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

被引:0
作者
Popovacki, Ena Spanic [1 ]
Vogrinc, Dora [1 ]
Fuller, Heidi R. [2 ,3 ]
Langer Horvat, Lea [1 ]
Mayer, Davor [4 ]
Kopic, Janja [1 ]
Pintaric, Klara [1 ]
Leko, Mirjana Babic [1 ]
Pravica, Mihaela [1 ]
Krsnik, Zeljka [1 ]
Marcinko, Darko [5 ,6 ]
Sagud, Marina [5 ,6 ]
Hof, Patrick R. [7 ]
Mladinov, Mihovil [8 ]
Simic, Goran [1 ]
机构
[1] Univ Zagreb, Sch Med, Croatian Inst Brain Res, Dept Neurosci, Zagreb 10000, Croatia
[2] RJAH Orthopaed Hosp, Wolfson Ctr Inherited Neuromuscular Dis, Oswestry SY10 7AG, England
[3] Keele Univ, Sch Pharm & Bioengn, Keele ST5 5BG, England
[4] Univ Zagreb, Sch Med, Dept Forens Med, Zagreb 10000, Croatia
[5] Univ Hosp Ctr Zagreb, Dept Psychiat & Psychol Med, Zagreb 10000, Croatia
[6] Univ Zagreb, Sch Med, Zagreb 10000, Croatia
[7] Friedman Brain Inst, Ctr Discovery & Innovat, Icahn Sch Med Mt Sinai, Nash Family Dept Neurosci, New York, NY 10019 USA
[8] Univ Rostock, Dept Psychiat & Psychotherapy, Gehlsheimer Str 20, D-18147 Rostock, Germany
关键词
schizophrenia; NLRP1; inflammasome; predictive processing; prefrontal cortex; pyramidal neurons; MATERNAL IMMUNE ACTIVATION; ZAGREB COLLECTION; CONSCIOUS ACCESS; MICROGLIA; NEUROINFLAMMATION; PATHOPHYSIOLOGY; NORMALIZATION; PATHOGENESIS; INNERVATION; DISEASE;
D O I
10.3390/biom14030302
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 NLRP1 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 NLRP1 mRNA expression was significantly higher than in six control brains (p < 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 (p < 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.
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页数:22
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