free Radicals and Polyamines May Have a Role in the Membrane Pathology of Schizophrenia

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