Increased NLRP1 mRNA and Protein Expression Suggests Inflammasome Activation in the Dorsolateral Prefrontal and Medial Orbitofrontal Cortex in Schizophrenia

• Published in: Biomolecules (Basel, Switzerland) Vol. 14; no. 3; p. 302
• Main Authors: Španić Popovački, Ena, Vogrinc, Dora, Fuller, Heidi R, Langer Horvat, Lea, Mayer, Davor, Kopić, Janja, Pintarić, Klara, Babić Leko, Mirjana, Pravica, Mihaela, Krsnik, Željka, Marčinko, Darko, Šagud, Marina, Hof, Patrick R, Mladinov, Mihovil, Šimić, Goran
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.03.2024; MDPI
• Subjects: Antipsychotics; Brain; Care and treatment; Cerebral Cortex - metabolism; Child development; Disease; Dopamine; Drug use; Gene expression; Genetic aspects; Hallucinations; Health aspects; Hemispheric laterality; Humans; Hypotheses; Immune response; Inflammasomes; Inflammasomes - genetics; Inflammasomes - metabolism; Inflammation; Medical imaging; Mental disorders; Messenger RNA; Metabolism; Neuroimaging; NLR Proteins - genetics; NLR Proteins - metabolism; NLRP proteins; NLRP1 inflammasome; Pathogenesis; Physiological aspects; predictive processing; Prefrontal cortex; Prefrontal Cortex - metabolism; Proteins; Psychotropic drugs; Pyramidal cells; Pyramidal Cells - metabolism; pyramidal neurons; Schizophrenia; Therapeutic targets; United Kingdom; pyramidal neurons; predictive processing; NLRP1 inflammasome; schizophrenia; prefrontal cortex
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom14030302

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 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 mRNA expression was significantly higher than in six control brains ( < 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 ( < 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.