DNA methylation levels of RELN promoter region in ultra-high risk, first episode and chronic schizophrenia cohorts of schizophrenia.

The essential role of the Reelin gene (RELN) during brain development makes it a prominent candidate in human epigenetic studies of Schizophrenia. Previous literature has reported differing levels of DNA methylation (DNAm) in patients with psychosis. Therefore, this study aimed to (1) examine and compare RELN DNAm levels in subjects at different stages of psychosis cross-sectionally, (2) analyse the effect of antipsychotics (AP) on DNAm, and (3) evaluate the effectiveness and applicability of RELN promoter DNAm as a possible biological-based marker for symptom severity in psychosis.

MEF2C and HDAC5 regulate and genes to increase dendritic spine density and complexity in early enriched environment.

We investigated the effects of environmental enrichment during critical period of early postnatal life and how it interplays with the epigenome to affect experience-dependent visual cortical plasticity. Mice raised in an EE from birth to during CP have increased spine density and dendritic complexity in the visual cortex. EE upregulates synaptic plasticity genes, and , and a transcription factor MEF2C.

Plasticity of DNA methylation, functional brain connectivity and efficiency in cognitive remediation for schizophrenia.

Cognitive remediation (CR) is predicated on principles of neuroplasticity, but the actual molecular and neurocircuitry changes underlying cognitive change in individuals with impaired neuroplastic processes is poorly understood. The present study examined epigenetic-neurocircuitry-behavioral outcome measures in schizophrenia, before and after participating in a CR program that targeted higher-order cognitive functions. Outcome measures included DNA methylation of genes central to synaptic plasticity (CpG sites of Reelin promoter and BDNF promoter) from buccal swabs, resting-state functional brain connectivity and topological network efficiency, and global scores of a cognitive battery from 35 inpatients in a rehabilitative ward (18 CR, 17 non-CR) with similar premorbid IQ to 15 healthy controls.

Defining a critical period for inhibitory circuits within the somatosensory cortex.

Although experience-dependent changes in brain inhibitory circuits are thought to play a key role during the "critical period" of brain development, the nature and timing of these changes are poorly understood. We examined the role of sensory experience in sculpting an inhibitory circuit in the primary somatosensory cortex (S1) of mice by using optogenetics to map the connections between parvalbumin (PV) expressing interneurons and layer 2/3 pyramidal cells. Unilateral whisker deprivation decreased the strength and spatial range of inhibitory input provided to pyramidal neurons by PV interneurons in layers 2/3, 4 and 5.

Molecular mechanisms of experience-dependent maturation in cortical GABAergic inhibition.

Critical periods (CP) in early post-natal life are periods of plasticity during which the neuronal circuitry is most receptive to environmental stimuli. These early experiences translate to a more permanent and sophisticated neuronal connection in the adult brain systems. Multiple studies have pointed to the development of inhibitory circuitry as one of the central factors for the onset of critical periods.

Changes in Hepatic TRβ Protein Expression, Lipogenic Gene Expression, and Long-Chain Acylcarnitine Levels During Chronic Hyperthyroidism and Triiodothyronine Withdrawal in a Mouse Model.

Background: Thyroid hormone (TH) has important roles in regulating hepatic metabolism. It was previously reported that most hepatic genes activated by a single triiodothyronine (T3) injection became desensitized after multiple injections, and that approximately 10% of target genes did not return to basal expression levels after T3 withdrawal, despite normalization of serum TH and thyrotropin (TSH) levels. To determine the possible mechanism(s) for desensitization and incomplete recovery of hepatic target gene transcription and their effects on metabolism, mRNA and/or protein expression levels of key regulators of TH action were measured, as well as metabolomic changes after chronic T3 treatment and withdrawal.

Network-based characterization of the synaptic proteome reveals that removal of epigenetic regulator Prmt8 restricts proteins associated with synaptic maturation.

The brain adapts to dynamic environmental conditions by altering its epigenetic state, thereby influencing neuronal transcriptional programs. An example of an epigenetic modification is protein methylation, catalyzed by protein arginine methyltransferases (PRMT). One member, Prmt8, is selectively expressed in the central nervous system during a crucial phase of early development, but little else is known regarding its function.

HDAC1 negatively regulates Bdnf and Pvalb required for parvalbumin interneuron maturation in an experience-dependent manner.

During early postnatal development, neuronal circuits are sculpted by sensory experience provided by the external environment. This experience-dependent regulation of circuitry development consolidates the balance of excitatory-inhibitory (E/I) neurons in the brain. The cortical barrel-column that innervates a single principal whisker is used to provide a clear reference frame for studying the consolidation of E/I circuitry.

Desensitization and Incomplete Recovery of Hepatic Target Genes After Chronic Thyroid Hormone Treatment and Withdrawal in Male Adult Mice.

Clinical symptoms may vary and not necessarily reflect serum thyroid hormone (TH) levels during acute and chronic hyperthyroidism as well as recovery from hyperthyroidism. We thus examined changes in hepatic gene expression and serum TH/TSH levels in adult male mice treated either with a single T3 (20 μg per 100 g body weight) injection (acute T3) or daily injections for 14 days (chronic T3) followed by 10 days of withdrawal. Gene expression arrays from livers harvested at these time points showed that among positively-regulated target genes, 320 were stimulated acutely and 429 chronically by T3.

Analysing extremely small sized ratio datasets.

