Early weaning increases anxiety via brain-derived neurotrophic factor signaling in the mouse prefrontal cortex.

Deprivation of maternal care during early development markedly affects emotional development, but the underlying neuromolecular mechanisms are not fully understood. In a mouse model of disrupted mother-infant relationship, early weaning causes long-term impacts on pups to exhibit increased corticosterone secretion, anxiety, and stress responses in their adulthood. Revealing the molecular mechanisms behind it would beneficial to ameliorating mental problems caused by abuse in childhood. We report that normalizing circulating corticosterone in early-weaned mice, either in adulthood or soon after weaning, ameliorated anxiety levels assessed in the plus maze test. Administering a glucocorticoid receptor antagonist into the prefrontal cortex (PFC) reversed the effects of early weaning, whereas administering corticosterone increased anxiety levels, suggesting that the PFC is corticosterone's target brain region. In the PFCs of early-weaned mice, we observed prolonged reductions in the expression of brain-derived neurotrophic factor (BDNF) and associated mRNAs. Anxiety in early-weaned mice was ameliorated by pretreatment with BDNF or a BDNF receptor agonist. In summary, early weaning increased anxiety levels by modulating glucocorticoid and BDNF signaling in the PFC.

Effect of the misoprostol-rebamipide combination on iron deficiency anemia in patients under long-term cyclooxygenase-2 selective inhibitor treatment for small bowel ulcers.

The use of cyclooxygenase-2 (COX-2) selective inhibitors has been recommended to reduce the risk of upper and lower gastrointestinal adverse events. However, it is not clear whether the long-term use of COX-2 inhibitors reduces the risk of gastrointestinal injury. We report the case of a 60-year-old woman with rheumatoid arthritis who had ongoing anemia and intermittent tarry stools after the long-term use of meloxicam, a COX-2 selective inhibitor. Although gastrointestinal injuries were suspected, the findings of gastroduodenoscopy and ileocolonoscopy were normal. However, capsule endoscopy revealed multiple circumferential ulcers with bleeding in the small bowel. With the patient requiring continued meloxicam use, misoprostol, a prostaglandin (PG) analog and rebamipide, an endothelial PG inducer and cytoprotective agents were prescribed for the ulcers. After treatment, her anemia improved promptly, but it relapsed after she stopped regular use of these drugs. However, the anemia improved again after resumption of treatment. In conclusion, the long-term use of a COX-2 selective inhibitor may induce small intestinal injuries and multiple circumferential ulcers. Combination therapy with misoprostol and rebamipide may be useful for treating COX-2 selective inhibitor-induced anemia and small intestinal injuries.