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Sample records for cardiac neuronal function

  1. Assessment of cardiac neuronal function with iodine-123 MIBG scintigraphy in children with idiopathic dilated cardiomyopathy

    International Nuclear Information System (INIS)

    Maunoury, Ch.; Sebahoun, St.; Hallaj, I.; Barritault, L.; Acar, Ph.; Sidi, D.; Kachaner, J.; Agostini, D.; Bouvard, G.

    2000-01-01

    The I-123 MIBG cardiac scintigraphy can assess norepinephrine uptake. It has been showed that cardiac adrenergic neuronal function was impaired in adults with dilated cardiomyopathy. The aim of this prospective study was to assess cardiac neuronal function in children with idiopathic dilated cardiomyopathy (DCM) and to compare cardiac uptake of I-123 MIBG with left ventricular ejection fraction (LVEF). We studied 26 consecutive patients with idiopathic DCM, aged 44 ± 50 months, and 12 controls, aged 49 ±65 months. A planar scintigraphy was performed in all children 4 hours after intravenous injection of 20 to 75 MBq of I-123 MIBG. A static anterior view was acquired for 10 minutes. Cardiac uptake of I-123 MIBG was expressed as the heart to mediastinum count ratio (HMR). Equilibrium radionuclide angiography was performed following a standard protocol. Cardiac uptake of I-123 MIBG was significantly decreased in patients with idiopathic DCM when compared with cardiac uptake in controls (172±34% vs 277±14%, P<0.0001. There was a good correlation between RCM and LVEF in patients with idiopathic DCM (y = 2.5 x +113.3, r = 0.80, P < 0.0001). In conclusion, cardiac neuronal function was impaired in children with idiopathic DCM and related to impairment of left ventricular function. (author)

  2. Methyl-CpG binding-protein 2 function in cholinergic neurons mediates cardiac arrhythmogenesis.

    Science.gov (United States)

    Herrera, José A; Ward, Christopher S; Wehrens, Xander H T; Neul, Jeffrey L

    2016-11-15

    Sudden unexpected death occurs in one quarter of deaths in Rett Syndrome (RTT), a neurodevelopmental disorder caused by mutations in Methyl-CpG-binding protein 2 (MECP2). People with RTT show a variety of autonomic nervous system (ANS) abnormalities and mouse models show similar problems including QTc interval prolongation and hypothermia. To explore the role of cardiac problems in sudden death in RTT, we characterized cardiac rhythm in mice lacking Mecp2 function. Male and female mutant mice exhibited spontaneous cardiac rhythm abnormalities including bradycardic events, sinus pauses, atrioventricular block, premature ventricular contractions, non-sustained ventricular arrhythmias, and increased heart rate variability. Death was associated with spontaneous cardiac arrhythmias and complete conduction block. Atropine treatment reduced cardiac arrhythmias in mutant mice, implicating overactive parasympathetic tone. To explore the role of MeCP2 within the parasympathetic neurons, we selectively removed MeCP2 function from cholinergic neurons (MeCP2 ChAT KO), which recapitulated the cardiac rhythm abnormalities, hypothermia, and early death seen in RTT male mice. Conversely, restoring MeCP2 only in cholinergic neurons rescued these phenotypes. Thus, MeCP2 in cholinergic neurons is necessary and sufficient for autonomic cardiac control, thermoregulation, and survival, and targeting the overactive parasympathetic system may be a useful therapeutic strategy to prevent sudden unexpected death in RTT.

  3. Use of I-123 MIBG cardiac scintigraphy to assess the impact of carvedilol on cardiac adrenergic neuronal function in childhood dilated cardiomyopathy

    International Nuclear Information System (INIS)

    Maunoury, C.; Acar, P.; Sidi, D.

    2006-01-01

    I-123 MIBG cardiac scintigraphy is a useful tool to assess cardiac adrenergic neuronal function, which is impaired in children with dilated cardiomyopathy (DCM). In adults with DCM, long-term treatment with carvedilol improves both cardiac adrenergic neuronal function and left ventricular function. The aim of this prospective study was to evaluate the impact of carvedilol on cardiac adrenergic neuronal function and on left ventricular function in seventeen patients (11 female, 6 male, mean age 39 ± 57 months, range 1 - 168 months) with DCM. All patients underwent I-123 MIBG cardiac scintigraphy and equilibrium radio-nuclide angiography before and after a 6 month period of carvedilol therapy. A static anterior view of the chest was acquired 4 hours after intravenous injection of 20 to 75 MBq of I-123 MIBG. Cardiac neuronal uptake of I-123 MIBG was measured using the heart to mediastinum count ratio (HMR). Radionuclide left ventricular ejection fraction (LVEF) was assessed following a standard protocol. There was no major cardiac events (death or transplantation) during the follow-up period. I-123 MIBG cardiac uptake and left ventricular function respectively increased by 38% and 65% after 6 months of treatment with carvedilol (HMR 223 ± 49% vs 162 ± 26%, p < 0.0001 and LVEF = 43 ± 17% vs 26 ± 11%, p < 0.0001). Carvedilol can improve cardiac adrenergic neuronal function and left ventricular function in children with DCM. Further studies are needed to assess the relationship between improvement in I-123 MIBG cardiac uptake and the beneficial effects of carvedilol on morbidity and mortality. (authors)

  4. Optogenetic release of norepinephrine from cardiac sympathetic neurons alters mechanical and electrical function.

    Science.gov (United States)

    Wengrowski, Anastasia M; Wang, Xin; Tapa, Srinivas; Posnack, Nikki Gillum; Mendelowitz, David; Kay, Matthew W

    2015-02-01

    Release of norepinephrine (NE) from sympathetic neurons enhances heart rate (HR) and developed force through activation of β-adrenergic receptors, and this sympathoexcitation is a key risk for the generation of cardiac arrhythmias. Studies of β-adrenergic modulation of cardiac function typically involve the administration of exogenous β-adrenergic receptor agonists to directly elicit global β-adrenergic receptor activation by bypassing the involvement of sympathetic nerve terminals. In this work, we use a novel method to activate sympathetic fibres within the myocardium of Langendorff-perfused hearts while measuring changes in electrical and mechanical function. The light-activated optogenetic protein channelrhodopsin-2 (ChR2) was expressed in murine catecholaminergic sympathetic neurons. Sympathetic fibres were then photoactivated to examine changes in contractile force, HR, and cardiac electrical activity. Incidence of arrhythmia was measured with and without exposure to photoactivation of sympathetic fibres, and hearts were optically mapped to detect changes in action potential durations and conduction velocities. Results demonstrate facilitation of both developed force and HR after photostimulated release of NE, with increases in contractile force and HR of 34.5 ± 5.5 and 25.0 ± 9.3%, respectively. Photostimulation of sympathetic fibres also made hearts more susceptible to arrhythmia, with greater incidence and severity. In addition, optically mapped action potentials displayed a small but significant shortening of the plateau phase (-5.5 ± 1.0 ms) after photostimulation. This study characterizes a powerful and clinically relevant new model for studies of cardiac arrhythmias generated by increasing the activity of sympathetic nerve terminals and the resulting activation of myocyte β-adrenergic receptors. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

  5. Impact of exercise rehabilitation on cardiac neuronal function in heart failure. An iodine-123 metaiodobenzylguanidine scintigraphy study

    Energy Technology Data Exchange (ETDEWEB)

    Agostini, D.; Bouvard, G. [Service de Medecine Nucleaire, CHU Cote de Nacre, Caen (France); Lecluse, E.; Grollier, G.; Potier, J.C. [Service de Cardiologie, CHU Cote de Nacre, Caen (France); Belin, A. [Service de Readaptation Cardiaque, CHU Cote de Nacre, Caen (France); Babatasi, G. [Service de Chirurgie Cardio-Thoracique, CHU Cote de Nacre, Caen (France); Amar, M.H. [Centre Francois Baclesse, Caen (France). Service de Recherche Clinique

    1998-03-01

    Exercise training can induce important haemodynamic and metabolic adaptations in patients with chronic heart failure due to severe left ventricular dysfunction. This study examined the impact of exercise rehabilitation on cardiac neuronal function using iodine-123 metaiobodenzylguanidine (MIBG) scintigraphy. Fourteen patients (11 men, 3 women; mean age 48 years; range: 36-66 years) with stable chronic heart failure of NYHA class II-III and an initial resting radionuclide left ventricular ejection fraction (LVEF) <50% were enrolled in the study. Patients underwent progressive, supervised endurance training (treadmill test, Bruce protocol) during a 6-month period (60 sessions, 3 sessions per week) at a cardiac rehabilitation referral centre in order to measure exercise parameters. Planar {sup 123}I-MIBG scintigraphy provided measurements of cardiac neuronal uptake (heart-mediastinum ratio activity, 4 h after intravenous injection of 185 MBq of MIBG). Radionuclide LVEF was also assessed at the outset and after 6 months of exercise training. Workload (801{+-}428 vs 1229{+-}245 kpm.min{sup -1}, P=0.001), exercise duration (504{+-}190 vs 649{+-}125 s, P=0.02), and myocardial MIBG uptake (135%{+-}19% vs 156%{+-}25%, P=0.02) increased significantly after rehabilitation. However, LVEF did not change significantly (23%{+-}9% vs 21%{+-}10%, p=NS). It is concluded that exercise rehabilitation induces improvement of cardiac neuronal function without having negative effects on cardiac contractility in patients with stable chronic heart failure. (orig.)

  6. Impact of exercise rehabilitation on cardiac neuronal function in heart failure. An iodine-123 metaiodobenzylguanidine scintigraphy study

    International Nuclear Information System (INIS)

    Agostini, D.; Bouvard, G.; Lecluse, E.; Grollier, G.; Potier, J.C.; Belin, A.; Babatasi, G.; Amar, M.H.

    1998-01-01

    Exercise training can induce important haemodynamic and metabolic adaptations in patients with chronic heart failure due to severe left ventricular dysfunction. This study examined the impact of exercise rehabilitation on cardiac neuronal function using iodine-123 metaiobodenzylguanidine (MIBG) scintigraphy. Fourteen patients (11 men, 3 women; mean age 48 years; range: 36-66 years) with stable chronic heart failure of NYHA class II-III and an initial resting radionuclide left ventricular ejection fraction (LVEF) 123 I-MIBG scintigraphy provided measurements of cardiac neuronal uptake (heart-mediastinum ratio activity, 4 h after intravenous injection of 185 MBq of MIBG). Radionuclide LVEF was also assessed at the outset and after 6 months of exercise training. Workload (801±428 vs 1229±245 kpm.min -1 , P=0.001), exercise duration (504±190 vs 649±125 s, P=0.02), and myocardial MIBG uptake (135%±19% vs 156%±25%, P=0.02) increased significantly after rehabilitation. However, LVEF did not change significantly (23%±9% vs 21%±10%, p=NS). It is concluded that exercise rehabilitation induces improvement of cardiac neuronal function without having negative effects on cardiac contractility in patients with stable chronic heart failure. (orig.)

  7. Use of {sup 123}I-MIBG scintigraphy to assess the impact of carvedilol on cardiac adrenergic neuronal function in childhood dilated cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Maunoury, Christophe [Service de Medecine Nucleaire, Hopital Necker-Enfants Malades, 149 rue de Sevres, 75743, Paris Cedex 15 (France); Acar, Philippe; Sidi, Daniel [Service de Cardiologie Pediatrique, Hopital Necker-Enfants Malades, Paris (France)

    2003-12-01

    Iodine-123 metaiodobenzylguanidine (MIBG) cardiac scintigraphy is a useful tool for the assessment of cardiac adrenergic neuronal function, which is impaired in children with idiopathic dilated cardiomyopathy (DCM). In adults with DCM, long-term treatment with carvedilol improves both cardiac adrenergic neuronal function and left ventricular function. The aim of this prospective study was to evaluate the impact of carvedilol on cardiac adrenergic neuronal function using {sup 123}I-MIBG scintigraphy and on left ventricular function using equilibrium radionuclide angiography in children with DCM. Seventeen patients (11 female, six male; mean age 39{+-}57 months, range 1-168 months) with DCM and left ventricular dysfunction underwent {sup 123}I-MIBG cardiac scintigraphy and equilibrium radionuclide angiography before and after a 6-month period of carvedilol therapy. A static anterior view of the chest was acquired 4 h after intravenous injection of 20-75 MBq of {sup 123}I-MIBG. Cardiac neuronal uptake of {sup 123}I-MIBG was measured using the heart to mediastinum count ratio (HMR). Radionuclide left ventricular ejection fraction (LVEF) was assessed following a standard protocol. MIBG cardiac uptake and left ventricular function respectively increased by 38% and 65% after 6 months of treatment with carvedilol (HMR=223%{+-}49% vs 162%{+-}26%, P<0.0001, and LVEF=43%{+-}17% vs 26%{+-}11%, P<0.0001). Carvedilol can improve cardiac adrenergic neuronal and left ventricular function in children with dilated cardiomyopathy. Further studies are needed to assess the relationship between improvement in MIBG cardiac uptake and the beneficial effects of carvedilol on morbidity and mortality. (orig.)

  8. Use of 123I-MIBG scintigraphy to assess the impact of carvedilol on cardiac adrenergic neuronal function in childhood dilated cardiomyopathy

    International Nuclear Information System (INIS)

    Maunoury, Christophe; Acar, Philippe; Sidi, Daniel

    2003-01-01

    Iodine-123 metaiodobenzylguanidine (MIBG) cardiac scintigraphy is a useful tool for the assessment of cardiac adrenergic neuronal function, which is impaired in children with idiopathic dilated cardiomyopathy (DCM). In adults with DCM, long-term treatment with carvedilol improves both cardiac adrenergic neuronal function and left ventricular function. The aim of this prospective study was to evaluate the impact of carvedilol on cardiac adrenergic neuronal function using 123 I-MIBG scintigraphy and on left ventricular function using equilibrium radionuclide angiography in children with DCM. Seventeen patients (11 female, six male; mean age 39±57 months, range 1-168 months) with DCM and left ventricular dysfunction underwent 123 I-MIBG cardiac scintigraphy and equilibrium radionuclide angiography before and after a 6-month period of carvedilol therapy. A static anterior view of the chest was acquired 4 h after intravenous injection of 20-75 MBq of 123 I-MIBG. Cardiac neuronal uptake of 123 I-MIBG was measured using the heart to mediastinum count ratio (HMR). Radionuclide left ventricular ejection fraction (LVEF) was assessed following a standard protocol. MIBG cardiac uptake and left ventricular function respectively increased by 38% and 65% after 6 months of treatment with carvedilol (HMR=223%±49% vs 162%±26%, P<0.0001, and LVEF=43%±17% vs 26%±11%, P<0.0001). Carvedilol can improve cardiac adrenergic neuronal and left ventricular function in children with dilated cardiomyopathy. Further studies are needed to assess the relationship between improvement in MIBG cardiac uptake and the beneficial effects of carvedilol on morbidity and mortality. (orig.)

  9. Reduced capacity of cardiac efferent sympathetic neurons to release noradrenaline and modify cardiac function in tachycardia-induced canine heart failure.

    Science.gov (United States)

    Cardinal, R; Nadeau, R; Laurent, C; Boudreau, G; Armour, J A

    1996-09-01

    To investigate the capacity of efferent sympathetic neurons to modulate the failing heart, stellate ganglion stimulation was performed in dogs with biventricular heart failure induced by rapid ventricular pacing (240 beats/min) for 4-6 weeks. Less noradrenaline was released from cardiac myoneural junctions into coronary sinus blood in response to left stellate ganglion stimulation in anesthetized failing heart preparations (582 pg/mL, lower and upper 95% confidence intervals of 288 and 1174 pg/mL, n = 19) compared with healthy heart preparations (6391 pg/mL, 95% confidence intervals of 4180 and 9770 pg/mL, n = 14; p < 0.001). There was substantial adrenaline extraction by failing hearts (49 +/- 6%), although it was slightly lower than in healthy heart preparations (65 +/- 9%, p = 0.055). In contrast with healthy heart preparations, no net release of adrenaline occurred during stellate ganglion stimulation in any of the failing heart preparations, and ventricular tissue levels of adrenaline fell below the sensitivity limit of the HPLC technique. In failing heart preparations, maximal electrical stimulation of right or left stellate ganglia resulted in minimal augmentation of left ventricular intramyocardial (17%) and chamber (12%) systolic pressures. These indices were augmented by 145 and 97%, respectively, following exogenous noradrenaline administration. Thus, the cardiac efferent sympathetic neurons' reduced capacity to release noradrenaline and modify cardiac function can contribute to reduction of sympathetic support to the failing heart.

  10. Chronic activation of hypothalamic oxytocin neurons improves cardiac function during left ventricular hypertrophy-induced heart failure.

    Science.gov (United States)

    Garrott, Kara; Dyavanapalli, Jhansi; Cauley, Edmund; Dwyer, Mary Kate; Kuzmiak-Glancy, Sarah; Wang, Xin; Mendelowitz, David; Kay, Matthew W

    2017-09-01

    A distinctive hallmark of heart failure (HF) is autonomic imbalance, consisting of increased sympathetic activity, and decreased parasympathetic tone. Recent work suggests that activation of hypothalamic oxytocin (OXT) neurons could improve autonomic balance during HF. We hypothesized that a novel method of chronic selective activation of hypothalamic OXT neurons will improve cardiac function and reduce inflammation and fibrosis in a rat model of HF. Two groups of male Sprague-Dawley rats underwent trans-ascending aortic constriction (TAC) to induce left ventricular (LV) hypertrophy that progresses to HF. In one TAC group, OXT neurons in the paraventricular nucleus of the hypothalamus were chronically activated by selective expression and activation of excitatory DREADDs receptors with daily injections of clozapine N-oxide (CNO) (TAC + OXT). Two additional age-matched groups received either saline injections (Control) or CNO injections for excitatory DREADDs activation (OXT NORM). Heart rate (HR), LV developed pressure (LVDP), and coronary flow rate were measured in isolated heart experiments. Isoproterenol (0.01 nM-1.0 µM) was administered to evaluate β-adrenergic sensitivity. We found that increases in cellular hypertrophy and myocardial collagen density in TAC were blunted in TAC + OXT animals. Inflammatory cytokine IL-1β expression was more than twice higher in TAC than all other hearts. LVDP, rate pressure product (RPP), contractility, and relaxation were depressed in TAC compared with all other groups. The response of TAC and TAC + OXT hearts to isoproterenol was blunted, with no significant increase in RPP, contractility, or relaxation. However, HR in TAC + OXT animals increased to match Control at higher doses of isoproterenol. Activation of hypothalamic OXT neurons to elevate parasympathetic tone reduced cellular hypertrophy, levels of IL-1β, and fibrosis during TAC-induced HF in rats. Cardiac contractility parameters were

  11. Functional Na(V)1.8 Channels in Intracardiac Neurons The Link Between SCN10A and Cardiac Electrophysiology

    NARCIS (Netherlands)

    Verkerk, Arie O.; Remme, Carol Ann; Schumacher, Cees A.; Scicluna, Brendon P.; Wolswinkel, Rianne; de Jonge, Berend; Bezzina, Connie R.; Veldkamp, Marieke W.

    2012-01-01

    Rationale: The SCN10A gene encodes the neuronal sodium channel isoform Na(V)1.8. Several recent genome-wide association studies have linked SCN10A to PR interval and QRS duration, strongly suggesting an as-yet unknown role for Na(V)1.8 in cardiac electrophysiology. Objective: To demonstrate the

  12. Measure of synchrony in the activity of intrinsic cardiac neurons

    International Nuclear Information System (INIS)

    Longpré, Jean-Philippe; Salavatian, Siamak; Jacquemet, Vincent; Beaumont, Eric; Armour, J Andrew; Ardell, Jeffrey L

    2014-01-01

    Recent multielectrode array recordings in ganglionated plexi of canine atria have opened the way to the study of population dynamics of intrinsic cardiac neurons. These data provide critical insights into the role of local processing that these ganglia play in the regulation of cardiac function. Low firing rates, marked non-stationarity, interplay with the cardiovascular and pulmonary systems and artifacts generated by myocardial activity create new constraints not present in brain recordings for which almost all neuronal analysis techniques have been developed. We adapted and extended the jitter-based synchrony index (SI) to (1) provide a robust and computationally efficient tool for assessing the level and statistical significance of SI between cardiac neurons, (2) estimate the bias on SI resulting from neuronal activity possibly hidden in myocardial artifacts, (3) quantify the synchrony or anti-synchrony between neuronal activity and the phase in the cardiac and respiratory cycles. The method was validated on firing time series from a total of 98 individual neurons identified in 8 dog experiments. SI ranged from −0.14 to 0.66, with 23 pairs of neurons with SI > 0.1. The estimated bias due to artifacts was typically <1%. Strongly cardiovascular- and pulmonary-related neurons (SI > 0.5) were found. Results support the use of jitter-based SI in the context of intrinsic cardiac neurons. (paper)

  13. Characterization of Glutamatergic Neurons in the Rat Atrial Intrinsic Cardiac Ganglia that Project to the Cardiac Ventricular Wall

    Science.gov (United States)

    Wang, Ting; Miller, Kenneth E.

