Myelination in the human hippocampal formation from midgestation to adulthood

Myelination, one of the last steps of neuronal development, was examined in the human fetal and postnatal hippocampal formation using immunohistochemistry to detect a protein component of the myelin sheath, the myelin basic protein synthesized by oligodendroglial cells. Myelin basic protein-immunoreactive oligodendroglial cells were first seen at the 20th gestational week in the fimbria fornicis and in the alveus. Between the 21st and 35th weeks, myelinated axons also appeared in the fimbria fornicis. At the age of 39 gestational weeks, short and thin myelinated fibers were present in the fimbria, in the alveus, and less so in the stratum oriens of the hippocampus, while the first oligodendroglial cells appeared in the stratum lacunosum-moleculare and in the hilus. By the 2nd postnatal week myelinated fibers appeared in the stratum lacunosum-moleculare of Ammon's horn. At the 3rd month, myelination was strong in the alveus, moderate in the strata oriens, lacunosum-moleculare and radiatum of Ammon's horn, while only a small number of myelinated fibers were detected in the hilus. By the 5th month, the first oligodendroglial cells were detected in the molecular layer of the dentate gyrus. Myelination continued in the following years, particularly in the dentate gyrus, where even at the age of 11 years the density of myelinated fibers did not reach the adult level. It appears that the first myelinated axons belong to the long-projecting large hippocampal pyramidal cells and/or to their subcortical and cortical afferents. The sequence of myelination follows the known developmental pattern of hippocampal afferent and efferent pathways, and the prolonged myelination might be a factor in the prolonged functional maturation of hippocampal circuitry.     

A review of the epidemiological evidence on tea, flavonoids, and lung cancer

Tea and its main bioactive ingredients, the flavonoids, have been associated with human cancer for several decades. In this article, an overview is provided of observational epidemiological studies of lung cancer incidence in relation to intake of green tea, black tea, flavonols/flavones, and catechins. A PubMed search was conducted in September 2007. Articles were selected if they provided risk ratios (relative risk or odds ratio) for lung cancer and were of observational design (cohort, case-control, or case-cohort). Three of 12 studies reported a significantly lower risk of lung cancer with a high intake of flavonoids, whereas 1 study reported a significantly increased risk. After stratification by type of flavonoid, catechin intake was no longer associated with lung cancer risk in 3 of 4 studies available. For tea, 4 of 20 studies reported significantly reduced risks with high intake. Two studies found significantly increased risk ratios, but both were older studies. Findings were similar for green and black tea but became more significant when only methodologically sounder cohort studies were considered. When tea intake and lung cancer were studied among never- or former smokers to eliminate the confounding effect of smoking, 4 of 7 reported associations were significantly protective. In general, the studies on tea, flavonoids, and lung cancer risk indicate a small beneficial association, particularly among never-smokers. More well-designed cohort studies, in particular for catechins, are needed to strengthen the evidence on effects of long-term exposure to physiological doses of dietary flavonoids.     

Associations between genetic risk,functional brain network organization and neuroticism

Neuroticism and genetic variation in the serotonin-transporter (SLC6A4) and catechol-O-methyltransferase (COMT) gene are risk factors for psychopathology. Alterations in the functional integration and segregation of neural circuits have recently been found in individuals scoring higher on neuroticism. The aim of the current study was to investigate how genetic risk factors impact functional network organization and whether genetic risk factors moderate the association between neuroticism and functional network organization. We applied graph theory analysis on resting-state fMRI data in a sample of 120 women selected based on their neuroticism score, and genotyped two polymorphisms: 5-HTTLPR (S-carriers and L-homozygotes) and COMT (rs4680-rs165599; COMT risk group and COMT non-risk group). For the 5-HTTLPR polymorphism, we found that subnetworks related to cognitive control show less connections with other subnetworks in S-carriers compared to L-homozygotes. The COMT polymorphism moderated the association between neuroticism and functional network organization. We found that neuroticism was associated with lower efficiency coefficients in visual and somatosensory-motor subnetworks in the COMT risk group compared to the COMT non-risk group. The findings of altered topology of specific subnetworks point to different cognitive-emotional processes that may be affected in relation to the genetic risk factors, concerning emotion regulation in S-carriers (5-HTTLPR) and emotional salience processing in COMT risk carriers.     

