Synaptic plasticity by antidromic firing during hippocampal network oscillations

Learning and other cognitive tasks require integrating new experiences into context. In contrast to sensory-evoked synaptic plasticity, comparatively little is known of how synaptic plasticity may be regulated by intrinsic activity in the brain, much of which can involve nonclassical modes of neuronal firing and integration. Coherent high-frequency oscillations of electrical activity in CA1 hippocampal neurons [sharp-wave ripple complexes (SPW-Rs)] functionally couple neurons into transient ensembles. These oscillations occur during slow-wave sleep or at rest. Neurons that participate in SPW-Rs are distinguished from adjacent nonparticipating neurons by firing action potentials that are initiated ectopically in the distal region of axons and propagate antidromically to the cell body. This activity is facilitated by GABA_A-mediated depolarization of axons and electrotonic coupling. The possible effects of antidromic firing on synaptic strength are unknown. We find that facilitation of spontaneous SPW-Rs in hippocampal slices by increasing gap-junction coupling or by GABA_A-mediated axon depolarization resulted in a reduction of synaptic strength, and electrical stimulation of axons evoked a widespread, long-lasting synaptic depression. Unlike other forms of synaptic plasticity, this synaptic depression is not dependent upon synaptic input or glutamate receptor activation, but rather requires L-type calcium channel activation and functional gap junctions. Synaptic stimulation delivered after antidromic firing, which was otherwise too weak to induce synaptic potentiation, triggered a long-lasting increase in synaptic strength. Rescaling synaptic weights in subsets of neurons firing antidromically during SPW-Rs might contribute to memory consolidation by sharpening specificity of subsequent synaptic input and promoting incorporation of novel information.     

PCR detection of periodontal bacteria and Streptococcus mutans in the biological samples from the oral cavity

The paper describes an optimized technique for DNA isolation from the Streptococcus mutans cultures and from the clinical samples including proteinase K treatment and detergent lysis, followed by sorbent-based enrichment. This technique was employed for isolating DNA from the periodontal bacteria Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, and Bacteroides forsythus. A multiplex PCR technique was adapted for large-scale studies of clinical samples. An original PCR method was developed for the semiquantitative detection of Str. mutans, showing the sensitivity of 100 genome copies per reaction. Extensive studies of approximately 2,000 individuals have demonstrated that these methods are applicable to the study of the dental and gingival microflora in the biological sample from the oral cavity of persons with dental diseases from various age groups.     

Glutathione depletion in hippocampal cells increases levels of H and L ferritin and glutathione S-transferase mRNAs

Glutathione plays an essential role in maintaining cellular redox balance, protecting cells from oxidative stress and detoxifying xenobiotic compounds. Glutathione depletion has been implicated in neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. Cells of neuronal origin are acutely sensitive to glutathione depletion, providing an avenue for studying the mechanisms invoked for neuronal survival in response to oxidant challenge. We investigated the changes in mRNA profile in HT22 hippocampal cells following administration of homocysteic acid (HCA), a glutathione-depleting drug. We report that HCA treatment of HT22 murine hippocampal cells increases the levels of the mRNAs encoding at least three proteins involved in protection from oxidant injury, the mRNAs encoding heavy (H) and light (L) ferritin and glutathione S-transferase (GST).     

Phylogenetic comparison of the VP7, VP4, VP6, and NSP4 genes of rotaviruses isolated from children in Nizhny Novgorod,Russia, 2015–2016, with cogent genes of the Rotarix and RotaTeq vaccine strains

Group A rotaviruses (RVA) are one of the leading causes of gastroenteritis in young children worldwide. The introduction of universal mass vaccination around the world has contributed to a reduction in hospitalizations and outpatient visits associated with rotavirus infection. Continued surveillance of RVA strains is needed to determine long-term effects of vaccine introduction. In the present work, we carried out the analysis of the genotypic diversity of RVA strains isolated in Nizhny Novgorod (Russia) during the 2015–2016 epidemic season. Also we conducted a comparative analysis of the amino acid sequences of T-cell epitopes of wild-type and vaccine (RotaTeq and Rotarix) strains. In total, 1461 samples were examined. RVAs were detected in 30.4% of cases. Rotaviruses with genotype G9P[8] (40.5%) dominated in the 2015-16 epidemic season. Additionally, RVAs with the following genotypes were detected: G4P[8] (25.4%), G1P[8] (13%), G2P[4] (3.2%). Rotaviruses with genotypes G3P[9], G6P[9], and G1P[9] totaled 3%. The number of partially typed and untyped RVA samples was 66 (14.9%). The findings of a RVA of G6P[9] genotype in Russia were an original observation. Our analysis of VP6 and NSP4 T-cell epitopes showed highly conserved amino acid sequences. The found differences seem not to be caused by the immune pressure but were rather related to the genotypic affiliations of the proteins. Vaccination against rotavirus infection is not included in the national vaccination schedule in Russia. Monitoring of the genotypic and antigenic diversity of contemporary RVA will allow providing a comparative analysis of wild-type strains in areas with and without vaccine campaign.     

The use of polyhydroxylated carboxylic acids and lactones to diminish biofilm formation of the pathogenic yeast Candida albicans

The vaginal microbiome of healthy women is a diverse and dynamic system of various microorganisms. Any sudden change in microbe composition can increase the vaginal pH and thus lead to vaginal infections, conditions that affect a large percentage of women each year. The most common fungal strains involved in infections belong to the yeast species Candida albicans. The main virulence factor of C. albicans is the ability to transform from planktonic yeast-form cells into a filamentous form (hyphae or pseudohyphae), with the subsequent formation of biofilm. The hyphal form, constituted by filamentous cells, has the ability to invade tissue and induce inflammation. Our hypothesis is that certain polyhydroxylated carboxylic acids, that may serve as an alternative carbohydrate source and at the same time lower the pH, function as an indicator of a nutrient-rich environment for C. albicans, which favors planktonic cells over hyphae, and thus diminish the formation of biofilm. We have shown that the biofilm formation in C. albicans and other Candida species can be significantly reduced by the addition of glucono-δ-lactone (GDL).

Treatment of Candida albicans with glucono δ-lactone results in less formation of hyphae and diminish biofilm formation.     

Pregnancy: The effect of RU486 on progesterone and oestrogen receptor concentration in human decidua on early pregnancy

Concentrations of progesterone receptor (PR) and oestrogen receptor(ER) were measured by radioligand assay in decidual tissue ofwomen undergoing termination of early pregnancy (amenorrhoeaup to 49 days). Pregnancies were terminated by vacuum aspirationat 12 or 36 h after oral administration of placebo or antiprogestinRU486 in different doses. Treatment with RU486 decreased decidualPR content, the effect being observed at 12 h as well as at36 h after 600 mg RU486 and at 36 h after 3 x 25 mg RU486 givenat 12 h intervals. PR concentration 12 h after a single doseof 25 mg RU486 was not affected. ER content was unchanged at12 h after RU486 but increased 36 h after 600 mg and 3 x 25mg RU486. Our data suggest that apart from blocking progesteroneaction, RU486 may exert its abortifacient effect through decreasingthe PR concentration. The simultaneous decrease of PR concentrationand an increase of ER concentration changes the balance betweenthem in favour of ER, which might also play a role in the abortifacienteffect of RU486.