Background: Alzheimer’s disease (AD) is a complex neurodegenerative disease with multifactorial etiology, unsatisfactory treatment, and a necessity for broad-spectrum active substances for cure. The mucus from Helix aspersa snail is a mixture of bioactive molecules with antimicrobial, anti-inflammatory, antioxidant, and anti-apoptotic effects. So far there are no data concerning the capacity of snail extract (SE) to affect neurodegenerative disorders. Objective: The effects of SE from Helix aspersa on learning and memory deficits in Alzheimer’s type dementia (ATD) induced by scopolamine (Sco) in male Wistar rats were examined and some mechanisms of action underlying these effects were evaluated. Methods: SE (0.5 mL/100 g) was applied orally through a food tube for 16 consecutive days: 5 days before and 11 days simultaneously with Sco (2 mg/kg, intraperitoneally). At the end of Sco treatment, using behavioral methods, we evaluated memory performance. Additionally, in cortex and hippocampus the acetylcholinesterase (AChE) activity, acetylcholine and monoamines (dopamine, noradrenaline, and serotonin) content, levels of main oxidative stress markers, and expression of brain-derived neurotrophic factor (BDNF) and cAMP response element-binding protein (CREB) were determined. Results: We demonstrated that, according to all behavioral tests used, SE significantly improved the cognitive deficits induced by Sco. Furthermore, SE possessed AChE inhibitory activity, moderate antioxidant properties and the ability to modulate monoamines content in two brain structures. Moreover, multiple SE applications not only restored the depressed by Sco expression of CREB and BDNF, but significantly upregulated it. Conclusion: Summarizing results, we conclude that complex mechanisms underlie the beneficial effects of SE on impaired memory in Alzheimer’s type dementia.

Background and objectives. Though numerous studies have shown that the dysregulation of the epigenetic control is involved in disease manifestation, limited data is available on the transcriptional activity of DNA methylation related genes in alcohol and drug addiction. With regard to this, in this study we analyzed the expression levels of genes involved in DNA methylation, including DNMT1, DNMT3a, MeCP2, MBD1, MBD2, MBD3 and MBD4, in blood samples of alcohol and drug dependent persons in comparison to healthy abstainers.Methods. The study included 51 participants: 16 persons with alcohol dependence, 17 persons with drug dependence and 18 clinically healthy controls. To detect the relative mRNA expression levels of the studied genes, Quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis was applied.Results. Of the seven studied genes, four showed altered expression. MeCP2 and MBD1 were downregulated in the alcohol dependent group (FC = 0.805, p = 0.015 and FC = 0.846, p = 0.034, respectively), while DNMT1 and MBD4 were upregulated in the group with drug dependence (FC = 1.262, p = 0.001 and FC = 1.249, p = 0.005, respectively). No statistically significant changes in the relative mRNA expression were found for DNMT3a, MBD2 and MBD3 genes.Conclusions. Our results are indicative for a role of DNA methylation related genes in alcohol and drug addiction mediated through changes in their transcriptional activity. Studies in this direction will enable better understanding of the underlying mechanisms of addictions supporting the development of more effective therapeutic strategies.

FMR1 gene (fragile X mental retardation 1) represents a genetic and epigenetic factor in a number of human diseases. Though the role of FMR1 gene in substance use disorders (SUDs) is not well studied, a number of investigations indicate that SUDs and FMR1 -accociated disorders may share common underlying mechanisms. We examined the relative FMR1 mRNA levels and their sex-distribution in leukocytes from patients with alcohol and drug dependence compared to healthy controls. The study included 44 participants, 16 with alcohol dependence (mean age 43, 10 males and 6 females), 17 with drug dependence (mean age 41, 12 males and 5 females) and 11 healthy controls (mean age 47, 5 males and 6 females). Participants donated 5–6 ml of blood and completed a specialized questionnaire. Total RNA was isolated and cDNA was synthesized and used as a template for qRT-PCR analysis. The studied persons with alcohol and drug dependence share common socio-demographic and substance-use related characteristics. Significant FMR1 down-regulation was observed in the alcohol dependent group (25 % decrease; p = 0.005). Sex-associated analysis revealed that FMR1 down-regulation was primarily in alcohol-dependent men (40% decrease; p = 0.001) and did not reach significance in women. A similar sex-dependent pattern was observed among drug-dependent individuals. Drug-dependent men had significantly lower FMR1 mRNA levels (24% decrease; p = 0.015) compared with controls, while no significant difference was observed in drug-dependent females. These data indicate FMR1 mRNA down-regulation in persons with alcohol- and drug-dependence, relative to controls, is sex-dependent. This implies a role for FMR1 in substance use disorders. These findings require confirmation by including protein measures and the recruitment of larger cohorts.