    2016-01-01

    The intrinsic cardiac nervous system modulates cardiac function by acting as an integration site for regulating autonomic efferent cardiac output. This intrinsic system is proposed to be composed of a short cardio-cardiac feedback control loop within the cardiac innervation hierarchy. For example, electrophysiological studies have postulated the presence of sensory neurons in intrinsic cardiac ganglia for regional cardiac control. There is still a knowledge gap, however, about the anatomical location and neurochemical phenotype of sensory neurons inside intrinsic cardiac ganglia. In the present study, rat intrinsic cardiac ganglia neurons were characterized neurochemically with immunohistochemistry using glutamatergic markers: vesicular glutamate transporters 1 and 2 (VGLUT1; VGLUT2), and glutaminase (GLS), the enzyme essential for glutamate production. Glutamatergic neurons (VGLUT1/VGLUT2/GLS) in the ICG that have axons to the ventricles were identified by retrograde tracing of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) injected in the ventricular wall. Co-labeling of VGLUT1, VGLUT2, and GLS with the vesicular acetylcholine transporter (VAChT) was used to evaluate the relationship between post-ganglionic autonomic neurons and glutamatergic neurons. Sequential labeling of VGLUT1 and VGLUT2 in adjacent tissue sections was used to evaluate the co-localization of VGLUT1 and VGLUT2 in ICG neurons. Our studies yielded the following results: (1) intrinsic cardiac ganglia contain glutamatergic neurons with GLS for glutamate production and VGLUT1 and 2 for transport of glutamate into synaptic vesicles; (2) atrial intrinsic cardiac ganglia contain neurons that project to ventricle walls and these neurons are glutamatergic; (3) many glutamatergic ICG neurons also were cholinergic, expressing VAChT. (4) VGLUT1 and VGLUT2 co-localization occurred in ICG neurons with variation of their protein expression level. Investigation of both glutamatergic and cholinergic ICG

  14. Use of I-123 MIBG cardiac scintigraphy to assess the impact of carvedilol on cardiac adrenergic neuronal function in childhood dilated cardiomyopathy; Interet de la scintigraphie cardiaque a l'I-123 MIBG pour evaluer l'impact du carvedilol sur la fonction neuronale adrenergique cardiaque dans les myocardiopathies dilatees de l'enfant

    Energy Technology Data Exchange (ETDEWEB)

    Maunoury, C. [Hopital Europeen Georges Pompidou (HEGP), Dept. de Physiologie et Radio-Isotopes, 75 - Paris (France); Acar, P. [Centre Hospitalier Universitaire, Service de Cardiologie Pediatrique, Hopital des Enfants, 31 - Toulouse (France); Sidi, D. [Centre Hospitalier Universitaire Necker-Enfants-Malades, 75 - Paris (France)

    2006-04-15

    I-123 MIBG cardiac scintigraphy is a useful tool to assess cardiac adrenergic neuronal function, which is impaired in children with dilated cardiomyopathy (DCM). In adults with DCM, long-term treatment with carvedilol improves both cardiac adrenergic neuronal function and left ventricular function. The aim of this prospective study was to evaluate the impact of carvedilol on cardiac adrenergic neuronal function and on left ventricular function in seventeen patients (11 female, 6 male, mean age 39 {+-} 57 months, range 1 - 168 months) with DCM. All patients underwent I-123 MIBG cardiac scintigraphy and equilibrium radio-nuclide angiography before and after a 6 month period of carvedilol therapy. A static anterior view of the chest was acquired 4 hours after intravenous injection of 20 to 75 MBq of I-123 MIBG. Cardiac neuronal uptake of I-123 MIBG was measured using the heart to mediastinum count ratio (HMR). Radionuclide left ventricular ejection fraction (LVEF) was assessed following a standard protocol. There was no major cardiac events (death or transplantation) during the follow-up period. I-123 MIBG cardiac uptake and left ventricular function respectively increased by 38% and 65% after 6 months of treatment with carvedilol (HMR 223 {+-} 49% vs 162 {+-} 26%, p < 0.0001 and LVEF = 43 {+-} 17% vs 26 {+-} 11%, p < 0.0001). Carvedilol can improve cardiac adrenergic neuronal function and left ventricular function in children with DCM. Further studies are needed to assess the relationship between improvement in I-123 MIBG cardiac uptake and the beneficial effects of carvedilol on morbidity and mortality. (authors)

  15. Direct projections from hypothalamic orexin neurons to brainstem cardiac vagal neurons.

    Science.gov (United States)

    Dergacheva, Olga; Yamanaka, Akihiro; Schwartz, Alan R; Polotsky, Vsevolod Y; Mendelowitz, David

    2016-12-17

    Orexin neurons are known to augment the sympathetic control of cardiovascular function, however the role of orexin neurons in parasympathetic cardiac regulation remains unclear. To test the hypothesis that orexin neurons contribute to parasympathetic control we selectively expressed channelrhodopsin-2 (ChR2) in orexin neurons in orexin-Cre transgenic rats and examined postsynaptic currents in cardiac vagal neurons (CVNs) in the dorsal motor nucleus of the vagus (DMV). Simultaneous photostimulation and recording in ChR2-expressing orexin neurons in the lateral hypothalamus resulted in reliable action potential firing as well as large whole-cell currents suggesting a strong expression of ChR2 and reliable optogenetic excitation. Photostimulation of ChR2-expressing fibers in the DMV elicited short-latency (ranging from 3.2ms to 8.5ms) postsynaptic currents in 16 out of 44 CVNs tested. These responses were heterogeneous and included excitatory glutamatergic (63%) and inhibitory GABAergic (37%) postsynaptic currents. The results from this study suggest different sub-population of orexin neurons may exert diverse influences on brainstem CVNs and therefore may play distinct functional roles in parasympathetic control of the heart. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  16. Function and modulation of premotor brainstem parasympathetic cardiac neurons that control heart rate by hypoxia-, sleep-, and sleep-related diseases including obstructive sleep apnea.

    Science.gov (United States)

    Dergacheva, Olga; Weigand, Letitia A; Dyavanapalli, Jhansi; Mares, Jacquelyn; Wang, Xin; Mendelowitz, David

    2014-01-01

    Parasympathetic cardiac vagal neurons (CVNs) in the brainstem dominate the control of heart rate. Previous work has determined that these neurons are inherently silent, and their activity is largely determined by synaptic inputs to CVNs that include four major types of synapses that release glutamate, GABA, glycine, or serotonin. Whereas prior reviews have focused on glutamatergic, GABAergic and glycinergic pathways, and the receptors in CVNs activated by these neurotransmitters, this review focuses on the alterations in CVN activity with hypoxia-, sleep-, and sleep-related cardiovascular diseases including obstructive sleep apnea. © 2014 Elsevier B.V. All rights reserved.

  17. Cardiac function studies

    International Nuclear Information System (INIS)

    Horn, H.J.

    1986-01-01

    A total of 27 patients were subjected tointramyocardial sequential scintiscanning (first pass) using 99m-Tc human serum albumin. A refined method is described that is suitable to analyse clinically relevant parameters like blood volume, cardiac output, ejection fraction, stroke volume, enddiastolic and endsystolic volumes as well as pulmonal transition time and uses a complete camaracomputer system adapted to the requirements of a routine procedure. Unless there is special hardware available, the method does not yet appear mature enough to be put into general practice. Its importance recently appeared in a new light due to the advent of particularly shortlived isotopes. For the time being, however, ECG-triggered equilibrium studies are to be preferred for cardiac function tests. (TRV) [de

  18. Cardiac function in acute hypothyroidism

    International Nuclear Information System (INIS)

    Donaghue, K.; Hales, I.; Allwright, S.; Cooper, R.; Edwards, A.; Grant, S.; Morrow, A.; Wilmshurst, E.; Royal North Shore Hospital, Sydney

    1985-01-01

    It has been established that chronic hypothyroidism may affect cardiac function by several mechanisms. It is not known how long the patient has to be hypothyroid for cardiac involvement to develop. This study was undertaken to assess the effect of a short period of hypothyroidism (10 days) on cardiac function. Nine patients who had had total tyroidectomy, had received ablative radioiodine for thyroid cancer and were euthyroid on replacement therapy were studied while both euthyroid and hypothyroid. Cardiac assessment was performed by X-ray, ECG, echocardiography and gated blood-pool scans. After 10 days of hypothyroidisms, the left-ventricular ejection fraction failed to rise after exercise in 4 of the 9 patients studied, which was significant (P<0.002). No significant changes in cardiac size or function at rest were detected. This functional abnormality in the absence of any demonstrable change in cardiac size and the absence of pericardial effussion with normal basal function suggest that short periods of hypothyroidism may reduce cardiac reserve, mostly because of alterations in metabolic function. (orig.)

  19. Cardiac sympathetic neuronal imaging using PET

    International Nuclear Information System (INIS)

    Lautamaeki, Riikka; Tipre, Dnyanesh; Bengel, Frank M.

    2007-01-01

    Balance of the autonomic nervous system is essential for adequate cardiac performance, and alterations seem to play a key role in the development and progression of various cardiac diseases. PET imaging of the cardiac autonomic nervous system has advanced extensively in recent years, and multiple pre- and postsynaptic tracers have been introduced. The high spatial and temporal resolution of PET enables noninvasive quantification of neurophysiologic processes at the tissue level. Ligands for catecholamine receptors, along with radiolabeled catecholamines and catecholamine analogs, have been applied to determine involvement of sympathetic dysinnervation at different stages of heart diseases such as ischemia, heart failure, and arrhythmia. This review summarizes the recent findings in neurocardiological PET imaging. Experimental studies with several radioligands and clinical findings in cardiac dysautonomias are discussed. (orig.)

  20. Premature Ventricular Contraction Coupling Interval Variability Destabilizes Cardiac Neuronal and Electrophysiological Control: Insights From Simultaneous Cardioneural Mapping.

    Science.gov (United States)

    Hamon, David; Rajendran, Pradeep S; Chui, Ray W; Ajijola, Olujimi A; Irie, Tadanobu; Talebi, Ramin; Salavatian, Siamak; Vaseghi, Marmar; Bradfield, Jason S; Armour, J Andrew; Ardell, Jeffrey L; Shivkumar, Kalyanam

    2017-04-01

    Variability in premature ventricular contraction (PVC) coupling interval (CI) increases the risk of cardiomyopathy and sudden death. The autonomic nervous system regulates cardiac electrical and mechanical indices, and its dysregulation plays an important role in cardiac disease pathogenesis. The impact of PVCs on the intrinsic cardiac nervous system, a neural network on the heart, remains unknown. The objective was to determine the effect of PVCs and CI on intrinsic cardiac nervous system function in generating cardiac neuronal and electric instability using a novel cardioneural mapping approach. In a porcine model (n=8), neuronal activity was recorded from a ventricular ganglion using a microelectrode array, and cardiac electrophysiological mapping was performed. Neurons were functionally classified based on their response to afferent and efferent cardiovascular stimuli, with neurons that responded to both defined as convergent (local reflex processors). Dynamic changes in neuronal activity were then evaluated in response to right ventricular outflow tract PVCs with fixed short, fixed long, and variable CI. PVC delivery elicited a greater neuronal response than all other stimuli ( P <0.001). Compared with fixed short and long CI, PVCs with variable CI had a greater impact on neuronal response ( P <0.05 versus short CI), particularly on convergent neurons ( P <0.05), as well as neurons receiving sympathetic ( P <0.05) and parasympathetic input ( P <0.05). The greatest cardiac electric instability was also observed after variable (short) CI PVCs. Variable CI PVCs affect critical populations of intrinsic cardiac nervous system neurons and alter cardiac repolarization. These changes may be critical for arrhythmogenesis and remodeling, leading to cardiomyopathy. © 2017 American Heart Association, Inc.

  1. NADPH- Diaphorase positive cardiac neurons in the atria of mice. A morphoquantitative study

    Directory of Open Access Journals (Sweden)

    Castelucci Patrícia

    2006-02-01

    Full Text Available Abstract Background The present study was conducted to determine the location, the morphology and distribution of NADPH-diaphorase positive neurons in the cardiac nerve plexus of the atria of mice (ASn. This plexus lies over the muscular layer of the atria, dorsal to the muscle itself, in the connective tissue of the subepicardium. NADPH- diaphorase staining was performed on whole-mount preparations of the atria mice. For descriptive purposes, all data are presented as means ± SEM. Results The majority of the NADPH-diaphorase positive neurons were observed in the ganglia of the plexus. A few single neurons were also observed. The number of NADPH-d positive neurons was 57 ± 4 (ranging from 39 to 79 neurons. The ganglion neurons were located in 3 distinct groups: (1 in the region situated cranial to the pulmonary veins, (2 caudally to the pulmonary veins, and (3 in the atrial groove. The largest group of neurons was located cranially to the pulmonary veins (66.7%. Three morphological types of NADPH-diaphorase neurons could be distinguished on the basis of their shape: unipolar cells, bipolar cells and cells with three processes (multipolar cells. The unipolar neurons predominated (78.9%, whereas the multipolar were encountered less frequently (5,3%. The sizes (area of maximal cell profile of the neurons ranged from about 90 μm2to about 220 μm2. Morphometrically, the three types of neurons were similar and there were no significant differences in their sizes. The total number of cardiac neurons (obtained by staining the neurons with NADH-diaphorase method was 530 ± 23. Therefore, the NADPH-diaphorase positive neurons of the heart represent 10% of the number of cardiac neurons stained by NADH. Conclusion The obtained data have shown that the NADPH-d positive neurons in the cardiac plexus of the atria of mice are morphologically different, and therefore, it is possible that the function of the neurons may also be different.

  2. Network interactions within the canine intrinsic cardiac nervous system: implications for reflex control of regional cardiac function

    Science.gov (United States)

    Beaumont, Eric; Salavatian, Siamak; Southerland, E Marie; Vinet, Alain; Jacquemet, Vincent; Armour, J Andrew; Ardell, Jeffrey L

    2013-01-01

    The aims of the study were to determine how aggregates of intrinsic cardiac (IC) neurons transduce the cardiovascular milieu versus responding to changes in central neuronal drive and to determine IC network interactions subsequent to induced neural imbalances in the genesis of atrial fibrillation (AF). Activity from multiple IC neurons in the right atrial ganglionated plexus was recorded in eight anaesthetized canines using a 16-channel linear microelectrode array. Induced changes in IC neuronal activity were evaluated in response to: (1) focal cardiac mechanical distortion; (2) electrical activation of cervical vagi or stellate ganglia; (3) occlusion of the inferior vena cava or thoracic aorta; (4) transient ventricular ischaemia, and (5) neurally induced AF. Low level activity (ranging from 0 to 2.7 Hz) generated by 92 neurons was identified in basal states, activities that displayed functional interconnectivity. The majority (56%) of IC neurons so identified received indirect central inputs (vagus alone: 25%; stellate ganglion alone: 27%; both: 48%). Fifty per cent transduced the cardiac milieu responding to multimodal stressors applied to the great vessels or heart. Fifty per cent of IC neurons exhibited cardiac cycle periodicity, with activity occurring primarily in late diastole into isovolumetric contraction. Cardiac-related activity in IC neurons was primarily related to direct cardiac mechano-sensory inputs and indirect autonomic efferent inputs. In response to mediastinal nerve stimulation, most IC neurons became excessively activated; such network behaviour preceded and persisted throughout AF. It was concluded that stochastic interactions occur among IC local circuit neuronal populations in the control of regional cardiac function. Modulation of IC local circuit neuronal recruitment may represent a novel approach for the treatment of cardiac disease, including atrial arrhythmias. PMID:23818689

  3. Premature Ventricular Contraction Coupling Interval Variability Destabilizes Cardiac Neuronal and Electrophysiological Control: Insights from Simultaneous Cardio-Neural Mapping

    Science.gov (United States)

    Hamon, David; Rajendran, Pradeep S.; Chui, Ray W.; Ajijola, Olujimi A.; Irie, Tadanobu; Talebi, Ramin; Salavatian, Siamak; Vaseghi, Marmar; Bradfield, Jason S.; Armour, J. Andrew; Ardell, Jeffrey L.; Shivkumar, Kalyanam

    2017-01-01

    Background Variability in premature ventricular contraction (PVC) coupling interval (CI) increases the risk of cardiomyopathy and sudden death. The autonomic nervous system regulates cardiac electrical and mechanical indices, and its dysregulation plays an important role in cardiac disease pathogenesis. The impact of PVCs on the intrinsic cardiac nervous system (ICNS), a neural network on the heart, remains unknown. The objective was to determine the effect of PVCs and CI on ICNS function in generating cardiac neuronal and electrical instability using a novel cardio-neural mapping approach. Methods and Results In a porcine model (n=8) neuronal activity was recorded from a ventricular ganglion using a microelectrode array, and cardiac electrophysiological mapping was performed. Neurons were functionally classified based on their response to afferent and efferent cardiovascular stimuli, with neurons that responded to both defined as convergent (local reflex processors). Dynamic changes in neuronal activity were then evaluated in response to right ventricular outflow tract PVCs with fixed short, fixed long, and variable CI. PVC delivery elicited a greater neuronal response than all other stimuli (P<0.001). Compared to fixed short and long CI, PVCs with variable CI had a greater impact on neuronal response (P<0.05 versus short CI), particularly on convergent neurons (P<0.05), as well as neurons receiving sympathetic (P<0.05) and parasympathetic input (P<0.05). The greatest cardiac electrical instability was also observed following variable (short) CI PVCs. Conclusions Variable CI PVCs affect critical populations of ICNS neurons and alter cardiac repolarization. These changes may be critical for arrhythmogenesis and remodeling leading to cardiomyopathy. PMID:28408652

  4. Cardiac retention of PET neuronal imaging agent LMI1195 in different species: Impact of norepinephrine uptake-1 and -2 transporters

    International Nuclear Information System (INIS)

    Yu, Ming; Bozek, Jody; Kagan, Mikhail; Guaraldi, Mary; Silva, Paula; Azure, Michael; Onthank, David; Robinson, Simon P.

    2013-01-01

    Introduction: Released sympathetic neurotransmitter norepinephrine (NE) in the heart is cleared by neuronal uptake-1 and extraneuronal uptake-2 transporters. Cardiac uptake-1 and -2 expression varies among species, but the uptake-1 is the primary transporter in humans. LMI1195 is an NE analog labeled with 18 F for PET evaluation of cardiac neuronal function. This study investigated the impact of cardiac neuronal uptake-1 associated with different species on LMI1195 heart uptake. Methods: Cardiac uptake-1 was blocked by desipramine, a selective uptake-1 inhibitor, and sympathetic neuronal denervation was induced by 6-hydroxydopamine, a neurotoxin, in rats, rabbits and nonhuman primates (NHP). Tissue biodistribution and cardiac imaging of LMI1195 and 123 I-metaiodobenzylguanidine (MIBG) were performed. Results: In rats, uptake-1 blockade did not alter LMI1195 heart uptake compared to the control at 60-min post injection [1.41 ± 0.07 vs. 1.47 ± 0.23 % injected dose per gram tissue (%ID/g)]. In contrast, LMI1195 heart uptake was reduced by 80% in uptake-1 blocked rabbits. In sympathetically denervated rats, LMI1195 heart uptake was similar to the control (2.18 ± 0.40 vs. 2.58 ± 0.76 %ID/g). However, the uptake decreased by 79% in denervated rabbits. Similar results were found in MIBG heart uptake in rats and rabbits with uptake-1 blockade. Consistently, LMI1195 cardiac imaging showed comparable myocardial activity in uptake-1 blocked or sympathetically denervated rats to the control, but marked activity reduction in uptake-1 blocked or denervated rabbits and NHPs. Conclusions: LMI1195 is retained in the heart of rabbits and NHPs primarily via the neuronal uptake-1 with high selectivity and can be used for evaluation of cardiac sympathetic denervation. Similar to the human, the neuronal uptake-1 is the dominant transporter for cardiac retention of NE analogs in rabbits and NHPs, but not in rats

  5. Decreased adrenoceptor stimulation in heart failure rats reduces NGF expression by cardiac parasympathetic neurons

    OpenAIRE

    Hasan, Wohaib; Smith, Peter G

    2013-01-01

    Postganglionic cardiac parasympathetic and sympathetic nerves are physically proximate in atrial cardiac tissue allowing reciprocal inhibition of neurotransmitter release, depending on demands from central cardiovascular centers or reflex pathways. Parasympathetic cardiac ganglion (CG) neurons synthesize and release the sympathetic neurotrophin nerve growth factor (NGF), which may serve to maintain these close connections. In this study we investigated whether NGF synthesis by CG neurons is a...

