bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pressure-volume analysis reveals characteristic sex-related differences in cardiac function in a rat model of aortic banding-induced myocardial hypertrophy
Authors: Ruppert Mihály , Korkmaz-Icöz Sevil , Loganathan Sivakkanan , Jiang Weipeng , Lehmann Lorenz , Oláh Attila , Sayour Alex Ali , Barta Bálint András , Merkely Béla , Karck Matthias , Radovits Tamás , Szabó Gábor 
Published: May 2018

Sex differences in pressure overload (PO)-induced left ventricular (LV) myocardial hypertrophy (LVH) have been intensely investigated. Nevertheless, sex-related disparities of LV hemodynamics in LVH were not examined in detail. Therefore, we aimed to provide a detailed characterization of distinct aspects of LV function in male and female rats during different stages of LVH. Banding of the abdominal aorta (AB) was performed to induce PO for 6 or 12 wk in male and female rats. Control animals underwent sham operation. The development of LVH was followed by serial echocardiography. Cardiac function was assessed by pressure-volume analysis. Cardiomyocyte hypertrophy and fibrosis were evaluated by histology. At week 6, increased LV mass index, heart weight-to-tibial length, cardiomyocyte diameter, concentric LV geometry, and moderate interstitial fibrosis were detected in both male and female AB rats, indicating the development of an early stage of LVH. Functionally, at this time, impaired active relaxation, increased contractility, and preserved ventricular-arterial coupling were observed in the AB groups in both sexes. In contrast, at week 12, progressive deterioration of LVH-associated structural and functional alterations occurred in male but not female animals with sustained PO. Accordingly, at this later stage, LVH was associated with eccentric remodeling, exacerbated fibrosis, and increased chamber stiffness in male AB rats. Furthermore, augmented contractility declined in male but not female AB animals, resulting in contractility-afterload mismatch. Maintained contractility augmentation, preserved ventricular-arterial coupling, and better myocardial compliance in female rats contribute to sex differences in LV function during the progression of PO-induced LVH. NEW & NOTEWORTHY We investigated sex differences in pressure overload-induced left ventricular myocardial hypertrophy for the first time on the functional level by pressure-volume analysis. We found that left ventricular hypertrophy was initially characterized by prolonged active relaxation, increased contractility, and maintained ventricular-arterial coupling in both sexes. However, at a later stage, augmented contractility declined in mate but not female rats, resulting in contractility-afterload mismatch. Furthermore, in male rats, increased myocardial stiffness also contributed to hypertrophy-associated diastolic dysfunction.
Effect of acetazolamide and methazolamide on diaphragm and dorsiflexor fatigue: a randomized controlled trial
Authors: Dominelli Paolo B. , McNeil Chris J. , Vermeulen Tyler D. , Stuckless Troy J. R. , Brown Courtney V. , Dominelli Giulio S. , Swenson Erik R. , Teppema Lucas J. , Foster Glen E. 
Published: May 2018

Acetazolamide, a carbonic anhydrase (CA) inhibitor used clinically and to prevent acute mountain sickness, worsens skeletal muscle fatigue in animals and humans. In animals, methazolamide, a methylated analog of acetazolamide and an equally potent CA inhibitor, reportedly exacerbates fatigue less than acetazolamide. Accordingly, we sought to determine, in humans, if methazolamide would attenuate diaphragm and dorsiflexor fatigue compared with acetazolamide. Healthy men (dorsiflexor: n = 12; diaphragm: n = 7) performed fatiguing exercise on three occasions, after ingesting acetazolamide (250 mg three times a day) and then in random order, methazolamide (100 mg twice a day) or placebo for 48 h. For both muscles, subjects exercised at a fixed intensity until exhaustion on acetazolamide, with subsequent iso-time and -workload trials. Diaphragm exercise was performed using a threshold-loading device, while dorsiflexor exercise was isometric. Neuromuscular function was determined pre- and postexercise by potentiated transdiaphragmatic twitch pressure and dorsiflexor torque in response to stimulation of the phrenic and fibular nerve, respectively. Diaphragm contractility 3–10 min postexercise was impaired more for acetazolamide than methazolamide or placebo (82 ± 10, 87 ± 9, and 91 ± 8% of pre-exercise value; P < 0.05). Similarly, dorsiflexor fatigue was greater for acetazolamide than methazolamide (mean twitch torque of 61 ± 11 vs. 57 ± 13% of baseline, P < 0.05). In normoxia, methazolamide leads to less neuromuscular fatigue than acetazolamide, indicating a possible benefit for clinical use or in the prophylaxis of acute mountain sickness. NEW & NOTEWORTHY Acetazolamide, a carbonic anhydrase inhibitor, may worsen diaphragm and locomotor muscle fatigue after exercise; whereas, in animals, methazolamide does not impair diaphragm function. Compared with both methazolamide and the placebo, acetazolamide significantly compromised dorsiflexor function at rest and after exhaustive exercise. Similarly, diaphragm function was most compromised on acetazolamide followed by methazolamide and placebo. Methazolamide may be preferable over acetazolamide for clinical use and altitude illness prophylaxis to avoid skeletal muscle dysfunction.
Immobilization rapidly induces thioredoxin-interacting protein gene expression together with insulin resistance in rat skeletal muscle
Authors: Kawamoto Emi , Tamakoshi Keigo , Ra Song-Gyu , Masuda Hiroyuki , Kawanaka Kentaro 
Published: May 2018

