BDNF Val66Met Polymorphism Influences Age Differences in Microstructure of the Corpus Callosum

Brain-derived neurotrophic factor (BDNF) plays an important role in neuroplasticity and promotes axonal growth, but its secretion, regulated by a BDNF gene, declines with age. The low-activity (met) allele of common polymorphism BDNF val66met is associated with reduced production of BDNF. We examined whether age-related reduction in the integrity of cerebral white matter (WM) depends on the BDNF val66met genotype. Forty-one middle-aged and older adults participated in the study. Regional WM integrity was assessed by fractional anisotropy (FA) computed from manually drawn regions of interest in the genu and splenium of the corpus callosum on diffusion tensor imaging scans. After controlling for effects of sex and hypertension, we found that only the BDNF 66met carriers displayed age-related declines in the splenium FA, whereas no age-related declines were shown by BDNF val homozygotes. No genotype-related differences were observed in the genu of the corpus callosum. This finding is consistent with a view that genetic risk for reduced BDNF affects posterior regions that otherwise are considered relatively insensitive to normal aging. Those individuals with a genetic predisposition for decreased BDNF expression may not be able to fully benefit from BDNF-based plasticity and repair mechanisms

Within- and between-person variability of exhaled breath condensate pH and NH4+ in never and current smokers

SummaryRecent studies have suggested that the collection of exhaled breath condensate (EBC) may be a viable method in occupational field studies to sample secretions of the lower airway because it is simple to perform and non-invasive. However, there are unresolved questions about whether certain laboratory conditions may influence the analysis of EBC biomarker measurements. A total of 12 subjects performed 116 EBC tests. The effect of short and long-term sample storage and sample volume on two biomarkers of acid stress, pH and NH4+, in EBC were investigated and did not significantly influence either marker measurement after argon deaeration. We also investigated the variability and the effect of smoking on the biomarkers by collecting six samples each from five adult never smokers and five adult current smokers over a period of 1 month (n=60 total). For pH, the within-person and between-person variability was larger in current smokers compared to never smokers. Similar results were found for NH4+. Cigarette packs smoked per day now was also associated with both pH (p=0.01) and NH4+ (p=0.04) using mixed effects regression analysis. The variability and smoking results suggest that repeated measurements of EBC pH and NH4+ from the same individual may accurately predict the biological state of the airways of current smokers when compared to never smokers

Subchondral osteopenia and accelerated bone remodelling post-ovariectomy - a possible mechanism for subchondral microfractures in the aetiology of spontaneous osteonecrosis of the knee?

Osteopenia and subchondral microfractures are implicated in the aetiology of spontaneous osteonecrosis of the knee. The ovine tibia shows significant alterations of the trabecular architecture within the subchondral bone of the medial tibial plateau post-ovariectomy, including reduced trabecular bone volume fraction. We hypothesise that accelerated subchondral bone resorption may also play a role in increasing microfracture risk at this site. 23 sheep were examined in this study; 10 of the sheep underwent ovariectomy (OVX), while the remainder (n=13) were kept as controls (CON). Five fluorochrome dyes were administered intravenously at 12 week intervals via the jugular vein to both groups, to label sites of bone turnover. These animals were then sacrificed at 12 months post-operatively. Bone turnover was significantly increased in the OVX group in both trabecular bone (2.024 vs. 1.047, p = 0.05) and within the subchondral bone plate (4.68 vs. 0.69 # / mm2; p \u3c 0.001). In addition to the classically-described turnover visible along trabecular surfaces, we also found visual evidence of intra-trabecular osteonal remodelling. In conclusion, this study shows significant alterations in bone turnover in both trabecular bone and within the subchondral bone plate at one-year post-ovariectomy. Remodelling of trabecular bone was due to both classically described hemi-osteonal and intra-trabecular osteonal remodelling. The presence of both localised osteopenia and accelerated bone remodelling within the medial tibial plateau provide a possible mechanism for subchondral microfractures in the aetiology of spontaneous osteonecrosis of the knee. Further utilisation of the ovariectomised ewe may be useful for further study in this field

Configural Scoring of Simulator Sickness, Cybersickness and Space Adaptation Syndrome: Similarities and Differences?

From a survey of ten U.S. Navy flight simulators a large number (N > 1,600 exposures) of self-reports of motion sickness symptomatology were obtained. Using these data, scoring algorithms were derived, which permit examination of groups of individuals that can be scored either for 1) their total sickness experience in a particular device; or, 2) according to three separable symptom clusters which emerged from a Factor Analysis. Scores from this total score are found to be proportional to other global motion sickness symptom checklist scores with which they correlate (r = 0.82). The factors that surfaced from the analysis include clusters of symptoms referable as nausea, oculomotor disturbances, and disorientation (N, 0, and D). The factor scores may have utility in differentiating the source of symptoms in different devices. The present chapter describes our experience with the use of both of these types of scores and illustrates their use with examples from flight simulators, space sickness and virtual environments

Brain-Derived Neurotrophic Factor Val66Met and Blood Glucose: A Synergistic Effect on Memory

Age-related declines in episodic memory performance are frequently reported, but their mechanisms remain poorly understood. Although several genetic variants and vascular risk factors have been linked to mnemonic performance in general and age differences therein, it is unknown whether and how they modify age-related memory declines. To address that question, we investigated the effect of Brain-Derived Neurotrophic Factor (BDNF) Val66Met polymorphism that affects secretion of BDNF, and fasting blood glucose level (a vascular risk factor) on episodic memory in a sample of healthy volunteers (age 19–77). We found that advanced age and high-normal blood glucose levels were associated with reduced recognition memory for name-face associations and poorer prose recall. However, elevated blood glucose predicted lower memory scores only in carriers of the BDNF 66Met allele. The effect on associative memory was stronger than on free recall. These findings indicate that even low-level vascular risk can produce negative cognitive effects in genetically susceptible individuals. Alleviation of treatable vascular risks in such persons may have a positive effect on age-related cognitive declines