Increased NLRP1 mRNA and Protein Expression Suggests Inflammasome Activation in the Dorsolateral Prefrontal and Medial Orbitofrontal Cortex in Schizophrenia
Schizophrenia is a complex mental condition, with key symptoms marked for diagnosis including delusions, hallucinations, disorganized thinking, reduced emotional expression, and social dysfunction. In the context of major developmental hypotheses of schizophrenia, notably those concerning maternal i...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
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MDPI AG
2024-03-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/14/3/302 |
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| author | Ena Španić Popovački Dora Vogrinc Heidi R. Fuller Lea Langer Horvat Davor Mayer Janja Kopić Klara Pintarić Mirjana Babić Leko Mihaela Pravica Željka Krsnik Darko Marčinko Marina Šagud Patrick R. Hof Mihovil Mladinov Goran Šimić |
| author_facet | Ena Španić Popovački Dora Vogrinc Heidi R. Fuller Lea Langer Horvat Davor Mayer Janja Kopić Klara Pintarić Mirjana Babić Leko Mihaela Pravica Željka Krsnik Darko Marčinko Marina Šagud Patrick R. Hof Mihovil Mladinov Goran Šimić |
| author_sort | Ena Španić Popovački |
| collection | DOAJ |
| description | Schizophrenia is a complex mental condition, with key symptoms marked for diagnosis including delusions, hallucinations, disorganized thinking, reduced emotional expression, and social dysfunction. In the context of major developmental hypotheses of schizophrenia, notably those concerning maternal immune activation and neuroinflammation, we studied <i>NLRP1</i> expression and content in the postmortem brain tissue of 10 schizophrenia and 10 control subjects. In the medial orbitofrontal cortex (Brodmann’s area 11/12) and dorsolateral prefrontal cortex (area 46) from both hemispheres of six schizophrenia subjects, the <i>NLRP1</i> mRNA expression was significantly higher than in six control brains (<i>p</i> < 0.05). As the expression difference was highest for the medial orbitofrontal cortex in the right hemisphere, we assessed NLRP1-immunoreactive pyramidal neurons in layers III, V, and VI in the medial orbitofrontal cortex in the right hemisphere of seven schizophrenia and five control brains. Compared to controls, we quantified a significantly higher number of NLRP1-positive pyramidal neurons in the schizophrenia brains (<i>p</i> < 0.01), suggesting NLRP1 inflammasome activation in schizophrenia subjects. Layer III pyramidal neuron dysfunction aligns with working memory deficits, while impairments of pyramidal neurons in layers V and VI likely disrupt predictive processing. We propose NLRP1 inflammasome as a potential biomarker and therapeutic target in schizophrenia. |
| first_indexed | 2024-04-24T18:30:40Z |
| format | Article |
| id | doaj.art-e34270c8e3fc4196bdbbbdb3795de0d9 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-04-24T18:30:40Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-e34270c8e3fc4196bdbbbdb3795de0d92024-03-27T13:27:54ZengMDPI AGBiomolecules2218-273X2024-03-0114330210.3390/biom14030302Increased NLRP1 mRNA and Protein Expression Suggests Inflammasome Activation in the Dorsolateral Prefrontal and Medial Orbitofrontal Cortex in SchizophreniaEna Španić Popovački0Dora Vogrinc1Heidi R. Fuller2Lea Langer Horvat3Davor Mayer4Janja Kopić5Klara Pintarić6Mirjana Babić Leko7Mihaela Pravica8Željka Krsnik9Darko Marčinko10Marina Šagud11Patrick R. Hof12Mihovil Mladinov13Goran Šimić14Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, 10000 Zagreb, CroatiaDepartment of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, 10000 Zagreb, CroatiaWolfson Centre for Inherited Neuromuscular Disease, RJAH Orthopaedic Hospital, Oswestry SY10 7AG, UKDepartment of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, 10000 Zagreb, CroatiaDepartment of Forensic Medicine, University of Zagreb School of Medicine, 10000 Zagreb, CroatiaDepartment of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, 10000 Zagreb, CroatiaDepartment of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, 10000 Zagreb, CroatiaDepartment of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, 