Experience-dependent plasticity shapes postnatal development of neural circuits, but the mechanisms that refine dendritic arbors, remodel spines, and impair synaptic activity are poorly understood. ...Mature brain-derived neurotrophic factor (BDNF) modulates neuronal morphology and synaptic plasticity, including long-term potentiation (LTP) via TrkB activation. BDNF is initially translated as proBDNF, which binds p75NTR. In vitro, recombinant proBDNF modulates neuronal structure and alters hippocampal long-term plasticity, but the actions of endogenously expressed proBDNF are unclear. Therefore, we generated a cleavage-resistant probdnf knockin mouse. Our results demonstrate that proBDNF negatively regulates hippocampal dendritic complexity and spine density through p75NTR. Hippocampal slices from probdnf mice exhibit depressed synaptic transmission, impaired LTP, and enhanced long-term depression (LTD) in area CA1. These results suggest that proBDNF acts in vivo as a biologically active factor that regulates hippocampal structure, synaptic transmission, and plasticity, effects that are distinct from those of mature BDNF.
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•A cleavage-resistant proBDNF knockin mouse probes role of proBDNF•Results are distinct from bdnf+/− mice and define proBDNF-specific effects•ProBDNF impairs dendritic structure, basal transmission, and LTP but enhances LTD
Postnatal formation of synaptic connections is highly regulated, and BDNF has been postulated to be involved in this process. Here, Yang et al. demonstrate that proBDNF is expressed during postnatal development and evaluate its actions on hippocampal structure and synaptic plasticity in a probdnf knockin mouse. Endogenously expressed proBDNF reduces dendritic arbors and spine density and alters synaptic plasticity. These data suggest that proBDNF is a key regulator shaping neural circuitry and synaptic plasticity.
Summary
Objective
Common data elements (CDEs) are currently unavailable for mobile health (mHealth) in epilepsy devices and related applications. As a result, despite expansive growth of new digital ...services for people with epilepsy, information collected is often not interoperable or directly comparable. We aim to correct this problem through development of industry‐wide standards for mHealth epilepsy data.
Methods
Using a group of stakeholders from industry, academia, and patient advocacy organizations, we offer a consensus statement for the elements that may facilitate communication among different systems.
Results
A consensus statement is presented for epilepsy mHealth CDEs.
Significance
Although it is not exclusive, we believe that the use of a minimal common information denominator, specifically these CDEs, will promote innovation, accelerate scientific discovery, and enhance clinical usage across applications and devices in the epilepsy mHealth space. As a consequence, people with epilepsy will have greater flexibility and ultimately more powerful tools to improve their lives.
Summary
The major objective of preclinical translational epilepsy research is to advance laboratory findings toward clinical application by testing potential treatments in animal models of seizures ...and epilepsy. Recently there has been a focus on the failure of preclinical discoveries to translate reliably, or even to be reproduced in different laboratories. One potential cause is a lack of standardization in preclinical data collection. The resulting difficulties in comparing data across studies have led to high cost and missed opportunity, which in turn impede clinical trials and advances in medical care. Preclinical epilepsy research has successfully brought numerous antiseizure treatments into the clinical practice, yet the unmet clinical needs have prompted the reconsideration of research strategies to optimize epilepsy therapy development. In the field of clinical epilepsy there have been successful steps to improve such problems, such as generation of common data elements (CDEs) and case report forms (CRFs and standards of data collection and reporting) by a team of leaders in the field. Therefore, the Translational Task Force was appointed by the International League Against Epilepsy (ILAE) and the American Epilepsy Society (AES), in partnership with the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institutes of Health (NIH) to define CDEs for animal epilepsy research studies and prepare guidelines for data collection and experimental procedures. If adopted, the preclinical CDEs could facilitate collaborative epilepsy research, comparisons of data across different laboratories, and promote rigor, transparency, and impact, particularly in therapy development.
Androgens have dramatic effects on neuronal structure and function in hippocampus. However, androgen depletion does not always lead to hippocampal impairment. To address this apparent paradox, we ...evaluated the hippocampus of adult male rats after gonadectomy (Gdx) or sham surgery. Surprisingly, Gdx rats showed increased synaptic transmission and long-term potentiation of the mossy fiber (MF) pathway. Gdx rats also exhibited increased excitability and MF sprouting. We then addressed the possible underlying mechanisms and found that Gdx induced a long-lasting upregulation of MF BDNF immunoreactivity. Antagonism of Trk receptors, which bind neurotrophins, such as BDNF, reversed the increase in MF transmission, excitability, and long-term potentiation in Gdx rats, but there were no effects of Trk antagonism in sham controls. To determine which androgens were responsible, the effects of testosterone metabolites DHT and 5α-androstane-3α,17β-diol were examined. Exposure of slices to 50 nm DHT decreased the effects of Gdx on MF transmission, but 50 nm 5α-androstane-3α,17β-diol had no effect. Remarkably, there was no effect of DHT in control males. The data suggest that a Trk- and androgen receptor-sensitive form of MF transmission and synaptic plasticity emerges after Gdx. We suggest that androgens may normally be important in area CA3 to prevent hyperexcitability and aberrant axon outgrowth but limit MF synaptic transmission and some forms of plasticity. The results also suggest a potential explanation for the maintenance of hippocampal-dependent cognitive function after androgen depletion: a reduction in androgens may lead to compensatory upregulation of MF transmission and plasticity.