Acute short duration of disuse induces the development of insulin resistance for glucose uptake in rodent skeletal muscle. Because thioredoxin-interacting protein (TXNIP) has been implicated in the downregulation of insulin signaling and glucose uptake, we examined the possibility that muscle disuse rapidly induces insulin resistance via increased TXNIP mRNA and protein expression. Male Wistar rats were subjected to unilateral 6-h hindlimb immobilization by plaster cast. At the end of this period, the soleus muscles from both immobilized and contralateral nonimmobilized hindlimbs were excised and examined. The 6-h immobilization resulted in an increase in TXNIP mRNA and protein expressions together with a decrease in insulin-stimulated 2-deoxyglucose uptake in the rat soleus muscle. Additionally, in the rats euthanized 6 h after the plaster cast removal, TXNIP protein expression and insulin-stimulated glucose uptake in the immobilized muscle had both been restored to a normal level. Various interventions (pretreatment with transcription inhibitor actinomycin D or AMP-dependent protein kinase activator 5-aminoimidazole-4-carboxamide ribonucleotide) also suppressed the increase in TXNIP protein expression in 6-h-immobilized muscle together with partial prevention of insulin resistance for glucose uptake. These results suggested the possibility that increased TXNIP protein expression in immobilized rat soleus muscles was associated with the rapid induction of insulin resistance for glucose uptake in that tissue. NEW & NOTEWORTHY The cellular mechanism by which disuse rapidly induces muscle insulin resistance for glucose uptake remains to be identified. Using a rat hindlimb immobilization model, our findings suggest the possibility that transcriptional upregulation of thioredoxin-interacting protein is associated with the immobilization-induced rapid development of insulin resistance in skeletal muscle.
Tuning for rate and duration of frequency-modulated sweeps in the mammalian inferior colliculus
Authors: Morrison James A. , Valdizón-Rodríguez Roberto , Goldreich Daniel , Faure Paul A. 
Published: May 2018

Responses of auditory duration-tuned neurons (DTNs) are selective for stimulus duration. We used single-unit extracellular recording to investigate how the inferior colliculus (IC) encodes frequency-modulated (FM) sweeps in the big brown bat. It was unclear whether the responses of so-called “FM DTNs” encode signal duration, like classic pure-tone DTNs, or the FM sweep rate. Most FM cells had spiking responses selective for downward FM sweeps. We presented cells with linear FM sweeps whose center frequency (CEF) was set to the best excitatory frequency and whose bandwidth (BW) maximized the spike count. With these baseline parameters, we stimulated cells with linear FM sweeps randomly varied in duration to measure the range of excitatory FM durations and/or sweep rates. To separate FM rate and FM duration tuning, we doubled (and halved) the BW of the baseline FM stimulus while keeping the CEF constant and then recollected each cell’s FM duration tuning curve. If the cell was tuned to FM duration, then the best duration (or range of excitatory durations) should remain constant despite changes in signal BW; however, if the cell was tuned to the FM rate, then the best duration should covary with the same FM rate at each BW. A Bayesian model comparison revealed that the majority of neurons were tuned to the FM sweep rate, although a few cells showed tuning for FM duration. We conclude that the dominant parameter for temporal tuning of FM neurons in the IC is FM sweep rate and not FM duration.NEW & NOTEWORTHY Reports of inferior colliculus neurons with response selectivity to the duration of frequency-modulated (FM) stimuli exist, yet it remains unclear whether such cells are tuned to the FM duration or the FM sweep rate. To disambiguate these hypotheses, we presented neurons with variable-duration FM signals that were systematically manipulated in bandwidth. A Bayesian model comparison revealed that most temporally selective midbrain cells were tuned to the FM sweep rate and not the FM duration.
Crossed corticospinal facilitation between arm and trunk muscles in humans
Authors: Chiou Shin-Yi , Strutton Paul H. , Perez Monica A. 
Published: May 2018