  6. Age-related changes of neurochemically different subpopulations of cardiac spinal afferent neurons in rats.

    Science.gov (United States)

    Guić, Maja Marinović; Runtić, Branka; Košta, Vana; Aljinović, Jure; Grković, Ivica

    2013-08-01

    This study investigated the effect of aging on cardiac spinal afferent neurons in the rat. A patch loaded with retrograde tracer Fast Blue (FB) was applied to all chambers of the rat heart. Morphological and neurochemical characteristics of labeled cardiac spinal afferent neurons were assessed in young (2 months) and old (2 years) rats using markers for likely unmyelinated (isolectin B4; IB4) and myelinated (neurofilament 200; N52) neurons. The number of cardiac spinal afferent neurons decreased in senescence to 15% of that found in young rats (1604 vs. 248). The size of neuronal soma as well as proportion of IB4+ neurons increased significantly, whereas the proportion of N52+ neurons decreased significantly in senescence. Unlike somatic spinal afferents, neurochemically different populations of cardiac spinal afferent neurons experience morphological and neurochemical changes related to aging. A major decrease in total number of cardiac spinal afferent neurons occurs in senescence. The proportion of N52+ neurons decreased in senescence, but it seems that nociceptive innervation is preserved due to increased proportion and size of IB4+ unmyelinated neurons. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Cardiac function and cognition in older community-dwelling cardiac patients

    NARCIS (Netherlands)

    Eggermont, Laura H.P.; Aly, Mohamed F.A.; Vuijk, Pieter J.; de Boer, Karin; Kamp, Otto; van Rossum, Albert C.; Scherder, Erik J.A.

    2017-01-01

    Background: Cognitive deficits have been reported in older cardiac patients. An underlying mechanism for these findings may be reduced cardiac function. The relationship between cardiac function as represented by different echocardiographic measures and different cognitive function domains in older

  8. Nesfatin-1 activates cardiac vagal neurons of nucleus ambiguus and elicits bradycardia in conscious rats.

    Science.gov (United States)

    Brailoiu, G Cristina; Deliu, Elena; Tica, Andrei A; Rabinowitz, Joseph E; Tilley, Douglas G; Benamar, Khalid; Koch, Walter J; Brailoiu, Eugen

    2013-09-01

    Nesfatin-1, a peptide whose receptor is yet to be identified, has been involved in the modulation of feeding, stress, and metabolic responses. More recently, increasing evidence supports a modulatory role for nesfatin-1 in autonomic and cardiovascular activity. This study was undertaken to test if the expression of nesfatin-1 in the nucleus ambiguus, a key site for parasympathetic cardiac control, may be correlated with a functional role. As we have previously demonstrated that nesfatin-1 elicits Ca²⁺ signaling in hypothalamic neurons, we first assessed the effect of this peptide on cytosolic Ca²⁺ in cardiac pre-ganglionic neurons of nucleus ambiguus. We provide evidence that nesfatin-1 increases cytosolic Ca²⁺ concentration via a Gi/o-coupled mechanism. The nesfatin-1-induced Ca²⁺ rise is critically dependent on Ca²⁺ influx via P/Q-type voltage-activated Ca²⁺ channels. Repeated administration of nesfatin-1 leads to tachyphylaxis. Furthermore, nesfatin-1 produces a dose-dependent depolarization of cardiac vagal neurons via a Gi/o-coupled mechanism. In vivo studies, using telemetric and tail-cuff monitoring of heart rate and blood pressure, indicate that microinjection of nesfatin-1 into the nucleus ambiguus produces bradycardia not accompanied by a change in blood pressure in conscious rats. Taken together, our results identify for the first time that nesfatin-1 decreases heart rate by activating cardiac vagal neurons of nucleus ambiguus. Our results indicate that nesfatin-1, one of the most potent feeding peptides, increases cytosolic Ca²⁺ by promoting Ca²⁺ influx via P/Q channels and depolarizes nucleus ambiguus neurons; both effects are Gi/o-mediated. In vivo studies indicate that microinjection of nesfatin-1 into nucleus ambiguus produces bradycardia in conscious rats. This is the first report that nesfatin-1 increases the parasympathetic cardiac tone. © 2013 International Society for Neurochemistry.

  9. Developmental changes in GABAergic neurotransmission to presympathetic and cardiac parasympathetic neurons in the brainstem.

    Science.gov (United States)

    Dergacheva, Olga; Boychuk, Carie R; Mendelowitz, David

    2013-08-01

    Cardiovascular function is regulated by a dynamic balance composed of sympathetic and parasympathetic activity. Sympathoexcitatory presympathetic neurons (PSNs) in the rostral ventrolateral medulla project directly to cardiac and vasomotor sympathetic preganglionic neurons in the spinal cord. In proximity to the PSNs in the medulla, there are preganglionic cardiac vagal neurons (CVNs) within the nucleus ambiguus, which are critical for parasympathetic control of heart rate. Both CVNs and PSNs receive GABAergic synaptic inputs that change with challenges such as hypoxia and hypercapnia (H/H). Autonomic control of cardiovascular function undergoes significant changes during early postnatal development; however, little is known regarding postnatal maturation of GABAergic neurotransmission to these neurons. In this study, we compared changes in GABAergic inhibitory postsynaptic currents (IPSCs) in CVNs and PSNs under control conditions and during H/H in postnatal day 2-5 (P5), 16-20 (P20), and 27-30 (P30) rats using an in vitro brainstem slice preparation. There was a significant enhancement in GABAergic neurotransmission to both CVNs and PSNs at age P20 compared with P5 and P30, with a more pronounced increase in PSNs. H/H did not significantly alter this enhanced GABAergic neurotransmission to PSNs in P20 animals. However, the frequency of GABAergic IPSCs in PSNs was reduced by H/H in P5 and P30 animals. In CVNs, H/H elicited an inhibition of GABAergic neurotransmission in all ages studied, with the most pronounced inhibition occurring at P20. In conclusion, there are critical development periods at which significant rearrangement occurs in the central regulation of cardiovascular function.

  10. Pathological effects of chronic myocardial infarction on peripheral neurons mediating cardiac neurotransmission.

    Science.gov (United States)

    Nakamura, Keijiro; Ajijola, Olujimi A; Aliotta, Eric; Armour, J Andrew; Ardell, Jeffrey L; Shivkumar, Kalyanam

    2016-05-01

    To determine whether chronic myocardial infarction (MI) induces structural and neurochemical changes in neurons within afferent and efferent ganglia mediating cardiac neurotransmission. Neuronal somata in i) right atrial (RAGP) and ii) ventral interventricular ganglionated plexi (VIVGP), iii) stellate ganglia (SG) and iv) T1-2 dorsal root ganglia (DRG) bilaterally derived from normal (n=8) vs. chronic MI (n=8) porcine subjects were studied. We examined whether the morphology and neuronal nitric oxide synthase (nNOS) expression in soma of RAGP, VIVGP, DRG and SG neurons were altered as a consequence of chronic MI. In DRG, we also examined immunoreactivity of calcitonin gene related peptide (CGRP), a marker of afferent neurons. Chronic MI increased neuronal size and nNOS immunoreactivity in VIVGP (but not RAGP), as well as in the SG bilaterally. Across these ganglia, the increase in neuronal size was more pronounced in nNOS immunoreactive neurons. In the DRG, chronic MI also caused neuronal enlargement, and increased CGRP immunoreactivity. Further, DRG neurons expressing both nNOS and CGRP were increased in MI animals compared to controls, and represented a shift from double negative neurons. Chronic MI impacts diverse elements within the peripheral cardiac neuraxis. That chronic MI imposes such widespread, diverse remodeling of the peripheral cardiac neuraxis must be taken into consideration when contemplating neuronal regulation of the ischemic heart. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. PATHOLOGICAL EFFECTS OF CHRONIC MYOCARDIAL INFARCTION ON PERIPHERAL NEURONS MEDIATING CARDIAC NEUROTRANSMISSION

    Science.gov (United States)

    Nakamura, Keijiro; Ajijola, Olujimi A.; Aliotta, Eric; Armour, J. Andrew; Ardell, Jeffrey L.; Shivkumar, Kalyanam

    2016-01-01

    Objective To determine whether chronic myocardial infarction (MI) induces structural and neurochemical changes in neurons within afferent and efferent ganglia mediating cardiac neurotransmission. Methods Neuronal somata in i) right atrial (RAGP) and ii) ventral interventricular ganglionated plexi (VIVGP), iii) stellate ganglia (SG) and iv) T1-2 dorsal root ganglia (DRG) bilaterally derived from normal (n = 8) vs. chronic MI (n = 8) porcine subjects were studied. We examined whether the morphology and neuronal nitric oxide synthase (nNOS) expression in soma of RAGP, VIVGP, DRG and SG neurons were altered as a consequence of chronic MI. In DRG, we also examined immunoreactivity of calcitonin gene related peptide (CGRP), a marker of afferent neurons. Results Chronic MI increased neuronal size and nNOS immunoreactivity in VIVGP (but not RAGP), as well as in the SG bilaterally. Across these ganglia, the increase in neuronal size was more pronounced in nNOS immunoreacitive neurons. In the DRG, chronic MI also caused neuronal enlargement, and increased CGRP immunoreactivity. Further, DRG neurons expressing both nNOS and CGRP were increased in MI animals compared to controls, and represented a shift from double negative neurons. Conclusions Chronic MI impacts diverse elements within the peripheral cardiac neuraxis. That chronic MI imposes such widespread, diverse remodeling of the peripheral cardiac neuraxis must be taken into consideration when contemplating neuronal regulation of the ischemic heart. PMID:27209472

  12. Mirror neurons: From origin to function

    OpenAIRE

    Cook, R; Bird, G; Catmur, C; Press, C; Heyes, C

    2014-01-01

    This article argues that mirror neurons originate in sensorimotor associative learning and therefore a new approach is needed to investigate their functions. Mirror neurons were discovered about 20 years ago in the monkey brain, and there is now evidence that they are also present in the human brain. The intriguing feature of many mirror neurons is that they fire not only when the animal is performing an action, such as grasping an object using a power grip, but also when the animal passively...

  13. Mathematical Models of Cardiac Pacemaking Function

    Science.gov (United States)

    Li, Pan; Lines, Glenn T.; Maleckar, Mary M.; Tveito, Aslak

    2013-10-01

    Over the past half century, there has been intense and fruitful interaction between experimental and computational investigations of cardiac function. This interaction has, for example, led to deep understanding of cardiac excitation-contraction coupling; how it works, as well as how it fails. However, many lines of inquiry remain unresolved, among them the initiation of each heartbeat. The sinoatrial node, a cluster of specialized pacemaking cells in the right atrium of the heart, spontaneously generates an electro-chemical wave that spreads through the atria and through the cardiac conduction system to the ventricles, initiating the contraction of cardiac muscle essential for pumping blood to the body. Despite the fundamental importance of this primary pacemaker, this process is still not fully understood, and ionic mechanisms underlying cardiac pacemaking function are currently under heated debate. Several mathematical models of sinoatrial node cell membrane electrophysiology have been constructed as based on different experimental data sets and hypotheses. As could be expected, these differing models offer diverse predictions about cardiac pacemaking activities. This paper aims to present the current state of debate over the origins of the pacemaking function of the sinoatrial node. Here, we will specifically review the state-of-the-art of cardiac pacemaker modeling, with a special emphasis on current discrepancies, limitations, and future challenges.

  14. Mathematical Models of Cardiac Pacemaking Function

    Directory of Open Access Journals (Sweden)

    Pan eLi

    2013-10-01

    Full Text Available Over the past half century, there has been intense and fruitful interaction between experimental and computational investigations of cardiac function. This interaction has, for example, led to deep understanding of cardiac excitation-contraction coupling; how it works, as well as how it fails. However, many lines of inquiry remain unresolved, among them the initiation of each heartbeat. The sinoatrial node, a cluster of specialized pacemaking cells in the right atrium of the heart, spontaneously generates an electro-chemical wave that spreads through the atria and through the cardiac conduction system to the ventricles, initiating the contraction of cardiac muscle essential for pumping blood to the body. Despite the fundamental importance of this primary pacemaker, this process is still not fully understood, and ionic mechanisms underlying cardiac pacemaking function are currently under heated debate. Several mathematical models of sinoatrial node cell membrane electrophysiology have been constructed as based on different experimental data sets and hypotheses. As could be expected, these differing models offer diverse predictions about cardiac pacemaking activities. This paper aims to present the current state of debate over the origins of the pacemaking function of the sinoatrial node. Here, we will specifically review the state-of-the-art of cardiac pacemaker modeling, with a special emphasis on current discrepancies, limitations, and future challenges.

  15. Interaction function of coupled bursting neurons

    International Nuclear Information System (INIS)

    Shi Xia; Zhang Jiadong

    2016-01-01

    The interaction functions of electrically coupled Hindmarsh–Rose (HR) neurons for different firing patterns are investigated in this paper. By applying the phase reduction technique, the phase response curve (PRC) of the spiking neuron and burst phase response curve (BPRC) of the bursting neuron are derived. Then the interaction function of two coupled neurons can be calculated numerically according to the PRC (or BPRC) and the voltage time course of the neurons. Results show that the BPRC is more and more complicated with the increase of the spike number within a burst, and the curve of the interaction function oscillates more and more frequently with it. However, two certain things are unchanged: ϕ = 0, which corresponds to the in-phase synchronization state, is always the stable equilibrium, while the anti-phase synchronization state with ϕ = 0.5 is an unstable equilibrium. (paper)

  16. Neuronal coherence and its functional role in communication between neurons

    NARCIS (Netherlands)

    Zeitler-Geurds, M.

    2010-01-01

    Neuronal oscillations are observed in many brain areas in various frequency bands. Each of the frequency bands is associated with a particular functional role. Gamma oscillations (30-80 Hz) are thought to be related to cognitive tasks like memory and attention and possibly also involved in the

  17. Clonidine, an α2 receptor agonist, diminishes GABAergic neurotransmission to cardiac vagal neurons in the nucleus ambiguus

    OpenAIRE

    Philbin, Kerry E.; Bateman, Ryan J.; Mendelowitz, David

    2010-01-01

    In hypertension there is an autonomic imbalance in which sympathetic activity dominates over parasympathetic control. Parasympathetic activity to the heart originates from cardiac vagal neurons located in the nucleus ambiguus. Pre-sympathetic neurons that project to sympathetic neurons in the spinal cord are located in the ventral brainstem in close proximity to cardiac vagal neurons, and many of these pre-sympathetic neurons are catecholaminergic. In addition to their projection to the spina...

  18. Mirror neurons: from origin to function.

    Science.gov (United States)

    Cook, Richard; Bird, Geoffrey; Catmur, Caroline; Press, Clare; Heyes, Cecilia

    2014-04-01

    This article argues that mirror neurons originate in sensorimotor associative learning and therefore a new approach is needed to investigate their functions. Mirror neurons were discovered about 20 years ago in the monkey brain, and there is now evidence that they are also present in the human brain. The intriguing feature of many mirror neurons is that they fire not only when the animal is performing an action, such as grasping an object using a power grip, but also when the animal passively observes a similar action performed by another agent. It is widely believed that mirror neurons are a genetic adaptation for action understanding; that they were designed by evolution to fulfill a specific socio-cognitive function. In contrast, we argue that mirror neurons are forged by domain-general processes of associative learning in the course of individual development, and, although they may have psychological functions, they do not necessarily have a specific evolutionary purpose or adaptive function. The evidence supporting this view shows that (1) mirror neurons do not consistently encode action "goals"; (2) the contingency- and context-sensitive nature of associative learning explains the full range of mirror neuron properties; (3) human infants receive enough sensorimotor experience to support associative learning of mirror neurons ("wealth of the stimulus"); and (4) mirror neurons can be changed in radical ways by sensorimotor training. The associative account implies that reliable information about the function of mirror neurons can be obtained only by research based on developmental history, system-level theory, and careful experimentation.

  19. Vagus nerve stimulation mitigates intrinsic cardiac neuronal and adverse myocyte remodeling postmyocardial infarction

    Science.gov (United States)

    Beaumont, Eric; Southerland, Elizabeth M.; Hardwick, Jean C.; Wright, Gary L.; Ryan, Shannon; Li, Ying; KenKnight, Bruce H.; Armour, J. Andrew

    2015-01-01

    This paper aims to determine whether chronic vagus nerve stimulation (VNS) mitigates myocardial infarction (MI)-induced remodeling of the intrinsic cardiac nervous system (ICNS), along with the cardiac tissue it regulates. Guinea pigs underwent VNS implantation on the right cervical vagus. Two weeks later, MI was produced by ligating the ventral descending coronary artery. VNS stimulation started 7 days post-MI (20 Hz, 0.9 ± 0.2 mA, 14 s on, 48 s off; VNS-MI, n = 7) and was compared with time-matched MI animals with sham VNS (MI n = 7) vs. untreated controls (n = 8). Echocardiograms were performed before and at 90 days post-MI. At termination, IC neuronal intracellular voltage recordings were obtained from whole-mount neuronal plexuses. MI increased left ventricular end systolic volume (LVESV) 30% (P = 0.027) and reduced LV ejection fraction (LVEF) 6.5% (P < 0.001) at 90 days post-MI compared with baseline. In the VNS-MI group, LVESV and LVEF did not differ from baseline. IC neurons showed depolarization of resting membrane potentials and increased input resistance in MI compared with VNS-MI and sham controls (P < 0.05). Neuronal excitability and sensitivity to norepinephrine increased in MI and VNS-MI groups compared with controls (P < 0.05). Synaptic efficacy, as determined by evoked responses to stimulating input axons, was reduced in VNS-MI compared with MI or controls (P < 0.05). VNS induced changes in myocytes, consistent with enhanced glycogenolysis, and blunted the MI-induced increase in the proapoptotic Bcl-2-associated X protein (P < 0.05). VNS mitigates MI-induced remodeling of the ICNS, correspondingly preserving ventricular function via both neural and cardiomyocyte-dependent actions. PMID:26276818

  20. Clinical evaluation of carbon-11-phenylephrine: MAO-sensitive marker of cardiac sympathetic neurons.

    Science.gov (United States)

    Raffel, D M; Corbett, J R; del Rosario, R B; Gildersleeve, D L; Chiao, P C; Schwaiger, M; Wieland, D M

    1996-12-01

    The sympathomimetic drug phenylephrine recently has been labeled with 11C for use in PET studies of cardiac sympathetic innervation. Previous reports using isolated perfused rat heart models indicate that phenylephrine is metabolized by intraneuronal monoamine oxidase (MAO). This report compares the imaging characteristics, neuronal selectivity and kinetics of (-)-[11C]phenylephrine (PHEN) to the structurally similar but MAO-resistant analog (-)-[11C]-meta-hydroxyephedrine (HED), an established heart neuronal marker. Fourteen healthy volunteers were studied with PET and PHEN. Ten had paired studies with HED; four of the 10 were scanned a second time with each tracer after oral administration of desipramine, a selective neuronal transport blocker. Hemodynamic and electrocardiographic responses were monitored. Blood levels of intact radiotracer and radiolabeled metabolites were determined from venous blood samples taken during the PET study. Myocardial retention indices for both tracers were calculated. No hemodynamic or electrocardiographic effects were observed with either tracer. PHEN showed reduced myocardial retention at 50 min compared to HED; however, image quality and uniformity of distribution were comparable. PHEN cleared from myocardium with a mean half-time of 59 +/- 5 min, while myocardial levels of HED remained constant. PHEN metabolites appeared in the blood approximately three times faster than HED metabolites. Desipramine pretreatment markedly reduced (> 60%) myocardial retention of both PHEN and HED. PHEN provides PET images of human heart comparable in quality and uniformity to HED. Like HED, PHEN localizes in the sympathetic nerves of the heart. However, the more rapid efflux of PHEN, that is likely mediated by MAO, may provide information on the functional status of cardiac sympathetic neurons unobtainable with HED.

  1. Urotensin II promotes vagal-mediated bradycardia by activating cardiac-projecting parasympathetic neurons of nucleus ambiguus.

