Effect of Circadian Rhythm Disruption and Alcohol on the Oxidative Stress Level in Rat Brain.

Alcohol abuse is often associated with disrupted circadian rhythms and sleep, and the link seems to be bidirectional. In addition, it has been shown that exposure to constant illumination may increase lipid peroxidation in tissues. In this study, we investigated the effects of circadian rhythm disruption (CRD) and chronic alcohol intake (A) alone and in combination (CRD+A), on the oxidative stress in total rat brain homogenate. Our results demonstrated that lipid peroxidation was increased in the brain samples of all experimental animals compared with the control ones. The oxidative stress levels increased in the order: C

Epigenetic mechanisms: A possible link between autism spectrum disorders and fetal alcohol spectrum disorders.

The etiology of autism spectrum disorders (ASDs) still remains unclear and seems to involve a considerable overlap between polygenic, epigenetic and environmental factors. We have summarized the current understanding of the interplay between gene expression dysregulation via epigenetic modifications and the potential epigenetic impact of environmental factors in neurodevelopmental deficits. Furthermore, we discuss the scientific controversies of the relationship between prenatal exposure to alcohol and alcohol-induced epigenetic dysregulations, and gene expression alterations which are associated with disrupted neural plasticity and causal pathways for ASDs. The review of the literature suggests that a better understanding of developmental epigenetics should contribute to furthering our comprehension of the etiology and pathogenesis of ASDs and fetal alcohol spectrum disorders.

Effects of anthocyanins on active avoidance test of rats exposed to disruption of diurnal rhythm.

The present study was undertaken to assess the effects of the natural antioxidant anthocyanins on learning and memory of rats in experimental model of oxidative stress. Our preliminary experiments demonstrated that disruption of diurnal rhythm via exposition of rats to constant light for 14 days caused excessive generation of free radicals in their brains. It is known that free radicals impair cognitive functions. This study investigated the effects of anthocyanins on cognitive functions of rats in a shuttle-box active avoidance test. In the shuttle-box, stressed rats showed significantly increased latency time and decreased number of avoidances and escapes in the learning sessions. Rats treated with anthocyanins had increased number of avoidances and escapes and significantly decreased latency time during the learning sessions. Our results demonstrated that this model of oxidative stress impaired learning and memory of experimental rats. Moreover, chronic administration of anthocyanins (200 mg/kg orally) improved brain functions of the rats. Our data suggest that anthocyanins have a protective role on rat brain and improve cognitive functions in this model of oxidative stress.

Epigenetics of psychoactive drugs.

OBJECTIVES: Epigenetics refers to the heritable, but reversible regulation of various biological functions. Changes in DNA methylation and chromatin structure derived from histone modifications are involved in the brain development, pathogenesis and pharmacotherapy of brain disorders. KEY FINDINGS: Evidence suggests that epigenetic modulations play key roles in psychiatric diseases such as schizophrenia and bipolar disorder. The analysis of epigenetic aberrations in the mechanisms of psychoactive drugs helps to determine dysfunctional genes and pathways in the brain, to predict side effects of drugs on human genome and identify new pharmaceutical targets for treatment of psychiatric diseases. SUMMARY: Although numerous studies have concentrated on epigenetics of psychosis, the epigenetic studies of antipsychotics are limited. Here we present epigenetic mechanisms of various psychoactive drugs and review the current literature on psychiatric epigenomics. Furthermore, we discuss various epigenetic modulations in the pharmacology and toxicology of typical and atypical antipsychotics, methionine, lithium and valproic acid.

Rosiglitazone and pioglitazone alter aromatase kinetic properties in human granulosa cells.

We have previously reported that, in human granulosa cells, thiazolidinediones rosiglitazone and pioglitazone inhibit estrogen synthesis by interfering with androgen binding to aromatase, without an effect on aromatase mRNA or protein expression. In the current paper, we explore the effects of rosiglitazone and pioglitazone on the aromatase enzyme kinetic properties in human granulosa cells. The cells were incubated with various concentrations of testosterone or androstenedione, with or without rosiglitazone or pioglitazone. Estradiol and estrone concentrations in the conditioned tissue culture medium were measured by radioimmunoassay or immunosorbent assay. When testosterone was used as substrate, rosiglitazone or pioglitazone inhibited the V(max) by 35% (P < 0.001) and 24% (P < 0.001), respectively. When androstenedione was used as substrate, both rosiglitazone or pioglitazone inhibited V(max) by 13% (P < 0.007). We conclude that rosiglitazone or pioglitazone has no effect on K(m) but inhibits V(max) of aromatase in human granulosa cells, therefore, acting as noncompetitive inhibitors.

Effects of anthocyanins on learning and memory of ovariectomized rats.

OBJECTIVE: Estrogen deficit is associated with mental health disorders, emotional difficulties, memory impairment, and other cognitive failures. Recently, considerable attention has been paid to bioflavonoids and their properties as phytoestrogens to alleviate symptoms related to estrogen deficit. Anthocyanins are antioxidant flavonoids with various physiological activities. We have previously shown that anthocyanins inhibited depression-like symptoms in ovariectomized rats. The aim of the present study was to investigate the effects of anthocyanins on learning and memory of ovariectomized rats in a shuttle-box active avoidance test. METHODS: Female Wistar rats (250-280 g) were housed in three groups: group 1, control, nonovariectomized rats; group 2, ovariectomized rats; and group 3, ovariectomized rats, treated with anthocyanins (200 mg/kg PO) for 15 days after ovariectomy. On the 25th day after ovariectomy, an active avoidance shuttle-box test was performed. RESULTS: In the shuttle-box test, ovariectomized rats showed significantly increased latency time and total errors and decreased number of avoidances in the learning sessions. The group of ovariectomized rats treated with anthocyanins had considerably increased number of avoidances and significantly decreased latency time and total errors during the learning sessions. In memory retention tests, significant differences were observed between control, ovariectomized rats and ovariectomized rats treated with anthocyanins. CONCLUSIONS: Our results suggest that anthocyanins improve learning and memory of rats with estrogen deficit caused by ovariectomy.