A decrease in interleukin-1 receptor antagonist expression in the prefrontal cortex of schizophrenic patients

Toyooka, Kazuhiko; Watanabe, Yuichiro; Iritani, Shuji; Shimizu, Eiji; Iyo, Masaomi; Nakamura, Ryosuke; Asama, Koue; Makifuchi, Takao; Kakita, Akiyoshi; Takahashi, Hitoshi; Someya, Toshiyuki; Nawa, Hiroyuki

doi:10.1016/s0168-0102(03)00093-2

Cited by 53 publications

(29 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The VNTR polymorphism in intron 2 of IL1RN has been linked with disease susceptibility and activity in schizophrenia [18,19], but reported results are contradictory [20,21]. It has been reported that specifically mRNA expression and protein levels of IL1RN were decreased in patients with schizophrenia [22]. On the other hand, it has been demonstrated that chronic treatment with antipsychotic drugs increases the mRNA levels of IL-1β and IL-1Ra in the rat brain.…”

Section: Introductionmentioning

confidence: 99%

Influence of IL-1RN Intron 2 Variable Number of Tandem Repeats (VNTR) Polymorphism on Bipolar Disorder

et al. 2013

View full text Add to dashboard Cite

Background/Aims: Several lines of evidence point to the role of neurobiological mechanisms and genetic background in bipolar disorder (BD). The interleukin-1 receptor antagonist (IL-1Ra) is the principal regulator of IL-1α and IL-1β bioactivities. This study aimed to investigate the potential role of the variable number of tandem repeats (VNTR) polymorphisms of the IL-1Ra gene (IL1RN) in conferring susceptibility to BD. Methods: In total, 217 patients meeting DSM-IV-TR criteria for BD and 212 controls were recruited for the study. Genotyping of IL1RN was determined by polymerase chain reaction amplification of VNTR of 86 base pairs in intron 2 of IL1RN. Results: The genotype distribution of IL1RN polymorphism was significantly different between BD patients and controls. The IL1RN*1/2 genotype was more prevalent in BD patients than in controls (44.2 vs. 30.2%, p = 0.003). Multiple logistic regression analysis demonstrated that IL1RN*1/2 heterozygotes had a significantly higher risk for BD (OR 1.83 and 95% CI 1.22–2.74, p = 0.003). Further stratification of the BD patients into IL1RN*2 allele carrier and noncarrier subgroups revealed a strong association between IL1RN*2 carriage and prolongation of the disease (p = 0.02). Conclusions: These findings suggest a positive association between VNTR polymorphism in IL1RN and BD. Additional studies, particularly with a prospective approach, are necessary to clarify the precise role of the VNTR polymorphism on the disease in different ethnic populations.

show abstract

Section: Introductionmentioning

confidence: 99%

Influence of IL-1RN Intron 2 Variable Number of Tandem Repeats (VNTR) Polymorphism on Bipolar Disorder

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Patients with schizophrenia often exhibit impaired autoimmune responses and abnormal levels of cytokines (Licinio et al, 1993;Lin et al, 1998;Toyooka et al, 2003). Interestingly, there is also a reverse correlation between neuroinflammation and psychiatric symptoms.…”

Section: Introductionmentioning

confidence: 99%

A Cyclooxygenase-2 Inhibitor Ameliorates Behavioral Impairments Induced by Striatal Administration of Epidermal Growth Factor

