Rabbit Anti-Human HCRTR2 Polyclonal Antibody

Methamphetamine (METH) and modafinil are psychostimulants with different long-term cognitive profiles: METH is addictive and leads to cognitive decline, whereas modafinil has little abuse liability and is a cognitive enhancer. Increasing evidence implicates epigenetic mechanisms of gene regulation behind the lasting changes that drugs of abuse and other psychotropic compounds induce in the brain, like the control of gene expression by histones 3 and 4 tails acetylation (H3ac and H4ac) and DNA cytosine methylation (5-mC). Mice were treated with a seven-day repeated METH, modafinil or vehicle protocol and evaluated in the novel object recognition (NOR) test or sacrificed 4 days after last injection for molecular assays. We evaluated total H3ac, H4ac and 5-mC levels in the medial prefrontal cortex (mPFC), H3ac and H4ac promotor enrichment (ChIP) and mRNA expression (RT-PCR) of neurotransmitter systems involved in arousal, wakefulness and cognitive control, like dopaminergic (Drd1 and Drd2), alpha-adrenergic (Adra1a and Adra1b), orexinergic (Hcrtr1 and Hcrtr2), histaminergic (Hrh1 and Hrh3) and glutamatergic (AMPA Gria1 and NMDA Grin1) receptors. Repeated METH and modafinil treatment elicited different cognitive outcomes in the NOR test, where modafinil-treated mice performed as controls and METH-treated mice showed impaired recognition memory. METH-treated mice also showed i) decreased levels of total H3ac and H4ac, and increased levels of 5-mC, ii) decreased H3ac enrichment at promoters of Drd2, Hcrtr1/2, Hrh1 and Grin1, and increased H4ac enrichment at Drd1, Hrh1 and Grin1, iii) increased mRNA of Drd1a, Grin1 and Gria1. Modafinil-treated mice shared none of these effects and showed increased H3ac enrichment and mRNA expression at Adra1b. Modafinil and METH showed similar effects linked to decreased H3ac in Hrh3, increased H4ac in Hcrtr1, and decreased mRNA expression of Hcrtr2. The specific METH-induced epigenetic and transcriptional changes described here may be related to the long-term cognitive decline effects of the drug and its detrimental effects on mPFC function. The lack of similar epigenetic effects of chronic modafinil administration supports this notion.

Improvement of the growth rate is a challenge in the pig industry, the Average Daily Gain (ADG) and Days (AGE) to 100 kg are directly related to growth performance. We performed genome-wide association study (GWAS) and genetic parameters estimation for ADG and AGE using the genomic and phonemic from four breed (Duroc, Yorkshire, Landrace, and Pietrain) populations. All analyses were performed by a multi-loci GWAS model, FarmCPU. The GWAS results of all four breeds indicate that five genome-wide significant SNPs were associated with ADG, and the nearby genomic regions explained 4.08% of the genetic variance and 1.90% of the phenotypic variance, respectively. For AGE, six genome-wide significant SNPs were detected, and the nearby genomic regions explained 8.09% of the genetic variance and 3.52% of phenotypic variance, respectively. In total, nine candidate genes were identified to be associated with growth and metabolism. Among them, TRIB3 was reported to associate with pig growth, GRP, TTR, CNR1, GLP1R, BRD2, HCRTR2, SEC11C, and ssc-mir-122 were reported to associate with growth traits in human and mouse. The newly detected candidate genes will advance the understanding of growth related traits and the identification of the novel variants will suggest a potential use in pig genomic breeding programs.