Fatemi SH, Earle JA, McMenomy T. Reduction in Reelin immunoreactivity in hippocampus of subjects with schizophrenia, bipolar disorder and major depression. Mol Psychiatry 5: 654-663, 571

Department of Psychiatry, University of Minnesota Medical School, Minneapolis 55455, USA.
Molecular Psychiatry (Impact Factor: 14.5). 11/2000; 5(6):654-63, 571. DOI: 10.1038/
Source: PubMed


Accumulation of neurobiological knowledge points to neurodevelopmental origins for certain psychotic and mood disorders. Recent landmark postmortem reports implicate Reelin, a secretory glycoprotein responsible for normal lamination of brain, in the pathology of schizophrenia and bipolar disorders. We employed quantitative immunocytochemistry to measure levels of Reelin protein in various compartments of hippocampal formation in subjects diagnosed with schizophrenia, bipolar disorder and major depression compared to normal controls. Significant reductions were observed in Reelin-positive adjusted cell densities in the dentate molecular layer (ANOVA, P < 0.001), CA4 area (ANOVA, P < 0.001), total hippocampal area (ANOVA, P < 0.038) and in Reelin-positive cell counts in CA4 (ANOVA, P < 0.042) of schizophrenics vs controls. Adjusted Reelin-positive cell densities were also reduced in CA4 areas of subjects with bipolar disorder (ANOVA, P < 0.001) and nonsignificantly in those with major depression. CA4 areas were also significantly reduced in schizophrenic (ANOVA, P < 0.009) patients. No significant effects of confounding variables were found. The exception was that family history of psychiatric illness correlated strongly with Reelin reductions in several areas of hippocampus (CA4, adjusted cell density, F = 13.77, P = 0.001). We present new immunocytochemical evidence showing reductions in Reelin expression in hippocampus of subjects with schizophrenia, bipolar disorder and major depression and confirm recent reports documenting a similar deficit involving Reelin expression in brains of subjects with schizophrenia and bipolar disorder.

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Available from: S.Hossein Fatemi, Mar 29, 2014
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    • "Reelin (RELN) is located on chromosome 7q22 (DeSilva et al., 1997) and various RELN SNPs, DNA methylation sites and GGC polymorphic repeats (Figure 1) have been shown to regulate reelin mRNA expression and protein translational levels (Abdolmaleky et al., 2005; Persico, Levitt, & Pimenta, 2006; Tamura, Kunugi, Ohashi, & Hohjoh, 2007). These aberrations have been confirmed by reduced and increased reelin mRNA and protein levels in GABAergic neurons in the brain (basal ganglia, cerebellum, hippocampus and prefrontal cortex) based on their genetic makeup (Fatemi et al., 2000; Guidotti et al., 2000; Veldic et al., 2007). Research using the reeler mouse model (reelin deficient mice) have shown that mutations in the reelin gene contributes to malformations of cortical development (MCD) (Hartfuss et al., 2003; Niu, Renfro, Quattrocchi, Sheldon, & D'Arcangelo, 2004; Tueting et al., 1999). "
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    ABSTRACT: Stress is clearly associated with the quality of life and many diseases, including mental disorders, with cortisol being a recognized biomarker for stress. Polymorphisms of the serotonin transporter gene (5-HTT), which results in long and short forms, have been reported to be associated with depression among major depressive disorder (MDD) patients. We have previously shown that 5-HTTLPR and waking cortisol do not predict depression in a general population sample, however, psychological resilience is a defence against depression. Reelin is an emerging biomarker for psychological resilience that plays an active role in neuronal migration. It is responsible for cytoarchitechtonic pattern formation in brain and modulates the migration of newly generated postmitotic neurons from the ventricular zone. In mice, overexpression of reelin in the hippocampus has anti-depressant activity by increasing neurogenesis and improving learning. A number of single nucleotide polymorphisms (SNPs), methylation of the promoter and coding region of the reelin (RELN) gene have been identified which affect the level of RELN mRNA and protein expression. Thus RELN is a potential candidate as a biomarker of psychological resilience and we have developed a rapid high-resolution melting (HRM) PCR analysis technique for the RELN SNPs and loci using gDNA isolated from buccal cells to test this hypothesis.
    Full-text · Article · Jun 2015
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    • "This idea has gained traction from several sets of previous findings. For example, work with postmortem tissue from depressed patients has revealed general decreases in reelin expression in the hippocampus (Fatemi et al., 2000). Similarly, preclinical studies have shown that repeated CORT, but not restraint stress, reduces the number of reelin + cells selectively in the subgranular zone and the CA1 stratum-lacunosum moleculare (Lussier et al., 2009). "
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    Full-text · Article · Feb 2015 · Progress in Neuro-Psychopharmacology and Biological Psychiatry
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    • "Antipsychotic drugs have also been shown to have an effect on specific epigenetic mechanisms involving the regulation of specific gene regulations. This notion initially came from findings that there are low levels of reelin and glutamic acid decarboxylase 67 (GAD67) are in the brains of people with schizophrenia and bipolar disorder.18,19,20) These data suggested that the down regulation of these transcripts were due to hyper-methylation of their gene promoters.21,22,23) "
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