scholarly journals NGF and Neurotrophin-3 Both Activate TrkA on Sympathetic Neurons but Differentially Regulate Survival and Neuritogenesis

1997 ◽  
Vol 136 (2) ◽  
pp. 375-388 ◽  
Author(s):  
Daniel J. Belliveau ◽  
Irena Krivko ◽  
Judi Kohn ◽  
Christian Lachance ◽  
Christine Pozniak ◽  
...  
Keyword(s):  
Time Course ◽  
Sympathetic Neurons ◽  
Sympathetic Neuron ◽  
Activation Time ◽  
Short Term ◽  
Trka Receptor ◽  
Trk Receptor ◽  
Neurotrophin 3 ◽  
Differential Responsiveness

In this report we examine the biological and molecular basis of the control of sympathetic neuron differentiation and survival by NGF and neurotrophin-3 (NT-3). NT-3 is as efficient as NGF in mediating neuritogenesis and expression of growth-associated genes in NGF-dependent sympathetic neurons, but it is 20–40fold less efficient in supporting their survival. Both NT-3 and NGF induce similar sustained, long-term activation of TrkA, while NGF is 10-fold more efficient than NT-3 in mediating acute, short-term TrkA activity. At similar acute levels of TrkA activation, NT-3 still mediates neuronal survival two- to threefold less well than NGF. However, a mutant NT-3 that activates TrkC, but not TrkA, is unable to support sympathetic neuron survival or neuritogenesis, indicating that NT3–mediated TrkA activation is necessary for both of these responses. On the basis of these data, we suggest that NGF and NT-3 differentially regulate the TrkA receptor both with regard to activation time course and downstream targets, leading to selective regulation of neuritogenesis and survival. Such differential responsiveness to two ligands acting through the same Trk receptor has important implications for neurotrophin function throughout the nervous system.

Anticipatory saccades in sequential procedural learning in monkeys

1996 ◽  
Vol 76 (2) ◽  
pp. 1361-1366 ◽  
Author(s):  
K. Miyashita ◽  
M. K. Rand ◽  
S. Miyachi ◽  
O. Hikosaka
Keyword(s):  
Time Course ◽  
Preceding Paper ◽  
Button Press ◽  
Visually Guided ◽  
Short Term ◽  
Skilled Performance ◽  
Opposite Hand ◽  
Sequential Procedures ◽  
Correct Target

1. In a preceding paper we examined the short-term and long-term processes of learning of sequential procedures in monkeys. We now report that the pattern of eye movements changed along with the long-term learning. 2. The monkey's task was to press five consecutive pairs of target buttons (indicated by illumination) in the correct order for every pair, which the monkey had to find by trial and error (2 x 5 task). The whole sequence was called the "hyperset"; each pair was called the "set." 3. Initially, the saccade toward the correct target occurred after illumination of the targets (visually guided saccade). After sufficient learning, the saccade tended to occur before the target illumination (anticipatory saccade). This was true only for the hyperset that had been learned. 4. The likelihood of anticipatory saccade increased gradually over 20-30 days of practice of the particular hyperset. The time course was similar to how the hand learned (button press latency). 5. The monkeys were required to use the same hand for each hyperset throughout learning, except when we asked them to use the opposite hand. The nearly perfect performance due to the extensive practice was then deteriorated by the use of the opposite hand. We found, in addition, that anticipatory saccades became much less frequent. This finding suggests that critical for the skilled performance was the combination of the eyes and the side of the hand that was used for the practice of a given sequence.

Identification and characterization of mRNAs regulated by nerve growth factor in PC12 cells

1987 ◽  
Vol 7 (9) ◽  
pp. 3156-3167
Author(s):  
D G Leonard ◽  
E B Ziff ◽  
L A Greene
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Pc12 Cells ◽  
Time Course ◽  
Sympathetic Neuron ◽  
Sympathetic Ganglia ◽  
Cdna Libraries ◽  
Nerve Growth ◽  
Rat Tissue