    Science.gov (United States)

    Brailoiu, Gabriela Cristina; Deliu, Elena; Rabinowitz, Joseph E; Tilley, Douglas G; Koch, Walter J; Brailoiu, Eugen

    2014-05-01

    Urotensin II (U-II) is a cyclic undecapeptide that regulates cardiovascular function at central and peripheral sites. The functional role of U-II nucleus ambiguus, a key site controlling cardiac tone, has not been established, despite the identification of U-II and its receptor at this level. We report here that U-II produces an increase in cytosolic Ca(2+) concentration in retrogradely labeled cardiac vagal neurons of nucleus ambiguus via two pathways: (i) Ca(2+) release from the endoplasmic reticulum via inositol 1,4,5-trisphosphate receptor; and (ii) Ca(2+) influx through P/Q-type Ca(2+) channels. In addition, U-II depolarizes cultured cardiac parasympathetic neurons. Microinjection of increasing concentrations of U-II into nucleus ambiguus elicits dose-dependent bradycardia in conscious rats, indicating the in vivo activation of the cholinergic pathway controlling the heart rate. Both the in vitro and in vivo effects were abolished by the urotensin receptor antagonist, urantide. Our findings suggest that, in addition, to the previously reported increase in sympathetic outflow, U-II activates cardiac vagal neurons of nucleus ambiguus, which may contribute to cardioprotection. © 2014 International Society for Neurochemistry.

  2. Positron emission tomographic imaging of cardiac sympathetic innervation and function

    International Nuclear Information System (INIS)

    Goldstein, D.S.; Chang, P.C.; Eisenhofer, G.; Miletich, R.; Finn, R.; Bacher, J.; Kirk, K.L.; Bacharach, S.; Kopin, I.J.

    1990-01-01

    Sites of uptake, storage, and metabolism of [ 18 F]fluorodopamine and excretion of [ 18 F]fluorodopamine and its metabolites were visualized using positron emission tomographic (PET) scanning after intravenous injection of the tracer into anesthetized dogs. Radioactivity was concentrated in the renal pelvis, heart, liver, spleen, salivary glands, and gall bladder. Uptake of 18F by the heart resulted in striking delineation of the left ventricular myocardium. Pretreatment with desipramine markedly decreased cardiac positron emission, consistent with dependence of the heart on neuronal uptake (uptake-1) for removal of circulating catecholamines. In reserpinized animals, cardiac positron emission was absent within 30 minutes after injection of [ 18 F]-6-fluorodopamine, demonstrating that the emission in untreated animals was from radioactive labeling of the sympathetic storage vesicles. Decreased positron emission from denervated salivary glands confirmed that the tracer was concentrated in sympathetic neurons. Radioactivity in the gall bladder and urinary system depicted the hepatic and renal excretion of the tracer and its metabolites. Administration of tyramine or nitroprusside increased and ganglionic blockade with trimethaphan decreased the rate of loss of myocardial radioactivity. The results show that PET scanning after administration of [ 18 F]fluorodopamine can be used to visualize sites of sympathetic innervation, follow the metabolism and renal and hepatic excretion of catecholamines, and examine cardiac sympathetic function

  3. Mirror neurons: functions, mechanisms and models.

    Science.gov (United States)

    Oztop, Erhan; Kawato, Mitsuo; Arbib, Michael A

    2013-04-12

    Mirror neurons for manipulation fire both when the animal manipulates an object in a specific way and when it sees another animal (or the experimenter) perform an action that is more or less similar. Such neurons were originally found in macaque monkeys, in the ventral premotor cortex, area F5 and later also in the inferior parietal lobule. Recent neuroimaging data indicate that the adult human brain is endowed with a "mirror neuron system," putatively containing mirror neurons and other neurons, for matching the observation and execution of actions. Mirror neurons may serve action recognition in monkeys as well as humans, whereas their putative role in imitation and language may be realized in human but not in monkey. This article shows the important role of computational models in providing sufficient and causal explanations for the observed phenomena involving mirror systems and the learning processes which form them, and underlines the need for additional circuitry to lift up the monkey mirror neuron circuit to sustain the posited cognitive functions attributed to the human mirror neuron system. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  4. Functional cardiac imaging: positron emission tomography

    International Nuclear Information System (INIS)

    Mullani, N.A.; Gould, K.L.

    1984-01-01

    Dynamic cardiovascular imaging plays a vital role in the diagnosis and treatment of cardiac disease by providing information about the function of the heart. During the past 30 years, cardiovascular imaging has evolved from the simple chest x-ray and fluoroscopy to such sophisticated techniques as invasive cardiac angiography and cinearteriography and, more recently, to noninvasive cardiac CT scanning, nuclear magnetic resonance, and positron emission tomography, which reflect more complex physiologic functions. As research tools, CT, NMR, and PET provide quantitative information on global as well as regional ventricular function, coronary artery stenosis, myocardial perfusion, glucose and fatty acid metabolism, or oxygen utilization, with little discomfort or risk to the patient. As imaging modalities become more sophisticated and more oriented toward clinical application, the prospect of routinely obtaining such functional information about the heart is becoming realistic. However, these advances are double-edged in that the interpretation of functional data is more complex than that of the anatomic imaging familiar to most physicians. They will require an enhanced understanding of the physiologic and biochemical processes, as well as of the instrumentation and techniques for analyzing the data. Of the new imaging modalities that provide functional information about the heart, PET is the most useful because it quantitates the regional distribution of radionuclides in vivo. Clinical applications, interpretation of data, and the impact of PET on our understanding of cardiac pathophysiology are discussed. 5 figures

  5. Optogenetic stimulation of locus ceruleus neurons augments inhibitory transmission to parasympathetic cardiac vagal neurons via activation of brainstem α1 and β1 receptors.

    Science.gov (United States)

    Wang, Xin; Piñol, Ramón A; Byrne, Peter; Mendelowitz, David

    2014-04-30

    Locus ceruleus (LC) noradrenergic neurons are critical in generating alertness. In addition to inducing cortical arousal, the LC also orchestrates changes in accompanying autonomic system function that compliments increased attention, such as during stress, excitation, and/or exposure to averse or novel stimuli. Although the association between arousal and increased heart rate is well accepted, the neurobiological link between the LC and parasympathetic neurons that control heart rate has not been identified. In this study, we test directly whether activation of noradrenergic neurons in the LC influences brainstem parasympathetic cardiac vagal neurons (CVNs). CVNs were identified in transgenic mice that express channel-rhodopsin-2 (ChR2) in LC tyrosine hydroxylase neurons. Photoactivation evoked a rapid depolarization, increased firing, and excitatory inward currents in ChR2-expressing neurons in the LC. Photostimulation of LC neurons did not alter excitatory currents, but increased inhibitory neurotransmission to CVNs. Optogenetic activation of LC neurons increased the frequency of isolated glycinergic IPSCs by 27 ± 8% (p = 0.003, n = 26) and augmented GABAergic IPSCs in CVNs by 21 ± 5% (p = 0.001, n = 26). Inhibiting α1, but not α2, receptors blocked the evoked responses. Inhibiting β1 receptors prevented the increase in glycinergic, but not GABAergic, IPSCs in CVNs. This study demonstrates LC noradrenergic neurons inhibit the brainstem CVNs that generate parasympathetic activity to the heart. This inhibition of CVNs would increase heart rate and risks associated with tachycardia. The receptors activated within this pathway, α1 and/or β1 receptors, are targets for clinically prescribed antagonists that promote slower, cardioprotective heart rates during heightened vigilant states.

  6. HCN Channels—Modulators of Cardiac and Neuronal Excitability

    Directory of Open Access Journals (Sweden)

    Stefan Herrmann

    2015-01-01

    Full Text Available Hyperpolarization-activated cyclic nucleotide-gated (HCN channels comprise a family of cation channels activated by hyperpolarized membrane potentials and stimulated by intracellular cyclic nucleotides. The four members of this family, HCN1–4, show distinct biophysical properties which are most evident in the kinetics of activation and deactivation, the sensitivity towards cyclic nucleotides and the modulation by tyrosine phosphorylation. The four isoforms are differentially expressed in various excitable tissues. This review will mainly focus on recent insights into the functional role of the channels apart from their classic role as pacemakers. The importance of HCN channels in the cardiac ventricle and ventricular hypertrophy will be discussed. In addition, their functional significance in the peripheral nervous system and nociception will be examined. The data, which are mainly derived from studies using transgenic mice, suggest that HCN channels contribute significantly to cellular excitability in these tissues. Remarkably, the impact of the channels is clearly more pronounced in pathophysiological states including ventricular hypertrophy as well as neural inflammation and neuropathy suggesting that HCN channels may constitute promising drug targets in the treatment of these conditions. This perspective as well as the current therapeutic use of HCN blockers will also be addressed.

  7. Toward functional classification of neuronal types.

    Science.gov (United States)

    Sharpee, Tatyana O

    2014-09-17

    How many types of neurons are there in the brain? This basic neuroscience question remains unsettled despite many decades of research. Classification schemes have been proposed based on anatomical, electrophysiological, or molecular properties. However, different schemes do not always agree with each other. This raises the question of whether one can classify neurons based on their function directly. For example, among sensory neurons, can a classification scheme be devised that is based on their role in encoding sensory stimuli? Here, theoretical arguments are outlined for how this can be achieved using information theory by looking at optimal numbers of cell types and paying attention to two key properties: correlations between inputs and noise in neural responses. This theoretical framework could help to map the hierarchical tree relating different neuronal classes within and across species. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Zebrafish chemical screening reveals the impairment of dopaminergic neuronal survival by cardiac glycosides.

    Directory of Open Access Journals (Sweden)

    Yaping Sun

    Full Text Available Parkinson's disease is a neurodegenerative disorder characterized by the prominent degeneration of dopaminergic (DA neurons among other cell types. Here we report a first chemical screen of over 5,000 compounds in zebrafish, aimed at identifying small molecule modulators of DA neuron development or survival. We find that Neriifolin, a member of the cardiac glycoside family of compounds, impairs survival but not differentiation of both zebrafish and mammalian DA neurons. Cardiac glycosides are inhibitors of Na(+/K(+ ATPase activity and widely used for treating heart disorders. Our data suggest that Neriifolin impairs DA neuronal survival by targeting the neuronal enriched Na(+/K(+ ATPase α3 subunit (ATP1A3. Modulation of ionic homeostasis, knockdown of p53, or treatment with antioxidants protects DA neurons from Neriifolin-induced death. These results reveal a previously unknown effect of cardiac glycosides on DA neuronal survival and suggest that it is mediated through ATP1A3 inhibition, oxidative stress, and p53. They also elucidate potential approaches for counteracting the neurotoxicity of this valuable class of medications.

  9. Dexmedetomidine decreases inhibitory but not excitatory neurotransmission to cardiac vagal neurons in the nucleus ambiguus.

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    Sharp, Douglas B; Wang, Xin; Mendelowitz, David

    2014-07-29

    Dexmedetomidine, an α2 adrenergic agonist, is a useful sedative but can also cause significant bradycardia. This decrease in heart rate may be due to decreased central sympathetic output as well as increased parasympathetic output from brainstem cardiac vagal neurons. In this study, using whole cell voltage clamp methodology, the actions of dexmedetomidine on excitatory glutamatergic and inhibitory GABAergic and glycinergic neurotransmission to parasympathetic cardiac vagal neurons in the rat nucleus ambiguus was determined. The results indicate that dexmedetomidine decreases both GABAergic and glycinergic inhibitory input to cardiac vagal neurons, with no significant effect on excitatory input. These results provide a mechanism for dexmedetomidine induced bradycardia and has implications for the management of this potentially harmful side effect. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. The transfer function of neuron spike.

    Science.gov (United States)

    Palmieri, Igor; Monteiro, Luiz H A; Miranda, Maria D

    2015-08-01

    The mathematical modeling of neuronal signals is a relevant problem in neuroscience. The complexity of the neuron behavior, however, makes this problem a particularly difficult task. Here, we propose a discrete-time linear time-invariant (LTI) model with a rational function in order to represent the neuronal spike detected by an electrode located in the surroundings of the nerve cell. The model is presented as a cascade association of two subsystems: one that generates an action potential from an input stimulus, and one that represents the medium between the cell and the electrode. The suggested approach employs system identification and signal processing concepts, and is dissociated from any considerations about the biophysical processes of the neuronal cell, providing a low-complexity alternative to model the neuronal spike. The model is validated by using in vivo experimental readings of intracellular and extracellular signals. A computational simulation of the model is presented in order to assess its proximity to the neuronal signal and to observe the variability of the estimated parameters. The implications of the results are discussed in the context of spike sorting. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Spatially divergent cardiac responses to nicotinic stimulation of ganglionated plexus neurons in the canine heart.

    Science.gov (United States)

    Cardinal, René; Pagé, Pierre; Vermeulen, Michel; Ardell, Jeffrey L; Armour, J Andrew

    2009-01-28

    Ganglionated plexuses (GPs) are major constituents of the intrinsic cardiac nervous system, the final common integrator of regional cardiac control. We hypothesized that nicotinic stimulation of individual GPs exerts divergent regional influences, affecting atrial as well as ventricular functions. In 22 anesthetized canines, unipolar electrograms were recorded from 127 atrial and 127 ventricular epicardial loci during nicotine injection (100 mcg in 0.1 ml) into either the 1) right atrial (RA), 2) dorsal atrial, 3) left atrial, 4) inferior vena cava-inferior left atrial, 5) right ventricular, 6) ventral septal ventricular or 7) cranial medial ventricular (CMV) GP. In addition to sinus and AV nodal function, neural effects on atrial and ventricular repolarization were identified as changes in the area subtended by unipolar recordings under basal conditions and at maximum neurally-induced effects. Animals were studied with intact AV node or following ablation to achieve ventricular rate control. Atrial rate was affected in response to stimulation of all 7 GPs with an incidence of 50-95% of the animals among the different GPs. AV conduction was affected following stimulation of 6/7 GP with an incidence of 22-75% among GPs. Atrial and ventricular repolarization properties were affected by atrial as well as ventricular GP stimulation. Distinct regional patterns of repolarization changes were identified in response to stimulation of individual GPs. RAGP predominantly affected the RA and posterior right ventricular walls whereas CMVGP elicited biatrial and biventricular repolarization changes. Spatially divergent and overlapping cardiac regions are affected in response to nicotinic stimulation of neurons in individual GPs.

  12. Magnocellular Neurons and Posterior Pituitary Function.

    Science.gov (United States)

    Brown, Colin H

    2016-09-15

    The posterior pituitary gland secretes oxytocin and vasopressin (the antidiuretic hormone) into the blood system. Oxytocin is required for normal delivery of the young and for delivery of milk to the young during lactation. Vasopressin increases water reabsorption in the kidney to maintain body fluid balance and causes vasoconstriction to increase blood pressure. Oxytocin and vasopressin secretion occurs from the axon terminals of magnocellular neurons whose cell bodies are principally found in the hypothalamic supraoptic nucleus and paraventricular nucleus. The physiological functions of oxytocin and vasopressin depend on their secretion, which is principally determined by the pattern of action potentials initiated at the cell bodies. Appropriate secretion of oxytocin and vasopressin to meet the challenges of changing physiological conditions relies mainly on integration of afferent information on reproductive, osmotic, and cardiovascular status with local regulation of magnocellular neurons by glia as well as intrinsic regulation by the magnocellular neurons themselves. This review focuses on the control of magnocellular neuron activity with a particular emphasis on their regulation by reproductive function, body fluid balance, and cardiovascular status. © 2016 American Physiological Society. Compr Physiol 6:1701-1741, 2016. Copyright © 2016 John Wiley & Sons, Inc.

  13. Decreased adrenoceptor stimulation in heart failure rats reduces NGF expression by cardiac parasympathetic neurons.

    Science.gov (United States)

    Hasan, Wohaib; Smith, Peter G

    2014-04-01

    Postganglionic cardiac parasympathetic and sympathetic nerves are physically proximate in atrial cardiac tissue allowing reciprocal inhibition of neurotransmitter release, depending on demands from central cardiovascular centers or reflex pathways. Parasympathetic cardiac ganglion (CG) neurons synthesize and release the sympathetic neurotrophin nerve growth factor (NGF), which may serve to maintain these close connections. In this study we investigated whether NGF synthesis by CG neurons is altered in heart failure, and whether norepinephrine from sympathetic neurons promotes NGF synthesis. NGF and proNGF immunoreactivity in CG neurons in heart failure rats following chronic coronary artery ligation was investigated. NGF immunoreactivity was decreased significantly in heart failure rats compared to sham-operated animals, whereas proNGF expression was unchanged. Changes in neurochemistry of CG neurons included attenuated expression of the cholinergic marker vesicular acetylcholine transporter, and increased expression of the neuropeptide vasoactive intestinal polypeptide. To further investigate norepinephrine's role in promoting NGF synthesis, we cultured CG neurons treated with adrenergic receptor (AR) agonists. An 82% increase in NGF mRNA levels was detected after 1h of isoproterenol (β-AR agonist) treatment, which increased an additional 22% at 24h. Antagonist treatment blocked isoproterenol-induced increases in NGF transcripts. In contrast, the α-AR agonist phenylephrine did not alter NGF mRNA expression. These results are consistent with β-AR mediated maintenance of NGF synthesis in CG neurons. In heart failure, a decrease in NGF synthesis by CG neurons may potentially contribute to reduced connections with adjacent sympathetic nerves. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Correlation of Ventricular Arrhythmogenesis with Neuronal Remodeling of Cardiac Postganglionic Parasympathetic Neurons in the Late Stage of Heart Failure after Myocardial Infarction.

    Science.gov (United States)

    Zhang, Dongze; Tu, Huiyin; Wang, Chaojun; Cao, Liang; Muelleman, Robert L; Wadman, Michael C; Li, Yu-Long

    2017-01-01

    Introduction: Ventricular arrhythmia is a major cause of sudden cardiac death in patients with chronic heart failure (CHF). Our recent study demonstrates that N-type Ca 2+ currents in intracardiac ganglionic neurons are reduced in the late stage of CHF rats. Rat intracardiac ganglia are divided into the atrioventricular ganglion (AVG) and sinoatrial ganglion. Only AVG nerve terminals innervate the ventricular myocardium. In this study, we tested the correlation of electrical remodeling in AVG neurons with ventricular arrhythmogenesis in CHF rats. Methods and Results: CHF was induced in male Sprague-Dawley rats by surgical ligation of the left coronary artery. The data from 24-h continuous radiotelemetry ECG recording in conscious rats showed that ventricular tachycardia/fibrillation (VT/VF) occurred in 3 and 14-week CHF rats but not 8-week CHF rats. Additionally, as an index for vagal control of ventricular function, changes of left ventricular systolic pressure (LVSP) and the maximum rate of left ventricular pressure rise (LV dP/dt max ) in response to vagal efferent nerve stimulation were blunted in 14-week CHF rats but not 3 or 8-week CHF rats. Results from whole-cell patch clamp recording demonstrated that N-type Ca 2+ currents in AVG neurons began to decrease in 8-week CHF rats, and that there was also a significant decrease in 14-week CHF rats. Correlation analysis revealed that N-type Ca 2+ currents in AVG neurons negatively correlated with the cumulative duration of VT/VF in 14-week CHF rats, whereas there was no correlation between N-type Ca 2+ currents in AVG neurons and the cumulative duration of VT/VF in 3-week CHF. Conclusion: Malignant ventricular arrhythmias mainly occur in the early and late stages of CHF. Electrical remodeling of AVG neurons highly correlates with the occurrence of ventricular arrhythmias in the late stage of CHF.

  15. Clonidine, an alpha2-receptor agonist, diminishes GABAergic neurotransmission to cardiac vagal neurons in the nucleus ambiguus.

    Science.gov (United States)

    Philbin, Kerry E; Bateman, Ryan J; Mendelowitz, David

    2010-08-06

    In hypertension, there is an autonomic imbalance in which sympathetic activity dominates over parasympathetic control. Parasympathetic activity to the heart originates from cardiac vagal neurons located in the nucleus ambiguus. Presympathetic neurons that project to sympathetic neurons in the spinal cord are located in the ventral brainstem in close proximity to cardiac vagal neurons, and many of these presympathetic neurons are catecholaminergic. In addition to their projection to the spinal cord, many of these presympathetic neurons have axon collaterals that arborize into neighboring cardiorespiratory locations and likely release norepinephrine onto nearby neurons. Activation of alpha(2)-adrenergic receptors in the central nervous system evokes a diverse range of physiological effects, including reducing blood pressure. This study tests whether clonidine, an alpha(2)-adrenergic receptor agonist, alters excitatory glutamatergic, and/or inhibitory GABAergic or glycinergic synaptic neurotransmission to cardiac vagal neurons in the nucleus ambiguus. Cardiac vagal neurons were identified in an in vitro brainstem slice preparation, and synaptic events were recording using whole cell voltage clamp methodologies. Clonidine significantly inhibited GABAergic neurotransmission but had no effect on glycinergic or glutamatergic pathways to cardiac vagal neurons. This diminished inhibitory GABAergic neurotransmission to cardiac vagal neurons would increase parasympathetic activity to the heart, decreasing heart rate and blood pressure. The results presented here provide a cellular substrate for the clinical use of clonidine as a treatment for hypertension as well as a role in alleviating posttraumatic stress disorder by evoking an increase in parasympathetic cardiac vagal activity, and a decrease in heart rate and blood pressure. Copyright 2010 Elsevier B.V. All rights reserved.

