Chiral exponents in O(N) x O(m) spin models at O(1/N^2)

The critical exponents corresponding to chirality are computed at O(1/N^2) in d-dimensions at the stable chiral fixed point of a scalar field theory with an O(N) x O(m) symmetry. Pade-Borel estimates for the exponents are given in three dimensions for the Landau-Ginzburg-Wilson model at m = 2.Comment: 8 latex page

Metabolic Therapy for Temporal Lobe Epilepsy in a Dish: Investigating Mechanisms of Ketogenic Diet using Electrophysiological Recordings in Hippocampal Slices

The hippocampus is prone to epileptic seizures and is a key brain region and experimental platform for investigating mechanisms associated with the abnormal neuronal excitability that characterizes a seizure. Accordingly, the hippocampal slice is a common in vitro model to study treatments that may prevent or reduce seizure activity. The ketogenic diet is a metabolic therapy used to treat epilepsy in adults and children for nearly 100 years; it can reduce or eliminate even severe or refractory seizures. New insights into its underlying mechanisms have been revealed by diverse types of electrophysiological recordings in hippocampal slices. Here we review these reports and their relevant mechanistic findings. We acknowledge that a major difficulty in using hippocampal slices is the inability to reproduce precisely the in vivo condition of ketogenic diet feeding in any in vitro preparation, and progress has been made in this in vivo/in vitro transition. Thus far at least three different approaches are reported to reproduce relevant diet effects in the hippocampal slices: (1) direct application of ketone bodies; (2) mimicking the ketogenic diet condition during a whole-cell patch-clamp technique; and (3) reduced glucose incubation of hippocampal slices from ketogenic diet–fed animals. Significant results have been found with each of these methods and provide options for further study into short- and long-term mechanisms including Adenosine triphosphate (ATP)-sensitive potassium (KATP) channels, vesicular glutamate transporter (VGLUT), pannexin channels and adenosine receptors underlying ketogenic diet and other forms of metabolic therapy

Metabolic Autocrine Regulation of Neurons Involves Cooperation Among Pannexin Hemichannels, Adenosine Receptors and KATP Channels

Metabolic perturbations that decrease or limit blood glucose—such as fasting or adhering to a ketogenic diet—reduce epileptic seizures significantly. To date, the critical links between altered metabolism and decreased neuronal activity remain unknown. More generally, metabolic changes accompany numerous CNS disorders, and the purines ATP and its core molecule adenosine are poised to translate cell energy into altered neuronal activity. Here we show that nonpathological changes in metabolism induce a purinergic autoregulation of hippocampal CA3 pyramidal neuron excitability. During conditions of sufficient intracellular ATP, reducing extracellular glucose induces pannexin-1 hemichannel-mediated ATP release directly from CA3 neurons. This extracellular ATP is dephosphorylated to adenosine, activates neuronal adenosine A1 receptors, and, unexpectedly, hyperpolarizes neuronal membrane potential via ATP-sensitive K+ channels. Together, these data delineate an autocrine regulation of neuronal excitability via ATP and adenosine in a seizure-prone subregion of the hippocampus and offer new mechanistic insight into the relationship between decreased glucose and increased seizure threshold. By establishing neuronal ATP release via pannexin hemichannels, and hippocampal adenosine A1 receptors coupled to ATP-sensitive K+ channels, we reveal detailed information regarding the relationship between metabolism and neuronal activity and new strategies for adenosine-based therapies in the CNS

Adenosine and Autism - Recent Research and a New Perspective

Autism Spectrum Disorders (ASD) are associated with atypical social, behavioral and physiological characteristics. Here we outline an emerging connection among the increased incidence of epilepsy, disrupted sleep and perseverative behaviors exhibited and sought by persons with autism. Specifically, we propose that persons with autism can benefit from increased levels of adenosine, a powerful inhibitory neuromodulator and the core molecule of adenosine triphosphate (ATP). We review the literature and present recent data obtained via a customized questionnaire administered to parents of children with a confirmed autism diagnosis. This customized questionnaire demonstrates that symptoms of autism are reduced subsequent to stimuli predicted to increase adenosine. In addition, we present evidence from the literature and pilot data from a retrospective study of children with epilepsy or epilepsy and autistic behavior who were treated with a ketogenic diet, a long established anticonvulsant therapy that recently has been shown to suppress seizures via the adenosine A1 receptor (A1R) subtype. Our discussion focuses on the actions of adenosine in the central nervous system, with multiple implications for ASD, and the potential for developing new evidence-based therapies. Taken together, published peer-reviewed research and recent preliminary research suggest that adenosine could help resolve multiple physiological and behavioral symptoms of ASD

Adenosine and Autism: A Spectrum of Opportunities [post-print]

In rodents, insufficient adenosine produces behavioral and physiological symptoms consistent with several comorbidities of autism. In rodents and humans, stimuli postulated to increase adenosine can ameliorate these comorbidities. Because adenosine is a broad homeostatic regulator of cell function and nervous system activity, increasing adenosine\u27s influence might be a new therapeutic target for autism with multiple beneficial effects

