Astrocyte calcium signaling: the third wave

The discovery that transient elevations of calcium concentration occur in astrocytes, and release 'gliotransmitters' which act on neurons and vascular smooth muscle, led to the idea that astrocytes are powerful regulators of neuronal spiking, synaptic plasticity and brain blood flow. These findings were challenged by a second wave of reports that astrocyte calcium transients did not mediate functions attributed to gliotransmitters and were too slow to generate blood flow increases. Remarkably, the tide has now turned again: the most important calcium transients occur in fine astrocyte processes not resolved in earlier studies, and new mechanisms have been discovered by which astrocyte [Ca(2+)]i is raised and exerts its effects. Here we review how this third wave of discoveries has changed our understanding of astrocyte calcium signaling and its consequences for neuronal function

Developmental changes in effective connectivity associated with relational reasoning

Rostrolateral prefrontal cortex (RLPFC) is part of a frontoparietal network of regions involved in relational reasoning, the mental process of working with relationships between multiple mental representations. RLPFC has shown functional and structural changes with age, with increasing specificity of left RLPFC activation for relational integration during development. Here, we used dynamic causal modeling (DCM) to investigate changes in effective connectivity during a relational reasoning task through the transition from adolescence into adulthood. We examined fMRI data of 37 healthy female participants (11–30 years old) performing a relational reasoning paradigm. Comparing relational integration to the manipulation of single relations revealed activation in five regions: the RLPFC, anterior insula, dorsolateral PFC, inferior parietal lobe, and medial superior frontal gyrus. We used a new exhaustive search approach and identified a full DCM model, which included all reciprocal connections between the five clusters in the left hemisphere, as the optimal model. In line with previous resting state fMRI results, we showed distinct developmental effects on the strength of long-range frontoparietal versus frontoinsular short-range fixed connections. The modulatory connections associated with relational integration increased with age. Gray matter volume in left RLPFC, which decreased with age, partly accounted for changes in fixed PFC connectivity. Finally, improvements in relational integration performance were associated with greater modulatory and weaker fixed PFC connectivity. This pattern provides further evidence of increasing specificity of left PFC function for relational integration compared to the manipulation of single relations, and demonstrates an association between effective connectivity and performance during development. Hum Brain Mapp, 2013

Amines, Astrocytes and Arousal

Amine neurotransmitters, such as noradrenaline, mediate arousal, attention, and reward in the CNS. New data suggest that, from flies to mammals, a major mechanism for amine transmitter action is to raise astrocyte [Ca2+]i and release gliotransmitters that modulate neuronal activity and behavior

G protein-coupled receptor 37-like 1 modulates astrocyte glutamate transporters and neuronal NMDA receptors and is neuroprotective in ischemia

We show that the G protein-coupled receptor GPR37-like 1 (GPR37L1) is expressed in most astrocytes and some oligodendrocyte precursors in the mouse central nervous system. This contrasts with GPR37, which is mainly in mature oligodendrocytes. Comparison of wild type and Gpr37l1(-/-) mice showed that loss of GPR37L1 did not affect the input resistance or resting potential of astrocytes or neurons in the hippocampus. However, GPR37L1-mediated signalling inhibited astrocyte glutamate transporters and - surprisingly, given its lack of expression in neurons - reduced neuronal NMDA receptor (NMDAR) activity during prolonged activation of the receptors as occurs in ischemia. This effect on NMDAR signalling was not mediated by a change in the release of D-serine or TNF-α, two astrocyte-derived agents known to modulate NMDAR function. After middle cerebral artery occlusion, Gpr37l1 expression was increased around the lesion. Neuronal death was increased by ∼40% in Gpr37l1(-/-) brain compared to wild type in an in vitro model of ischemia. Thus, GPR37L1 protects neurons during ischemia, presumably by modulating extracellular glutamate concentration and NMDAR activation

Epidemiological Patterns of Road Traffic Crashes During the Last Two Decades in Iran: A Review of the Literature from 1996 to 2014

Context: Despite considerable attention given to health statistics of road traffic crashes (RTCs), the epidemiological aspects of injuries resulting from RTCs are not fully understood in Iran and other developing countries. The aim of this review was to study the epidemiological pattern and issues arising due to RTCs in Iran. Evidence Acquisition: The scope of this study involves data from a broad range of published literature on RTCs in Iran. Data collection for this study was conducted by searching for keywords such as traffic accidents, traffic crashes, motorcycle accidents, motorcycle crashes, motorcycle injury, motor vehicle injury, motor vehicle crashes and motor vehicle accidents, Iran and Iranian in various databases such as Embase, PubMed, Google Scholar, Scopus, Magiran, Iranian scientific information database (SID) and IranMedex. Results: This study comprised of 95 articles. It is evident from this review that a large number of severe RTCs occur due to collision of two or more vehicles and most of the victims are males aged between 30 and 39 years. Male pedestrian, drivers and passengers are more likely to be severely injured in comparison to females. One of the most prevalent causes of death among adults involved in the RTCs are head injuries and the majority of deaths occur prior to hospitalization. Mortality rates for RTCs are higher in summer, especially during midnight among all age groups. The most common individual and environmental risk factors associated with RTCs include lack of attention, getting trapped in the car, listening to music, fatigue and sleepiness, duration and distance and negligence of seatbelt usage while driving. Conclusions: The findings of the current study will be beneficial in prevention of RTCs and its associated complications and hence will be vital for policy makers, health service managers and stakeholders

