Voluntary exercise increases oligodendrogenesis in spinal cord.

Exercise has been shown to increase hippocampal neurogenesis, but the effects of exercise on oligodendrocyte generation have not yet been reported. In this study, we evaluated the hypothesis that voluntary exercise may affect neurogenesis, and more in particular, oligodendrogenesis in the thoracic segment of the intact spinal cord of adult nestin-GFP transgenic mice. Voluntary exercise for 7 and 14 days increased nestin-GFP expression around the ependymal area. In addition, voluntary exercise for 7 days significantly increased nestin-GFP expression in both the white and gray matter of the thoracic segment of the intact spinal cord, whereas, 14-day exercise decreased nestin-GFP expression. Markers for immature oligodendrocytes (transferrin and CNPase) were significantly increased after 7 days of voluntary exercise. These results suggest that voluntary exercise positively influences oligodendrogenesis in the intact spinal cord, emphasizing the beneficial effects of voluntary exercise as a possible co-treatment for spinal cord injury.

Developing ICF Core Sets for persons with sleep disorders based on the International Classification of Functioning, Disability and Health.

BACKGROUND: With the International Classification of Functioning, Disability and Health (ICF), we can now rely on a globally agreed-upon framework and system for classifying the typical spectrum of problems in the functioning of persons given the environmental context in which they live. ICF Core Sets are subgroups of ICF items selected to capture those aspects of functioning that are most likely to be affected by sleep disorders. OBJECTIVE: The objective of this paper is to outline the developmental process for the ICF Core Sets for Sleep. METHODS: The ICF Core Sets for Sleep will be defined at an ICF Core Sets Consensus Conference, which will integrate evidence from preliminary studies, namely (a) a systematic literature review regarding the outcomes used in clinical trials and observational studies, (b) focus groups with people in different regions of the world who have sleep disorders, (c) an expert survey with the involvement of international clinical experts, and (d) a cross-sectional study of people with sleep disorders in different regions of the world. CONCLUSION: The ICF Core Sets for Sleep are being designed with the goal of providing useful standards for research, clinical practice and teaching. It is hypothesized that the ICF Core Sets for Sleep will stimulate research that leads to an improved understanding of functioning, disability, and health in sleep medicine. It is of further hope that such research will lead to interventions and accommodations that improve the restoration and maintenance of functioning and minimize disability among people with sleep disorders throughout the world.

Differential effect of alpha-syntrophin knockout on aquaporin-4 and Kir4.1 expression in retinal macroglial cells in mice.

Aquaporin-4 water channels and the inwardly rectifying potassium channels Kir4.1 are coexpressed in a highly polarized manner at the perivascular and subvitreal endfeet of retinal Müller cells and astrocytes. The present study was aimed at resolving the anchoring mechanisms responsible for the coexpression of these molecules. Both aquaporin-4 and Kir4.1 contain PDZ-domain binding motifs at their C-termini and it was recently shown that mice with targeted disruption of the dystrophin gene display altered distribution of aquaporin-4 and Kir4.1 in the retina. To test our hypothesis that alpha-syntrophin (a PDZ-domain containing protein of the dystrophin associated protein complex) is involved in aquaporin-4 and Kir4.1 anchoring in retinal cells, we studied the expression pattern of these molecules in alpha-syntrophin null mice. Judged by quantitative immunogold cytochemistry, deletion of the alpha-syntrophin gene causes a partial loss (by 70%) of aquaporin-4 labeling at astrocyte and Müller cell endfeet but no decrease in Kir4.1 labeling at these sites. These findings suggest that alpha-syntrophin is not involved in the anchoring of Kir4.1 and only partly responsible for the anchoring of aquaporin-4 in retinal endfeet membranes. Furthermore we show that wild type and alpha-syntrophin null mice exhibit strong beta1 syntrophin labeling at perivascular and subvitreal Müller cell endfeet, raising the possibility that beta1 syntrophin might be involved in the anchoring of Kir4.1 and the alpha-syntrophin independent pool of aquaporin-4.