  16. GLP-1 receptor stimulation depresses heart rate variability and inhibits neurotransmission to cardiac vagal neurons.

    Science.gov (United States)

    Griffioen, Kathleen J; Wan, Ruiqian; Okun, Eitan; Wang, Xin; Lovett-Barr, Mary Rachael; Li, Yazhou; Mughal, Mohamed R; Mendelowitz, David; Mattson, Mark P

    2011-01-01

    glucagon-like peptide 1 (GLP-1) is an incretin hormone released from the gut in response to food intake. Whereas GLP-1 acts in the periphery to inhibit glucagon secretion and stimulate insulin release, it also acts in the central nervous system to mediate autonomic control of feeding, body temperature, and cardiovascular function. Because of its role as an incretin hormone, GLP-1 receptor analogs are used as a treatment for type 2 diabetes. Central or peripheral administration of GLP-1 increases blood pressure and heart rate, possibly by activating brainstem autonomic nuclei and increasing vagus nerve activity. However, the mechanism(s) by which GLP-1 receptor stimulation affects cardiovascular function are unknown. We used the long-lasting GLP-1 receptor agonist Exendin-4 (Ex-4) to test the hypothesis that GLP-1 signalling modulates central parasympathetic control of heart rate. using a telemetry system, we assessed heart rate in mice during central Ex-4 administration. Heart rate was increased by both acute and chronic central Ex-4 administration. Spectral analysis indicated that the high frequency and low frequency powers of heart rate variability were diminished by Ex-4 treatment. Finally, Ex-4 decreased both excitatory glutamatergic and inhibitory glycinergic neurotransmission to preganglionic parasympathetic cardiac vagal neurons. these data suggest that central GLP-1 receptor stimulation diminishes parasympathetic modulation of the heart thereby increasing heart rate.

  17. β adrenergic receptor modulation of neurotransmission to cardiac vagal neurons in the nucleus ambiguus.

    Science.gov (United States)

    Bateman, R J; Boychuk, C R; Philbin, K E; Mendelowitz, D

    2012-05-17

    β-adrenergic receptors are a class of G protein-coupled receptors that have essential roles in regulating heart rate, blood pressure, and other cardiorespiratory functions. Although the role of β adrenergic receptors in the peripheral nervous system is well characterized, very little is known about their role in the central nervous system despite being localized in many brain regions involved in autonomic activity and regulation. Since parasympathetic activity to the heart is dominated by cardiac vagal neurons (CVNs) originating in the nucleus ambiguus (NA), β adrenergic receptors localized in the NA represent a potential target for modulating cardiac vagal activity and heart rate. This study tests the hypothesis that activation of β adrenergic receptors alters the membrane properties and synaptic neurotransmission to CVNs. CVNs were identified in brainstem slices, and membrane properties and synaptic events were recorded using the whole-cell voltage-clamp technique. The nonselective β agonist isoproterenol significantly decreased inhibitory GABAergic and glycinergic as well as excitatory glutamatergic neurotransmission to CVNs. In addition, the β(1)-selective receptor agonist dobutamine, but not β(2) or β(3) receptor agonists, significantly decreased inhibitory GABAergic and glycinergic and excitatory glutamatergic neurotransmission to CVNs. These decreases in neurotransmission to CVNs persisted in the presence of tetrodotoxin (TTX). These results provide a mechanism by which activation of adrenergic receptors in the brainstem can alter parasympathetic activity to the heart. Likely physiological roles for this adrenergic receptor activation are coordination of parasympathetic-sympathetic activity and β receptor-mediated increases in heart rate upon arousal. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  18. Cardiac function and cognition in older community-dwelling cardiac patients.

    Science.gov (United States)

    Eggermont, Laura H P; Aly, Mohamed F A; Vuijk, Pieter J; de Boer, Karin; Kamp, Otto; van Rossum, Albert C; Scherder, Erik J A

    2017-11-01

    Cognitive deficits have been reported in older cardiac patients. An underlying mechanism for these findings may be reduced cardiac function. The relationship between cardiac function as represented by different echocardiographic measures and different cognitive function domains in older cardiac patients remains unknown. An older (≥70 years) heterogeneous group of 117 community-dwelling cardiac patients under medical supervision by a cardiologist underwent thorough echocardiographic assessment including left ventricular ejection fraction, cardiac index, left atrial volume index, left ventricular mass index, left ventricular diastolic function, and valvular calcification. During a home visit, a neuropsychological assessment was performed within 7.1 ± 3.8 months after echocardiographic assessment; the neuropsychological assessment included three subtests of a word-learning test (encoding, recall, recognition) to examine one memory function domain and three executive function tests, including digit span backwards, Trail Making Test B minus A, and the Stroop colour-word test. Regression analyses showed no significant linear or quadratic associations between any of the echocardiographic functions and the cognitive function measures. None of the echocardiographic measures as representative of cardiac function was correlated with memory or executive function in this group of community-dwelling older cardiac patients. These findings contrast with those of previous studies. © 2017 Japanese Psychogeriatric Society.

  19. Cardiac Function Remains Impaired Despite Reversible Cardiac Remodeling after Acute Experimental Viral Myocarditis

    Directory of Open Access Journals (Sweden)

    Peter Moritz Becher

    2017-01-01

    Full Text Available Background. Infection with Coxsackievirus B3 induces myocarditis. We aimed to compare the acute and chronic phases of viral myocarditis to identify the immediate effects of cardiac inflammation as well as the long-term effects after resolved inflammation on cardiac fibrosis and consequently on cardiac function. Material and Methods. We infected C57BL/6J mice with Coxsackievirus B3 and determined the hemodynamic function 7 as well as 28 days after infection. Subsequently, we analyzed viral burden and viral replication in the cardiac tissue as well as the expression of cytokines and matrix proteins. Furthermore, cardiac fibroblasts were infected with virus to investigate if viral infection alone induces profibrotic signaling. Results. Severe cardiac inflammation was determined and cardiac fibrosis was consistently colocalized with inflammation during the acute phase of myocarditis. Declined cardiac inflammation but no significantly improved hemodynamic function was observed 28 days after infection. Interestingly, cardiac fibrosis declined to basal levels as well. Both cardiac inflammation and fibrosis were reversible, whereas the hemodynamic function remains impaired after healed viral myocarditis in C57BL/6J mice.

  20. Hypocretin-1 (orexin A) prevents the effects of hypoxia/hypercapnia and enhances the GABAergic pathway from the lateral paragigantocellular nucleus to cardiac vagal neurons in the nucleus ambiguus.

    Science.gov (United States)

    Dergacheva, O; Philbin, K; Bateman, R; Mendelowitz, D

    2011-02-23

    Hypocretins (orexins) are hypothalamic neuropeptides that play a crucial role in regulating sleep/wake states and autonomic functions including parasympathetic cardiac activity. We have recently demonstrated stimulation of the lateral paragigantocellular nucleus (LPGi), the nucleus which is thought to play a role in rapid eye movement (REM) sleep control, activates an inhibitory pathway to preganglionic cardiac vagal neurons in the nucleus ambiguus (NA). In this study we test the hypothesis that hypocretin-1 modulates the inhibitory neurotransmission to cardiac vagal neurons evoked by stimulation of the LPGi using whole-cell patch-clamp recordings in an in vitro brain slice preparation from rats. Activation of hypocretin-1 receptors produced a dose-dependent and long-term facilitation of GABAergic postsynaptic currents evoked by electrical stimulation of the LPGi. Hypoxia/hypercapnia diminished LPGi-evoked GABAergic current in cardiac vagal neurons and this inhibition by hypoxia/hypercapnia was prevented by pre-application of hypocretin-1. The action of hypocretin-1 was blocked by the hypocretin-1 receptor antagonist SB-334867. Facilitation of LPGi-evoked GABAergic current in cardiac vagal neurons under both normal condition and during hypoxia/hypercapnia could be the mechanism by which hypocretin-1 affects parasympathetic cardiac function and heart rate during REM sleep. Furthermore, our findings indicate a new potential mechanism that might be involved in the cardiac arrhythmias, bradycardia, and sudden cardiac death that can occur during sleep. Copyright © 2011. Published by Elsevier Ltd.

  1. Astrocyte-neuron communication: functional consequences.

    Science.gov (United States)

    Ben Achour, Sarrah; Pascual, Olivier

    2012-11-01

    Astrocyte-neuron communication has recently been proposed as a potential mechanism participating to synaptic transmission. With the development of this concept and accumulating evidences in favor of a modulation of synaptic transmission by astrocytes, has emerged the term gliotransmission. It refers to the capacity of astrocytes to release various transmitters, such as ATP, glutamate, D-serine, and GABA in the vicinity of synapses. While the cellular mechanisms involved in gliotransmission still need to be better described and, for some, identified, the aim of more and more studies is to determine the role of astrocytes from a functional point of view. This review will summarize the principal studies that have investigated a potential role of astrocytes in the various functions regulated by the brain (sleep, breathing, perception, learning and memory…). This will allow us to highlight the similarities and discrepancies in the signaling pathways involved in the different areas of the brain related to these functions.

  2. Short-term effects of cardiac steroids on intracellular membrane traffic in neuronal NT2 cells.

    Science.gov (United States)

    Rosen, H; Glukmann, V; Feldmann, T; Fridman, E; Lichtstein, D

    2006-12-30

    Cardiac steroids (CS) are specific inhibitors of Na+, K+-ATPase activity. Although the presence of CS-like compounds in animal tissues has been established, their physiological role is not clear. In a previous study we showed that in pulse-chase membrane-labeling experiments, long term (hours) interaction of CS at physiological concentrations (nM) with Na+, K+-ATPase, caused changes in endocytosed membrane traffic in human NT2 cells. This was associated with the accumulation of large vesicles adjacent to the nucleus. For this sequence of events to function in the physiological setting, however, CS would be expected to modify membrane traffic upon short term (min) exposure and membrane labeling. We now demonstrate that CS affects membrane traffic also following a short exposure. This was reflected by the CS-induced accumulation of FM1-43 and transferrin in the cells, as well as by changes in their colocalization with Na+, K+-ATPase. We also show that the CS-induced changes in membrane traffic following up to 2 hrs exposure are reversible, whereas longer treatment induces irreversible effects. Based on these observations, we propose that endogenous CS-like compounds are physiological regulators of the recycling of endocytosed membrane proteins and cargo in neuronal cells, and may affect basic mechanisms such as neurotransmitter release and reuptake.

  3. Vagus nerve stimulation mitigates intrinsic cardiac neuronal remodeling and cardiac hypertrophy induced by chronic pressure overload in guinea pig

    Science.gov (United States)

    Beaumont, Eric; Wright, Gary L.; Southerland, Elizabeth M.; Li, Ying; Chui, Ray; KenKnight, Bruce H.; Armour, J. Andrew

    2016-01-01

    Our objective was to determine whether chronic vagus nerve stimulation (VNS) mitigates pressure overload (PO)-induced remodeling of the cardioneural interface. Guinea pigs (n = 48) were randomized to right or left cervical vagus (RCV or LCV) implant. After 2 wk, chronic left ventricular PO was induced by partial (15–20%) aortic constriction. Of the 31 animals surviving PO induction, 10 were randomized to RCV VNS, 9 to LCV VNS, and 12 to sham VNS. VNS was delivered at 20 Hz and 1.14 ± 0.03 mA at a 22% duty cycle. VNS commenced 10 days after PO induction and was maintained for 40 days. Time-matched controls (n = 9) were evaluated concurrently. Echocardiograms were obtained before and 50 days after PO. At termination, intracellular current-clamp recordings of intrinsic cardiac (IC) neurons were studied in vitro to determine effects of therapy on soma characteristics. Ventricular cardiomyocyte sizes were assessed with histology along with immunoblot analysis of selected proteins in myocardial tissue extracts. In sham-treated animals, PO increased cardiac output (34%, P < 0.004), as well as systolic (114%, P < 0.04) and diastolic (49%, P < 0.002) left ventricular volumes, a hemodynamic response prevented by VNS. PO-induced enhancements of IC synaptic efficacy and muscarinic sensitivity of IC neurons were mitigated by chronic VNS. Increased myocyte size, which doubled in PO (P < 0.05), was mitigated by RCV. PO hypertrophic myocardium displayed decreased glycogen synthase (GS) protein levels and accumulation of the phosphorylated (inactive) form of GS. These PO-induced changes in GS were moderated by left VNS. Chronic VNS targets IC neurons accompanying PO to obtund associated adverse cardiomyocyte remodeling. PMID:26993230

  4. Cross-organ sensitization of thoracic spinal neurons receiving noxious cardiac input in rats with gastroesophageal reflux.

    Science.gov (United States)

    Qin, Chao; Malykhina, Anna P; Thompson, Ann M; Farber, Jay P; Foreman, Robert D

    2010-06-01

    Gastroesophageal reflux (GER) frequently triggers or worsens cardiac pain or symptoms in patients with coronary heart disease. This study aimed to determine whether GER enhances the activity of upper thoracic spinal neurons receiving noxious cardiac input. Gastric fundus and pyloric ligations as well as a longitudinal myelotomy at the gastroesophageal junction induced acute GER in pentobarbital-anesthetized, paralyzed, and ventilated male Sprague-Dawley rats. Manual manipulations of the stomach and lower esophagus were used as surgical controls in another group. At 4-9 h after GER surgery, extracellular potentials of single neurons were recorded from the T3 spinal segment. Intrapericardial bradykinin (IB) (10 microg/ml, 0.2 ml, 1 min) injections were used to activate cardiac nociceptors, and esophageal distensions were used to activate esophageal afferent fibers. Significantly more spinal neurons in the GER group responded to IB compared with the control group (69.1 vs. 38%, P neurons in the superficial laminae of GER animals was significantly different from those in deeper layers (1/8 vs. 46/60, P 0.05). Excitatory responses of spinal neurons to IB in the GER group were greater than in the control group [32.4 +/- 3.5 impulses (imp)/s vs. 13.3 +/- 2.3 imp/s, P neurons responded to cardiac input and ED, which was higher than the control group (61.5%, P neurons in deeper laminae of the dorsal horn to noxious cardiac stimulus.

  5. Vagal stimulation targets select populations of intrinsic cardiac neurons to control neurally induced atrial fibrillation.

    Science.gov (United States)

    Salavatian, Siamak; Beaumont, Eric; Longpré, Jean-Philippe; Armour, J Andrew; Vinet, Alain; Jacquemet, Vincent; Shivkumar, Kalyanam; Ardell, Jeffrey L

    2016-11-01

    Mediastinal nerve stimulation (MNS) reproducibly evokes atrial fibrillation (AF) by excessive and heterogeneous activation of intrinsic cardiac (IC) neurons. This study evaluated whether preemptive vagus nerve stimulation (VNS) impacts MNS-induced evoked changes in IC neural network activity to thereby alter susceptibility to AF. IC neuronal activity in the right atrial ganglionated plexus was directly recorded in anesthetized canines (n = 8) using a linear microelectrode array concomitant with right atrial electrical activity in response to: 1) epicardial touch or great vessel occlusion vs. 2) stellate or vagal stimulation. From these stressors, post hoc analysis (based on the Skellam distribution) defined IC neurons so recorded as afferent, efferent, or convergent (afferent and efferent inputs) local circuit neurons (LCN). The capacity of right-sided MNS to modify IC activity in the induction of AF was determined before and after preemptive right (RCV)- vs. left (LCV)-sided VNS (15 Hz, 500 μs; 1.2× bradycardia threshold). Neuronal (n = 89) activity at baseline (0.11 ± 0.29 Hz) increased during MNS-induced AF (0.51 ± 1.30 Hz; P neuronal synchrony increased during neurally induced AF, a local neural network response mitigated by preemptive VNS. These antiarrhythmic effects persisted post-VNS for, on average, 26 min. In conclusion, VNS preferentially targets convergent LCNs and their interactive coherence to mitigate the potential for neurally induced AF. The antiarrhythmic properties imposed by VNS exhibit memory. Copyright © 2016 the American Physiological Society.

  6. The neuron identity problem: form meets function.

    Science.gov (United States)

    Fishell, Gord; Heintz, Nathaniel

    2013-10-30

    A complete understanding of nervous system function cannot be achieved without the identification of its component cell types. In this Perspective, we explore a series of related issues surrounding cell identity and how revolutionary methods for labeling and probing specific neuronal types have clarified this question. Specifically, we ask the following questions: what is the purpose of such diversity, how is it generated, how is it maintained, and, ultimately, how can one unambiguously identity one cell type from another? We suggest that each cell type can be defined by a unique and conserved molecular ground state that determines its capabilities. We believe that gaining an understanding of these molecular barcodes will advance our ability to explore brain function, enhance our understanding of the biochemical basis of CNS disorders, and aid in the development of novel therapeutic strategies. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. The origin and function of mirror neurons: the missing link.

    Science.gov (United States)

    Lingnau, Angelika; Caramazza, Alfonso

    2014-04-01

    We argue, by analogy to the neural organization of the object recognition system, that demonstration of modulation of mirror neurons by associative learning does not imply absence of genetic adaptation. Innate connectivity defines the types of processes mirror neurons can participate in while allowing for extensive local plasticity. However, the proper function of these neurons remains to be worked out.

  8. Novel axolotl cardiac function analysis method using magnetic resonance imaging

    NARCIS (Netherlands)

    Sanches, Pedro Gomes; Op 't Veld, Roel C.; de Graaf, Wolter; Strijkers, Gustav J.; Grüll, Holger

    2017-01-01

    The salamander axolotl is capable of complete regeneration of amputated heart tissue. However, non-invasive imaging tools for assessing its cardiac function were so far not employed. In this study, cardiac magnetic resonance imaging is introduced as a non-invasive technique to image heart function

  9. Novel axolotl cardiac function analysis method using magnetic resonance imaging

    NARCIS (Netherlands)

    Sanches, P.G.; Op ‘t Veld, R.C.; de Graaf, W.; Strijkers, G.J.; Grüll, H.

    2017-01-01

    The salamander axolotl is capable of complete regeneration of amputated heart tissue. However, non-invasive imaging tools for assessing its cardiac function were so far not employed. In this study, cardiac magnetic resonance imaging is introduced as a noninvasive technique to image heart function of

  10. Heart failure-induced changes of voltage-gated Ca2+ channels and cell excitability in rat cardiac postganglionic neurons.

    Science.gov (United States)

    Tu, Huiyin; Liu, Jinxu; Zhang, Dongze; Zheng, Hong; Patel, Kaushik P; Cornish, Kurtis G; Wang, Wei-Zhong; Muelleman, Robert L; Li, Yu-Long

    2014-01-15

    Chronic heart failure (CHF) is characterized by decreased cardiac parasympathetic and increased cardiac sympathetic nerve activity. This autonomic imbalance increases the risk of arrhythmias and sudden death in patients with CHF. We hypothesized that the molecular and cellular alterations of cardiac postganglionic parasympathetic (CPP) neurons located in the intracardiac ganglia and sympathetic (CPS) neurons located in the stellate ganglia (SG) possibly link to the cardiac autonomic imbalance in CHF. Rat CHF was induced by left coronary artery ligation. Single-cell real-time PCR and immunofluorescent data showed that L (Ca(v)1.2 and Ca(v)1.3), P/Q (Ca(v)2.1), N (Ca(v)2.2), and R (Ca(v)2.3) types of Ca2+ channels were expressed in CPP and CPS neurons, but CHF decreased the mRNA and protein expression of only the N-type Ca2+ channels in CPP neurons, and it did not affect mRNA and protein expression of all Ca2+ channel subtypes in the CPS neurons. Patch-clamp recording confirmed that CHF reduced N-type Ca2+ currents and cell excitability in the CPP neurons and enhanced N-type Ca2+ currents and cell excitability in the CPS neurons. N-type Ca2+ channel blocker (1 μM ω-conotoxin GVIA) lowered Ca2+ currents and cell excitability in the CPP and CPS neurons from sham-operated and CHF rats. These results suggest that CHF reduces the N-type Ca2+ channel currents and cell excitability in the CPP neurons and enhances the N-type Ca2+ currents and cell excitability in the CPS neurons, which may contribute to the cardiac autonomic imbalance in CHF.