A voluntary contraction of muscles with one arm increases the excitability of corticospinal projections to the contralateral resting arm, a phenomenon known as crossed facilitation. Although many motor tasks engage simultaneous activation of the arm and trunk, interactions between corticospinal projections targeting these segments remain largely unknown. Using transcranial magnetic stimulation over the trunk representation of the primary motor cortex, we examined motor-evoked potentials (MEPs) in the resting erector spinae (ES) muscle when the contralateral arm remained at rest or performed 20% of isometric maximal voluntary contraction (MVC) into index finger abduction, thumb abduction, elbow flexion, and elbow extension. We found that MEP size in the ES increased during all voluntary contractions, with greater facilitation occurring during elbow flexion and index finger abduction. To further examine the origin of changes in MEP size, we measured short-interval intracortical inhibition (SICI) and cervicomedullary MEPs (CMEPs) in the ES muscle during elbow flexion and index finger abduction and when the arm remained at rest. Notably, SICI decreased and CMEPs remained unchanged in the ES during both voluntary contractions compared with rest, suggesting a cortical origin for the effects. Our findings reveal crossed facilitatory interactions between trunk extensor and proximal and distal arm muscles, particularly for elbow flexor and index finger muscles, likely involving cortical mechanisms. These interactions might reflect the different role of these muscles during functionally relevant arm and trunk movements. NEW & NOTEWORTHY Many of the tasks of daily life involve simultaneous activation of the arm and trunk. We found that responses in the erector spinae muscles evoked by motor cortical stimulation increased in size during elbow flexion and extension and during index finger abduction and thumb abduction. Crossed facilitation with the trunk was more pronounced during elbow flexion and index finger abduction. These results might reflect the different role of these muscles during arm and trunk movements.
Combining biophysical modeling and deep learning for multielectrode array neuron localization and classification
Authors: Buccino Alessio P. , Kordovan Michael , Ness Torbjørn V. , Merkt Benjamin , Häfliger Philipp D. , Fyhn Marianne , Cauwenberghs Gert , Rotter Stefan , Einevoll Gaute T. 
Published: May 2018

Neural circuits typically consist of many different types of neurons, and one faces a challenge in disentangling their individual contributions in measured neural activity. Classification of cells into inhibitory and excitatory neurons and localization of neurons on the basis of extracellular recordings are frequently employed procedures. Current approaches, however, need a lot of human intervention, which makes them slow, biased, and unreliable. In light of recent advances in deep learning techniques and exploiting the availability of neuron models with quasi-realistic three-dimensional morphology and physiological properties, we present a framework for automatized and objective classification and localization of cells based on the spatiotemporal profiles of the extracellular action potentials recorded by multielectrode arrays. We train convolutional neural networks on simulated signals from a large set of cell models and show that our framework can predict the position of neurons with high accuracy, more precisely than current state-of-the-art methods. Our method is also able to classify whether a neuron is excitatory or inhibitory with very high accuracy, substantially improving on commonly used clustering techniques. Furthermore, our new method seems to have the potential to separate certain subtypes of excitatory and inhibitory neurons. The possibility of automatically localizing and classifying all neurons recorded with large high-density extracellular electrodes contributes to a more accurate and more reliable mapping of neural circuits. NEW & NOTEWORTHY We propose a novel approach to localize and classify neurons from their extracellularly recorded action potentials with a combination of biophysically detailed neuron models and deep learning techniques. Applied to simulated data, this new combination of forward modeling and machine learning yields higher performance compared with state-of-the-art localization and classification methods.
Minocycline promotes posthemorrhagic neurogenesis via M2 microglia polarization via upregulation of the TrkB/BDNF pathway in rats
Authors: Miao Hongsheng , Li Runming , Han Cong , Lu Xiuzhen , Zhang Hang 
Published: May 2018