Differential screening of cDNA libraries was used to detect and prepare probes for mRNAs that are regulated in PC12 rat pheochromocytoma cells by long-term (2-week) treatment with nerve growth factor (NGF). In response to NGF, PC12 cells change from a chromaffin cell-like to a sympathetic-neuron-like phenotype. Thus, one aim of this study was to identify NGF-regulated mRNAs that may be associated with the attainment of neuronal properties. Eight NGF-regulated mRNAs are described. Five of these increase 3- to 10-fold and three decrease 2- to 10-fold after long-term NGF exposure. Each mRNA was characterized with respect to the time course of the NGF response, regulation by agents other than NGF, and rat tissue distribution. Partial sequences of the cDNAs were used to search for homologies to known sequences. Homology analysis revealed that one mRNA (increased 10-fold) encodes the peptide thymosin beta 4 and a second mRNA (decreased 2-fold) encodes tyrosine hydroxylase. Another of the increased mRNAs was very abundant in sympathetic ganglia, barely detectable in brain and adrenals, and undetectable in all other tissues surveyed. One of the decreased mRNAs, by contrast, was very abundant in the adrenals and nearly absent in the sympathetic ganglia. With the exception of fibroblast growth factor, which is the only other agent known to mimic the differentiating effects of NGF on PC12 cells, none of the treatments tested (epidermal growth factor, insulin, dibutyryl cyclic AMP, dexamethasone, phorbol ester, and depolarization) reproduced the regulation observed with NGF. These and additional findings suggest that the NGF-regulated mRNAs may play roles in the establishment of the neuronal phenotype and that the probes described here will be useful to study the mechanism of action of NGF and the development and differentiation of neurons.

scholarly journals Pharmacokinetics and pharmacodynamics of natalizumab in pediatric patients with RRMS

2019 ◽  
Vol 6 (5) ◽  
pp. e591 ◽  
Author(s):  
Angelo Ghezzi ◽  
Giancarlo Comi ◽  
Luigi Maria Grimaldi ◽  
Lucia Moiola ◽  
Carlo Pozzilli ◽  
...  
Keyword(s):  
Safety Profile ◽  
Time Course ◽  
Pediatric Patients ◽  
Short Term ◽  
Elimination Phase ◽  
Relapsing Remitting ◽  
Distribution Phase

ObjectiveThis phase I study investigated pharmacokinetic (PK) and pharmacodynamic (PD) profiles of natalizumab in pediatric patients with relapsing-remitting MS (RRMS).MethodsPediatric patients with RRMS who were prescribed natalizumab 300 mg IV every 4 weeks were enrolled. Blood samples were collected on days 1, 2, 8, 15, and 22 and at weeks 4, 8, 12, and 16 to estimate PK parameters; PD properties were evaluated by measuring α4-integrin saturation and lymphocyte counts over time. Natalizumab's safety profile was also evaluated.ResultsPK parameters were similar to those reported in adult patients; natalizumab concentrations peaked approximately 1 day after infusion in most of the participants (Cmax 142.9 μg/mL, AUClast 47389.4 hr*μg/mL), followed by a biphasic decline with a rapid distribution phase and a slow elimination phase, with a terminal half-life of 215.1 hours. In terms of PD, both time course and magnitude of α4-integrin saturation and increase in lymphocyte counts were similar to those observed in adults. During the 16-week study follow-up, 3 adverse events attributed to natalizumab were observed; no unexpected safety events occurred.ConclusionsPK profile, α4-integrin saturation, lymphocyte counts, and safety observed in these pediatric patients are comparable to those reported in adults.Classification of evidenceThis study provides Class I evidence that natalizumab PK/PD parameters and safety profile are similar in adults and pediatric patients in the short term. Longer studies, also including a larger number of younger subjects (aged 10–12 years), are required to further inform about long-term PK and PD parameters in pediatric patients with MS.

The Time Course of Stimulus Expectation in a Saccadic Decision Task

2007 ◽  
Vol 97 (4) ◽  
pp. 2722-2730 ◽  
Author(s):  
A. Oswal ◽  
Miriam Ogden ◽  
R.H.S. Carpenter
Keyword(s):  
Reaction Time ◽  
Time Course ◽  
Prior Probability ◽  
Quantitative Relationship ◽  
Neural Representation ◽  
Decision Task ◽  
Short Term ◽  
Low Pass ◽  
Quantitative Explanation

Because the time to respond to a stimulus depend markedly on expectation, measurements of reaction time can, conversely, provide information about the brain's estimate of the probability of a stimulus. Previous studies have shown that the quantitative relationship between reaction time and static, long-term expectation or prior probability can be explained economically by the LATER model of decision reaction time. What is not known, however, is how the neural representation of expectation changes in the short term, as a result of immediate cues. Here, we manipulate the foreperiod—the delay between the start of a trial and the appearance of the stimulus—to see how saccadic latency, and thus expectation, varies with different delays. It appears that LATER can provide a quantitative explanation of this relationship, in terms both of average latencies and of their statistical distribution. We also show that expectancy appears to be subject to a process of low-pass filtering, analogous to the spatial blur that degrades visual acuity.

scholarly journals Effects of alcohol on food and energy intake in human subjects: evidence for passive and active over-consumption of energy

