Nicotinic α7 acetylcholine receptor-mediated currents are not modulated by the tryptophan metabolite kynurenic acid in adult hippocampal interneurons

The  tryptophan  metabolite,  kynurenic  acid (KYNA),  is  classically  known  to  be  an antagonist  of ionotropic glutamate receptors. Within the last decade several reports have been published suggesting that KYNA also blocks nicotinic acetylcholine receptors (nAChRs) containing the α7 subunit (α7*). Most of these reports involve either indirect measurements of KYNA effects on α7 nAChR function, or are reports of KYNA effects in complicated in vivo systems.  However, a recent report investigating KYNA interactions with α7 nAChRs failed to detect an interaction using direct measurements of α7 nAChRs function.  Further, it showed that a KYNA blockade of α7 nAChR stimulated GABA release (an indirect measure of α7 nAChR function) was not due to KYNA blockade of the α7 nAChRs. The current study measured the direct effects of KYNA on α7-containing nAChRs expressed on interneurons in the hilar and CA1 stratum radiatum regions of the mouse hippocampus and on interneurons in the CA1 region of the rat hippocampus.  Here we show that KYNA does not block α7* nACHRs using direct patch-­clamp recording of α7 currents in adult brain slices

Optogenetic control of genetically-targeted pyramidal neuron activity in prefrontal cortex

A salient feature of prefrontal cortex organization is the vast diversity of cell types that support the temporal integration of events required for sculpting future responses. A major obstacle in understanding the routing of information among prefrontal neuronal subtypes is the inability to manipulate the electrical activity of genetically defined cell types over behaviorally relevant timescales and activity patterns. To address these constraints, we present here a simple approach for selective activation of prefrontal excitatory neurons in both in vitro and in vivo preparations. Rat prelimbic pyramidal neurons were genetically targeted to express a light-­activated nonselective cation channel, channelrhodopsin-­2, or a light-­driven inward chloride pump, halorhodopsin, which enabled them to be rapidly and reversibly activated or inhibited by pulses of light. These light responsive tools provide a spatially and temporally precise means of studying how different cell types contribute to information processing in cortical circuits. Our customized optrodes and optical commutators for in vivo recording allow for efficient light delivery and recording and can be requested at www.neuro-­cloud.net/nature-precedings/baratta

Network RTK performance analysis: a case study in Latvia

Nowadays the RTK (Real Time Kinematic) method for positioning is used in daily life by different consumers for many purposes. Several different RTK correction techniques are used, starting from single site to network approaches. The GNSS market is filled with receivers from different manufacturers and different capabilities. In this paper we assess the stability of the reference station network transmitted RTK correction. Two different surveying class GNSS receivers in combination with four varied RTK correction techniques under diverse observation conditions are analyzed. This study has been conducted in Latvia, where state wide permanent GNSS reference station network has been maintained since year 2005

Prenatal inhibition of the kynurenine pathway leads to structural changes in the hippocampus of adult rat offspring

Glutamate receptors for N-methyl-d-aspartate (NMDA) are involved in early brain development. The kynurenine pathway of tryptophan metabolism includes the NMDA receptor agonist quinolinic acid and the antagonist kynurenic acid. We now report that prenatal inhibition of the pathway in rats with 3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulphonamide (Ro61-8048) produces marked changes in hippocampal neuron morphology, spine density and the immunocytochemical localisation of developmental proteins in the offspring at postnatal day 60. Golgi–Cox silver staining revealed decreased overall numbers and lengths of CA1 basal dendrites and secondary basal dendrites, together with fewer basal dendritic spines and less overall dendritic complexity in the basal arbour. Fewer dendrites and less complexity were also noted in the dentate gyrus granule cells. More neurons containing the nuclear marker NeuN and the developmental protein sonic hedgehog were detected in the CA1 region and dentate gyrus. Staining for doublecortin revealed fewer newly generated granule cells bearing extended dendritic processes. The number of neuron terminals staining for vesicular glutamate transporter (VGLUT)-1 and VGLUT-2 was increased by Ro61-8048, with no change in expression of vesicular GABA transporter or its co-localisation with vesicle-associated membrane protein-1. These data support the view that constitutive kynurenine metabolism normally plays a role in early embryonic brain development, and that interfering with it has profound consequences for neuronal structure and morphology, lasting into adulthood

Changes in synaptic transmission and protein expression in the brains of adult offspring after prenatal inhibition of the kynurenine pathway

During early brain development, N-methyl-d-aspartate (NMDA) receptors are involved in cell migration, neuritogenesis, axon guidance and synapse formation, but the mechanisms which regulate NMDA receptor density and function remain unclear. The kynurenine pathway of tryptophan metabolism includes an agonist (quinolinic acid) and an antagonist (kynurenic acid) at NMDA receptors and we have previously shown that inhibition of the pathway using the kynurenine-3-monoxygenase inhibitor Ro61-8048 in late gestation produces rapid changes in protein expression in the embryos and effects on synaptic transmission lasting until postnatal day 21 (P21). The present study sought to determine whether any of these effects are maintained into adulthood. After prenatal injections of Ro61-8048 the litter was allowed to develop to P60 when some offspring were euthanized and the brains removed for examination. Analysis of protein expression by Western blotting revealed significantly reduced expression of the GluN2A subunit (32%) and the morphogenetic protein sonic hedgehog (31%), with a 29% increase in the expression of doublecortin, a protein associated with neurogenesis. No changes were seen in mRNA abundance using quantitative real-time polymerase chain reaction. Neuronal excitability was normal in the CA1 region of hippocampal slices but paired-pulse stimulation revealed less inhibition at short interpulse intervals. The amount of long-term potentiation was decreased by 49% in treated pups and recovery after low-frequency stimulation was delayed. The results not only strengthen the view that basal, constitutive kynurenine metabolism is involved in normal brain development, but also show that changes induced prenatally can affect the brains of adult offspring and those changes are quite different from those seen previously at weaning (P21). Those changes may be mediated by altered expression of NMDAR subunits and sonic hedgehog