  11. Development of cardiac parasympathetic neurons, glial cells, and regional cholinergic innervation of the mouse heart.

    Science.gov (United States)

    Fregoso, S P; Hoover, D B

    2012-09-27

    Very little is known about the development of cardiac parasympathetic ganglia and cholinergic innervation of the mouse heart. Accordingly, we evaluated the growth of cholinergic neurons and nerve fibers in mouse hearts from embryonic day 18.5 (E18.5) through postnatal day 21(P21). Cholinergic perikarya and varicose nerve fibers were identified in paraffin sections immunostained for the vesicular acetylcholine transporter (VAChT). Satellite cells and Schwann cells in adjacent sections were identified by immunostaining for S100β calcium binding protein (S100) and brain-fatty acid binding protein (B-FABP). We found that cardiac ganglia had formed in close association to the atria and cholinergic innervation of the atrioventricular junction had already begun by E18.5. However, most cholinergic innervation of the heart, including the sinoatrial node, developed postnatally (P0.5-P21) along with a doubling of the cross-sectional area of cholinergic perikarya. Satellite cells were present throughout neonatal cardiac ganglia and expressed primarily B-FABP. As they became more mature at P21, satellite cells stained strongly for both B-FABP and S100. Satellite cells appeared to surround most cardiac parasympathetic neurons, even in neonatal hearts. Mature Schwann cells, identified by morphology and strong staining for S100, were already present at E18.5 in atrial regions that receive cholinergic innervation at later developmental times. The abundance and distribution of S100-positive Schwann cells increased postnatally along with nerve density. While S100 staining of cardiac Schwann cells was maintained in P21 and older mice, Schwann cells did not show B-FABP staining at these times. Parallel development of satellite cells and cholinergic perikarya in the cardiac ganglia and the increase in abundance of Schwann cells and varicose cholinergic nerve fibers in the atria suggest that neuronal-glial interactions could be important for development of the parasympathetic nervous

  12. Role of neuronal activity in regulating the structure and function of auditory neurons

    International Nuclear Information System (INIS)

    Born, D.E.

    1986-01-01

    The role of afferent activity in maintaining neuronal structure and function was investigated in second order auditory neurons in nucleus magnocellularis (NM) of the chicken. The cochlea provides the major excitatory input to NM neurons via the eighth nerve. Removal of the cochlea causes dramatic changes in NM neurons. To determine if the elimination of neuronal activity is responsible for the changes in NM seen after cochlea removal, tetrodotoxin was used block action potentials in the cochlear ganglion cells. Tetrodotoxin injections into the perilymph reliably blocked neuronal activity in the cochlear nerve and NM. Far field recordings of sound-evoked potentials revealed that responses returned within 6 hours. Changes in amino acid incorporation in NM neurons were measured by giving intracardiac injections of 3 H-leucine and preparing tissue for autoradiographic demonstration of incorporated amino acid. Grain counts over individual neurons revealed that a single injection of tetrodotoxin produced a 40% decrease in grain density in ipsilateral NM neurons. It is concluded that neuronal activity plays an important contribution to the maintenance of the normal properties of NM neurons

  13. Chemically Functionalized Carbon Nanotubes as Substrates for Neuronal Growth

    Science.gov (United States)

    Hu, Hui; Ni, Yingchun; Montana, Vedrana; Haddon, Robert C.; Parpura, Vladimir

    2009-01-01

    We report the use of chemically modified carbon nanotubes as a substrate for cultured neurons. The morphological features of neurons that directly reflect their potential capability in synaptic transmission are characterized. The chemical properties of carbon nanotubes are systematically varied by attaching different functional groups that confer known characteristics to the substrate. By manipulating the charge carried by functionalized carbon nanotubes we are able to control the outgrowth and branching pattern of neuronal processes. PMID:21394241

  14. Cardiac sympathetic neuronal damage precedes myocardial fibrosis in patients with Anderson-Fabry disease

    International Nuclear Information System (INIS)

    Imbriaco, Massimo; Piscopo, Valentina; Ponsiglione, Andrea; Nappi, Carmela; Puglia, Marta; Dell'Aversana, Serena; Spinelli, Letizia; Cuocolo, Alberto; Pellegrino, Teresa; Petretta, Mario; Riccio, Eleonora; Pisani, Antonio

    2017-01-01

    Cardiac sympathetic denervation may be detectable in patients with Anderson-Fabry disease (AFD), suggesting its usefulness for early detection of the disease. However, the relationship between sympathetic neuronal damage measured by 123 I-metaiodobenzylguanidine (MIBG) imaging with myocardial fibrosis on cardiac magnetic resonance (CMR) is still unclear. Cardiac sympathetic innervation was assessed by 123 I-MIBG single-photon emission computed tomography (SPECT) in 25 patients with genetically proved AFD. Within one month from MIBG imaging, all patients underwent contrast-enhanced CMR. MIBG defect size and fibrosis size on CMR were measured for the left ventricle (LV) and expressed as %LV. Patients were divided into three groups according to MIBG and CMR findings: (1) matched normal, without MIBG defects and without fibrosis on CMR (n = 10); (2) unmatched, with MIBG defect but without fibrosis (n = 5); and (3) matched abnormal, with MIBG defect and fibrosis (n = 10). The three groups did not differ with respect to age, gender, α-galactosidase, proteinuria, glomerular filtration rate, and troponin I, while New York Heart Association class (p = 0.008), LV hypertrophy (p = 0.05), and enzyme replacement therapy (p = 0.02) were different among groups. Although in patients with matched abnormal findings, there was a significant correlation between MIBG defect size and area of fibrosis at CMR (r 2 = 0.98, p < 0.001), MIBG defect size was larger than fibrosis size (26 ± 23 vs. 18 ± 13%LV, p = 0.02). Sympathetic neuronal damage is frequent in AFD patients, and it may precede myocardial damage, such as fibrosis. Thus, 123 I-MIBG imaging can be considered a challenging technique for early detection of cardiac involvement in AFD. (orig.)

  15. Cardiac sympathetic neuronal damage precedes myocardial fibrosis in patients with Anderson-Fabry disease

    Energy Technology Data Exchange (ETDEWEB)

    Imbriaco, Massimo; Piscopo, Valentina; Ponsiglione, Andrea; Nappi, Carmela; Puglia, Marta; Dell' Aversana, Serena; Spinelli, Letizia; Cuocolo, Alberto [University Federico II, Department of Advanced Biomedical Sciences, Naples (Italy); Pellegrino, Teresa [National Council of Research, Institute of Biostructure and Bioimaging, Naples (Italy); Petretta, Mario [University Federico II, Department of Translational Medical Sciences, Naples (Italy); Riccio, Eleonora; Pisani, Antonio [University of Naples Federico II, Department of Public Health, Naples (Italy)

    2017-12-15

    Cardiac sympathetic denervation may be detectable in patients with Anderson-Fabry disease (AFD), suggesting its usefulness for early detection of the disease. However, the relationship between sympathetic neuronal damage measured by {sup 123}I-metaiodobenzylguanidine (MIBG) imaging with myocardial fibrosis on cardiac magnetic resonance (CMR) is still unclear. Cardiac sympathetic innervation was assessed by {sup 123}I-MIBG single-photon emission computed tomography (SPECT) in 25 patients with genetically proved AFD. Within one month from MIBG imaging, all patients underwent contrast-enhanced CMR. MIBG defect size and fibrosis size on CMR were measured for the left ventricle (LV) and expressed as %LV. Patients were divided into three groups according to MIBG and CMR findings: (1) matched normal, without MIBG defects and without fibrosis on CMR (n = 10); (2) unmatched, with MIBG defect but without fibrosis (n = 5); and (3) matched abnormal, with MIBG defect and fibrosis (n = 10). The three groups did not differ with respect to age, gender, α-galactosidase, proteinuria, glomerular filtration rate, and troponin I, while New York Heart Association class (p = 0.008), LV hypertrophy (p = 0.05), and enzyme replacement therapy (p = 0.02) were different among groups. Although in patients with matched abnormal findings, there was a significant correlation between MIBG defect size and area of fibrosis at CMR (r{sup 2} = 0.98, p < 0.001), MIBG defect size was larger than fibrosis size (26 ± 23 vs. 18 ± 13%LV, p = 0.02). Sympathetic neuronal damage is frequent in AFD patients, and it may precede myocardial damage, such as fibrosis. Thus, {sup 123}I-MIBG imaging can be considered a challenging technique for early detection of cardiac involvement in AFD. (orig.)

  16. Assessment of cardiac sympathetic nerve integrity with positron emission tomography

    International Nuclear Information System (INIS)

    Raffel, David M.; Wieland, Donald M.

    2001-01-01

    The autonomic nervous system plays a critical role in the regulation of cardiac function. Abnormalities of cardiac innervation have been implicated in the pathophysiology of many heart diseases, including sudden cardiac death and congestive heart failure. In an effort to provide clinicians with the ability to regionally map cardiac innervation, several radiotracers for imaging cardiac sympathetic neurons have been developed. This paper reviews the development of neuronal imaging agents and discusses their emerging role in the noninvasive assessment of cardiac sympathetic innervation

  17. Vagal stimulation targets select populations of intrinsic cardiac neurons to control neurally induced atrial fibrillation

    Science.gov (United States)

    Salavatian, Siamak; Beaumont, Eric; Longpré, Jean-Philippe; Armour, J. Andrew; Vinet, Alain; Jacquemet, Vincent; Shivkumar, Kalyanam

    2016-01-01

    Mediastinal nerve stimulation (MNS) reproducibly evokes atrial fibrillation (AF) by excessive and heterogeneous activation of intrinsic cardiac (IC) neurons. This study evaluated whether preemptive vagus nerve stimulation (VNS) impacts MNS-induced evoked changes in IC neural network activity to thereby alter susceptibility to AF. IC neuronal activity in the right atrial ganglionated plexus was directly recorded in anesthetized canines (n = 8) using a linear microelectrode array concomitant with right atrial electrical activity in response to: 1) epicardial touch or great vessel occlusion vs. 2) stellate or vagal stimulation. From these stressors, post hoc analysis (based on the Skellam distribution) defined IC neurons so recorded as afferent, efferent, or convergent (afferent and efferent inputs) local circuit neurons (LCN). The capacity of right-sided MNS to modify IC activity in the induction of AF was determined before and after preemptive right (RCV)- vs. left (LCV)-sided VNS (15 Hz, 500 μs; 1.2× bradycardia threshold). Neuronal (n = 89) activity at baseline (0.11 ± 0.29 Hz) increased during MNS-induced AF (0.51 ± 1.30 Hz; P < 0.001). Convergent LCNs were preferentially activated by MNS. Preemptive RCV reduced MNS-induced changes in LCN activity (by 70%) while mitigating MNS-induced AF (by 75%). Preemptive LCV reduced LCN activity by 60% while mitigating AF potential by 40%. IC neuronal synchrony increased during neurally induced AF, a local neural network response mitigated by preemptive VNS. These antiarrhythmic effects persisted post-VNS for, on average, 26 min. In conclusion, VNS preferentially targets convergent LCNs and their interactive coherence to mitigate the potential for neurally induced AF. The antiarrhythmic properties imposed by VNS exhibit memory. PMID:27591222

  18. Hypertrophy of neurons within cardiac ganglia in human, canine, and rat heart failure: the potential role of nerve growth factor.

    Science.gov (United States)

    Singh, Sanjay; Sayers, Scott; Walter, James S; Thomas, Donald; Dieter, Robert S; Nee, Lisa M; Wurster, Robert D

    2013-08-19

    Autonomic imbalances including parasympathetic withdrawal and sympathetic overactivity are cardinal features of heart failure regardless of etiology; however, mechanisms underlying these imbalances remain unknown. Animal model studies of heart and visceral organ hypertrophy predict that nerve growth factor levels should be elevated in heart failure; whether this is so in human heart failure, though, remains unclear. We tested the hypotheses that neurons in cardiac ganglia are hypertrophied in human, canine, and rat heart failure and that nerve growth factor, which we hypothesize is elevated in the failing heart, contributes to this neuronal hypertrophy. Somal morphology of neurons from human (579.54±14.34 versus 327.45±9.17 μm(2); Phearts (767.80±18.37 versus 650.23±9.84 μm(2); Pneurons from spontaneously hypertensive rat hearts (327.98±3.15 versus 271.29±2.79 μm(2); Pneurons in cardiac ganglia compared with controls. Western blot analysis shows that nerve growth factor levels in the explanted, failing human heart are 250% greater than levels in healthy donor hearts. Neurons from cardiac ganglia cultured with nerve growth factor are significantly larger and have greater dendritic arborization than neurons in control cultures. Hypertrophied neurons are significantly less excitable than smaller ones; thus, hypertrophy of vagal postganglionic neurons in cardiac ganglia would help to explain the parasympathetic withdrawal that accompanies heart failure. Furthermore, our observations suggest that nerve growth factor, which is elevated in the failing human heart, causes hypertrophy of neurons in cardiac ganglia.

  19. Neuronal medium that supports basic synaptic functions and activity of human neurons in vitro.

    Science.gov (United States)

    Bardy, Cedric; van den Hurk, Mark; Eames, Tameji; Marchand, Cynthia; Hernandez, Ruben V; Kellogg, Mariko; Gorris, Mark; Galet, Ben; Palomares, Vanessa; Brown, Joshua; Bang, Anne G; Mertens, Jerome; Böhnke, Lena; Boyer, Leah; Simon, Suzanne; Gage, Fred H

    2015-05-19

    Human cell reprogramming technologies offer access to live human neurons from patients and provide a new alternative for modeling neurological disorders in vitro. Neural electrical activity is the essence of nervous system function in vivo. Therefore, we examined neuronal activity in media widely used to culture neurons. We found that classic basal media, as well as serum, impair action potential generation and synaptic communication. To overcome this problem, we designed a new neuronal medium (BrainPhys basal + serum-free supplements) in which we adjusted the concentrations of inorganic salts, neuroactive amino acids, and energetic substrates. We then tested that this medium adequately supports neuronal activity and survival of human neurons in culture. Long-term exposure to this physiological medium also improved the proportion of neurons that were synaptically active. The medium was designed to culture human neurons but also proved adequate for rodent neurons. The improvement in BrainPhys basal medium to support neurophysiological activity is an important step toward reducing the gap between brain physiological conditions in vivo and neuronal models in vitro.

  20. Cytoskeleton Molecular Motors: Structures and Their Functions in Neuron.

    Science.gov (United States)

    Xiao, Qingpin; Hu, Xiaohui; Wei, Zhiyi; Tam, Kin Yip

    2016-01-01

    Cells make use of molecular motors to transport small molecules, macromolecules and cellular organelles to target region to execute biological functions, which is utmost important for polarized cells, such as neurons. In particular, cytoskeleton motors play fundamental roles in neuron polarization, extension, shape and neurotransmission. Cytoskeleton motors comprise of myosin, kinesin and cytoplasmic dynein. F-actin filaments act as myosin track, while kinesin and cytoplasmic dynein move on microtubules. Cytoskeleton motors work together to build a highly polarized and regulated system in neuronal cells via different molecular mechanisms and functional regulations. This review discusses the structures and working mechanisms of the cytoskeleton motors in neurons.

  1. Neuronal medium that supports basic synaptic functions and activity of human neurons in vitro

    NARCIS (Netherlands)

    Bardy, C.; Hurk, M. van den; Eames, T.; Marchand, C.; Hernandez, R.V.; Kellogg, M.; Gorris, M.A.J.; Galet, B.; Palomares, V.; Brown, J.; Bang, A.G.; Mertens, J.; Bohnke, L.; Boyer, L.; Simon, S.; Gage, F.H.

    2015-01-01

    Human cell reprogramming technologies offer access to live human neurons from patients and provide a new alternative for modeling neurological disorders in vitro. Neural electrical activity is the essence of nervous system function in vivo. Therefore, we examined neuronal activity in media widely

  2. Dicer maintains the identity and function of proprioceptive sensory neurons.

    Science.gov (United States)

    O'Toole, Sean M; Ferrer, Monica M; Mekonnen, Jennifer; Zhang, Haihan; Shima, Yasuyuki; Ladle, David R; Nelson, Sacha B

    2017-03-01

    Neuronal cell identity is established during development and must be maintained throughout an animal's life (Fishell G, Heintz N. Neuron 80: 602-612, 2013). Transcription factors critical for establishing neuronal identity can be required for maintaining it (Deneris ES, Hobert O. Nat Neurosci 17: 899-907, 2014). Posttranscriptional regulation also plays an important role in neuronal differentiation (Bian S, Sun T. Mol Neurobiol 44: 359-373, 2011), but its role in maintaining cell identity is less established. To better understand how posttranscriptional regulation might contribute to cell identity, we examined the proprioceptive neurons in the dorsal root ganglion (DRG), a highly specialized sensory neuron class, with well-established properties that distinguish them from other neurons in the ganglion. By conditionally ablating Dicer in mice, using parvalbumin (Pvalb)-driven Cre recombinase, we impaired posttranscriptional regulation in the proprioceptive sensory neuron population. Knockout (KO) animals display a progressive form of ataxia at the beginning of the fourth postnatal week that is accompanied by a cell death within the DRG. Before cell loss, expression profiling shows a reduction of proprioceptor specific genes and an increased expression of nonproprioceptive genes normally enriched in other ganglion neurons. Furthermore, although central connections of these neurons are intact, the peripheral connections to the muscle are functionally impaired. Posttranscriptional regulation is therefore necessary to retain the transcriptional identity and support functional specialization of the proprioceptive sensory neurons. NEW & NOTEWORTHY We have demonstrated that selectively impairing Dicer in parvalbumin-positive neurons, which include the proprioceptors, triggers behavioral changes, a lack of muscle connectivity, and a loss of transcriptional identity as observed through RNA sequencing. These results suggest that Dicer and, most likely by extension, micro

  3. Evaluation of cardiac function in active and hibernating grizzly bears.

    Science.gov (United States)

    Nelson, O Lynne; McEwen, Margaret-Mary; Robbins, Charles T; Felicetti, Laura; Christensen, William F

    2003-10-15

    To evaluate cardiac function parameters in a group of active and hibernating grizzly bears. Prospective study. 6 subadult grizzly bears. Indirect blood pressure, a 12-lead ECG, and a routine echocardiogram were obtained in each bear during the summer active phase and during hibernation. All measurements of myocardial contractility were significantly lower in all bears during hibernation, compared with the active period. Mean rate of circumferential left ventricular shortening, percentage fractional shortening, and percentage left ventricular ejection fraction were significantly lower in bears during hibernation, compared with the active period. Certain indices of diastolic function appeared to indicate enhanced ventricular compliance during the hibernation period. Mean mitral inflow ratio and isovolumic relaxation time were greater during hibernation. Heart rate was significantly lower for hibernating bears, and mean cardiac index was lower but not significantly different from cardiac index during the active phase. Contrary to results obtained in hibernating rodent species, cardiac index was not significantly correlated with heart rate. Cardiac function parameters in hibernating bears are opposite to the chronic bradycardic effects detected in nonhibernating species, likely because of intrinsic cardiac muscle adaptations during hibernation. Understanding mechanisms and responses of the myocardium during hibernation could yield insight into mechanisms of cardiac function regulation in various disease states in nonhibernating species.

  4. Regulatory Mechanisms Controlling Maturation of Serotonin Neuron Identity and Function.

    Science.gov (United States)

    Spencer, William C; Deneris, Evan S

    2017-01-01

    The brain serotonin (5-hydroxytryptamine; 5-HT) system has been extensively studied for its role in normal physiology and behavior, as well as, neuropsychiatric disorders. The broad influence of 5-HT on brain function, is in part due to the vast connectivity pattern of 5-HT-producing neurons throughout the CNS. 5-HT neurons are born and terminally specified midway through embryogenesis, then enter a protracted period of maturation, where they functionally integrate into CNS circuitry and then are maintained throughout life. The transcriptional regulatory networks controlling progenitor cell generation and terminal specification of 5-HT neurons are relatively well-understood, yet the factors controlling 5-HT neuron maturation are only recently coming to light. In this review, we first provide an update on the regulatory network controlling 5-HT neuron development, then delve deeper into the properties and regulatory strategies governing 5-HT neuron maturation. In particular, we discuss the role of the 5-HT neuron terminal selector transcription factor (TF) Pet-1 as a key regulator of 5-HT neuron maturation. Pet-1 was originally shown to positively regulate genes needed for 5-HT synthesis, reuptake and vesicular transport, hence 5-HT neuron-type transmitter identity. It has now been shown to regulate, both positively and negatively, many other categories of genes in 5-HT neurons including ion channels, GPCRs, transporters, neuropeptides, and other transcription factors. Its function as a terminal selector results in the maturation of 5-HT neuron excitability, firing characteristics, and synaptic modulation by several neurotransmitters. Furthermore, there is a temporal requirement for Pet-1 in the control of postmitotic gene expression trajectories thus indicating a direct role in 5-HT neuron maturation. Proper regulation of the maturation of cellular identity is critical for normal neuronal functioning and perturbations in the gene regulatory networks controlling

  5. Role of adrenal hormones in the synthesis of noradrenaline in cardiac sympathetic neurones

    Science.gov (United States)

    Bhagat, B.

