Epidemiology of primary central nervous system tumors in Estonia

During the period from 1986 to 1996, 1,665 cases of primary central nervous system (CNS) tumors were identified in the resident population of Estonia. Histological verification was available in 81% of the cases. Gliomas were more common in men, while meningiomas and neurinomas were more common in women. No significant difference was observed between the sexes for all primary CNS tumors. The age-specific incidence increased from the age of 30, reached a maximum in the age range of 50-69 years and declined in the elderly which may reflect under-diagnosis. The age-adjusted incidence rate for CNS tumors was 8.5/100,000 population. A comparison of our results with those of a previous study carried out in Estonia revealed a significant histology-specific increase in incidence in all age groups.     

The Lactate/Pyruvate Ratios of Cerebrospinal Fluid of Rats and Cats Related to the Lactate/Pyruvate,the ATP/ADP,and the Phosphocreatine/Creatine Ratios of Brain Tissue

The CSF and brain tissue concentrations of lactate and pyruvate were measured in cats and rats, and related to the corresponding tissue concentrations of ATP, ADP, phosphocreatine and creatine. A comparison between superficial and deep phenobarbital anaesthesia, and nitrous oxide anaesthesia, showed that the type of anaesthesia had a marked effect on the tissue metabolites with a differential influence on the lactate/pyruvate, and on the ATP/ADP and the phosphocreatine/creatine ratios. Optimal conditions for freezing and extracting the tissue were sought and were found to include freezing of the head in such a way that the ventilation and the circulation of the animals were upheld during the freezing, as well as extraction of the tissue at ?15 to ?20° C. The distribution of lactate and pyruvate between extra- and intracellular phases was investigated in both rats and cats. In all groups studied lactate and pyruvate were found in higher concentrations in CSF than in the tissue, suggesting a pH-dependent distribution of the weak acids. In the cat, the CSF pyruvate occurred in a relatively higher concentration than lactate, indicating a specific transport mechanism for pyruvic acid.     

Local blood flow in the thalamus and frontal cortex in alert and narcotized dogs

The magnitude of the local blood flow in the thalamus and cerebral cortex is studied on 22 sexually mature nonpedigree dogs. Mean values of local blood flow are obtained in alert animals, and the effect of narcosis (nitrous oxide) on the local cerebral blood flow is studied. The mean local blood flow in alert dogs is found to be 84.8±2.9 ml/100 g/min in the cerebral cortex and 68.7±1.6 ml/100 g/min in the thalamus. Insignificant fluctuations are found during a dynamic recording of the local blood flow during 7 days. Under narcosis (70% nitrous oxide) the local blood flow decreases 3–12%. According to the findings, nitrous oxide narcosis does not significantly affect the brain circulation, so that it is suitable for an experimental study of the latter.Translated from Fiziologicheskii Zhurnal SSSR imeni I. M. Sechenova, Vol. 73, No. 10, pp. 1321–1324, October, 1987.     

Glucocorticoid-Induced Changes in Rat Skeletal Muscle Biomechanical and Viscoelastic Properties: Aspects of Aging

Objectives

The purpose of this study was to estimate the state of tension (tone) and the biomechanical and viscoelastic properties of skeletal muscle in aging rats during the administration of different doses of dexamethasone and to find the relationships among the state of muscle atrophy, muscle strength, and the abovementioned muscle properties.

A PERIOD3 variant causes a circadian phenotype and is associated with a seasonal mood trait

In humans, the connection between sleep and mood has long been recognized, although direct molecular evidence is lacking. We identified two rare variants in the circadian clock gene PERIOD3 (PER3-P415A/H417R) in humans with familial advanced sleep phase accompanied by higher Beck Depression Inventory and seasonality scores. hPER3-P415A/H417R transgenic mice showed an altered circadian period under constant light and exhibited phase shifts of the sleep-wake cycle in a short light period (photoperiod) paradigm. Molecular characterization revealed that the rare variants destabilized PER3 and failed to stabilize PERIOD1/2 proteins, which play critical roles in circadian timing. Although hPER3-P415A/H417R-Tg mice showed a mild depression-like phenotype, Per3 knockout mice demonstrated consistent depression-like behavior, particularly when studied under a short photoperiod, supporting a possible role for PER3 in mood regulation. These findings suggest that PER3 may be a nexus for sleep and mood regulation while fine-tuning these processes to adapt to seasonal changes.In human populations, alterations in circadian timing can result in mood-related problems (1). An example of this is seasonal affective disorder, also known as “winter depression,” which is among the most common mood disorders, with a reported prevalence of 1.5–9%, depending on latitude (2). In addition, shift work has been suggested as a risk factor for major depressive disorder (3), and depression severity correlates with the degree of circadian misalignment (4, 5). A number of genetic variants in core clock genes have been reported as statistically associated with mood disorders, including seasonal affective disorder and major depressive disorder (6–14), but to date none has been causally related with an understanding of specific molecular links.Familial advanced sleep phase (FASP) is a human behavioral phenotype defined by early sleep time and early morning awakening (15). We previously identified mutations in core clock genes that cause FASP by linkage analysis/positional cloning (16) and candidate gene sequencing (17, 18). Here we identify two rare missense variants in PER3 (PER3-P415A/H417R) that cause FASP and are associated with elevated Beck Depression Inventory (BDI) and seasonality scores. Transgenic mice carrying human PER3-P415A/H417R exhibit delayed phase in a short photoperiod and a lengthened period of wheel-running rhythms in constant light. At a molecular level, the rare variants lead to decreased PER3 protein levels, likely due to decreased protein stability. Moreover, we found that PER3-P415A/H417R can exert effects on the clock (at least in part) by reducing its stabilizing effect on PER1 and PER2. Although hPER3-P415A/H417R transgenic mice display mild measures of depression-like phenotype, Per3^−/− mice exhibit consistent depression-like behaviors in multiple tests. The differences are particularly evident in short photoperiods, implying a role for PER3 in mood regulation. Taken together, these results support a role for PER3 in modulating circadian clock and mood that may be especially critical under conditions of short photoperiod (e.g., during the winter season).