Aging and photoperiod regulate glutamic acid decarboxylase(67) messenger RNA expression.

Aging and short photoperiod exposure both induce similar long-term changes in circadian rhythms, including alterations in the timing and the amplitude of rhythms. Furthermore, these chronic conditions affect the function of the circadian pacemaker in the suprachiasmatic nuclei (SCN) by altering rhythmic expression of neuropeptide messenger RNAs (mRNAs). Because GABA modulates SCN neuronal activity, and GABAergic neurons innervate peptidergic neurons in the SCN, the present study investigated whether photoperiod or aging affect the expression of mRNA for GAD(67), the enzyme responsible for regulating the tonic levels of GABA. As a control for regional specificity, the reticular thalamic nucleus (RTN) was also examined. In situ hybridization for GAD(67) mRNA was performed on brain sections derived from Siberian hamsters exposed to a long day or a short day photoperiod for 15 days, and on brain sections from young (3-4 months old) and old (12-17 months old) Syrian hamsters exposed to a long photoperiod. The results showed that photoperiod and aging have different effects on GAD(67) mRNA expression. Exposure to short day photoperiod significantly increased GAD(67) mRNA expression in both the SCN and RTN of Siberian hamsters, while aging significantly decreased GAD(67) mRNA expression in the RTN of Syrian hamsters but had no effect on GAD(67) mRNA expression in the SCN. These findings suggest that modulation of GAD(67) mRNA expression in the SCN is associated with photoperiodic regulation of neuropeptide mRNA expression, but is not a common mechanism for chronic regulation of circadian rhythms. Also, GAD(67) mRNA expression in the RTN is differentially affected by photoperiod and aging.     

Comparison of brain metabolic activity patterns induced by ketamine, MK-801 and amphetamine in rats: support for NMDA receptor involvement in responses to subanesthetic dose of ketamine

Subanesthetic doses of NMDA receptor antagonists induce positive, negative and cognitive schizophrenia-like symptoms in healthy humans and precipitate psychotic reactions in stabilized schizophrenic patients. These findings suggest that defining neurobiologic effects induced by NMDA antagonists could guide the formulation of experimental models relevant to the pathophysiology of schizophrenia and antipsychotic drug action. Accordingly, the effects of subanesthetic doses of the non-competitive NMDA antagonists ketamine and MK-801 were examined on regional brain [¹⁴C]-2-deoxyglucose (2-DG) uptake in rats. The effects of these drugs were compared to those of amphetamine, in order to assess the potential role of generalized behavioral arousal, motor activity and dopamine release in brain metabolic responses to the NMDA antagonists. Subanesthetic doses of MK-801 and ketamine induced identical alterations in patterns of 2-DG uptake. The most pronounced increases in 2-DG for both NMDA antagonists were in the hippocampal formation and limbic cortical regions. By contrast, amphetamine treatment did not increase 2-DG uptake in these regions. In isocortical regions, ketamine and MK-801 reduced uptake in layers 3 and 4, creating a striking shift in the laminar pattern of 2-DG uptake in comparison to control conditions. After amphetamine, the fundamental laminar pattern of isocortical labeling was similar to saline-treated rats. Administration of ketamine and MK-801 decreased 2-DG uptake in the medial geniculate and inferior colliculus, whereas amphetamine tended to increase uptake in these regions. Since ketamine induced similar effects on regional 2-DG uptake as observed for the selective antagonists MK-801, the effects of ketamine are likely related to NMDA antagonistic properties of the drug. The distinct differences in brain 2-DG uptake induced by amphetamine and NMDA antagonists indicate that generalized behavioral arousal, and increased locomotor activity mediated by dopamine release, are not sufficient to account for the alterations in brain metabolic patterns induced by ketamine and MK-801. Thus, the dramatic alteration in regional 2-DG uptake induced by ketamine and MK-801 reflects a state selectively induced by reduced NMDA receptor function.     

QUICKI does not accurately reflect changes in insulin sensitivity with exercise training.

A novel index of insulin sensitivity, the quick insulin sensitivity check index, termed QUICKI (1/[log (insulin) + log (glucose)]), was recently developed. We examined whether QUICKI accurately reflects changes in insulin sensitivity after exercise training, a perturbation known to improve insulin sensitivity. Sedentary, nondiabetic adults underwent a frequently sampled iv glucose tolerance test before and after 6 months of training. Insulin sensitivity was estimated from the glucose tolerance test using Bergman's minimal model (insulin sensitivity-minimal model), and QUICKI was calculated from basal insulin and glucose. Exercise increased (P = 0.003) insulin sensitivity-minimal model but did not change (P = 0.12) QUICKI. Before and after training, the rank-correlation between QUICKI and insulin sensitivity-minimal model was significant (r = 0.79, P = 0.0005; r = 0.56, P = 0.03, respectively). However, the rank-correlation between fasting insulin alone with insulin sensitivity-minimal model was as good (before training r = -0.77, P = 0.0009; after training r = -0.55, P = 0.03) as that between QUICKI and insulin sensitivity-minimal model. Fasting glucose was not related to insulin sensitivity-minimal model at either time. When difference scores (i.e. after pretraining values) were examined, neither QUICKI nor fasting insulin correlated with insulin sensitivity-minimal model (QUICKI vs. insulin sensitivity-minimal model r = 0.24, P = 0.39; fasting insulin vs. insulin sensitivity-minimal model r = -0.40, P = 0.14). We conclude that fasting insulin is equivalent to fasting insulin plus glucose (i.e. QUICKI) at estimating basal insulin sensitivity in nondiabetic adults. However, QUICKI does not accurately reflect exercise-induced changes in insulin sensitivity within individual subjects.     

