| 1 | Mol. Psychiatry 2007 Jun 12: 562-71 |
|---|---|
| PMID | 17211438 |
| Title | Alterations of lipid metabolism and gene expression in rat adipocytes during chronic olanzapine treatment. |
| Abstract | Although antipsychotics are established drugs in schizophrenia treatment, they are admittedly known to induce side effects favoring the onset of obesity and worsening its complications. Despite potential involvement of histamine receptor antagonism, or of other neurotransmitter systems, the mechanism by which antipsychotic drugs increase body weight is not elucidated. The aim of the present study was to investigate whether chronic antipsychotic treatments can directly alter the regulation of two main functions of white adipose tissue: lipolysis and glucose utilization. The influence of a classical antipsychotic (haloperidol) was compared to that of two atypical antipsychotics, one known to favor weight gain (olanzapine), the other not (ziprasidone). Cell size, lipolytic capacity and glucose transport activity were determined in white adipocytes of rats subjected to 5-week oral treatment with these antipsychotics. Gene expression of adipocyte proteins involved in glucose transport or fat storage and mobilization, such as glucose transporters (GLUT1 and GLUT4), leptin, matrix metallo-proteinase-9 (MMP9), hormone-sensitive lipase (HSL) and fatty acid synthase (FAS) was also evaluated. Adipocytes from chronic olanzapine-treated rats exhibited decreased lipolytic activity, lowered HSL expression and increased FAS expression. These changes were concomitant to enlarged fat deposition and adipocyte size. Alterations were observed in adipocytes from olanzapine-treated rats whereas the other antipsychotics did not induce any notable disorder. Our results therefore show evidence of an effect of chronic antipsychotic treatment on rat adipocyte metabolism. Thus, impairment of fat cell lipolysis should be considered as a side effect of certain antipsychotics, leading, along with the already documented hyperphagia, to the excessive weight gain observed in patients under prolonged treatment.. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | Cardiovasc Psychiatry Neurol 2009 -1 2009: 904836 |
| PMID | 20037727 |
| Title | Matrix Metalloproteinase-9 (MMP9)-A Mediating Enzyme in Cardiovascular Disease, Cancer, and Neuropsychiatric Disorders. |
| Abstract | Matrix metalloproteinase-9 (MMP9) has been implicated in numerous somatic illnesses, including cardiovascular disorders and cancer. Recently, MMP9 has been shown to be increasingly important in several aspects of central nervous system activity. Furthermore, a pathogenic role for this enzyme has been suggested in such neuropsychiatric disorders as schizophrenia, bipolar illness, and multiple sclerosis. In this paper, the results of biochemical and molecular-genetic studies on MMP9 that have been performed in these pathological conditions will be summarized. Furthermore, I hypothesize that the MMP9 gene, as shown by functional -1562 C/T polymorphism studies, may be mediating the relationship of neuropsychiatric illnesses (schizophrenia, bipolar mood disorder, multiple sclerosis) that are comorbid with cardiovascular disease and cancer. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | Psychiatry Res 2011 May 187: 341-6 |
| PMID | 20510460 |
| Title | Expression of anti-cardiolipin antibodies and inflammatory associated factors in patients with schizophrenia. |
| Abstract | Numerous studies have implicated a connection between schizophrenia and autoimmune disorders. However, the precise relationship and underlying mechanism are still obscure. To further identify the association between autoimmune disorders and schizophrenia, the mRNA expressions of various cytokines and Toll-like receptors (TLRs) in monocytes are examined by using RT-PCR. Additionally, ELISA and zymography were performed to determine the anti-cardiolipin antibody (aCL) and MMP9 activity in serum form schizophrenic patients. Notably, significantly increased interleukin (IL)-6 and IL-10 mRNA were observed in schizophrenic patients, whereas significant reductions of TLR-3 and TLR-5 mRNA were detected. Moreover, significantly increased levels of aCL antibody and a higher frequency of positive-MMP9 activity were detected in serum from patients with schizophrenia. Meanwhile, no significant association was found between each of the medications and aCL activity. These findings demonstrated autoimmune-related phenomena in schizophrenic patients and further suggested a connection between schizophrenia and autoimmune disorders. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 4 | Psychiatry Res 2011 May 187: 341-6 |
| PMID | 20510460 |
| Title | Expression of anti-cardiolipin antibodies and inflammatory associated factors in patients with schizophrenia. |