Expression of Heat Shock Proteins after Ultrasound Exposure in HL-60 Cells

One of the important cellular defense mechanisms against stress is the induction of heat shock proteins (HSPs). We have recently demonstrated that a low frequency electromagnetic field is unable to induce the heat shock response (HSR). In the present study, we expanded our investigations to the induction of HSPs, particularly Hsp72, by ultrasound (US). Human promyelocytic leukemia HL-60 cells were exposed in suspension to US at 1, 3 and 10 MHz, as well as combinations of two of these frequencies. The ability of US to induce Hsp72 was tested for different frequencies, intensities and exposure times. In addition, the water bath temperature was varied from 30 to 36°C. The Hsp72 protein expression was determined 4 and 24 h after treatment. We found that the amount of Hsp72 increased with increasing US frequency, reaching its highest level of about 1800%, induced by 10 MHz. After increasing the temperature of the water bath, the amount of Hsp72 in the treated cells was also increased, whereas no induction was observed at 30°C. For all treatment conditions, ultrasound of 1 MHz was unable to significantly induce Hsp72. At 10 MHz, the exposure time was varied from 0 to 20 min. We found that the induction of Hsp72 took place after 5 min of exposure. For a fixed level of absorbed US energy, the continuous regime, as well as a pulsation of 1:2 (5 ms on and 5 ms off) induced the same Hsp72 level. Pulsation of 1:5 (2 ms on and 8 ms off) and 1:10 (1 ms on and 9 ms off) did not show any effect. A single sonication of 20 min, as well as a fractionated sonication of two 10 min exposures induced the same level of Hsp72, whereas four exposures of 5 min reduced the Hsp72 level. At the optimum exposure conditions (10 MHz, 10 min), the concentration of other HSPs was also determined. Hsp27 showed no effect but Hsp32, Hsp40 and Hsp72 were induced. Taken together, these results suggest a synergistic interaction between heat and US. (E-mail: werner.sontag@ibg.fzk.de)     

Caveolin-1 as a possible target in the treatment for acne

Expression of caveolin-1 (Cav-1) is an important pathophysiological factor in acne. Cav-1 strongly interacts with such well-recognized etiopathogenic factors such as hyperseborrhea, follicular hyperkeratinization and pathogenicity of Cutibacterium acnes. Cav-1 is a strong negative regulator of transforming growth factor beta (TGF-β) expression. It acts as a critical determinant of autophagy, which is significantly induced in acne lesions through C. acnes and by absorption of fatty acids. Cav-1 also demonstrates different correlations with the development of innate immunity. We propose that normalization of Cav-1 expression can serve as a target in anti-acne therapy.     

Fluorine-18 deoxyglucose PET for assessment of viable myocardium in perfusion defects in 99mTc-MIBI SPET: a comparative study in patients with coronary artery disease

Extent and frequency of viable tissue in myocardial segments yielding a perfusion defect on technetium-99m methoxyisobutylisonitrile (^99mTc-MIBI), single photon emission tomography (SPET) at rest was prospectively investigated with 2-¹⁸F-2-deoxyglucose (¹⁸FDG) positron emission tomography (PET) in 46 patients with chronic coronary artery disease (CAD). Of these, 43 had a history of old myocardial infarction. For comparative visual and quantitative evaluation of identical anatomical slices, PET image files were converted into the SPET file structure and into the same matrix size. SPET and PET images were documented and visually (9 segments/patient) or semiquantitatively evaluated by a target-like polar map. Relative perfusion was expressed in percentage of peak ^99mTc-MIBI uptake. Sample ¹⁸FDG uptake was related to the ¹⁸FDG uptake in the area of such maximal perfusion (¹⁸FDG uptake was 100% at the 100% ^99mTc-MIBI uptake area). Of 414 segments, 167 (40%) revealed a resting perfusion defect. ¹⁸FDG uptake was present in 38 (23%) of the defects, while another 40 (24%) segments yielded ¹⁸FDG uptake in the periphery of the defect. When grouped according to the degree of ^99mTc-MIBI uptake-reduction (in percentage of peak activity), 80% of severe defects (30% of peak uptake), 48% of moderate (31%–50% of peak uptake) and 31% of mild (>50% of peak uptake) defects were considered as non-viable on the basis of ¹⁸FDG uptake. Complete viability was found in none of the severe defects in contrast to 29% of moderate and 35% of mild perfusion defects. From these data we conclude that ^99mTc-MIBI uptake as a myocardial perfusion marker underestimates myocardial viability in patients with chronic CAD and after myocardial infarction. Nevertheless, only moderate reductions of ^99mTc-MIBI uptake seem to imply a greater likelihood for viability. Comparative analysis of metabolism and flow is possible with different tomographic systems and is valuable for clinical evaluation of the cardiac patient. Offprint requests to: C. AltehoeferThis paper presents in part results of the doctoral thesis of C. Feinendegen and was supported in part by the EEC Concerted Action on PET in Cardiology.It is dedicated to Prof. L.E. Feinendegen, Jülich/Düsseldorf on the occasion of his 65th birthday.     

Feeling older,walking slower—but only if someone’s watching. Subjective age is associated with walking speed in the laboratory,but not in real life

The huge inter-individual differences in how people age have prompted researchers to examine whether people’s own perception of how old they are—their subjective age—could be a better predictor of relevant outcomes than their actual chronological age. Indeed, how old people feel does predict mortality hazards, and health-related measures such as walking speed may account for this association. In the present study, we extended this line of work by investigating whether subjective age also predicts walking speed and running speed in daily life or whether the predictive effects of subjective age for behavior manifest only within a controlled performance situation. We used data from 80 older participants (age range 62–82 years; M = 69.50, SD = 4.47) from the Berlin Aging Study II (BASE-II). Subjective age was assessed by self-report. Walking speed in the laboratory was measured with the Timed Up and Go test, and walking speed and running speed in real life were measured with an accelerometer. Results showed that compared to participants who felt older, those who felt younger than they actually were indeed walked faster in the laboratory, but they did not walk or run faster in real life. These patterns of results held when age, gender, education, BMI, comorbidity, depression, physical activity, and cognition were covaried. We discuss the role of stereotype threat in accounting for these results.