scholarly journals Differential sphingosine-1-phosphate receptor-1 (S1PR1) protein expressions in the dorsolateral prefrontal cortex between schizophrenia Type 1 and Type 2

2021 ◽  
Author(s):  
Ganesh B Chand ◽  
Hao Jiang ◽  
Matthew Brier ◽  
Farzaneh Rahmani ◽  
Tammie L. S. Benzinger ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Protein Expression ◽  
Dorsolateral Prefrontal Cortex ◽  
Clinical Test ◽  
Messenger Ribonucleic Acid ◽  
Dorsolateral Prefrontal ◽  
Sphingosine 1 Phosphate ◽  
Schizophrenic Patients

There is growing evidence that there are subtypes of schizophrenia (Bowen et al., 2019; Chand et al., 2020). Specifically, messenger ribonucleic acid (mRNA) gene expression findings on postmortem dorsolateral prefrontal cortex (DLPFC) suggest that schizophrenia patients can be divided into two groups, those with a relatively normal DLPFC transcriptome (Type 1) and those with hundreds of differentially expressed genes (Type 2). The clinical relevance of that finding is limited by the fact that autopsy tissue is required to distinguish Type 1 from Type 2 patients, however the PET target sphingosine-1-phosphate receptor-1 (S1PR1) is among the genes whose mRNA expression is upregulated in Type 2 compared to Type 1 patients (Bowen et al., 2019). As a preliminary study to validate this PET target, S1PR1 protein expression was assessed by receptor autoradiography and immunohistochemistry in the DLPFC from schizophrenic patients classified as Type 1 or Type 2 based on their DLPFC transcriptomes and from controls. S1PR1 protein expression is upregulated in Type 2 compared to Type 1 (p < 0.05) supporting the possibility that positron emission tomography (PET) can be used as a clinical test to distinguish these subgroups of schizophrenic patients during life.

scholarly journals Protein expression of prenyltransferase subunits in postmortem schizophrenia dorsolateral prefrontal cortex

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Anita L. Pinner ◽  
Toni M. Mueller ◽  
Khaled Alganem ◽  
Robert McCullumsmith ◽  
James H. Meador-Woodruff
Keyword(s):  
Prefrontal Cortex ◽  
Protein Expression ◽  
Protein Interactions ◽  
Intracellular Signaling ◽  
Dorsolateral Prefrontal Cortex ◽  
Signaling Proteins ◽  
Protein Protein Interactions ◽  
Protein Prenylation ◽  
Lipid Modifications ◽  
Dorsolateral Prefrontal

AbstractThe pathophysiology of schizophrenia includes altered neurotransmission, dysregulated intracellular signaling pathway activity, and abnormal dendritic morphology that contribute to deficits of synaptic plasticity in the disorder. These processes all require dynamic protein–protein interactions at cell membranes. Lipid modifications target proteins to membranes by increasing substrate hydrophobicity by the addition of a fatty acid or isoprenyl moiety, and recent evidence suggests that dysregulated posttranslational lipid modifications may play a role in multiple neuropsychiatric disorders, including schizophrenia. Consistent with these emerging findings, we have recently reported decreased protein S-palmitoylation in schizophrenia. Protein prenylation is a lipid modification that occurs upstream of S-palmitoylation on many protein substrates, facilitating membrane localization and activity of key intracellular signaling proteins. Accordingly, we hypothesized that, in addition to palmitoylation, protein prenylation may be abnormal in schizophrenia. To test this, we assayed protein expression of the five prenyltransferase subunits (FNTA, FNTB, PGGT1B, RABGGTA, and RABGGTB) in postmortem dorsolateral prefrontal cortex from patients with schizophrenia and paired comparison subjects (n = 13 pairs). We found decreased levels of FNTA (14%), PGGT1B (13%), and RABGGTB (8%) in schizophrenia. To determine whether upstream or downstream factors may be driving these changes, we also assayed protein expression of the isoprenoid synthases FDPS and GGPS1 and prenylation-dependent processing enzymes RCE and ICMT. We found these upstream and downstream enzymes to have normal protein expression. To rule out effects from chronic antipsychotic treatment, we assayed FNTA, PGGT1B, and RABGGTB in the cortex from rats treated long-term with haloperidol decanoate and found no change in the expression of these proteins. Given the role prenylation plays in localization of key signaling proteins found at the synapse, these data offer a potential mechanism underlying abnormal protein–protein interactions and protein localization in schizophrenia.

Information Processing Flow and Neural Activations in the Dorsolateral Prefrontal Cortex in the Stroop Task in Schizophrenic Patients

2005 ◽  
Vol 51 (4) ◽  
pp. 191-203 ◽  
Author(s):  
Shunsuke Kawaguchi ◽  
Satoshi Ukai ◽  
Kazuhiro Shinosaki ◽  
Ryouhei Ishii ◽  
Masakiyo Yamamoto ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Information Processing ◽  
Stroop Task ◽  
Dorsolateral Prefrontal Cortex ◽  
Dorsolateral Prefrontal ◽  
Schizophrenic Patients ◽  
Processing Flow

Reduced GSK-3? mRNA levels in postmortem dorsolateral prefrontal cortex of schizophrenic patients

2004 ◽  
Vol 111 (12) ◽  
pp. 1583-1592 ◽  
Author(s):  
N. Kozlovsky ◽  
C. Shanon-Weickert ◽  
E. Tomaskovic-Crook ◽  
J. E. Kleinman ◽  
R. H. Belmaker ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Dorsolateral Prefrontal Cortex ◽  
Mrna Levels ◽  
Dorsolateral Prefrontal ◽  
Schizophrenic Patients

scholarly journals Alterations of perineuronal nets in the dorsolateral prefrontal cortex of neuropsychiatric patients