The olivocerebellar projection in the cat studied with the method of retrograde axonal transport of horseradish peroxidase. VII. The projection to lobulus simplex, crus I and II.

The olivocerebellar projection to lobulus simplex, crus I and II in the cat was investigated by means of retrograde axonal transport of horseradish peroxidase (HRP). The distribution of labeled cells in the inferior olive following HRP injections in lobulus simplex, crus I and II confirmed the findings by Brodal ('40b) that the rostral half of the principal olive projects to these areas of the cerebellar hemisphere. However, concerning details there are some differences in so far as the heaviest contribution to crus I comes from the medial parts of the ventral and dorsal lamella, that to crus II from its lateral part, especially the ventral bend. The present findings show that in addition the rostral part of the medial and the rostromedial part of the dorsal accessory olive project to these areas of the cerebellar cortex. Further details in the projection are shown in figure 8B. The findings agree fairly well with the electrophysiological results of Armstrong et al. ('74) and the experimental anatomical data of Groenewegen and Voogd ('77a,b). An attempt is made to correlate the findings with the pattern of longitudinal zonal subdivision of the cerebellum. There is evidence for a topical organization within the projection to crus I and II and parts of their projection areas in the principal olive. The distribution of the labeled cells which project to lobulus simplex, crus I and II is discussed in relation to afferent pathways to the inferior olive.

Iron deficiency and educational achievement in Thailand.

This double-blind clinical trial was conducted in Thailand to assess the impact of iron treatment on the IQ and educational attainment of 1358 9-11-y-old children. The children were classified into one of three groups: iron replete, iron depleted, and iron-deficient anemic. The Raven Progressive Matrices was used to measure IQ. A Thai language and a math test were administered to assess school attainment. A 50-mg/d tablet of ferrous sulphate was given for 2 wk and a 100 mg/d tablet, for 14 wk. An anthelminthic drug was given on the day of the blood test before treatment and 3 mo after the intervention started. There is evidence of a positive association between iron status and IQ and a language school achievement test but there is no support for the internal validity of the hypothesis that this association is causal.

Distinct deactivation and desensitization kinetics of recombinant GABAA receptors.

The functional role of the large heterogeneity in GABAA receptor subunit genes and its role in setting the properties of inhibitory synapses in the CNS is poorly understood. A kinetic comparison between currents elicited by ultra-rapid application with a piezoelectric translator of 1 mM GABA to mammalian cells transfected with cDNAs encoding distinct GABAA receptor subunits revealed that the intrinsic deactivation and desensitization properties depend on subunit combination. In particular, receptors containing alpha 6 with beta 2 gamma 2 subunits were endowed with a significantly slower deactivation as compared to those receptors containing alpha 1 with beta 2 gamma 2 subunits. While desensitization produced by prolonged GABA applications on alpha 1 beta 2 gamma 2 receptors was characterized by a rapid exponential decay followed by a slower decay and a steady state response, alpha 6 beta 2 gamma 2 receptors lacked desensitization. Furthermore, GABAA receptors lacking the gamma 2 subunit were characterized by a much larger non-desensitization component and a very rapid deactivation. Lastly, analysis of GABA-activated currents in cells cotransfected with alpha 1 and alpha 6 together with beta 2 gamma 2 subunit revealed unique kinetic properties. Our results suggest that distinct subunit composition confers specific deactivation and desensitization properties that may profoundly affect synaptic decay kinetics and the capability to sustain high frequency synaptic inputs.

Pseudoephedrine, a sympathomimetic agent, induces Fos-like immunoreactivity in rat nucleus accumbens and striatum.