Sequence learning in Associative Neuronal-Astrocytic Network

The neuronal paradigm of studying the brain has left us with limitations in both our understanding of how neurons process information to achieve biological intelligence and how such knowledge may be translated into artificial intelligence and its most brain-derived branch, neuromorphic computing. Overturning our fundamental assumptions of how the brain works, the recent exploration of astrocytes is revealing that these long-neglected brain cells dynamically regulate learning by interacting with neuronal activity at the synaptic level. Following recent experimental evidence, we designed an associative, Hopfield-type, neuronal-astrocytic network and analyzed the dynamics of the interaction between neurons and astrocytes. We show that astrocytes were sufficient to trigger transitions between learned memories in the neuronal component of the network. Further, we mathematically derived the timing of the transitions that was governed by the dynamics of the calcium-dependent slow-currents in the astrocytic processes. Overall, we provide a brain-morphic mechanism for sequence learning that is inspired by, and aligns with, recent experimental findings. To evaluate our model, we emulated astrocytic atrophy and showed that memory recall becomes significantly impaired after a critical point of affected astrocytes was reached. This brain-inspired and brain-validated approach supports our ongoing efforts to incorporate non-neuronal computing elements in neuromorphic information processing.Comment: 8 pages, 5 figure

May Measurement Month 2017: an analysis of blood pressure screening results from the United Arab Emirates-Northern Africa and Middle East

Elevated blood pressure (BP) is a growing burden worldwide, leading to over 10 million deaths each year. May Measurement Month (MMM) is a global initiative aimed at raising awareness of high BP and to act as a temporary solution to the lack of screening programmes worldwide. United Arab Emirates has a young population, but cardiovascular disease (CVD) is the commonest cause of death (40%). Myocardial infarction and stroke occurs at least a decade earlier than in western countries. Previous screening in our young population showed that 85% of the population had at least one CVD risk factor and about 62% of them were unaware of it. An opportunistic cross-sectional survey of volunteers aged ≥18 was carried out in May 2017. Blood pressure measurement, the definition of hypertension and statistical analysis followed the standard MMM protocol. Screening was held in 23 sites such as mosques, sports, and men's/ladies' clubs, airports, parks, shopping malls, work places as well as their residences, and in the public areas of hospitals or outpatient clinics. A total of 6193 individuals were screened during MMM17. The mean age was 39.2 ± 13.1 years. After multiple imputation, 1867 (30.2%) had hypertension. Of individuals not receiving anti-hypertensive medication, 813 (15.8%) were hypertensive. Of 1054 individuals receiving anti-hypertensive medication, 427 (40.6%) had uncontrolled BP. MMM17 was a useful screening model as it makes BP measurement easily accessible. Eight hundred and thirteen (16%) possibly new hypertensives were uncovered and 427(40.6%) of those on treatment for hypertension were found to be uncontrolled. These results suggest that opportunistic screening can identify significant numbers with raised BP

Disentangling astroglial physiology with a realistic cell model in silico

Electrically non-excitable astroglia take up neurotransmitters, buffer extracellular K+ and generate Ca2+ signals that release molecular regulators of neural circuitry. The underlying machinery remains enigmatic, mainly because the sponge-like astrocyte morphology has been difficult to access experimentally or explore theoretically. Here, we systematically incorporate multi-scale, tri-dimensional astroglial architecture into a realistic multi-compartmental cell model, which we constrain by empirical tests and integrate into the NEURON computational biophysical environment. This approach is implemented as a flexible astrocyte-model builder ASTRO. As a proof-of-concept, we explore an in silico astrocyte to evaluate basic cell physiology features inaccessible experimentally. Our simulations suggest that currents generated by glutamate transporters or K+ channels have negligible distant effects on membrane voltage and that individual astrocytes can successfully handle extracellular K+ hotspots. We show how intracellular Ca2+ buffers affect Ca2+ waves and why the classical Ca2+ sparks-and-puffs mechanism is theoretically compatible with common readouts of astroglial Ca2+ imaging

Risk factor investigation for cardiovascular health through WHO STEPS approach in Ardabil, Iran

Objectives: Reliable evidence is the keystone for any noncommunicable disease (NCD) prevention plan to be initiated. In this study we carried out a risk factor investigation based on the WHO Stepwise approach to Surveillance (STEPS). Methods: The study was conducted on 1000 adults between 15 and 64 years of age living in Ardabil province, north-west Iran during 2006, based on the WHO STEPS approach to surveillance of risk factors for NCD. At this stage only the first and second steps were carried out. Data were collected through standard questionnaires and methods analyzed using STATA version 8 statistical software package. Results: 29.0% of men and 2.6% of women were current daily tobacco smokers. The mean number of manufactured cigarettes smoked per day was 18.9 among current daily smokers. Smoking was most prevalent among men of low-income families and those of lower education The mean body mass index (BMI) was 26.6 kg/m2, and was significantly correlated with systolic blood pressure. 58.9% were overweight or obese; 18.0% had raised blood pressure and 3.7% had isolated systolic hypertension. The mean number of servings of fruit consumed per day was 1.1; 33.1% had low levels of activity. Combined risk factor analysis showed that 4.1%of participants were in the low-risk group (up to 5.1% among men and 3.2% among women).Those in the high-risk group comprised 25.6% in the 25- to 44-year age group and 49.7%in the 45- to 64-year age group. Mean BMI increased by age in both sexes at least at the firstthree decades of adult life. Conclusion: Based on observed status of risk for cardiovascular health, burden of cardiovascular diseases is expected to increase if an effective prevention strategy is not undertaken