10000 Zagreb, CroatiaDepartment of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, 10000 Zagreb, CroatiaDepartment of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, 10000 Zagreb, CroatiaDepartment of Psychiatry and Psychological Medicine, University Hospital Center Zagreb, 10000 Zagreb, CroatiaDepartment of Psychiatry and Psychological Medicine, University Hospital Center Zagreb, 10000 Zagreb, CroatiaNash Family Department of Neuroscience, Center for Discovery and Innovation, and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10019, USADepartment of Psychiatry and Psychotherapy, University of Rostock, Gehlsheimer Str. 20, 18147 Rostock, GermanyDepartment of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, 10000 Zagreb, CroatiaSchizophrenia is a complex mental condition, with key symptoms marked for diagnosis including delusions, hallucinations, disorganized thinking, reduced emotional expression, and social dysfunction. In the context of major developmental hypotheses of schizophrenia, notably those concerning maternal immune activation and neuroinflammation, we studied <i>NLRP1</i> expression and content in the postmortem brain tissue of 10 schizophrenia and 10 control subjects. In the medial orbitofrontal cortex (Brodmann’s area 11/12) and dorsolateral prefrontal cortex (area 46) from both hemispheres of six schizophrenia subjects, the <i>NLRP1</i> mRNA expression was significantly higher than in six control brains (<i>p</i> < 0.05). As the expression difference was highest for the medial orbitofrontal cortex in the right hemisphere, we assessed NLRP1-immunoreactive pyramidal neurons in layers III, V, and VI in the medial orbitofrontal cortex in the right hemisphere of seven schizophrenia and five control brains. Compared to controls, we quantified a significantly higher number of NLRP1-positive pyramidal neurons in the schizophrenia brains (<i>p</i> < 0.01), suggesting NLRP1 inflammasome activation in schizophrenia subjects. Layer III pyramidal neuron dysfunction aligns with working memory deficits, while impairments of pyramidal neurons in layers V and VI likely disrupt predictive processing. We propose NLRP1 inflammasome as a potential biomarker and therapeutic target in schizophrenia.https://www.mdpi.com/2218-273X/14/3/302schizophreniaNLRP1 inflammasomepredictive processingprefrontal cortexpyramidal neurons |
| spellingShingle | Ena Španić Popovački Dora Vogrinc Heidi R. Fuller Lea Langer Horvat Davor Mayer Janja Kopić Klara Pintarić Mirjana Babić Leko Mihaela Pravica Željka Krsnik Darko Marčinko Marina Šagud Patrick R. Hof Mihovil Mladinov Goran Šimić Increased NLRP1 mRNA and Protein Expression Suggests Inflammasome Activation in the Dorsolateral Prefrontal and Medial Orbitofrontal Cortex in Schizophrenia Biomolecules schizophrenia NLRP1 inflammasome predictive processing prefrontal cortex pyramidal neurons |
| title | Increased NLRP1 mRNA and Protein Expression Suggests Inflammasome Activation in the Dorsolateral Prefrontal and Medial Orbitofrontal Cortex in Schizophrenia |
| title_full | Increased NLRP1 mRNA and Protein Expression Suggests Inflammasome Activation in the Dorsolateral Prefrontal and Medial Orbitofrontal Cortex in Schizophrenia |
| title_fullStr | Increased NLRP1 mRNA and Protein Expression Suggests Inflammasome Activation in the Dorsolateral Prefrontal and Medial Orbitofrontal Cortex in Schizophrenia |
| title_full_unstemmed | Increased NLRP1 mRNA and Protein Expression Suggests Inflammasome Activation in the Dorsolateral Prefrontal and Medial Orbitofrontal Cortex in Schizophrenia |
| title_short | Increased NLRP1 mRNA and Protein Expression Suggests Inflammasome Activation in the Dorsolateral Prefrontal and Medial Orbitofrontal Cortex in Schizophrenia |
| title_sort | increased nlrp1 mrna and protein expression suggests inflammasome activation in the dorsolateral prefrontal and medial orbitofrontal cortex in schizophrenia |
| topic | schizophrenia NLRP1 inflammasome predictive processing prefrontal cortex pyramidal neurons |
| url | https://www.mdpi.com/2218-273X/14/3/302 |
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