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Julia Alcaide ◽  
Ramón Guirado ◽  
Carlos Crespo ◽  
José Miguel Blasco-Ibáñez ◽  
Emilio Varea ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Extracellular Matrix ◽  
Prefrontal Cortex ◽  
Major Depression ◽  
Dorsolateral Prefrontal Cortex ◽  
Demographic Data ◽  
Inverse Correlation ◽  
Perineuronal Nets ◽  
Dorsolateral Prefrontal ◽  
Schizophrenic Patients

Abstract Background Alterations in the structure and physiology of interneurons in the prefrontal cortex (PFC) are important factors in the etiopathology of different psychiatric disorders. Among the interneuronal subpopulations, parvalbumin (PV) expressing cells appear to be specially affected. Interestingly, during development and adulthood the connectivity of these interneurons is regulated by the presence of perineuronal nets (PNNs), specialized regions of the extracellular matrix, which are frequently surrounding PV expressing neurons. Previous reports have found anomalies in the density of PNNs in the PFC of schizophrenic patients. However, although some studies have described alterations in PNNs in some extracortical regions of bipolar disorder patients, there are no studies focusing on the prefrontocortical PNNs of bipolar or major depression patients. For this reason, we have analyzed the density of PNNs in post-mortem sections of the dorsolateral PFC (DLPFC) from the Stanley Neuropathology Consortium, which includes controls, schizophrenia, bipolar and major depression patients. Results We have not observed differences in the distribution of PV+ cells or PNNs, or in the percentage of PV+ interneurons surrounded by PNNs. The density of PV+ interneurons was similar in all the experimental groups, but there was a significantly lower density of PNNs in the DLPFC of bipolar disorder patients and a tendency towards a decrease in schizophrenic patients. No differences were found when evaluating the density of PV+ cells surrounded by PNNs. Interestingly, when assessing the influence of demographic data, we found an inverse correlation between the density of PNNs and the presence of psychosis. Conclusions The present results point to prefrontocortical PNNs and their role in the regulation of neuronal plasticity as putative players in the etiopathology of bipolar disorder and schizophrenia. Our findings also suggest a link between these specialized regions of the extracellular matrix and the presence of psychosis.

scholarly journals Protein expression of prenyltransferase subunits in postmortem schizophrenia dorsolateral prefrontal cortex

2019 ◽  
Author(s):  
Anita L. Pinner ◽  
Toni M. Mueller ◽  
Khaled Alganem ◽  
Robert McCullumsmith ◽  
James H. Meador-Woodruff
Keyword(s):  
Prefrontal Cortex ◽  
Protein Expression ◽  
Protein Interactions ◽  
Intracellular Signaling ◽  
Dorsolateral Prefrontal Cortex ◽  
Signaling Proteins ◽  
Protein Protein Interactions ◽  
Protein Prenylation ◽  
Lipid Modifications ◽  
Dorsolateral Prefrontal

AbstractThe pathophysiology of schizophrenia includes altered neurotransmission, dysregulated intracellular signaling pathway activity, and abnormal dendritic morphology that contribute to deficits of synaptic plasticity in the disorder. These processes all require dynamic protein-protein interactions at cell membranes. Lipid modifications target proteins to membranes by increasing substrate hydrophobicity by the addition of a fatty acid or isoprenyl moiety, and recent evidence suggests that dysregulated post-translational lipid modifications may play a role in multiple neuropsychiatric disorders including schizophrenia. Consistent with these emerging findings, we have recently reported decreased protein S-palmitoylation in schizophrenia. Protein prenylation is a lipid modification that occurs upstream of S-palmitoylation on many protein substrates, facilitating membrane localization and activity of key intracellular signaling proteins. Accordingly, we hypothesized that in addition to palmitoylation, protein prenylation may be abnormal in schizophrenia. To test this, we assayed protein expression of the five prenyltransferase subunits (FNTA, FNTB, PGGT1B, RABGGTA, and RABGGTB) in postmortem dorsolateral prefrontal cortex from patients with schizophrenia and paired comparison subjects (N = 13 pairs). We found decreased levels of FNTA (14%), PGGT1B (13%), and RABGGTB (8%) in schizophrenia. To determine if upstream or downstream factors may be driving these changes, we also assayed protein expression of the isoprenoid synthases FDPS and GGPS1, and prenylation-dependent processing enzymes REC and ICMT. We found these upstream and downstream enzymes to have normal protein expression. To rule out effects from chronic antipsychotic treatment, we assayed FNTA, PGGT1B and RABGGTB in cortex from rats treated long-term with haloperidol decanoate, and found no change in the expression of these proteins. Given the role prenylation plays in localization of key signaling proteins found at the synapse, these data offer a potential mechanism underlying abnormal protein-protein interactions and protein localization in schizophrenia.

scholarly journals Alterations in Gene and Protein Expression of Cannabinoid CB2 and GPR55 Receptors in the Dorsolateral Prefrontal Cortex of Suicide Victims

2018 ◽  
Vol 15 (3) ◽  
pp. 796-806 ◽  
Author(s):  
María S. García-Gutiérrez ◽  
Francisco Navarrete ◽  
Gemma Navarro ◽  
Irene Reyes-Resina ◽  
Rafael Franco ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Protein Expression ◽  
Dorsolateral Prefrontal Cortex ◽  
Gene And Protein Expression ◽  
Dorsolateral Prefrontal
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