Effects of voluntary running on plasma levels of neurotrophins, hippocampal cell proliferation and learning and memory in stressed rats.

Previous studies have shown that a 2-week treatment with 40 mg/kg corticosterone (CORT) in rats suppresses hippocampal neurogenesis and decreases hippocampal brain-derived neurotrophic factor (BDNF) levels and impairs spatial learning, all of which could be counteracted by voluntary wheel running. BDNF and insulin-like growth factor (IGF-1) have been suggested to mediate physical exercise-enhanced hippocampal neurogenesis and cognition. Here we examined whether such running-elicited benefits were accompanied by corresponding changes of peripheral BDNF and IGF-1 levels in a rat model of stress. We examined the effects of acute (5 days) and chronic (4 weeks) treatment with CORT and/or wheel running on (1) hippocampal cell proliferation, (2) spatial learning and memory and (3) plasma levels of BDNF and IGF-1. Acute CORT treatment improved spatial learning without altered cell proliferation compared to vehicle treatment. Acute CORT-treated non-runners showed an increased trend in plasma BDNF levels together with a significant increase in hippocampal BDNF levels. Acute running showed no effect on cognition, cell proliferation and peripheral BDNF and IGF-1 levels. Conversely, chronic CORT treatment in non-runners significantly impaired spatial learning and suppressed cell proliferation in association with a decreased trend in plasma BDNF level and a significant increase in hippocampal BDNF levels. Running counteracted cognitive deficit and restored hippocampal cell proliferation following chronic CORT treatment; but without corresponding changes in plasma BDNF and IGF-1 levels. The results suggest that the beneficial effects of acute stress on cognitive improvement may be mediated by BDNF-enhanced synaptic plasticity that is hippocampal cell proliferation-independent, whereas chronic stress may impair cognition by decreasing hippocampal cell proliferation and BDNF levels. Furthermore, the results indicate a trend in changes of plasma BDNF levels associated with a significant alteration in hippocampal levels, suggesting that treatment with running/CORT for 4 weeks may induce a change in central levels of hippocampal BDNF level, which may not lead to a significant change in peripheral levels.

rs660 polymorphism in Ro52 (SSA1; TRIM21) is a marker for age-dependent tolerance induction and efficiency of alloimmunization in sickle cell disease.

Patients with sickle cell disease (SCD) who receive red blood cell (RBC) transfusions have a higher rate of anti-RBC (allo and auto) antibody development than other transfused subjects. We hypothesized that an incidence and/or kinetics of RBC-specific antibody formation in SCD patients is influenced by a linked inheritance of the hemoglobin beta S (HbbetaS) allele and a polymorphism rs660C/T in the neighboring Ro52 gene. We found that 75% of C/T heterozygous and only 30.8% of T/T homozygous patients that developed antibodies were first transfused before the age of five. In addition, there was a significant inverse correlation between time of exposure to antigen or number of transfusions received and the age when T/T patients received first transfusion, indicating progressive development of competence of their immune system. In contrast, this correlation was not observed in patients with C/T genotype. Finally, increased expression of Ro52 was associated with the presence of the T/T genotype. These results suggest that rs660 polymorphism is a marker of efficiency of tolerance induction in early childhood and immune competence development to RBC antigens in SCD patients of pre-teen/teen age.