    1969-01-01

    1. Adrenalectomy or adrenal demedullation affected neither the levels of endogenous catecholamines in the rat heart nor the accumulation of 3H-noradrenaline 1 hr after its intravenous administration. 2. Twenty-four hours after intravenous administration of labelled amine, however, its retention was markedly reduced in the heart of adrenalectomized or demedullated rats. Ganglionic blockade prevented this reduction. 3. Rate calculations from the decline of catecholamine levels after blockade of synthesis with α-methyl-tyrosine showed that cardiac synthesis of noradrenaline increased about four-fold after demedullation and about three-fold after adrenalectomy. This increase in synthesis may compensate for the loss of circulating catecholamines. 4. There was no change in catechol-o-methyl-transferase activity, but monoamine oxidase activity was increased in the homogenates of the heart of adrenalectomized and demedullated rats. The increase in the cardiac monoamine oxidase activity was markedly greater in the adrenalectomized rats than in the demedullated rats. 5. It is suggested that adrenal cortex insufficiency may modulate the rate of synthesis of noradrenaline and monoamine oxidase activity in cardiac sympathetic neurones. PMID:5360339

  6. Layer 5 Callosal Parvalbumin-Expressing Neurons: A Distinct Functional Group of GABAergic Neurons.

    Science.gov (United States)

    Zurita, Hector; Feyen, Paul L C; Apicella, Alfonso Junior

    2018-01-01

    Previous studies have shown that parvalbumin-expressing neurons (CC-Parv neurons) connect the two hemispheres of motor and sensory areas via the corpus callosum, and are a functional part of the cortical circuit. Here we test the hypothesis that layer 5 CC-Parv neurons possess anatomical and molecular mechanisms which dampen excitability and modulate the gating of interhemispheric inhibition. In order to investigate this hypothesis we use viral tracing to determine the anatomical and electrophysiological properties of layer 5 CC-Parv and parvalbumin-expressing (Parv) neurons of the mouse auditory cortex (AC). Here we show that layer 5 CC-Parv neurons had larger dendritic fields characterized by longer dendrites that branched farther from the soma, whereas layer 5 Parv neurons had smaller dendritic fields characterized by shorter dendrites that branched nearer to the soma. The layer 5 CC-Parv neurons are characterized by delayed action potential (AP) responses to threshold currents, lower firing rates, and lower instantaneous frequencies compared to the layer 5 Parv neurons. Kv1.1 containing K + channels are the main source of the AP repolarization of the layer 5 CC-Parv and have a major role in determining both the spike delayed response, firing rate and instantaneous frequency of these neurons.

  7. Cardiac telomere length in heart development, function, and disease.

    Science.gov (United States)

    Booth, S A; Charchar, F J

    2017-07-01

    Telomeres are repetitive nucleoprotein structures at chromosome ends, and a decrease in the number of these repeats, known as a reduction in telomere length (TL), triggers cellular senescence and apoptosis. Heart disease, the worldwide leading cause of death, often results from the loss of cardiac cells, which could be explained by decreases in TL. Due to the cell-specific regulation of TL, this review focuses on studies that have measured telomeres in heart cells and critically assesses the relationship between cardiac TL and heart function. There are several lines of evidence that have identified rapid changes in cardiac TL during the onset and progression of heart disease as well as at critical stages of development. There are also many factors, such as the loss of telomeric proteins, oxidative stress, and hypoxia, that decrease cardiac TL and heart function. In contrast, antioxidants, calorie restriction, and exercise can prevent both cardiac telomere attrition and the progression of heart disease. TL in the heart is also indicative of proliferative potential and could facilitate the identification of cells suitable for cardiac rejuvenation. Although these findings highlight the involvement of TL in heart function, there are important questions regarding the validity of animal models, as well as several confounding factors, that need to be considered when interpreting results and planning future research. With these in mind, elucidating the telomeric mechanisms involved in heart development and the transition to disease holds promise to prevent cardiac dysfunction and potentiate regeneration after injury. Copyright © 2017 the American Physiological Society.

  8. Acupuncture-like stimulation at auricular point Heart evokes cardiovascular inhibition via activating the cardiac-related neurons in the nucleus tractus solitarius.

    Science.gov (United States)

    Gao, Xin Yan; Li, Yan Hua; Liu, Kun; Rong, Pei Jing; Ben, Hui; Li, Liang; Zhu, Bing; Zhang, Shi Ping

    2011-06-23

    Fifty-eight male Sprague-Dawley rats used in the present study to investigate the role of baroreceptor sensitive neurons of the nucleus tractus solitarius (NTS) in the regulation of cardiovascular inhibition during acupuncture at the auricular point Heart, single unit recording was made in anesthetized Sprague-Dawley rats. A neuron was considered to be excited or inhibited by acupuncture stimulation if it displayed 15% more or less spikes s(-1), respectively. NTS neurons were classified into cardiac-related (CR) neurons and non-cardiac-related neurons based on whether their rhythmic discharges were synchronized with the R-waves and responding to sodium nitroprusside (NP; 20 μg/kg, i.v.) administration. Manual acupuncture was applied at the auricular point Heart and somatic acupuncture points ST36 and PC6. Acupuncture at auricular point Heart showed a more significant inhibitory effect on arterial pressure (-22.1±2.4mm Hg; Pheart rate (-12.7±1.7 bpm; PHeart also increased the level of response of CR neurons in the NTS (93.8%±26.0% increase in discharge rate; Pneurons evoked by auricular acupuncture, but had no effect on the same responses evoked by somatic acupuncture. Inactivation of the NTS with local anesthetics also decreased the cardiovascular inhibitory responses evoked by auricular acupuncture. Our results show that acupuncture at the auricular point Heart regulates cardiovascular function by activating baroreceptor sensitive neurons in the NTS in a similar manner as the baroreceptor reflex in cardiovascular inhibition. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Bone Morphogenetic Protein 9 Reduces Cardiac Fibrosis and Improves Cardiac Function in Heart Failure.

    Science.gov (United States)

    Morine, Kevin J; Qiao, Xiaoying; York, Sam; Natov, Peter S; Paruchuri, Vikram; Zhang, Yali; Aronovitz, Mark J; Karas, Richard H; Kapur, Navin K

    2018-02-27

    Background -Heart failure is a growing cause of morbidity and mortality worldwide. Transforming growth factor beta (TGF-β1) promotes cardiac fibrosis, but also activates counter-regulatory pathways that serve to regulate TGF-β1 activity in heart failure. Bone morphogenetic protein 9 (BMP9) is a member of the TGFβ family of cytokines and signals via the downstream effector protein Smad1. Endoglin is a TGFβ co-receptor that promotes TGF-β1 signaling via Smad3 and binds BMP9 with high affinity. We hypothesized that BMP9 limits cardiac fibrosis by activating Smad1 and attenuating Smad3 and further that neutralizing endoglin activity promotes BMP9 activity. Methods -We examined BMP9 expression and signaling in human cardiac fibroblasts and human subjects with heart failure. We utilized the thoracic aortic constriction (TAC) induced model of heart failure to evaluate the functional effect of BMP9 signaling on cardiac remodeling. Results -BMP9 expression is increased in the circulation and left ventricle (LV) of human subjects with heart failure and is expressed by cardiac fibroblasts. Next, we observed that BMP9 attenuates Type I collagen synthesis in human cardiac fibroblasts using recombinant human BMP9 and an siRNA approach. In BMP9 -/- mice subjected to TAC, loss of BMP9 activity promotes cardiac fibrosis, impairs LV function, and increases LV levels of phosphorylated Smad3 (pSmad3), not pSmad1. In contrast, treatment of wild-type mice subjected to TAC with recombinant BMP9 limits progression of cardiac fibrosis, improves LV function, enhances myocardial capillary density, and increases LV levels of pSmad1, not pSmad3 compared to vehicle treated controls. Since endoglin binds BMP9 with high affinity, we explored the effect of reduced endoglin activity on BMP9 activity. Neutralizing endoglin activity in human cardiac fibroblasts or in wild-type mice subjected to TAC induced heart failure limits collagen production, increases BMP9 protein levels, and increases

  10. Axonal regeneration and neuronal function are preserved in motor neurons lacking ß-actin in vivo.

    Directory of Open Access Journals (Sweden)

    Thomas R Cheever

    2011-03-01

    Full Text Available The proper localization of ß-actin mRNA and protein is essential for growth cone guidance and axon elongation in cultured neurons. In addition, decreased levels of ß-actin mRNA and protein have been identified in the growth cones of motor neurons cultured from a mouse model of Spinal Muscular Atrophy (SMA, suggesting that ß-actin loss-of-function at growth cones or pre-synaptic nerve terminals could contribute to the pathogenesis of this disease. However, the role of ß-actin in motor neurons in vivo and its potential relevance to disease has yet to be examined. We therefore generated motor neuron specific ß-actin knock-out mice (Actb-MNsKO to investigate the function of ß-actin in motor neurons in vivo. Surprisingly, ß-actin was not required for motor neuron viability or neuromuscular junction maintenance. Skeletal muscle from Actb-MNsKO mice showed no histological indication of denervation and did not significantly differ from controls in several measurements of physiologic function. Finally, motor axon regeneration was unimpaired in Actb-MNsKO mice, suggesting that ß-actin is not required for motor neuron function or regeneration in vivo.

  11. Functional circuits of new neurons in the dentate gyrus

    Directory of Open Access Journals (Sweden)

    Carmen eVivar

    2013-02-01

    Full Text Available The hippocampus is crucial for memory formation. New neurons are added throughout life to the hippocampal dentate gyrus (DG, a brain area considered important for differential storage of similar experiences and contexts. To better understand the functional contribution of adult neurogenesis to pattern separation processes, we recently used a novel synapse specific trans-neuronal tracing approach to identify the (sub cortical inputs to new dentate granule cells. It was observed that newly born neurons receive sequential innervation from structures important for memory function. Initially, septal-hippocampal cells provide input to new neurons, followed after about one month by perirhinal and lateral entorhinal cortex. These cortical areas are deemed relevant to encoding of novel environmental information and may enable pattern separation. Here, we review the developmental time-course and proposed functional relevance of new neurons, within the context of their unique neural circuitry.  

  12. Evaluation of cardiac adrenergic neuronal damage in rats with doxorubicin-induced cardiomyopathy using iodine-131 MIBG autoradiography and PGP 9.5 immunohistochemistry

    International Nuclear Information System (INIS)

    Jeon, T.J.; Lee, J.D.; Ha, J.-W.; Yang, W.I.; Cho, S.H.

    2000-01-01

    Doxorubicin is one of the most useful anticancer agents, but its repeated administration can induce irreversible cardiomyopathy as a major complication. The purpose of this study was to investigate doxorubicin toxicity on cardiac sympathetic neurons using iodine-131-metaiodobenzylguanidine (MIBG) and protein gene product (PGP) 9.5 immunohistochemistry, which is a marker of cardiac innervation. Wistar rats were treated with doxorubicin (2 mg/kg, i.v.) once a week for 4 (n=5), 6 (n=6) or 8 (n=7) weeks consecutively. Left ventricular ejection fraction (LVEF), calculated by M-mode echocardiography, was used as an indicator of cardiac function. Plasma noradrenaline (NA) concentration was measured by high-performance liquid chromatography (HPLC). 131 I-MIBG uptake of the left ventricular wall (24 ROIs) was measured by autoradiography. 131 I-MIBG uptake pattern was compared with histopathological results, the neuronal population on PGP 9.5 immunohistochemistry and the degree of myocyte damage assessed using a visual scoring system on haematoxylin and eosin and Masson's trichrome staining. LVEF was significantly decreased in the 8-week group (P 131 I-MIBG uptake ratio of subepicardium to subendocardium were significantly increased (P<0.05) in the 8-week group as compared with the control group. It may be concluded that radioiodinated MIBG is a reliable marker for the detection of cardiac adrenergic neuronal damage in doxorubicin-induced cardiomyopathy; it detects such damage earlier than do other clinical parameters and in this study showed a good correlation with the reduction in the neuronal population on PGP 9.5 stain. The subendocardial layer appeared to be more vulnerable to doxorubicin than the subepicardium. (orig.)

  13. Competition model for aperiodic stochastic resonance in a Fitzhugh-Nagumo model of cardiac sensory neurons.

    Science.gov (United States)

    Kember, G C; Fenton, G A; Armour, J A; Kalyaniwalla, N

    2001-04-01

    Regional cardiac control depends upon feedback of the status of the heart from afferent neurons responding to chemical and mechanical stimuli as transduced by an array of sensory neurites. Emerging experimental evidence shows that neural control in the heart may be partially exerted using subthreshold inputs that are amplified by noisy mechanical fluctuations. This amplification is known as aperiodic stochastic resonance (ASR). Neural control in the noisy, subthreshold regime is difficult to see since there is a near absence of any correlation between input and the output, the latter being the average firing (spiking) rate of the neuron. This lack of correlation is unresolved by traditional energy models of ASR since these models are unsuitable for identifying "cause and effect" between such inputs and outputs. In this paper, the "competition between averages" model is used to determine what portion of a noisy, subthreshold input is responsible, on average, for the output of sensory neurons as represented by the Fitzhugh-Nagumo equations. A physiologically relevant conclusion of this analysis is that a nearly constant amount of input is responsible for a spike, on average, and this amount is approximately independent of the firing rate. Hence, correlation measures are generally reduced as the firing rate is lowered even though neural control under this model is actually unaffected.

  14. Soft chitosan microbeads scaffold for 3D functional neuronal networks.

    Science.gov (United States)

    Tedesco, Maria Teresa; Di Lisa, Donatella; Massobrio, Paolo; Colistra, Nicolò; Pesce, Mattia; Catelani, Tiziano; Dellacasa, Elena; Raiteri, Roberto; Martinoia, Sergio; Pastorino, Laura

    2018-02-01

    The availability of 3D biomimetic in vitro neuronal networks of mammalian neurons represents a pivotal step for the development of brain-on-a-chip experimental models to study neuronal (dys)functions and particularly neuronal connectivity. The use of hydrogel-based scaffolds for 3D cell cultures has been extensively studied in the last years. However, limited work on biomimetic 3D neuronal cultures has been carried out to date. In this respect, here we investigated the use of a widely popular polysaccharide, chitosan (CHI), for the fabrication of a microbead based 3D scaffold to be coupled to primary neuronal cells. CHI microbeads were characterized by optical and atomic force microscopies. The cell/scaffold interaction was deeply characterized by transmission electron microscopy and by immunocytochemistry using confocal microscopy. Finally, a preliminary electrophysiological characterization by micro-electrode arrays was carried out. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Multivesicular Bodies in Neurons: Distribution, Protein Content, and Trafficking Functions

    Science.gov (United States)

    VON BARTHELD, CHRISTOPHER S.; ALTICK, AMY L.

    2011-01-01

    Summary Multivesicular bodies (MVBs) are intracellular endosomal organelles characterized by multiple internal vesicles that are enclosed within a single outer membrane. MVBs were initially regarded as purely prelysosomal structures along the degradative endosomal pathway of internalized proteins. MVBs are now known to be involved in numerous endocytic and trafficking functions, including protein sorting, recycling, transport, storage, and release. This review of neuronal MVBs summarizes their research history, morphology, distribution, accumulation of cargo and constitutive proteins, transport, and theories of functions of MVBs in neurons and glia. Due to their complex morphologies, neurons have expanded trafficking and signaling needs, beyond those of “geometrically simpler” cells, but it is not known whether neuronal MVBs perform additional transport and signaling functions. This review examines the concept of compartment-specific MVB functions in endosomal protein trafficking and signaling within synapses, axons, dendrites and cell bodies. We critically evaluate reports of the accumulation of neuronal MVBs based on evidence of stress-induced MVB formation. Furthermore, we discuss potential functions of neuronal and glial MVBs in development, in dystrophic neuritic syndromes, injury, disease, and aging. MVBs may play a role in Alzheimer’s, Huntington’s, and Niemann-Pick diseases, some types of frontotemporal dementia, prion and virus trafficking, as well as in adaptive responses of neurons to trauma and toxin or drug exposure. Functions of MVBs in neurons have been much neglected, and major gaps in knowledge currently exist. Developing truly MVB-specific markers would help to elucidate the roles of neuronal MVBs in intra- and intercellular signaling of normal and diseased neurons. PMID:21216273

  16. Remodeling of intrinsic cardiac neurons: effects of β-adrenergic receptor blockade in guinea pig models of chronic heart disease.

    Science.gov (United States)

    Hardwick, Jean C; Southerland, E Marie; Girasole, Allison E; Ryan, Shannon E; Negrotto, Sara; Ardell, Jeffrey L

    2012-11-01

    Chronic heart disease induces remodeling of cardiac tissue and associated neuronal components. Treatment of chronic heart disease often involves pharmacological blockade of adrenergic receptors. This study examined the specific changes in neuronal sensitivity of guinea pig intrinsic cardiac neurons to autonomic modulators in animals with chronic cardiac disease, in the presence or absence of adrenergic blockage. Myocardial infarction (MI) was produced by ligature of the coronary artery and associated vein on the dorsal surface of the heart. Pressure overload (PO) was induced by a banding of the descending dorsal aorta (∼20% constriction). Animals were allowed to recover for 2 wk and then implanted with an osmotic pump (Alzet) containing either timolol (2 mg·kg(-1)·day(-1)) or vehicle, for a total of 6-7 wk of drug treatment. At termination, intracellular recordings from individual neurons in whole mounts of the cardiac plexus were used to assess changes in physiological responses. Timolol treatment did not inhibit the increased sensitivity to norepinephrine seen in both MI and PO animals, but it did inhibit the stimulatory effects of angiotensin II on the norepinephrine-induced increases in neuronal excitability. Timolol treatment also inhibited the increase in synaptically evoked action potentials observed in PO animals with stimulation of fiber tract bundles. These results demonstrate that β-adrenergic blockade can inhibit specific aspects of remodeling within the intrinsic cardiac plexus. In addition, this effect was preferentially observed with active cardiac disease states, indicating that the β-receptors were more influential on remodeling during dynamic disease progression.

  17. Postoperative cognitive dysfunction : Involvement of neuroinflammation and neuronal functioning

    NARCIS (Netherlands)

    Hovens, Iris B.; Schoemaker, Regien G.; van der Zee, Eddy A.; Absalom, Anthony R.; Heineman, Erik; van Leeuwen, Barbara L.

    Postoperative cognitive dysfunction (POCD) has been hypothesized to be mediated by surgery-induced inflammatory processes, which may influence neuronal functioning either directly or through modulation of intraneuronal pathways, such as the brain derived neurotrophic factor (BDNF) mediated pathway.

  18. Beyond Neuronal Activity Markers: Select Immediate Early Genes in Striatal Neuron Subtypes Functionally Mediate Psychostimulant Addiction

    Directory of Open Access Journals (Sweden)

    Ramesh Chandra

    2017-06-01

    Full Text Available Immediate early genes (IEGs were traditionally used as markers of neuronal activity in striatum in response to stimuli including drugs of abuse such as psychostimulants. Early studies using these neuronal activity markers led to important insights in striatal neuron subtype responsiveness to psychostimulants. Such studies have helped identify striatum as a critical brain center for motivational, reinforcement and habitual behaviors in psychostimulant addiction. While the use of IEGs as neuronal activity markers in response to psychostimulants and other stimuli persists today, the functional role and implications of these IEGs has often been neglected. Nonetheless, there is a subset of research that investigates the functional role of IEGs in molecular, cellular and behavioral alterations by psychostimulants through striatal medium spiny neuron (MSN subtypes, the two projection neuron subtypes in striatum. This review article will address and highlight the studies that provide a functional mechanism by which IEGs mediate psychostimulant molecular, cellular and behavioral plasticity through MSN subtypes. Insight into the functional role of IEGs in striatal MSN subtypes could provide improved understanding into addiction and neuropsychiatric diseases affecting striatum, such as affective disorders and compulsive disorders characterized by dysfunctional motivation and habitual behavior.