The pharmacological properties of the ephedrine derivative pseudoephedrine were investigated at the nuclear level. Following intraperitoneal injection of Sprague Dawley rats with pseudoephedrine, Fos induction was measured in various brain areas by Western blots and immunocytochemistry. Pseudoephedrine induced Fos-like immunoreactivity in the nucleus accumbens and striatum in a time and concentration-dependent manner with maximal effect at 60 mg/kg 2 h after injection. Immunocytochemical studies confirmed that the majority of the signal was detectable in the nucleus accumbens and striatum. Pre-injection with the D1 dopamine receptor antagonist SCH23390 partially and completely blocked pseudoephedrine-induced Fos-like immunoreactivity in the striatum and nucleus accumbens, respectively, suggesting that the action of pseudoephedrine is mediated via dopamine release and results in the activation of D1 dopamine receptors. With the exception of the higher doses required, the actions of pseudoephedrine were similar to those previously described for the psychostimulant amphetamine.

The olivocerebellar projections to the flocculus and paraflocculus in the cat, compared to those in the rabbit. A study using horseradish peroxidase as a tracer.

The projections from the inferior olive to the flocculus and paraflocculus in the cat have been mapped by means of the method of retrograde axonal transport of horseradish peroxidase. The findings show that the afferents to the flocculus are derived from the dorsal cap, ventrolateral outgrowth, the principal olive (the caudal parts of the ventral and dorsal lamella) and from the rostral part of the medial accessory olive. The fibres to the paraflocculus come from the caudal part of the principal and from the rostral part of the medial accessory olive. Details in the projections are seen from Figs. 1 and 2. Concerning some points the findings are at variance with those made in the rabbit by Hoddevik and Brodal, and suggest that there are species differences hitherto not known.

Ethanol alone or with dexamethasone alters the kinetics of choline acetyltransferase.

Choline acetyltransferase activity was measured in rats treated with daily injections of ethanol (0.1 g/kg body wt) and or dexamethasone (1 mg/kg body wt) for 5 consecutive days. Ethanol produced a biphasic reduction of choline acetyltransferase activity in rat cerebral cortex, which at most time points was further decreased by simultaneous injection of dexamethasone. Kinetic studies of cortex choline acetyltransferase activity in rats that had received 5 daily injections of ethanol or ethanol and dexamethasone indicated that the observed reduction in enzyme activity was due to an apparent reduction in affinity (K(m)) of the enzyme for acetyl coenzyme A with no significant change in the total amount of enzyme present (Vmax). This finding has implications with respect to the use of choline acetyltransferase as a marker for cholinergic neurons, and for the understanding of the regulation of choline acetyltransferase activity in the brain.

Dexamethasone, but not stress, induce measurable changes of mitochondrial benzodiazepine receptor mRNA levels in rats.

The expression of the mitochondrial benzodiazepine receptor gene was assayed by a semi-quantitative non-radioactive reverse transcriptase polymerase chain reaction (RT-PCR) assay. The level of amplified mitochondrial benzodiazepine receptor mRNA was expressed as a ratio of either glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or beta-actin mRNA co-amplified in the same RT-PCR assay. The relative amounts of mitochondrial benzodiazepine receptor RNA in several rat tissues were found to be similar to the previously reported relative amount of mitochondrial benzodiazepine receptor binding sites. The level of these binding sites has also been reported to be altered by stress stimuli. In this study we specifically measured the effect of stress on the mRNA levels of the mitochondrial benzodiazepine receptor as an alternative method to the binding assay in an attempt to understand the mechanism by which stress alters binding. Sprague-Dawley male rats were either forced to swim for 15 min in 18 degrees C water or restrained in a plastic cylinder for 45 min either once, or twice daily for 7 days. Neither the swim stress, nor acute or chronic restraint stress, caused a measurable statistically significant relative change in mitochondrial benzodiazepine receptor mRNA in the adrenal gland, kidney, testis and olfactory bulb. However, daily treatment of rats for 7 days with 4 mg/kg of dexamethasone caused a significant decrease in mitochondrial benzodiazepine receptor gene expression in adrenal glands. This finding and the measurement of the relative levels of mitochondrial benzodiazepine receptor mRNA in the various tissues indicate that mitochondrial benzodiazepine receptor density is regulated to some extent at the gene expression level. However, the lack of detectable stress-induced changes in mRNA levels for this receptor seem to indicate that either mRNA changes were below detectable levels or that other mechanisms may be involved in the previously reported stress-induced changes of mitochondrial benzodiazepine receptor density. Because the focus of this work was on the regulation of mitochondrial benzodiazepine receptor gene expression, ligand binding studies to determine changes in receptor densities were not performed.