Purines and Neuronal Excitability: Links to the Ketogenic Diet [post-print]

ATP and adenosine are purines that play dual roles in cell metabolism and neuronal signaling. Acting at the A(1) receptor (A(1)R) subtype, adenosine acts directly on neurons to inhibit excitability and is a powerful endogenous neuroprotective and anticonvulsant molecule. Previous research showed an increase in ATP and other cell energy parameters when an animal is administered a ketogenic diet, an established metabolic therapy to reduce epileptic seizures, but the relationship among purines, neuronal excitability and the ketogenic diet was unclear. Recent work in vivo and in vitro tested the specific hypothesis that adenosine acting at A(1)Rs is a key mechanism underlying the success of ketogenic diet therapy and yielded direct evidence linking A(1)Rs to the antiepileptic effects of a ketogenic diet. Specifically, an in vitro mimic of a ketogenic diet revealed an A(1)R-dependent metabolic autocrine hyperpolarization of hippocampal neurons. In parallel, applying the ketogenic diet in vivo to transgenic mouse models with spontaneous electrographic seizures revealed that intact A(1)Rs are necessary for the seizure-suppressing effects of the diet. This is the first direct in vivo evidence linking A(1)Rs to the antiepileptic effects of a ketogenic diet. Other predictions of the relationship between purines and the ketogenic diet are discussed. Taken together, recent research on the role of purines may offer new opportunities for metabolic therapy and insight into its underlying mechanisms

Homeostatic control of brain function – new approaches to understand epileptogenesis

Neuronal excitability of the brain and ongoing homeostasis depend not only on intrinsic neuronal properties, but also on external environmental factors; together these determine the functionality of neuronal networks. Homeostatic factors become critically important during epileptogenesis, a process that involves complex disruption of self-regulatory mechanisms. Here we focus on the bioenergetic homeostatic network regulator adenosine, a purine nucleoside whose availability is largely regulated by astrocytes. Endogenous adenosine modulates complex network function through multiple mechanisms including adenosine receptor-mediated pathways, mitochondrial bioenergetics, and adenosine receptor-independent changes to the epigenome. Accumulating evidence from our laboratories shows that disruption of adenosine homeostasis plays a major role in epileptogenesis. Conversely, we have found that reconstruction of adenosine’s homeostatic functions provides new hope for the prevention of epileptogenesis. We will discuss how adenosine-based therapeutic approaches may interfere with epileptogenesis on an epigenetic level, and how dietary interventions can be used to restore network homeostasis in the brain. We conclude that reconstruction of homeostatic functions in the brain offers a new conceptual advance for the treatment of neurological conditions which goes far beyond current target-centric treatment approaches

Renormalisation of heavy-light light ray operators

We calculate the renormalisation of different light ray operators with one light degree of freedom and a static heavy quark. Both $2\to2$- and $2\to3$-kernels are considered. A comparison with the light-light case suggests that the mixing with three-particle operators is solely governed by the light degrees of freedom. Additionally we show that conformal symmetry is already broken at the level of the one loop counterterms due to the additional UV-renormalisation of a cusp in the two contributing Wilson-lines. This general feature can be used to fix the $2\to2$-renormalisation kernels up to a constant. Some examples for applications of our results are given.Comment: 23 pages, 5 figures; v2: changed some wording, added a few references and one appendix concerning some subtleties related to gauge fixing and ghost terms; v3: clarified calculation in section 3.2., added an explicit calculation in section 5.2, corrected a few typos and one figure, added a few comments, results unchanged, except for typesetting matches version to appear in JHE

Purines and the Anti-Epileptic Actions of Ketogenic Diets

Ketogenic diets are high in fat and low in carbohydrates and represent a well-established and effective treatmentalternative to anti-epileptic drugs. Ketogenic diets are used for the management of a variety of difficult-to-treat or intractableseizure disorders, especially pediatric refractory epilepsy. However, it has been shown that this dietary therapycan reduce seizures in people of all ages, and ketogenic diets are being applied to other prevalent medical conditions suchas diabetes. Although used effectively to treat epilepsy for nearly 90 years, the mechanism(s) by which ketogenic dietswork to reduce seizures remain ill-understood. One mechanism receiving increased attention is based on findings that ketogenicdiets increase the brain energy molecule ATP, and may also increase the levels and actions of the related endogenousinhibitory neuromodulator adenosine. ATP and adenosine have both been identified as important modulators of seizures;seizures increase the actions of these purines, these purines regulate epileptic activity in brain, adenosine receptorantagonists are pro-convulsant, and adenosinergic mechanisms have been implicated previously in the actions of approvedanti-epileptic therapeutics. Here we will review recent literature and describe findings that shed light on mechanistic relationshipsbetween ketogenic diets and the purines ATP and adenosine. These emerging mechanisms hold great promisefor the effective therapeutic management of epileptic seizures and other neurological conditions