Intracerebral hemorrhage (ICH) is a devastating disease worldwide with increasing mortality. The present study investigated whether minocycline was neuroprotective and induced M2 microglial polarization via upregulation of the TrkB/BDNF pathway after ICH. ICH was induced via injection of autologous blood into 150 Sprague-Dawley rats. A selective TrkB antagonist [N2–2-2-oxoazepan-3-yl amino] carbonyl phenyl benzo (b) thiophene-2-carboxamide (ANA 12)] and agonist [ N-[2-(5-hydroxy-1H-indol-3-yl) ethyl]-2-oxopiperidine-3-carboxamide (HIOC)] were used to investigate the mechanism of minocycline-induced neuroprotection. Minocycline improved ICH-induced neurological deficits and reduced M1 microglia marker protein (CD68, CD16) expression as well as M2 microglial polarization (CD206 and arginase 1 protein). Minocycline administration enhanced microglia-neuron cross talk and promoted the proliferation of neuronal progenitor cells, such as DCX- and Tuj-1-positive cells, 24 h after ICH. Minocycline also increased M2 microglia-derived brain-derived neurotrophic factors (BDNF) and the upstream TrkB pathway. ANA 12 reversed the neuroprotective effects of minocycline. HIOC exhibited the same effects as minocycline and accelerated neurogenesis after ICH. This study demonstrated for the first time that minocycline promoted M2 microglia polarization via upregulation of the TrkB/BDNF pathway and promoted neurogenesis after ICH. This study contributes to our understanding of the therapeutic potential of minocycline in ICH. NEW & NOTEWORTHY The present study gives several novel points: 1) Minocycline promotes neurogenesis after intracerebral hemorrhage in rats. 2) Minocycline induces activated M1 microglia into M2 neurotrophic phenotype. 3) M2 microglia secreting BDNF remodel the damaged neurocircuit.
Developmental nicotine exposure alters glycinergic neurotransmission to hypoglossal motoneurons in neonatal rats
Authors: Wollman Lila Buls , Levine Richard B. , Fregosi Ralph F. 
Published: May 2018

We tested the hypothesis that nicotine exposure in utero and after birth [developmental nicotine exposure (DNE)] disrupts development of glycinergic synaptic transmission to hypoglossal motoneurons (XIIMNs). Glycinergic spontaneous and miniature inhibitory postsynaptic currents (sIPSC/mIPSC) were recorded from XIIMNs in brain stem slices from 1- to 5-day-old rat pups of either sex, under baseline conditions and following stimulation of nicotinic acetylcholine (ACh) receptors with nicotine (i.e., an acute nicotine challenge). Under baseline conditions, there were no significant effects of DNE on the amplitude or frequency of either sIPSCs or mIPSCs. In addition, DNE did not alter the magnitude of the whole cell current evoked by bath application of glycine, consistent with an absence of change in postsynaptic glycine-mediated conductance. An acute nicotine challenge (bath application of 0.5 μM nicotine) increased sIPSC frequency in the DNE cells, but not control cells. In contrast, nicotine challenge did not change mIPSC frequency in either control or DNE cells. In addition, there were no significant changes in the amplitude of either sIPSCs or mIPSCs in response to nicotine challenge. The increased frequency of sIPSCs in response to an acute nicotine challenge in DNE cells reflects an enhancement of action potential-mediated input from glycinergic interneurons to hypoglossal motoneurons. This could lead to more intense inhibition of hypoglossal motoneurons in response to exogenous nicotine or endogenous ACh. The former would occur with smoking or e-cigarette use while the latter occurs with changes in sleep state and with hypercapnia.NEW & NOTEWORTHY Here we show that perinatal nicotine exposure does not impact baseline glycinergic neurotransmission to hypoglossal motoneurons but enhances glycinergic inputs to hypoglossal motoneurons in response to activation of nicotinic acetylcholine (ACh) receptors with acute nicotine. Given that ACh is the endogenous ligand for nicotinic ACh receptors, the latter reveals a potential mechanism whereby perinatal nicotine exposure alters motor function under conditions where ACh release increases, such as the transition from non-rapid-eye movement to rapid-eye movement sleep, and during hypercapnia.
Dynamics of corticospinal motor control during overground and treadmill walking in humans
Authors: Roeder Luisa , Boonstra Tjeerd W. , Smith Simon S. , Kerr Graham K. 
Published: May 2018