Mind wandering and attention during focused meditation: a fine-grained temporal analysis of fluctuating cognitive states

Studies have suggested that the default mode network is active during mind wandering, which is often experienced intermittently during sustained attention tasks. Conversely, an anticorrelated task-positive network is thought to subserve various forms of attentional processing. Understanding how these two systems work together is central for understanding many forms of optimal and sub-optimal task performance. Here we present a basic model of naturalistic cognitive fluctuations between mind wandering and attentional states derived from the practice of focused attention meditation. This model proposes four intervals in a cognitive cycle: mind wandering, awareness of mind wandering, shifting of attention, and sustained attention. People who train in this style of meditation cultivate their abilities to monitor cognitive processes related to attention and distraction, making them well suited to report on these mental events. Fourteen meditation practitioners performed breath-focused meditation while undergoing fMRI scanning. When participants realized their mind had wandered, they pressed a button and returned their focus to the breath. The four intervals above were then constructed around these button presses. We hypothesized that periods of mind wandering would be associated with default mode activity, whereas cognitive processes engaged during awareness of mind wandering, shifting of attention and sustained attention would engage attentional subnetworks. Analyses revealed activity in brain regions associated with the default mode during mind wandering, and in salience network regions during awareness of mind wandering. Elements of the executive network were active during shifting and sustained attention. Furthermore, activations during these cognitive phases were modulated by lifetime meditation experience. These findings support and extend theories about cognitive correlates of distributed brain networks.     

Photically-induced retinal damage in diabetic rats

The present study examines the interaction of light damage to the retina and streptozotocin (SZ)-induced diabetes in male and female rats during the early development of the disease, when changes occur in the blood-retinal barrier and in pigment cell membranes. Exposure of rats to low illuminance was used to determine the relationship between photically-induced cell death and diabetes. Other groups of animals were exposed to a greater illuminance for shorter time periods (24 hours) in attempts to identify a specific post-treatment day for the effect of diabetes. Blood glucose levels were monitored to indicate the severity of the diabetes. Morphometric analyses and histopathologic observations demonstrated that the outer nuclear layer (ONL, photoreceptor nuclei) was reduced significantly in thickness in female rats exposed to light during a 9 day period after SZ injection, but was unchanged from the control groups when exposed beginning at 12 days after SZ treatment. Removal of the pituitary gland prior to SZ treatment and light exposure resulted in the survival of more photoreceptor cells and prevented the differential in ONL thickness observed between control and diabetic intact animals. Attempts to establish a period of greatest susceptibility of the diabetic retina to photic damage were unsuccessful, but results indicate that prior light history and/or shipment stress might be related to retinal damage from light exposure.     

Is there a relationship between Birthweight and subsequent growth on the development of Dental Caries at 5 years of age? A cohort study

Kay EJ, Northstone K, Ness A, Duncan K, Crean SJ. Is there a relationship between Birthweight and subsequent growth on the development of Dental Caries at 5 years of age? A cohort study. Community Dent Oral Epidemiol 2010; 38: 408–414. © 2010 John Wiley & Sons A/S Abstract – Objectives: To examine the associations between childhood growth and the presence of dental caries at age 5. Methods: Data from the Avon Longitudinal Study of Parents and Children (ALSPAC) a population‐based, prospective cohort study were used. We enrolled 14 541 pregnancies, and a 10% sample of these were dentally examined and measured at 61 months of age. Birthweight was obtained from medical records, and birth length and birthweight were assessed by trained ALSPAC measurers. A number of social and lifestyle factors were treated as potential confounding factors. Results: Of 985, children, 242 (24.6%) had caries at 61 months of age. After adjustment, increased weight at birth was associated with a small increased risk of caries at 61 months (OR: 1.08 (95% CI: 1.03, 1.13) per 100 g increase, P = 0.002). A similar association was noted with respect to increased length at birth. Current weight and height did not appear to be associated with caries risk. Children who had caries at 61 months had slower increases in weight and height between birth and 61 months than those without decay at 61 months. Conclusions: The weak associations we have demonstrated between weight and length at birth and risk of caries at age 61 months cannot be considered causal, however, the relationship between the two variables warrants further investigation.