Mizuno

Sotoyama²,

Narita³

et al. 2007

J. Neurosci.

View full text Add to dashboard Cite

Consistent with the hypothesis that neuroinflammatory processes contribute to the neuropathology of schizophrenia, the protein levels of epidermal growth factor (EGF) and its receptor ErbB1 are abnormal in patients with schizophrenia. To evaluate neuropathological significance of this abnormality, we established an animal model for behavioral deficits by administering EGF into the striatum and evaluated the effects of cyclooxygenase-2 (Cox-2) inhibitor celecoxib. Intracranial infusion of EGF into the striatum of adult male rats activated ErbB1 and induced neurobehavioral impairments observed in several schizophrenia models. Unilateral EGF infusion to the striatum lowered prepulse inhibition (PPI) in a dose-dependent manner and impaired latent learning of active shock avoidance without affecting basal learning ability. Bilateral EGF infusion similarly affected PPI. In contrast, EGF infusion to the nucleus accumbens did not induce a behavioral deficit. Intrastriatal EGF infusion also increased Cox-2 expression, elevated tyrosine hydroxylase activity, and upregulated the levels of dopamine and its metabolites. Subchronic administration of celecoxib (10 mg/kg, p.o.) ameliorated the abnormalities in PPI and latent learning as well as normalized dopamine metabolism. We conclude that this EGF-triggered neuroinflammatory process is mediated in part by Cox-2 activity and perturbs dopamine metabolism to generate neurobehavioral abnormalities.

show abstract

“…This broad region hosts multiple genes of interest (Table SI) that are expressed in brain. Interestingly, the list of genes includes interleukin 1 receptor antagonist (IL1RN) [Toyooka et al, 2003;Kim et al, 2004;Papiol et al, 2005;Shirts et al, 2006] and diazepam binding inhibitor (DBI) [Edgar et al, 1999], previously suggested to be involved in the development of schizophrenia.…”

Section: Discussion Susceptibility Loci For Schizophreniamentioning

confidence: 99%

Support for schizophrenia susceptibility locus on chromosome 2q detected in a Swedish isolate using a dense map of microsatellites and SNPs

Åberg¹,

Axelsson²,

Saetre³

et al. 2008

American J of Med Genetics Pt B

View full text Add to dashboard Cite

Extended pedigrees are not only very useful to identify disease genes for rare Mendelian conditions, but they may also help unravel the genetics of complex diseases such as schizophrenia. In this study we performed genome-wide multipoint non-parametric linkage (NPL) score calculations using 825 microsatellites and 5,366 single nucleotide polymorphisms (SNPs), respectively, and searched for haplotypes shared by affected individuals, in three multiplex families including 29 genotyped affected individuals which in total contains 49 relative pairs useful for linkage studies. The most consistent results for microsatellites and SNPs were observed on 2q12.3-q14.1 (NPL scores 2.0, empirical P-value 0.009). However, the overall highest NPL score was observed on chromosome 2q33.3 using SNPs (NPL score 2.2, empirical P-value 0.007). Other chromosomal regions were detected on 5q15-q22.1, with microsatellites (NPL scores 1.7, empirical P-value 0.021) and with SNPs (NPL scores 2.0, empirical P-value 0.010) and on 5q23.1 (NPL score 1.9, empirical P-value 0.012) and 8q24.1-q24.2 (NPL score 2.1, empirical P-value 0.009) when using SNPs. The analysis of extended pedigrees allowed the search for haplotypes inherited identical by decent (IBD) by affected individuals. In all regions with NPL score >1.9 we found haplotypes inherited IBD by multiple cases. However, no common haplotypes were found for affected individuals in all families. In conclusion our NPL results support earlier findings suggesting that 2q and possibly 5q and 8q contain susceptibility loci for schizophrenia. Haplotype sharing in families helped to delimit the detected regions that potentially are susceptibility loci for schizophrenia.

show abstract

A decrease in interleukin-1 receptor antagonist expression in the prefrontal cortex of schizophrenic patients

Cited by 53 publications

References 41 publications

Influence of IL-1RN Intron 2 Variable Number of Tandem Repeats (VNTR) Polymorphism on Bipolar Disorder

Influence of IL-1RN Intron 2 Variable Number of Tandem Repeats (VNTR) Polymorphism on Bipolar Disorder

A Cyclooxygenase-2 Inhibitor Ameliorates Behavioral Impairments Induced by Striatal Administration of Epidermal Growth Factor

Support for schizophrenia susceptibility locus on chromosome 2q detected in a Swedish isolate using a dense map of microsatellites and SNPs

Contact Info

Product

Resources

About