Schizophrenia (SZ) and bipolar disorder (BPD) patients show a downregulation of GAD67, reelin (RELN), brain-derived neurotrophic factor (BDNF), and other genes expressed in telencephalic GABAergic and glutamatergic neurons.
A down-regulation of reelin and glutamic acid decarboxylase (GAD) 67 mRNAs was detected in gamma-aminobutyric acid (GABA)ergic cortical interneurons of schizophrenia (SZ) postmortem brains (10), suggesting that the availability of GABA and reelin may be decreased in SZ cortex.
A protein putatively functioning as an intracellular target for the signal-transduction cascade triggered by RELN protein released into the extracellular matrix is termed mouse disabled-1 (DAB1) and is expressed at comparable levels in the neuroplasm of the PFC and hippocampal pyramidal neurons, cerebellar Purkinje neurons of schizophrenia patients, and nonpsychiatric subjects; these three types of neurons do not express RELN protein.
An understanding of the epigenetic regulation of reelin gene expression and of the possible pathogenetic role of reelin deficiency in schizophrenia, may become a major focus that will open new avenues for the treatment of this disease.
Based upon the assumption of parallel methylation changes in the brain and peripheral blood, we concluded that RELN DNA methylation might contribute to the pathogenesis of schizophrenia.
Besides LIS2 and ADLTE, <i>RELN</i> and/or other genes coding for the proteins of the Reln intracellular cascade have been associated substantially to other conditions such as spinocerebellar ataxia type 7 and 37, <i>VLDLR</i>-associated cerebellar hypoplasia, <i>PAFAH1B1</i>-associated lissencephaly, autism, and schizophrenia.
CRMP1 is a novel candidate protein for schizophrenia traits at the intersection of the reelin and DISC1 pathways that directly and functionally interacts with DISC1.
Despite the small sample size, these studies indicate that promoter hypermethylation of the RELN gene could be a significant contributor in effecting epigenetic alterations and provides a molecular basis for the RELN gene hypoactivity in schizophrenia.
Eight markers obtained nominal significance in both tests, and were located in intronic or 3'UTR regions of adhesion molecule MDGA1 and previously reported SZ candidate RELN.
In addition, reelin protein in the molecular layer of the dentate gyrus was decreased in schizophrenia, bipolar disorder, and depression at the trend level of statistical significance (P=0.065).
In our present study we investigated methylation of genomic DNA and promoter methylation of Reelin and SOX10 genes in peripheral blood of twins suffering from schizophrenia.
In summary, the reelin haploinsufficient mouse may provide a useful model for studying the interaction between reelin and hippocampal GABAergic system, its effect on dendritic spine maturation and plasticity related to schizophrenia.
In the same samples, the GABAergic neuron-specific glutamic acid-decarboxylase(67) (GAD(67)) and reelin mRNAs were underexpressed twofold in GABAergic interneurons isolated from layer I of SZP relative to GABAergic interneurons microdissected from layer I of NPS, and unaltered in GABAergic interneurons of layer V. These findings implicate an epigenetically mediated layer I GABAergic dysfunction in the pathogenesis of schizophrenia, and suggest novel strategies for treatment of the disease.
In this study, case-control association analyses were performed in the Han Chinese population to determine if the RELN gene is a susceptibility gene for SZ.
IN-derived Reelin has been associated with schizophrenia and temporal lobe epilepsy; however, the functional role of Reelin from INs is presently unclear.