The kynurenine pathway as a therapeutic target in cognitive and neurodegenerative disorders

Understanding the neurochemical basis for cognitive function is one of the major goals of neuroscience, with a potential impact on the diagnosis, prevention and treatment of a range of psychiatric and neurological disorders. In this review, the focus will be on a biochemical pathway that remains under-recognised in its implications for brain function, even though it can be responsible for moderating the activity of two neurotransmitters fundamentally involved in cognition – glutamate and acetylcholine. Since this pathway – the kynurenine pathway of tryptophan metabolism - is induced by immunological activation and stress it also stands in an unique position to mediate the effects of environmental factors on cognition and behaviour. Targetting the pathway for new drug development could, therefore, be of value not only for the treatment of existing psychiatric conditions, but also for preventing the development of cognitive disorders in response to environmental pressures

Effects of Curcuma longa (turmeric) on postprandial plasma glucose and insulin in healthy subjects

<p>Abstract</p> <p>Background</p> <p>Previous animal studies have shown that <it>Curcuma (C.) longa </it>lowers plasma glucose. <it>C. longa </it>may thus be a promising ingredient in functional foods aimed at preventing type 2 diabetes. The purpose of the study is to study the effect of <it>C. longa </it>on postprandial plasma glucose, insulin levels and glycemic index (GI) in healthy subjects.</p> <p>Methods</p> <p>Fourteen healthy subjects were assessed in a crossover trial. A standard 75 g oral glucose tolerance test (OGTT) was administered together with capsules containing a placebo or <it>C. longa</it>. Finger-prick capillary and venous blood samples were collected before, and 15, 30, 45, 60, 90, and 120 min after the start of the OGTT to measure the glucose and insulin levels, respectively.</p> <p>Results</p> <p>The ingestion of 6 g <it>C. longa </it>had no significant effect on the glucose response. The change in insulin was significantly higher 30 min (<it>P </it>= 0.03) and 60 min (<it>P </it>= 0.041) after the OGTT including <it>C. longa</it>. The insulin AUCs were also significantly higher after the ingestion of <it>C. longa</it>, 15 (<it>P </it>= 0.048), 30 (<it>P </it>= 0.035), 90 (<it>P </it>= 0.03), and 120 (<it>P </it>= 0.02) minutes after the OGTT.</p> <p>Conclusions</p> <p>The ingestion of 6 g <it>C. longa </it>increased postprandial serum insulin levels, but did not seem to affect plasma glucose levels or GI, in healthy subjects. The results indicate that <it>C. longa </it>may have an effect on insulin secretion.</p> <p>Trial registration number</p> <p>NCT01029327</p

From Toxins Targeting Ligand Gated Ion Channels to Therapeutic Molecules

Ligand-gated ion channels (LGIC) play a central role in inter-cellular communication. This key function has two consequences: (i) these receptor channels are major targets for drug discovery because of their potential involvement in numerous human brain diseases; (ii) they are often found to be the target of plant and animal toxins. Together this makes toxin/receptor interactions important to drug discovery projects. Therefore, toxins acting on LGIC are presented and their current/potential therapeutic uses highlighted

Engineering graphics role in CAD literacy

The paper outlines the importance of engineering graphics skills in the background knowledge of engineering education. This topic becomes especially important at the age of rapid economic and technologic changes in the society. An approach will be discussed about what and how we teach to develop the present-day engineering graphics communication skills in Riga Technical University in the context of general infomedia literacy

Legal reasoning style in decisions of Europen Court of Justice

Latvijas juridiskajā literatūrā ES Tiesas nolēmumos izmantotā argumentācija ir maz pētīta; nav skaidru kritēriju objektīvai ES Tiesas argumentācijas analīzei. Nereti Tiesas nolēmumos izmantotā argumentācija saņem kritiku, kas balstīta uz nacionālo tiesību sistēmu aspektiem, neņemot vērā to, ka pastāv autonoma ES tiesību sistēma, kas ir atšķirīga no dalībvalstu nacionālo tiesību sistēmām. Maģistra darba mērķis ir ES Tiesas nolēmumos lietotās argumentācijas analīze un kritika, kas balstīta uz vienotiem, ES Tiesas darbībai vispārpiemērojamiem kritērijiem. Lai šāda analīze un kritika būtu objektīvi iespējama, darbā tiek izvirzīti un izpildīti vairāki uzdevumi. Autors pievērš uzmanību nacionālo tiesību ietekmei uz ES Tiesas argumentācijas stilu; apskata Tiesas spriešanas paraugus un nonāk pie argumentācijas metodēm, caur kurām iespējama Tiesas spriešanas kritika un veic atsevišķu Tiesas nolēmumu analīzi un izdara secinājumus.In the judicial literature published in Latvia, the reasoning used in ECJ adjudication have been scarcely examined. Another problem is posed by the lack of clear criteria for objective analysis and criticism of the ECJ reasoning. The criticism of the ECJ adjudication is often based on national legal systems without regard to the existence of the EU legal system. The aim of the current Master Paper is to examine and analyse the legal reasoning of the ECJ adjudication using a set of united criteria that can be universally applied to the ECJ decisions. In order to facilitate such analysis, several objectives are set and achieved. First, the author examines the influence of national legal systems on the legal reasoning of the ECJ. Secondly, specific examples of the case law argumentation are analyzed in order to deduce methods of argumentation that can be used in an objective criticism of the ECJ adjudication. Finally, the author analyses several ECJ adjudications applying the criteria developed