Summary
Preclinical pharmacology studies in animal models of seizures and epilepsy have provided a platform to identify more than 20 antiseizure drugs in recent decades. To minimize variability in ...lab‐to‐lab studies and to harmonize approaches to data collection and reporting methodology in pharmacologic evaluations of the next generation of therapies, we present common data elements (CDEs), case report forms (CRFs), and this companion manuscript to help with the implementation of methods for studies in established preclinical seizure and epilepsy models in adult rodents. The development of and advocacy for CDEs in preclinical research has been encouraged previously by both clinical and preclinical groups. It is anticipated that adoption and implementation of these CDEs in preclinical studies may help standardize approaches to minimize variability and increase the reproducibility of preclinical studies. Moreover, they may provide a methodologic framework for pharmacology studies in atypical animal models or models in development, which may ultimately promote novel therapy development. In the present document, we refer selectively to animal models that have a long history of preclinical use, and in some cases, are clinically validated.
Summary
Common data elements (CDEs) are becoming more common as more areas of preclinical research have generated CDEs. Herein we provide an overview of the progress to date in generating CDEs for ...preclinical epilepsy research. Currently there are CDEs that have been developed for Physiology (in vivo), Behavior, Pharmacology, and Electroencephalography (EEG). Together the CDEs and methodologic considerations associated with these CDEs are laid out in consecutive manuscripts published in Epilepsia Open, each describing CDEs for their respective topic area. In addition to the overview of progress for the 4 subjects, core characteristics (Core CDEs) are described and explained. Data collection using a case report form (CRF) is described, and considerations that are involved in using the CDEs and CRFs are discussed.
EXO-200 is an experiment designed to search for double beta decay of super(136)Xe with a single-phase, liquid xenon detector. It uses an active mass of 110 kg of xenon enriched to 80.6% in the ...isotope 136 in an ultra-low background time projection chamber capable of simultaneous detection of ionization and scintillation. This paper describes the EXO-200 detector with particular attention to the most innovative aspects of the design that revolve around the reduction of backgrounds, the efficient use of the expensive isotopically enriched xenon, and the optimization of the energy resolution in a relatively large volume.
At the present time, CDEs are not usually available from published working groups in preclinical epilepsy research, so many types of data that one would theoretically want to know about when reading ...a publication about a study, such as sex, strain, or age, are often unavailable. To address these needs, the 4 working groups groups (abbreviated here as Behavior, Physiology, Pharmacology, and EEG) started to consider how to draft CDEs, case report forms (CRFs), and companion papers for their subtopic of preclinical epilepsy research. ...feedback may include the accuracy or level of detail of the information contained or the prioritization of the CDEs as “high priority,” “moderate,” or “optional,” meaning how important it is to obtain data on an element during an experiment using the specific technique. A. Galanopoulou acknowledges grant support by NINDS RO1 NS091170, U54 NS100064, the US Department of Defense (W81XWH‐13‐1‐0180), and research funding from the Heffer Family and the Segal Family Foundations and the Abbe Goldstein/Joshua Lurie and
Summary
We investigated the association of pre‐operative activity, reported by the Duke Activity Score Index, Short Form‐12 and measured by an accelerometer worn at home, with five cardiopulmonary ...exercise variables: peak power; peak oxygen consumption; anaerobic threshold; and ventilatory equivalents for oxygen and carbon dioxide. Fifty patients scheduled for major surgery underwent a standard pre‐operative cardiopulmonary exercise test and wore a chest‐mounted triaxial accelerometer for a mean (SD) duration of 3.2 (0.4) days. The Duke Activity Score Index and six accelerometer variables were significantly correlated with all five cardiopulmonary exercise variables, Pearson correlation coefficients 0.5–0.7, p = 0.02 to p < 0.001. Our results can guide future studies that measure physical activity for pre‐operative assessment and interventions.
It has been 13 years since the last comprehensive review of the performance management (PM) literature, and a lot has changed in both research and practice in that time. The current review updates ...(identifying new research directions post 2004) and extends this previous work by creating a systems-based taxonomy and conceptual model of PM. We then use this model to interpret and integrate the extensive work in this area and to identify fruitful and systems-based directions for future PM work. As input to our conclusions, we reviewed the last 36-plus years of PM research (1980–2017) and conducted a comprehensive coding of all empirical PM articles. We offer several specific directions for future PM research, with the ultimate goal of improving PM in practice.
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