2004 ◽  
Vol 92 (S1) ◽  
pp. S31-S34 ◽  
Author(s):  
Martin R. Yeomans
Keyword(s):  
Energy Intake ◽  
Time Course ◽  
Human Subjects ◽  
Pharmacological Action ◽  
Future Research ◽  
Appetite Control ◽  
Short Term ◽  
Term Energy ◽  
Appetite Stimulation

The effects of alcohol on food and energy intake in human subjects have been the subject of a number of controlled studies recently. Unlike the evidence for other macronutrients, there is minimal evidence for any compensatory reduction in food intake in response to energy ingested as alcohol. In contrast, all studies testing intake within 1 h of preload ingestion report a higher intake of food following alcohol relative to energy-matched controls, although this short-term stimulatory effect is not evident if the test meal is delayed beyond 1 h. This time-course suggests that short-term stimulation of appetite may be mediated by the pharmacological action of alcohol on the appetite control system, either through enhanced orosensory reward or impaired satiety. In the long term, energy ingested as alcohol is additive to energy from other sources, suggesting that moderate alcohol consumption results in long-term passive over-consumption alongside short-term active over-consumption of energy through appetite stimulation. Despite the consistency of enhanced energy intake after moderate alcohol, evidence of an association between alcohol in the diet and obesity remains contentious, although the most recent results suggest that alcohol intake correlates with BMI. Future research needs to address this issue and clarify the mechanisms underlying appetite stimulation by alcohol.

Variations in amplitude and time course of inhibitory postsynaptic currents

1986 ◽  
Vol 56 (5) ◽  
pp. 1424-1438 ◽  
Author(s):  
D. Gardner
Keyword(s):  
Time Constant ◽  
Decay Time ◽  
Time Course ◽  
Decay Time Constant ◽  
Peak Amplitude ◽  
Short Term ◽  
Presynaptic Neuron ◽  
Inhibitory Postsynaptic Currents ◽  
Postsynaptic Currents

In order to examine the relative contributions of changes in amplitude and time course to synaptic plasticity, variations in peak amplitude and time constant of decay have been analyzed from inhibitory postsynaptic currents (PSC) recorded in voltage-clamped Aplysia buccal ganglia neurons. In these cells, synaptic currents with single time constant decay can be recorded with low noise under well-controlled space clamp. Over a population of 36 neurons, duration was more narrowly distributed than amplitude, but each varied. The coefficient of variation (CV) was 0.21 for decay time constant (tau) and 0.87 for peak conductance (g peak). Population variances are larger than can be accounted for by such variables as temperature and noise amplitude, suggesting that functional modifications alter each of these determinants of synaptic effectiveness over the long term. Recordings of up to several hundred PSC in each of 16 neurons show that both PSC amplitude and time course recorded in a single cell can vary independently over short time spans. Decay remained single exponential as time course changed. CV for tau averaged 0.11; CV for g peak was 0.19. Variability of tau was not an artifact of amplitude; CV was relatively uncorrelated with current amplitudes or sample size. Smoothing and adding excess noise to each individual PSC of a set produced only small changes to CV, showing that variability was not an artifact of noise. Several specific manipulations of the presynaptic neuron altered both PSC amplitude and time course. Tetanic stimulation of the presynaptic neuron produced short-term potentiation of both amplitude and time course of subsequent PSCs. Peak amplitude was increased by 80%; tau by 12%. Reducing interspike intervals from 10 to 1 s produced habituation of both amplitude and time course, with g peak decreasing by 35 to 40% and tau by 10%. Conditioning DC depolarization of the presynaptic neuron enhanced PSC amplitude with little effect on decay time constant. Although short-term plastic changes affect PSC amplitude more than duration, each is alterable. Parallel changes in both can synergistically alter synaptic charge transfer, and therefore efficacy. Similar mechanisms may produce larger long-term differences seen between neurons.

scholarly journals Whole-Body 12C Irradiation Transiently Decreases Mouse Hippocampal Dentate Gyrus Proliferation and Immature Neuron Number, but Does Not Change New Neuron Survival Rate

2018 ◽  
Vol 19 (10) ◽  
pp. 3078 ◽  
Author(s):  
Giulia Zanni ◽  
Hannah Deutsch ◽  
Phillip Rivera ◽  
Hung-Ying Shih ◽  
Junie LeBlanc ◽  
...  
Keyword(s):  
Survival Rate ◽  
Dentate Gyrus ◽  
Cell Survival ◽  
Time Course ◽  
Whole Body ◽  
Short Term ◽  
Hze Particles ◽  
Immature Neurons ◽  
Time Point