Alteration of muscarinic acetylcholine receptors in rabies viral-infected dog brains.

Functions of the muscarinic acetylcholine receptor (mAChR) were studied in rabid dog brains using [3H]quinuclidinyl benzilate (QNB) as a radioligand. Of various brain regions, hippocampus and brainstem were the areas mostly affected in terms of impaired specific binding to [3H]QNB, as compared to other regions, as well as to those of controls. Saturation studies of the hippocampus revealed significantly elevated dissociation equilibrium constant (K(d)) values in both furious (n = 5) (9.80 + or - 2.77 nM) and dumb (n = 6) (6.01 + or - 1.08 nM) types of rabies as compared to 11 controls (2.15 + or - 0.31 nM), whereas the maximum number of receptor sites (B (max)) values were comparable among all subgroups of normal (1.38 + or - 0.10 pmol/mg protein), dumb (1.43 + or - 0.17 pmol/mg protein) and furious (1.28 + or - 0.12 pmol/mg protein) rabies types. Hippocampal K(d) values were comparable between high (fluorescent antibody test-FAT and polymerase chain reaction-PCR positive; n = 4) (7.47 + or - 3.27 nM), and low (FAT-negative and PCR-positive; n = 4) virus amount (8.34 + or - 3.93 nM) but these were significantly higher than controls (n = 4) (1.58 + or - 0.17 nM). Our data suggest a functional derangement of mAChR at specific sites of hippocampus and brainstem which is not dependent on the amount of virus.

Stress, anxiety and peripheral benzodiazepine receptor mRNA levels in human lymphocytes.

Peripheral benzodiazepine receptor (PBR) mRNA levels were measured in lymphocytes obtained from a cohort of university students and clinically diagnosed anxious patients. The average level of PBR mRNA was decreased in anxious patients compared to a control group. This data confirms previously published results, but it also indicates that PBR mRNA levels cannot be used as a sole diagnostic measure of anxiety because the range of the individual PBR mRNA levels of the anxious group overlapped the range of the PBR mRNA levels of the control group. PBR mRNA levels in students following academic examinations were increased in some individuals and decreased in others. In the same cohort of students individual levels of cortisol and prolactin were predominantly increased and decreased respectively. There was no correlation between the individual changes in the hormone levels or PBR mRNA, which suggests that each of these parameters is affected by different environmental and physiological factors. Lymphocyte PBR mRNA measurement is a useful additional methodology for studying human stress responses however, its use in clinical studies would require the elucidation of PBR's physiological role.

The reticulocerebellar projection in the cat as studied with retrograde transport of horseradish peroxidase.

Injections of horseradish peroxidase into the various parts of the cerebellar cortex and the cerebellar nuclei in the cat result in labelled cells within the reticular formation proper. All the reticular nuclei (with the exception of the reticular formation of the mesencephalon) send fibres to the cerebellum. The highest number of labelled neurons after cerebellar injections is found in the caudal reticular formation, especially within nucleus reticularis ventralis, nucleus reticularis lateralis and nucleus reticularis gigantocellularis. Another region for an accumulation of labelled cells is the rostral part of nucleus reticularis pontis caudalis. Except for the paraflocculus, all cerebellar cortical areas and all cerebellar nuclei receive afferents from one or more of the nuclei within the reticular formation proper, but the largest number of labelled neurons is observed in cases with injections including the intermediate-lateral part of lobulus simplex and the adjacent areas of the anterior lobe and crus I. the projection is bilateral with an ipsilateral preponderance (the cerebellar nuclei appear to receive a higher number of fibres from the contralateral side). Cells of all sizes are labelled, but labelled giant cells are found only after large cortical injections.