The naïve use of expression ratios in high-throughput biological studies can greatly limit analytical outcome especially when sample size is small. In the worst-case scenario, with only one reference and one test state each (often due to the severe lack of study material); such limitations make it difficult to perform statistically meaningful analysis. Workarounds include the single sample Z-test or through network inference.

Valproic acid mediates miR-124 to down-regulate a novel protein target, GNAI1.

Valproic acid (VPA) is an anti-convulsant drug that is recently shown to have neuroregenerative therapeutic actions. In this study, we investigate the underlying molecular mechanism of VPA and its effects on Bdnf transcription through microRNAs (miRNAs) and their corresponding target proteins. Using in silico algorithms, we predicted from our miRNA microarray and iTRAQ data that miR-124 is likely to target at guanine nucleotide binding protein alpha inhibitor 1 (GNAI1), an adenylate cyclase inhibitor.

All-optical mapping of barrel cortex circuits based on simultaneous voltage-sensitive dye imaging and channelrhodopsin-mediated photostimulation.

We describe an experimental approach that uses light to both control and detect neuronal activity in mouse barrel cortex slices: blue light patterned by a digital micromirror array system allowed us to photostimulate specific layers and columns, while a red-shifted voltage-sensitive dye was used to map out large-scale circuit activity. We demonstrate that such all-optical mapping can interrogate various circuits in somatosensory cortex by sequentially activating different layers and columns. Further, mapping in slices from whisker-deprived mice demonstrated that chronic sensory deprivation did not significantly alter feedforward inhibition driven by layer 5 pyramidal neurons.

Comparative network-based recovery analysis and proteomic profiling of neurological changes in valproic acid-treated mice.

Despite its prominence for characterization of complex mixtures, LC-MS/MS frequently fails to identify many proteins. Network-based analysis methods, based on protein-protein interaction networks (PPINs), biological pathways, and protein complexes, are useful for recovering non-detected proteins, thereby enhancing analytical resolution. However, network-based analysis methods do come in varied flavors for which the respective efficacies are largely unknown.

Contemporary network proteomics and its requirements.

The integration of networks with genomics (network genomics) is a familiar field. Conventional network analysis takes advantage of the larger coverage and relative stability of gene expression measurements. Network proteomics on the other hand has to develop further on two critical factors: (1) expanded data coverage and consistency, and (2) suitable reference network libraries, and data mining from them.

The role of miRNAs in complex formation and control.

Unlabelled: microRibonucleic acid (miRNAs) are small regulatory molecules that act by mRNA degradation or via translational repression. Although many miRNAs are ubiquitously expressed, a small subset have differential expression patterns that may give rise to tissue-specific complexes.

Motivation: This work studies gene targeting patterns amongst miRNAs with differential expression profiles, and links this to control and regulation of protein complexes.

Histone modifications in the brain.

Chromatin remodelling, including histone modifications has been recognized to play a central role in the regulation of gene expression. Histone modifications are mostly based on studies in cell culture systems in vitro. Recent evidence suggests that histone modifications are actively involved in activity-dependent neural plasticity via regulation of critical gene transcription necessary for the biological process in vivo.

Histone modifications in kainate-induced status epilepticus.

To understand the molecular actions of status epilepticus at the chromatin level, we studied the effects of kainate-induced status epilepticus on two different histone modifications at amino terminal tails: histone H3 phosphorylation at serine 10 and histone H4 acetylation. In addition to induction of c-fos and c-jun immediate early genes (IEGs) expression in mouse hippocampus, we also found the upregulation of acetylation and phosphorylation of histones, coupled with status epilepticus after kainate administration. c-fos and c-jun mRNA were sequentially induced in response to kainate, in different hippocampal subpopulations, starting from the dentate gyrus (DG) and spreading to the cornus ammonis regions.

Stimulation of ubiquitin-proteasome pathway through the expression of amidohydrolase for N-terminal asparagine (Ntan1) in cultured rat hippocampal neurons exposed to static magnetism.

In order to elucidate mechanisms underlying modulation by static magnetism of the cellular functionality and/or integrity in the brain, we screened genes responsive to brief magnetism in cultured rat hippocampal neurons using differential display analysis. We have for the first time cloned and identified Ntan1 (amidohydrolase for N-terminal asparagine) as a magnetism responsive gene in rat brain. Ntan1 is an essential component of a protein degradation signal, which is a destabilizing N-terminal residue of a protein, in the N-end rule.

Inhibition of histone deacetylation by trichostatin A intensifies the transcriptions of neuronal c-fos and c-jun genes after kainate stimulation.

Kainate stimulation induces the expression of immediate early genes, c-fos and c-jun genes. Trichostatin A (TSA), a potent histone deacetylase (HDAC) enzyme inhibitor was used to test the role of histone hyperacetylation in the transcriptional regulation of c-fos and c-jun genes in neuronal cells in vivo and in vitro. Intraperitoneal administration of TSA increased histone H4 acetylation in hippocampi.

A tale of early response genes.

Immediate early genes (IEG) are rapidly but transiently induced directly by intracellular signaling cascades to alter patterns of gene expression. It has been proposed that histone modifications could be the key to the quick alteration of chromatin structure, as this spread occurs too rapidly to be the consequence of passage of RNA polymerase II. In this review, we will discuss the different modifications on histones and the chromatin remodeling enzymes, allowing the promoter regions of two IEGs, c-fos and c-jun, to be accessed.