Increasing evidence suggests cortical involvement in the control of human gait. However, the nature of corticospinal interactions remains poorly understood. We performed time-frequency analysis of electrophysiological activity acquired during treadmill and overground walking in 22 healthy, young adults. Participants walked at their preferred speed (4.2, SD 0.4 km/h), which was matched across both gait conditions. Event-related power, corticomuscular coherence (CMC), and intertrial coherence (ITC) were assessed for EEG from bilateral sensorimotor cortices and EMG from the bilateral tibialis anterior (TA) muscles. Cortical power, CMC, and ITC at theta, alpha, beta, and gamma frequencies (4–45 Hz) increased during the double support phase of the gait cycle for both overground and treadmill walking. High beta (21–30 Hz) CMC and ITC of EMG was significantly increased during overground compared with treadmill walking, as well as EEG power in theta band (4–7 Hz). The phase spectra revealed positive time lags at alpha, beta, and gamma frequencies, indicating that the EEG response preceded the EMG response. The parallel increases in power, CMC, and ITC during double support suggest evoked responses at spinal and cortical populations rather than a modulation of ongoing corticospinal oscillatory interactions. The evoked responses are not consistent with the idea of synchronization of ongoing corticospinal oscillations but instead suggest coordinated cortical and spinal inputs during the double support phase. Frequency-band dependent differences in power, CMC, and ITC between overground and treadmill walking suggest differing neural control for the two gait modalities, emphasizing the task-dependent nature of neural processes during human walking. NEW & NOTEWORTHY We investigated cortical and spinal activity during overground and treadmill walking in healthy adults. Parallel increases in power, corticomuscular coherence, and intertrial coherence during double support suggest evoked responses at spinal and cortical populations rather than a modulation of ongoing corticospinal oscillatory interactions. These findings identify neurophysiological mechanisms that are important for understanding cortical control of human gait in health and disease.
Modulation of spinal motor networks by astrocyte-derived adenosine is dependent on D1-like dopamine receptor signaling
Authors: Acton David , Broadhead Matthew J. , Miles Gareth B. 
Published: May 2018

Astrocytes modulate many neuronal networks, including spinal networks responsible for the generation of locomotor behavior. Astrocytic modulation of spinal motor circuits involves release of ATP from astrocytes, hydrolysis of ATP to adenosine, and subsequent activation of neuronal A1 adenosine receptors (A1Rs). The net effect of this pathway is a reduction in the frequency of locomotor-related activity. Recently, it was proposed that A1Rs modulate burst frequency by blocking the D1-like dopamine receptor (D1LR) signaling pathway; however, adenosine also modulates ventral horn circuits by dopamine-independent pathways. Here, we demonstrate that adenosine produced upon astrocytic stimulation modulates locomotor-related activity by counteracting the excitatory effects of D1LR signaling and does not act by previously described dopamine-independent pathways. In spinal cord preparations from postnatal mice, a D1LR agonist, SKF 38393, increased the frequency of locomotor-related bursting induced by 5-hydroxytryptamine and N-methyl-d-aspartate. Bath-applied adenosine reduced burst frequency only in the presence of SKF 38393, as did adenosine produced after activation of protease-activated receptor-1 to stimulate astrocytes. Furthermore, the A1R antagonist 8-cyclopentyl-1,3-dipropylxanthine enhanced burst frequency only in the presence of SKF 38393, indicating that endogenous adenosine produced by astrocytes during network activity also acts by modulating D1LR signaling. Finally, modulation of bursting by adenosine released upon stimulation of astrocytes was blocked by protein kinase inhibitor-(14–22) amide, a protein kinase A (PKA) inhibitor, consistent with A1R-mediated antagonism of the D1LR/adenylyl cyclase/PKA pathway. Together, these findings support a novel, astrocytic mechanism of metamodulation within the mammalian spinal cord, highlighting the complexity of the molecular interactions that specify motor output. NEW & NOTEWORTHY Astrocytes within the spinal cord produce adenosine during ongoing locomotor-related activity or when experimentally stimulated. Here, we show that adenosine derived from astrocytes acts at A1 receptors to inhibit a pathway by which D1-like receptors enhance the frequency of locomotor-related bursting. These data support a novel form of metamodulation within the mammalian spinal cord, enhancing our understanding of neuron-astrocyte interactions and their importance in shaping network activity.