Drug discrimination analysis of pseudoephedrine in rats.

Rats were trained to discriminate amphetamine, 1 mg/kg given intraperitoneally, from saline injection in a two-lever operant drug discrimination task. Pseudoephedrine (a sympathomimetic drug with central and peripheral actions) at doses of 10 mg/kg failed to substitute for amphetamine, at 20 mg/kg partial substitution occurred, while at a 40 mg/kg full substitution was seen. The specificity of the amphetamine cue at the training dose used (1 mg/kg) was shown by the finding that a peripherally acting sympathomimetic drug phenylephrine at doses from 0.2 to 0.8 mg/kg failed to substitute for amphetamine. The potential for abuse of pseudoephedrine administered at high doses is discussed.

Effect of dietary vitamin E on L-[3H]glutamate binding in rabbit cerebellum.

To demonstrate the role of vitamin E on cerebellar function, studies on rabbits fed low and high levels of dietary vitamin E were performed. The L-[3H]glutamate binding to cerebellar membranes of rabbits fed normal, high and low vitamin E diet showed receptor density (Bmax) values (mean +/- SEM) of 274 +/- 13, 637 +/- 37, and 265 +/- 60 pmol/mg protein, respectively, and dissociation equilibrium constant (KD) values of 257 +/- 99, 233 +/- 77, and 120 +/- 15 nM, respectively. Significant difference of Bmax from control was observed in the high dietary vitamin E group and of KD from control for the low dietary vitamin E group. These results indicate that dietary vitamin E levels have demonstrable effects on the central nervous system, especially the glutamate neurotransmitter system in rabbit cerebellum.

Impact of a community-based program on early childhood development.

To determine the impact of an integrated community-based program in rural villages on early childhood development, a controlled trial was conducted in the Nakhon Sawan province of Thailand. The program involved the cooperation of governmental agencies, nongovernmental agencies, academic institutions, and community organizations. At baseline, 3 control and 3 program villages were similar in terms of nutritional status, developmental performance and parental care. After 2 years of intervention in the program villages, improvements were noted in nutritional status, developmental performance, and intelligence quotient scores, as well as overall utilization of health care resources and parental attitude and involvement.

Williams syndrome and the elastin gene in Thai patients.

Williams syndrome (WS) has long been known as a complex disorder of dysmorphic facial features, described as elfin face, mental retardation or learning disability, loquacious personality, and supravalvular aortic stenosis. The etiology is now known to be due to deletion of the elastin gene (ELN) on long arm of chromosome 7. Thai patients were previously reported by clinical diagnosis. This study reports the first two cases of WS with ELN deletion diagnosed by fluorescent in situ hybridization (FISH) technique. Clinically, hyperacusis is a common finding in WS associated with otitis media. Neither of the patients had hyperacusis, but one of them had bilateral sensorineural hearing loss, which to our knowledge, has never been reported.

Prevalence and clinical characteristics of fragile X syndrome at child development clinic, Ramathibodi Hospital.

Fragile X syndrome, the most common cause of inherited mental retardation, is an X-linked genetic disorder caused by an expanded CGG repeat in the fragile X mental retardation 1 gene. It is characterized by mental retardation, behavioral features, and physical features, such as a long face with large protruding ears and macro-orchidism. A screening for the syndrome was conducted in a representative sample of pediatric patients, who had developmental delay or mental retardation with unknown cause, at the Child Development Clinic, Ramathibodi Hospital. The DNA test was performed on all patients using PCR and southern blot techniques. Five positive cases were detected from 114 screened subjects, and more four cases confirmed among other family members. Two of five positive families initially denied a family history of mental retardation. Among 9 cases of fragile X syndrome, four had hyperactivity and two had autistic like behavior. More than half had rather a long face or prominent ears. Three boys had macro-orchidism.