High-charge and -energy (HZE) particles comprise space radiation and they pose a challenge to astronauts on deep space missions. While exposure to most HZE particles decreases neurogenesis in the hippocampus—a brain structure important in memory—prior work suggests that 12C does not. However, much about 12C’s influence on neurogenesis remains unknown, including the time course of its impact on neurogenesis. To address this knowledge gap, male mice (9–11 weeks of age) were exposed to whole-body 12C irradiation 100 cGy (IRR; 1000 MeV/n; 8 kEV/µm) or Sham treatment. To birthdate dividing cells, mice received BrdU i.p. 22 h post-irradiation and brains were harvested 2 h (Short-Term) or three months (Long-Term) later for stereological analysis indices of dentate gyrus neurogenesis. For the Short-Term time point, IRR mice had fewer Ki67, BrdU, and doublecortin (DCX) immunoreactive (+) cells versus Sham mice, indicating decreased proliferation (Ki67, BrdU) and immature neurons (DCX). For the Long-Term time point, IRR and Sham mice had similar Ki67+ and DCX+ cell numbers, suggesting restoration of proliferation and immature neurons 3 months post-12C irradiation. IRR mice had fewer surviving BrdU+ cells versus Sham mice, suggesting decreased cell survival, but there was no difference in BrdU+ cell survival rate when compared within treatment and across time point. These data underscore the ability of neurogenesis in the mouse brain to recover from the detrimental effect of 12C exposure.

scholarly journals Attenuated Late-PhaseArcTranscription in the Dentate Gyrus of Mice LackingEgr3

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Amanda Maple ◽  
Rachel E. Lackie ◽  
Diana I. Elizalde ◽  
Stephanie L. Grella ◽  
Chelsey C. Damphousse ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Time Course ◽  
Wild Type ◽  
Short Term ◽  
Unique Role ◽  
Late Protein ◽  
Dependent Learning

The dentate gyrus (DG) engages in sustainedArctranscription for at least 8 hours following behavioral induction, and this time course may be functionally coupled to the unique role of the DG in hippocampus-dependent learning and memory. The factors that regulate long-term DGArcexpression, however, remain poorly understood. Animals lackingEgr3show lessArcexpression following convulsive stimulation, but the effect ofEgr3ablation on behaviorally inducedArcremains unknown. To address this,Egr3−/−and wild-type (WT) mice explored novel spatial environments and were sacrificed either immediately or after 5, 60, 240, or 480 minutes, andArcexpression was quantified by fluorescence in situ hybridization. Although short-term (i.e., within 60 min)Arcexpression was equivalent across genotypes, DGArcexpression was selectively reduced at 240 and 480 minutes in mice lackingEgr3. These data demonstrate the involvement ofEgr3in regulating the late protein-dependent phase ofArcexpression in the DG.

scholarly journals The time course of recognition memory impairment and glial pathology in the hAPP-J20 mouse model of Alzheimer's disease.

2018 ◽  
Author(s):  
Kamar Eleanor Ameen-Ali ◽  
Julie E Simpson ◽  
Stephen B Wharton ◽  
Paul R Heath ◽  
Paul Sharp ◽  
...  
Keyword(s):  
Recognition Memory ◽  
Mouse Model ◽  
Memory Impairment ◽  
Time Course ◽  
Neurovascular Unit ◽  
Disease Process ◽  
Short Term ◽  
Reactive Microglia ◽  
Term Memory

The role of cellular changes in the neurovascular unit is increasingly being investigated to understand the pathogenesis of Alzheimers disease. The aim of the current study was to determine the time course of recognition memory impairment in the J20 mouse model of AD, in relation to neuroinflammatory responses and the pathology of Aβ. Male hAPP-J20 and wild-type mice were assessed at 3, 6, 9, and 12 months of age. The spontaneous object recognition (SOR) task provided a measure of memory, with assessment of both a short delay (1 min) and a long delay (4 hrs). Immunohistochemistry was used to characterise Aβ-deposition, and quantify astrocyte and microglial responses. At all ages tested J20 mice had impaired long-term, but preserved short-term, recognition memory. Wild-types demonstrated preserved long-term memory up to 9 months of age, and preserved short-term memory at all ages tested. Plaque pathology in the J20 mice was present from 6 months onwards, with co-localisation of reactive microglia and activated astrocytes. Reactive microglia and astrocyte activation in the hippocampus were significantly greater in the J20 mice at 9 months, compared to wild-types. This study contributes to our understanding of the pathological and cognitive mechanisms at play in AD. J20 mice showed impairment in retaining information over longer periods from an early age, preceding the deposition of Aβ and glial activation. Defining early physiological changes in relation to cognitive decline could provide insight into new therapeutic targets early in the disease process, when intervention is most likely to effectively slow disease progression.

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