Anti-PDYN polyclonal antibody

Prodynorphin (PDYN) binds to k-opioid receptors (KOPr; encoded by OPRK1) and is known to regulate dopaminergic tone, making this system important for drugs addiction. Dynorphin (Dyn)/KORr system are powerful effectors of stress-induced alterations in reward processing and dysphoric states. Thus, We identified 11 potential functional SNPs and one variable number of tandem repeat (VNTR) in this system, performed a case-control association analysis, investigated particular disease phenotypes, assessed the joint effect of variants in two genes, carried out a meta-analysis to analyze the association between this VNTR and Heroin dependence (HD) risk. Eleven single-nucleotide polymorphisms (SNPs) were genotyped using SNaPshot SNP technology. Participants included 566 healthy controls and 541 patients with HD. We found that PDYN polymorphisms modulate the susceptibility to HD. An increased risk of HD was significantly associated with H alleles of PDYN VNTR (chi(2) = 10.824, p = 0.001, OR = 1.419, 95% CI = 1.151-1.748). In addition, the results revealed the patients with the HH genotype showed greater number of withdrawal instances (F(2538) = 7.987, p = 0.0004) compared to the patients with the LL genotype. The Meta-analysis showed the pooled effect of the H allele at this locus is a risk factor for HD in Chinese Han. Gene-gene interaction analysis indicated strong interactions between PDYN rs3830064, 68-bp VNTR and OPRK1 rs16918842, rs3802279. These findings support the important role of PDYN polymorphism in HD, and may guide future studies to identify genetic risk factors for HD.

Methamphetamine (MA), a psychostimulant abused worldwide, gives rise to neurotoxicity in the hippocampus, resulting in cognitive impairments and hippocampal volume reduction. The cellular and molecular mechanisms associated with hippocampal impairments due to MA remain unknown. The aim of this study was to investigate the effects of MA on structural alterations and gene expressions in the hippocampus. We analyzed the pattern of volumetric changes in the hippocampus using magnetic resonance imaging (MRI) after acute and chronic administration of MA to cynomolgus macaques. In addition, we performed large-scale transcriptome profiling in the hippocampus using RNA-Seq technology. The hippocampus in response to acute and chronic MA exhibited a significant volumetric atrophy compared with the hippocampus of controls. The genes associated with cytoskeleton organization and phagocytosis were downregulated in the acute MA-treated group compared to the control group. On the other hand, genes associated with synaptic transmission, regulation of neuron differentiation and regulation of neurogenesis were downregulated in the chronic MA-treated group. We confirmed that expression patterns for ADM, BMP4, CHRD, PDYN, UBA1, profilin 2 (PFN2), ENO2 and NSE mRNAs were similar to the results from RNA-Seq based on quantitative RT-PCR. In particular, PFN2 mRNA and protein expression levels, which play important roles in actin cytoskeleton dynamics, were decreased by acute and chronic MA administration. These results not only aid the understanding of cellular and molecular mechanisms regulated by MA in the hippocampus but also suggest basic information aiding biomarker and novel drug development for treating hippocampal impairment caused by MA abuse.