Circadian glucocorticoid oscillations preserve a population of adult hippocampal neural stem cells in the aging brain.

A decrease in adult hippocampal neurogenesis has been linked to age-related cognitive impairment. However, the mechanisms involved in this age-related reduction remain elusive. Glucocorticoid hormones (GC) are important regulators of neural stem/precursor cells (NSPC) proliferation. GC are released from the adrenal glands in ultradian secretory pulses that generate characteristic circadian oscillations. Here, we investigated the hypothesis that GC oscillations prevent NSPC activation and preserve a quiescent NSPC pool in the aging hippocampus. We found that hippocampal NSPC populations lacking expression of the glucocorticoid receptor (GR) decayed exponentially with age, while GR-positive populations decayed linearly and predominated in the hippocampus from middle age onwards. Importantly, GC oscillations controlled NSPC activation and GR knockdown reactivated NSPC proliferation in aged mice. When modeled in primary hippocampal NSPC cultures, GC oscillations control cell cycle progression and induce specific genome-wide DNA methylation profiles. GC oscillations induced lasting changes in the methylation state of a group of gene promoters associated with cell cycle regulation and the canonical Wnt signaling pathway. Finally, in a mouse model of accelerated aging, we show that disruption of GC oscillations induces lasting changes in dendritic complexity, spine numbers and morphology of newborn granule neurons. Together, these results indicate that GC oscillations preserve a population of GR-expressing NSPC during aging, preventing their activation possibly by epigenetic programming through methylation of specific gene promoters. Our observations suggest a novel mechanism mediated by GC that controls NSPC proliferation and preserves a dormant NSPC pool, possibly contributing to a neuroplasticity reserve in the aging brain.

Persistence of Helicobacter pylori in the oral cavity after systemic eradication therapy.

AIM: The present study aimed to evaluate if the oral cavity of chronic periodontitis patients can harbor Helicobacter pylori after systemic eradication therapy. MATERIALS AND METHODS: Samples of 30 patients (15 with gingivitis and 15 with chronic periodontitis) positive for H. pylori in the stomach were evaluated. Samples were collected 3 months after triple systemic antibiotic therapy from saliva, microbiota from the dorsum of the tongue, supra- and sub-gingival plaque as well as gastric biopsies. DNA of each sample was extracted by the boiling method and used as a template in polymerase chain reaction with the primers JW22/23. RESULTS: Eighteen patients (60%) harboured H. pylori in their mouths. Five patients (16.6%) were positive in saliva, two (6.6%) on the dorsum of the tongue, nine (30%) in supra-gingival plaque, 14 (46.6%) in sub-gingival plaque and three (10%) in the stomach. There was no statistically significant difference between study groups. CONCLUSION: Eradication of H. pylori after therapy was more effective for the stomach than for the mouth (p<0.001). Mouths of patients with gingivitis or with chronic periodontitis, who are positive for H. pylori in their stomachs, may be considered as reservoirs of these bacteria.

Prevalence of Helicobacter pylori detected by polymerase chain reaction in the oral cavity of periodontitis patients.

Helicobacter pylori is an important gastrointestinal pathogen associated with gastritis, peptic ulcers, and an increased risk of gastric carcinoma. The oral cavity has been indicated as a possible H. pylori reservoir, and may therefore be involved in the reinfection of the stomach which sometimes follows treatment of H. pylori infection. The objective of the present study was to evaluate the prevalence of H. pylori as detected by polymerase chain reaction (PCR) in the oral cavity of periodontitis patients testing positive for this bacterium in the stomach. Thirty adult patients with alterations of the superior digestive tract, testing urease positive after endoscopy and biopsy, were selected. A full-mouth periodontal examination was performed in every patient and the subjects were allocated to two groups: gingivitis (15 patients) and chronic periodontitis (15 patients). Plaque and saliva samples collected from each patient were stored in 0.5 ml of TE buffer. DNA was extracted from the samples by the boiling method and was evaluated for the presence of H. pylori using the PCR method. JW 22/23 primers were used. The DNA of ATCC H. pylori 43629 (positive control) and water (negative control) were used for controlling the reactions. Of the 30 evaluated patients, 13 (43.3%) harbored H. pylori in the mouth. The bacterium was not found on the dorsum of the tongue of any patient, but was found in saliva in three patients (10%), in the supragingival plaque in six patients (20%), and in the subgingival plaque in eight patients (26.6%). The presence of H. pylori was similar in the gingivitis and chronic periodontitis groups. In conclusion, a high percentage of patients harbored H. pylori in their mouth. The bacterium was detected in saliva, supragingival and subgingival plaque, suggesting that these sites may be considered reservoirs for H. pylori in urease-positive patients.