| Abstract | Numerous studies have implicated a connection between schizophrenia and autoimmune disorders. However, the precise relationship and underlying mechanism are still obscure. To further identify the association between autoimmune disorders and schizophrenia, the mRNA expressions of various cytokines and Toll-like receptors (TLRs) in monocytes are examined by using RT-PCR. Additionally, ELISA and zymography were performed to determine the anti-cardiolipin antibody (aCL) and MMP9 activity in serum form schizophrenic patients. Notably, significantly increased interleukin (IL)-6 and IL-10 mRNA were observed in schizophrenic patients, whereas significant reductions of TLR-3 and TLR-5 mRNA were detected. Moreover, significantly increased levels of aCL antibody and a higher frequency of positive-MMP9 activity were detected in serum from patients with schizophrenia. Meanwhile, no significant association was found between each of the medications and aCL activity. These findings demonstrated autoimmune-related phenomena in schizophrenic patients and further suggested a connection between schizophrenia and autoimmune disorders. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 5 | Pharmacol Rep 2015 Jun 67: 442-5 |
| PMID | 25933951 |
| Title | Functional polymorphism of matrix metalloproteinase-9 (MMP9) gene is not associated with schizophrenia and with its deficit subtype. |
| Abstract | The deficit subtype of schizophrenia is hypothesized to constitute a pathophysiologically distinct subgroup of schizophrenia patients suffering from enduring, idiopathic negative symptoms and various neuropsychological deficits. Matrix metalloproteinases (MMPs) are extracellularly acting endopeptidases the substrates of which are matrix and adhesion molecules. Recently, MMP9 has been shown to be involved in various forms of synaptic plasticity, learning and memory consolidation. The primary aim of the present study was to evaluate associations between the functional MMP-9 -1562C/T gene polymorphism and the deficit and non-deficit subtypes of schizophrenia. The study was conducted between 2009 and 2012. Deficit schizophrenia was diagnosed using the SDS. The sample consisted of 468 patients, Caucasians, of Polish descent with ICD 10 diagnosis of schizophrenia: 189 [51% males] were included in a non-deficit subgroup, 279 patients [53% males] were included in a deficit subgroup. The control group consisted of 532 subjects, Caucasians, of Polish descent [51% males]. MMP-9 -1562C/T gene polymorphism was genotyped using the fluorescence resonance energy transfer (FRET) method and the Light Cycler System 2.0. The frequencies of genotypes and alleles did not differ between the schizophrenia patients and control group. The deficit and non-deficit patients did not differ in terms of the genotype and allele frequencies. No differences were found in genotype and allele frequencies between the deficit patients and the controls and between the non-deficit patients and the controls. We found no evidence for the association between the functional MMP-9 -1562C/T gene polymorphism and deficit/non-deficit subtypes of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 6 | Oncol. Rep. 2016 Feb 35: 999-1005 |
| PMID | 26719016 |
| Title | CHRNA7 inhibits cell invasion and metastasis of LoVo human colorectal cancer cells through PI3K/Akt signaling. |
| Abstract | The ?7 neuronal nicotinic receptor gene (CHRNA7) is widely expressed in both the brain and periphery whereas its encoding protein of ?7 neuronal acetylcholine receptor (?7nAChR) belongs to the nicotinic acetylcholine receptor family. Considerable evidence suggests that ?7nAChR plays an important role in chronic inflammatory and neuropathic pain signaling and thus has been proposed as a potential target for treating cognitive deficits in patients with schizophrenia, attention deficit hyperactivity disorder (ADHD) and Alzheimer's disease. The aim of the present study was to determine the role of endogenous ?7nAChR signaling in human colorectal cancer growth and metastasis. pLVX?CHRNA7 encoding the full length of CHRNA7 was constructed and transfected into LoVo human colorectal cancer cells. Cell proliferation was measured by Cell Counting Kit?8 (CCK?8), and cell migration and invasion were detected by Transwell chamber assays. Expression and activity of metastasis?related metalloproteinases (MMPs) were analyzed by western blotting and gelatin zymography, respectively. Activation of metastasis-related signaling molecules was detected by western blotting. LY294002 was used to specifically block the phosphatidylinositol 3?kinase/v?akt murine thymoma viral oncogene homologue (PI3K/Akt) pathway. We showed that concomitantly with an increase in ?7nAChR expression after transfection, LoVo cells presented reduced abilities for migration and invasion, which was accompanied by reduced expression levels of MMP?1 and MMP?9 as well as activation of the PI3K/Akt signaling pathway. The application of LY294002 restored the migration and invasion abilities of the LoVo cells bearing CHRNA7. Collectively, we conclude that overexpression of CHRNA7 negatively controls colorectal cancer LoVo cell invasion and metastasis via PI3K/Akt pathway activation and may serve as either a diagnostic marker or a therapeutic target for colorectal cancer metastasis. |
| SCZ Keywords | schizophrenia, schizophrenic |