User:Seppi333/sandbox4

- Exercise and sodium butyrate transform a subthreshold learning event into long-term memory via a brain-derived neurotrophic factor-dependent mechanism.

Butyrate has established antimicrobial properties in humans which are mediated through the antimicrobial peptide, LL-37, which it induces via HDAC inhibition on histone H3, where it subsequently increases gene expression of a regulatory T cell (Treg) known as FOXP3. Table 3: Select human antimicrobial peptides and their proposed targets Table 4: Some known factors that induce antimicrobial peptide expression  In particular, butyrate significantly inhibits the growth and destroys the cell envelope of the ubiquitous pathogen helicobacter pylori upon exposure, an effect consistent with the action of the LL-37 peptide on bacterial membranes. Among all the short-chain fatty acids that are produced in the microbiome, butyrate is the most potent promoter of intestinal Treg expression (e.g., FOXP3) and the only one among the group which is an NIACR1 ligand; these Tregs in turn increase interleukin 10 (an anti-inflammatory cytokine) synthesis in the cell. Figure 1: Microbial-derived molecules promote colonic Treg differentiation.

Censored text for lead of Addiction
 * - Very good review on addiction epidemiology + human impact: Current perspectives on the neurobiology of drug addiction: a focus on genetics and factors regulating gene expression

Reviews

 * Addiction and or amph epigenetics papers + reviews
 * - 2015 review on "Role of mecp2 in experience-dependent epigenetic programming" with addiction coverage
 * - MeCP2 phosphorylation limits psychostimulant-induced behavioral and neuronal plasticity.


 * Epigenetics of amphetamine's ΔFosB-mediated c-fos repression
 * - Delta FosB mediates epigenetic desensitization of the c-fos gene after chronic amphetamine exposure. (primary)
 * We therefore analyzed whether hypoacetylation of the c-fos gene, seen after chronic amphetamine administration, is also associated with alterations in H3K9 methylation. Consistent with this hypothesis, ChIP carried out on striatal tissue from rats treated with chronic amphetamine revealed that di-methylated H3K9 (H3K9me2) was significantly increased on the c-fos promoter

However, a recent study in NAc using ChIP-seq coupled with RNA-seq (Table 1) investi- gated how combinations of methylation marks (H3K4me1, H3K4me3, H3k36me3 — activating marks; and H3K9me2, H3k9me3, H3K27me3 — repressive marks) correlate with altered transcript levels after exposure to repeated cocaine. While global changes across the genome were not observed, enrichment of H3K4me1 or H3K4me3 at specific gene regions was correlated positively with increased transcription levels, whereas enrichment of H3K9me2, H3K9me3 or H3K27me3 was negatively correlated with transcription [32]. Other studies have found that repeated exposure to cocaine decreases global levels of H3K9me2 [33] and H3K9me3 [34] in NAc, whereas repeated opiate exposure [35] decreases only H3K9me2 in this brain region. In contrast, methamphetamine treatment decreases H3K27me2 and increases H3K4me2 and H3K4me3 globally in NAc when exposure is coupled with CPP but not in the animals’ home cage [36], again suggesting that regulation of histone methylation in response to drugs of abuse is complex and likely drug-specific, region-specific, and context-specific.''' -

Censored note

Intro notes
"Three major mechanisms of epigenetic regulation, chromatin/histone modifications, DNA methylation, and non-coding RNAs [(mainly micro-RNAs)], have been linked to gene expression changes following AMPH use (Table 1)."

"Chromatin remodeling complexes" can alter chromatin structure by acetylation, methylation, phosphorylation, ubiquitination, etc., by introducing variant histones s into the chromatin, by silencing genes ("in order to completely silence gene activity, additional mechanisms such as DNA methylation have evolved, which results in the establishment of a highly quiescent state at genes. Often, these different mechanisms occur in combination. For instance, epigenetic marks such as methylation of the histone H3 lysine 9 residue (H3K9 trimethylation) and DNA methylation are associated with repressed and/or silenced genes [29]"
 * Murine: "chronic (7 days) AMPH treatments causes instead a strong decrease of c-fos expression [19,20], and a several fold increase of ΔFosB [19,22], suggesting that acute and chronic AMPH exposures regulate the expression of c-fos through different and possibly opposite mechanisms."
 * Rats, cocaine, transgenerational epigenetic inheritance: "For instance, a recent study demonstrated that when male rats voluntarily ingested cocaine, their male, but not female, offspring exhibited increased levels in protein and mRNA of the brain-derived neurotrophic factor (Bdnf) in the medial prefrontal cortex [26]."

Amphetamine micro-RNAs

 * Mice: 5-day amph use in rats promotes miRNA-181 a (miR-181a) in ventral tegmental area projections to: ventral mid-brain, subcortical limbic forebrain, prefrontal cortex and the hippocampus. miR-181a is also induced by cocaine in the dopamine D2-like receptors expressing neurons
 * Mice: 5-day amph use produces a robust and significant increase of miR-29b, miR-142/5p, miR-183, miR-196b, miR-215, miR-216b, miR-217 and 292/3p in the hippocampus

Amphetamine notable epigenetic mechanisms

 * Mice, Nucleus accumbens: "viral manipulation of MeCP2 expression in the nucleus accumbens modulates AMPH-induced conditioned place preference (CPP). Specifically, lentiviral overexpression of MeCP2 inhibited the AMPH-induced CPP, whereas lentiviral knockdown of MeCP2 augmented both AMPH-induced CPP and locomotor activity. Furthermore, mice bearing a hypomorphic mutation in MeCP2 exhibited altered behavioral response to both acute and chronic AMPH treatments and obstructed dendritic plasticity induced by repeated AMPH treatments [20]. These results demonstrate that MeCP2 is a crucial component in the behavioral response to AMPH."
 * "in vitro data: co-treatment with VPA and AMPH further increased H4 acetylation [compared to when] VPA or AMPH were administrated individually.
 * mice: AMPH and [nonspecific] HDAC inhibitors administered together further increased the levels of H4 acetylation and phospho-CREB
 * Immuno-precipitation experiments demonstrated that repeated AMPH or VPA treatments decreased the amount of CREB proteins interacting with [HDAC1]
 * [AMPH administered together with VPA decreased the number of CREB proteins bound to HDAC1 even further]
 * These data suggest that both AMPH and HDAC inhibitors alter CREB phosphorylation, which in turn alter the interaction between HDAC1 and CREB

Acetylation
"Acetylation has been the most reported change at histones during exposure to the psychostimulant AMPH (Table 1). Acute AMPH treatments were shown to increase H4 acetylation at the c-fos promoter [19], and this increase disappears after chronic AMPH treatments. As histone deacetylation has been related to gene silencing, these results suggest histone deacetylation mediates the repression of c-fos expression following chronic AMPH treatments.
 * This conclusion was supported by the fact that histone deacetylase (HDAC) inhibitors reversed the AMPH-induced reduction of c-fos expression observed after chronic treatments [19].
 * Acute: These data suggest that in drug-naïve animals AMPH increases gene expression of c-fos by increasing acetylation of the H4 at the c-fos promoter
 * Chronic: Prolonged treatments with AMPH promote gene silencing by inhibiting acetylation.
 * Amphetamine acetylates H4K12ac

HDACi's from review
"Studies reporting histone acetylation have been particularly prolific thanks to the use of HDAC inhibitors such as butyric acid (BA) and valproic acid (VPA)."