Nerve Tissue Proteins

Publication Title: 
American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics: The Official Publication of the International Society of Psychiatric Genetics

DNA methylation changes could provide a mechanism for DNA plasticity and dynamism for short-term adaptation, enabling a type of cell memory to register cellular history under different environmental conditions. Some environmental insults may also result in pathological methylation with corresponding alteration of gene expression patterns.

Author(s): 
Abdolmaleky, Hamid Mostafavi
Cheng, Kuang-hung
Russo, Andrea
Smith, Cassandra L.
Faraone, Stephen V.
Wilcox, Marsha
Shafa, Rahim
Glatt, Stephen J.
Nguyen, Giang
Ponte, Joe F.
Thiagalingam, Sam
Tsuang, Ming T.
Publication Title: 
American Journal of Pharmacogenomics: Genomics-Related Research in Drug Development and Clinical Practice

No specific gene has been identified for any major psychiatric disorder, including schizophrenia, in spite of strong evidence supporting a genetic basis for these complex and devastating disorders. There are several likely reasons for this failure, ranging from poor study design with low statistical power to genetic mechanisms such as polygenic inheritance, epigenetic interactions, and pleiotropy. Most study designs currently in use are inadequate to uncover these mechanisms.

Author(s): 
Abdolmaleky, Hamid M.
Thiagalingam, Sam
Wilcox, Marsha
Publication Title: 
Pharmacology & Therapeutics

A recent report suggests that the down-regulation of reelin and glutamic acid decarboxylase (GAD(67)) mRNAs represents 2 of the more consistent findings thus far described in post-mortem material from schizophrenia (SZ) patients [reviewed in. Neurochemical markers for schizophrenia, bipolar disorder amd major depression in postmortem brains. Biol Psychiatry 57, 252-260]. To study mechanisms responsible for this down-regulation, we have analyzed the promoter of the human reelin gene.

Author(s): 
Grayson, Dennis R.
Chen, Ying
Costa, Erminio
Dong, Erbo
Guidotti, Alessandro
Kundakovic, Marija
Sharma, Rajiv P.
Publication Title: 
Trends in Neurosciences

Our understanding of human disorders that affect higher cognitive functions has greatly advanced in recent decades, and over 20 genes associated with non-syndromic mental retardation have been identified during the past 15 years. However, proteins encoded by "cognition genes" have such diverse neurodevelopmental functions that delineating specific pathogenetic pathways still poses a tremendous challenge.

Author(s): 
Persico, Antonio M.
Bourgeron, Thomas
Publication Title: 
Molecular Pharmacology

Reelin and glutamic acid decarboxylase 67 (GAD67) mRNAs and protein levels are substantially reduced in postmortem brains of patients with schizophrenia. Increasing evidence suggests that the observed down-regulation of reelin and GAD67 gene expression may be caused by dysfunction of the epigenetic regulatory mechanisms operative in cortical GABAergic interneurons.

Author(s): 
Kundakovic, Marija
Chen, Ying
Costa, Erminio
Grayson, Dennis R.
Publication Title: 
Clinical Endocrinology

OBJECTIVE: The pathogenesis of idiopathic hypogonadotrophic hypogonadism (IHH) is mostly unclear. We characterized the clinical findings and molecular analysis of GnRHR and KAL1 genes in 26 Brazilian males with IHH with and without hyposmia/anosmia. Design Clinical assessment was performed for endocrine status, olfactory structure and function, renal lesion, and mirror movement. The diagnosis of Kallmann syndrome (KS) included HH and the clinical complaint of hyposmia/anosmia or decreased olfactory acuity obtained by the Smell Identification Test (SIT).

Author(s): 
Versiani, Beatriz R.
Trarbach, Ericka
Koenigkam-Santos, Marcel
Dos Santos, Antonio Carlos
Elias, Lucila L. K.
Moreira, Ayrton C.
Latronico, Ana Claudia
de Castro, Margaret
Publication Title: 
Schizophrenia Research

In the cerebral prefrontal cortex (PFC), DNA-methyltransferase 1 (DNMT1), the enzyme that catalyzes the methylation of cytosine at carbon atoms in position 5 in CpG dinucleotides, is expressed selectively in GABAergic neurons and is upregulated in layers I and II of schizophrenia (SZ) and bipolar disorder patients with psychosis (BDP).

Author(s): 
Veldic, Marin
Kadriu, Bashkim
Maloku, Ekrem
Agis-Balboa, Roberto C.
Guidotti, Alessandro
Davis, John M.
Costa, Erminio
Publication Title: 
Molecular Psychiatry

Epigenetic genome modifications such as DNA methylation appear to be involved in various diseases. Here, we suggest that the levels of DNA methylation at the BssHII methylation-sensitive restriction enzyme sites in the human REELIN (RELN) gene in the forebrain vary among individuals. Interestingly, although a statistically significant correlation between the levels of DNA methylation in RELN and age was detected in healthy individuals, no such correlations were seen in either schizophrenic or bipolar patients.

Author(s): 
Tamura, Y.
Kunugi, H.
Ohashi, J.
Hohjoh, H.
Publication Title: 
Progress in Neurobiology

The ways in which gene transcription is investigated have undergone radical change since the turn of the millennium. Piece-meal approaches focussed upon model genes have increasingly been complemented by genome-wide approaches that allow interrogation of multiple cohorts of genes or even entire genomes. This sea change has been founded upon the increasing availability of whole genome sequences and the attendant evolution of microarray based discovery platforms.

Author(s): 
Buckley, Noel J.
Publication Title: 
Molecular Pharmacology

The epigenetic down-regulation of genes is emerging as a possible underlying mechanism of the GABAergic neuron dysfunction in schizophrenia. For example, evidence has been presented to show that the promoters associated with reelin and GAD67 are down-regulated as a consequence of DNA methyltransferase (DNMT)-mediated hypermethylation. Using neuronal progenitor cells to study this regulation, we have previously demonstrated that DNMT inhibitors coordinately increase reelin and GAD67 mRNAs.

Author(s): 
Kundakovic, Marija
Chen, Ying
Guidotti, Alessandro
Grayson, Dennis R.

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