  19. Toxoplasma gondii Actively Inhibits Neuronal Function in Chronically Infected Mice

    Science.gov (United States)

    Haroon, Fahad; Händel, Ulrike; Angenstein, Frank; Goldschmidt, Jürgen; Kreutzmann, Peter; Lison, Holger; Fischer, Klaus-Dieter; Scheich, Henning; Wetzel, Wolfram; Schlüter, Dirk; Budinger, Eike

    2012-01-01

    Upon infection with the obligate intracellular parasite Toxoplasma gondii, fast replicating tachyzoites infect a broad spectrum of host cells including neurons. Under the pressure of the immune response, tachyzoites convert into slow-replicating bradyzoites, which persist as cysts in neurons. Currently, it is unclear whether T. gondii alters the functional activity of neurons, which may contribute to altered behaviour of T. gondii–infected mice and men. In the present study we demonstrate that upon oral infection with T. gondii cysts, chronically infected BALB/c mice lost over time their natural fear against cat urine which was paralleled by the persistence of the parasite in brain regions affecting behaviour and odor perception. Detailed immunohistochemistry showed that in infected neurons not only parasitic cysts but also the host cell cytoplasm and some axons stained positive for Toxoplasma antigen suggesting that parasitic proteins might directly interfere with neuronal function. In fact, in vitro live cell calcium (Ca2+) imaging studies revealed that tachyzoites actively manipulated Ca2+ signalling upon glutamate stimulation leading either to hyper- or hypo-responsive neurons. Experiments with the endoplasmatic reticulum Ca2+ uptake inhibitor thapsigargin indicate that tachyzoites deplete Ca2+ stores in the endoplasmatic reticulum. Furthermore in vivo studies revealed that the activity-dependent uptake of the potassium analogue thallium was reduced in cyst harbouring neurons indicating their functional impairment. The percentage of non-functional neurons increased over time In conclusion, both bradyzoites and tachyzoites functionally silence infected neurons, which may significantly contribute to the altered behaviour of the host. PMID:22530040

  20. Toxoplasma gondii actively inhibits neuronal function in chronically infected mice.

    Directory of Open Access Journals (Sweden)

    Fahad Haroon

    Full Text Available Upon infection with the obligate intracellular parasite Toxoplasma gondii, fast replicating tachyzoites infect a broad spectrum of host cells including neurons. Under the pressure of the immune response, tachyzoites convert into slow-replicating bradyzoites, which persist as cysts in neurons. Currently, it is unclear whether T. gondii alters the functional activity of neurons, which may contribute to altered behaviour of T. gondii-infected mice and men. In the present study we demonstrate that upon oral infection with T. gondii cysts, chronically infected BALB/c mice lost over time their natural fear against cat urine which was paralleled by the persistence of the parasite in brain regions affecting behaviour and odor perception. Detailed immunohistochemistry showed that in infected neurons not only parasitic cysts but also the host cell cytoplasm and some axons stained positive for Toxoplasma antigen suggesting that parasitic proteins might directly interfere with neuronal function. In fact, in vitro live cell calcium (Ca(2+ imaging studies revealed that tachyzoites actively manipulated Ca(2+ signalling upon glutamate stimulation leading either to hyper- or hypo-responsive neurons. Experiments with the endoplasmatic reticulum Ca(2+ uptake inhibitor thapsigargin indicate that tachyzoites deplete Ca(2+ stores in the endoplasmatic reticulum. Furthermore in vivo studies revealed that the activity-dependent uptake of the potassium analogue thallium was reduced in cyst harbouring neurons indicating their functional impairment. The percentage of non-functional neurons increased over time In conclusion, both bradyzoites and tachyzoites functionally silence infected neurons, which may significantly contribute to the altered behaviour of the host.

  1. Building functional networks of spiking model neurons.

    Science.gov (United States)

    Abbott, L F; DePasquale, Brian; Memmesheimer, Raoul-Martin

    2016-03-01

    Most of the networks used by computer scientists and many of those studied by modelers in neuroscience represent unit activities as continuous variables. Neurons, however, communicate primarily through discontinuous spiking. We review methods for transferring our ability to construct interesting networks that perform relevant tasks from the artificial continuous domain to more realistic spiking network models. These methods raise a number of issues that warrant further theoretical and experimental study.

  2. Expressing exogenous functional odorant receptors in cultured olfactory sensory neurons

    Directory of Open Access Journals (Sweden)

    Fomina Alla F

    2008-09-01

    Full Text Available Abstract Background Olfactory discrimination depends on the large numbers of odorant receptor genes and differential ligand-receptor signaling among neurons expressing different receptors. In this study, we describe an in vitro system that enables the expression of exogenous odorant receptors in cultured olfactory sensory neurons. Olfactory sensory neurons in the culture express characteristic signaling molecules and, therefore, provide a system to study receptor function within its intrinsic cellular environment. Results We demonstrate that cultured olfactory sensory neurons express endogenous odorant receptors. Lentiviral vector-mediated gene transfer enables successful ectopic expression of odorant receptors. We show that the ectopically expressed mouse I7 is functional in the cultured olfactory sensory neurons. When two different odorant receptors are ectopically expressed simultaneously, both receptor proteins co-localized in the same olfactory sensory neurons up to 10 days in vitro. Conclusion This culture technique provided an efficient method to culture olfactory sensory neurons whose morphology, molecular characteristics and maturation progression resembled those observed in vivo. Using this system, regulation of odorant receptor expression and its ligand specificity can be studied in its intrinsic cellular environment.

  3. The effects of malnutrition on cardiac function in African children.

    Science.gov (United States)

    Silverman, Jonathan A; Chimalizeni, Yamikani; Hawes, Stephen E; Wolf, Elizabeth R; Batra, Maneesh; Khofi, Harriet; Molyneux, Elizabeth M

    2016-02-01

    Cardiac dysfunction may contribute to high mortality in severely malnourished children. Our objective was to assess the effect of malnutrition on cardiac function in hospitalised African children. Prospective cross-sectional study. Public referral hospital in Blantyre, Malawi. We enrolled 272 stable, hospitalised children ages 6-59 months, with and without WHO-defined severe acute malnutrition. Cardiac index, heart rate, mean arterial pressure, stroke volume index and systemic vascular resistance index were measured by the ultrasound cardiac output monitor (USCOM, New South Wales, Australia). We used linear regression with generalised estimating equations controlling for age, sex and anaemia. Our primary outcome, cardiac index, was similar between those with and without severe malnutrition: difference=0.22 L/min/m(2) (95% CI -0.08 to 0.51). No difference was found in heart rate or stroke volume index. However, mean arterial pressure and systemic vascular resistance index were lower in children with severe malnutrition: difference=-8.6 mm Hg (95% CI -12.7 to -4.6) and difference=-200 dyne s/cm(5)/m(2) (95% CI -320 to -80), respectively. In this largest study to date, we found no significant difference in cardiac function between hospitalised children with and without severe acute malnutrition. Further study is needed to determine if cardiac function is diminished in unstable malnourished children. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  4. Cardiac dimensions and function in female handball players.

    Science.gov (United States)

    Malmgren, A; Dencker, M; Stagmo, M; Gudmundsson, P

    2015-04-01

    Long-term intensive endurance training leads to increased left ventricular mass and increased left ventricular end-diastolic and left atrial end-systolic diameters. Different types of sports tend to give rise to distinct morphological forms of the athlete's heart. However, the sport-specific aspects have not been fully investigated in female athletes. The purpose of the present study was to investigate differences in left and right cardiac dimensions, cardiac volumes, and systolic and diastolic function in elite female handball players compared to sedentary controls. A cross-sectional study of 33 elite female handball players was compared to 33 matched sedentary controls. Mean age was 21.5±2 years. The subjects underwent echocardiography examinations, both 2-dimensional (2DE) and 3-dimensional (3DE). Cardiac dimensions and volumes were quantified using M-mode, 2DE and 3DE. Systolic and diastolic left ventricular functions were also evaluated. All cardiac dimensions and volumes were adjusted for body surface area (BSA). Left atrium and left ventricle volumes were significantly (Phandball players compared with sedentary controls. Even right atrium area as well as right ventricular end-diastolic and end-systolic area were significantly (Phandball players. Significant differences were observed in three out of five systolic parameters. Most diastolic function parameters did not differ between the two groups. The findings from the present study suggest that similar cardiac remodeling takes place in elite female handball players as it does in athletes pursuing endurance or team game sports.

  5. Mammalian enabled (Mena) is a critical regulator of cardiac function.

    Science.gov (United States)

    Aguilar, Frédérick; Belmonte, Stephen L; Ram, Rashmi; Noujaim, Sami F; Dunaevsky, Olga; Protack, Tricia L; Jalife, Jose; Todd Massey, H; Gertler, Frank B; Blaxall, Burns C

    2011-05-01

    Mammalian enabled (Mena) of the Drosophila enabled/vasodilator-stimulated phosphoprotein gene family is a cytoskeletal protein implicated in actin regulation and cell motility. Cardiac Mena expression is enriched in intercalated discs (ICD), the critical intercellular communication nexus between adjacent muscle cells. We previously identified Mena gene expression to be a key predictor of human and murine heart failure (HF). To determine the in vivo function of Mena in the heart, we assessed Mena protein expression in multiple HF models and characterized the effects of genetic Mena deletion on cardiac structure and function. Immunoblot analysis revealed significant upregulation of Mena protein expression in left ventricle tissue from patients with end-stage HF, calsequestrin-overexpressing mice, and isoproterenol-infused mice. Characterization of the baseline cardiac function of adult Mena knockout mice (Mena(-/-)) via echocardiography demonstrated persistent cardiac dysfunction, including a significant reduction in percent fractional shortening compared with wild-type littermates. Electrocardiogram PR and QRS intervals were significantly prolonged in Mena(-/-) mice, manifested by slowed conduction on optical mapping studies. Ultrastructural analysis of Mena(-/-) hearts revealed disrupted organization and widening of ICD structures, mislocalization of the gap junction protein connexin 43 (Cx43) to the lateral borders of cardiomyoycytes, and increased Cx43 expression. Furthermore, the expression of vinculin (an adherens junction protein) was significantly reduced in Mena(-/-) mice. We report for the first time that genetic ablation of Mena results in cardiac dysfunction, highlighted by diminished contractile performance, disrupted ICD structure, and slowed electrical conduction.

  6. Myostatin-like proteins regulate synaptic function and neuronal morphology.

    Science.gov (United States)

    Augustin, Hrvoje; McGourty, Kieran; Steinert, Joern R; Cochemé, Helena M; Adcott, Jennifer; Cabecinha, Melissa; Vincent, Alec; Halff, Els F; Kittler, Josef T; Boucrot, Emmanuel; Partridge, Linda

    2017-07-01

    Growth factors of the TGFβ superfamily play key roles in regulating neuronal and muscle function. Myostatin (or GDF8) and GDF11 are potent negative regulators of skeletal muscle mass. However, expression of myostatin and its cognate receptors in other tissues, including brain and peripheral nerves, suggests a potential wider biological role. Here, we show that Myoglianin (MYO), the Drosophila homolog of myostatin and GDF11, regulates not only body weight and muscle size, but also inhibits neuromuscular synapse strength and composition in a Smad2-dependent manner. Both myostatin and GDF11 affected synapse formation in isolated rat cortical neuron cultures, suggesting an effect on synaptogenesis beyond neuromuscular junctions. We also show that MYO acts in vivo to inhibit synaptic transmission between neurons in the escape response neural circuit of adult flies. Thus, these anti-myogenic proteins act as important inhibitors of synapse function and neuronal growth. © 2017. Published by The Company of Biologists Ltd.

  7. Extracting functionally feedforward networks from a population of spiking neurons.

    Science.gov (United States)

    Vincent, Kathleen; Tauskela, Joseph S; Thivierge, Jean-Philippe

    2012-01-01

    Neuronal avalanches are a ubiquitous form of activity characterized by spontaneous bursts whose size distribution follows a power-law. Recent theoretical models have replicated power-law avalanches by assuming the presence of functionally feedforward connections (FFCs) in the underlying dynamics of the system. Accordingly, avalanches are generated by a feedforward chain of activation that persists despite being embedded in a larger, massively recurrent circuit. However, it is unclear to what extent networks of living neurons that exhibit power-law avalanches rely on FFCs. Here, we employed a computational approach to reconstruct the functional connectivity of cultured cortical neurons plated on multielectrode arrays (MEAs) and investigated whether pharmacologically induced alterations in avalanche dynamics are accompanied by changes in FFCs. This approach begins by extracting a functional network of directed links between pairs of neurons, and then evaluates the strength of FFCs using Schur decomposition. In a first step, we examined the ability of this approach to extract FFCs from simulated spiking neurons. The strength of FFCs obtained in strictly feedforward networks diminished monotonically as links were gradually rewired at random. Next, we estimated the FFCs of spontaneously active cortical neuron cultures in the presence of either a control medium, a GABA(A) receptor antagonist (PTX), or an AMPA receptor antagonist combined with an NMDA receptor antagonist (APV/DNQX). The distribution of avalanche sizes in these cultures was modulated by this pharmacology, with a shallower power-law under PTX (due to the prominence of larger avalanches) and a steeper power-law under APV/DNQX (due to avalanches recruiting fewer neurons) relative to control cultures. The strength of FFCs increased in networks after application of PTX, consistent with an amplification of feedforward activity during avalanches. Conversely, FFCs decreased after application of APV

  8. Disruption of astrocyte-neuron cholesterol cross talk affects neuronal function in Huntington's disease.

    Science.gov (United States)

    Valenza, M; Marullo, M; Di Paolo, E; Cesana, E; Zuccato, C; Biella, G; Cattaneo, E

    2015-04-01

    In the adult brain, neurons require local cholesterol production, which is supplied by astrocytes through apoE-containing lipoproteins. In Huntington's disease (HD), such cholesterol biosynthesis in the brain is severely reduced. Here we show that this defect, occurring in astrocytes, is detrimental for HD neurons. Astrocytes bearing the huntingtin protein containing increasing CAG repeats secreted less apoE-lipoprotein-bound cholesterol in the medium. Conditioned media from HD astrocytes and lipoprotein-depleted conditioned media from wild-type (wt) astrocytes were equally detrimental in a neurite outgrowth assay and did not support synaptic activity in HD neurons, compared with conditions of cholesterol supplementation or conditioned media from wt astrocytes. Molecular perturbation of cholesterol biosynthesis and efflux in astrocytes caused similarly altered astrocyte-neuron cross talk, whereas enhancement of glial SREBP2 and ABCA1 function reversed the aspects of neuronal dysfunction in HD. These findings indicate that astrocyte-mediated cholesterol homeostasis could be a potential therapeutic target to ameliorate neuronal dysfunction in HD.

  9. EANM/ESC guidelines for radionuclide imaging of cardiac function

    DEFF Research Database (Denmark)

    Hesse, B.; Lindhardt, T.B.; Acampa, W.

    2008-01-01

    radionuclide ventriculography, gated myocardial perfusion scintigraphy, gated PET, and studies with non-imaging devices for the evaluation of cardiac function. The items covered are presented in 11 sections: clinical indications, radiopharmaceuticals and dosimetry, study acquisition, RV EF, LV EF, LV volumes...

  10. Analyzing the structure and function of neuronal circuits in zebrafish

    Directory of Open Access Journals (Sweden)

    Rainer eFriedrich

    2013-04-01

    Full Text Available The clever choice of animal models has been instrumental for many breakthrough discoveries in life sciences. One of the outstanding challenges in neuroscience is the in-depth analysis of neuronal circuits to understand how interactions between large numbers of neurons give rise to the computational power of the brain. A promising model organism to address this challenge is the zebrafish, not only because it is cheap, transparent and accessible to sophisticated genetic manipulations but also because it offers unique advantages for quantitative analyses of circuit structure and function. One of the most important advantages of zebrafish is its small brain size, both at larval and adult stages. Small brains enable exhaustive measurements of neuronal activity patterns by optical imaging and facilitate large-scale reconstructions of wiring diagrams by electron microscopic approaches. Such information is important, and probably essential, to obtain mechanistic insights into neuronal computations underlying higher brain functions and dysfunctions. This review provides a brief overview over current methods and motivations for dense reconstructions of neuronal activity and connectivity patterns. It then discusses selective advantages of zebrafish and provides examples how these advantages are exploited to study neuronal computations in the olfactory bulb.

  11. Pharmacological Bypass of Cockayne Syndrome B Function in Neuronal Differentiation

    Directory of Open Access Journals (Sweden)

    Yuming Wang

    2016-03-01

    Full Text Available Cockayne syndrome (CS is a severe neurodevelopmental disorder characterized by growth abnormalities, premature aging, and photosensitivity. Mutation of Cockayne syndrome B (CSB affects neuronal gene expression and differentiation, so we attempted to bypass its function by expressing downstream target genes. Intriguingly, ectopic expression of Synaptotagmin 9 (SYT9, a key component of the machinery controlling neurotrophin release, bypasses the need for CSB in neuritogenesis. Importantly, brain-derived neurotrophic factor (BDNF, a neurotrophin implicated in neuronal differentiation and synaptic modulation, and pharmacological mimics such as 7,8-dihydroxyflavone and amitriptyline can compensate for CSB deficiency in cell models of neuronal differentiation as well. SYT9 and BDNF are downregulated in CS patient brain tissue, further indicating that sub-optimal neurotrophin signaling underlies neurological defects in CS. In addition to shedding light on cellular mechanisms underlying CS and pointing to future avenues for pharmacological intervention, these data suggest an important role for SYT9 in neuronal differentiation.

  12. [Structure and functional organization of integrated cardiac intensive care].

    Science.gov (United States)

    Scherillo, Marino; Miceli, Domenico; Tubaro, Marco; Guiducci, Umberto

    2007-05-01

    The early invasive strategy for the treatment of acute coronary syndromes and the increasing number of older and sicker patients requiring prolonged and more complex intensive care have induced many changes in the function of the intensive care units. These changes include the statement that specially trained cardiologists and cardiac nurses who can manage patients with acute cardiac conditions should staff the intensive care units. This document indicates the structure of the units and specific recommendations for the number of beds, monitoring system, respirators, pacemaker/defibrillators and additional equipment.

  13. Autoimmune Response Confers Decreased Cardiac Function in ...

    African Journals Online (AJOL)

    inflammatory response; rather, autoimmune response would keep affecting decreased heart function in. RHD patients who ... untreated children. Nearly 30 - 45 % of the affected children could ..... Technology Department of Anhui Province (PR.

  14. Cardiac, renal, and neurological benefits of preoperative levosimendan administration in patients with right ventricular dysfunction and pulmonary hypertension undergoing cardiac surgery: evaluation with two biomarkers neutrophil gelatinase-associated lipocalin and neuronal enolase

    Directory of Open Access Journals (Sweden)

    Guerrero-Orriach JL

    2016-04-01

    Full Text Available José Luis Guerrero-Orriach,1 Daniel Ariza-Villanueva,1 Ana Florez-Vela,1 Lourdes Garrido-Sánchez,2,3 María Isabel Moreno-Cortés,1 Manuel Galán-Ortega,1 Alicia Ramírez-Fernández,1 Juan Alcaide Torres,3 Concepción Santiago Fernandez,3 Isabel Navarro Arce,1 José María Melero-Tejedor,4 Manuel Rubio-Navarro,1 José Cruz-Mañas1 1Department of Cardio-Anaesthesiology, University Hospital Virgen de la Victoria, Málaga, Spain; 2CIBER Fisiología de la Obesidad y Nutrición (CIBEROBN, Instituto de Salud Carlos III, Málaga, Spain; 3Department of Nutrition and Endocrinology, Instituto de Investigaciones Biomédicas de Málaga (IBIMA, University Hospital Virgen de la Victoria, Málaga, Spain; 4Department of Cardiovascular Surgery, University Hospital Virgen de la Victoria, Málaga, Spain Purpose: To evaluate if the preoperative administration of levosimendan in patients with right ventricular (RV dysfunction, pulmonary hypertension, and high perioperative risk would improve cardiac function and would also have a protective effect on renal and neurological functions, assessed using two biomarkers neutrophil gelatinase-associated lipocalin (N-GAL and neuronal enolase. Methods: This is an observational study. Twenty-seven high-risk cardiac patients with RV dysfunction and pulmonary hypertension, scheduled for cardiac valve surgery, were prospectively followed after preoperative administration of levosimendan. Levosimendan was administered preoperatively on the day before surgery. All patients were considered high risk of cardiac and perioperative renal complications. Cardiac function was assessed by echocardiography, renal function by urinary N-GAL levels, and the acute kidney injury scale. Neuronal damage was assessed by neuron-specific enolase levels. Results: After surgery, no significant variations were found in mean and SE levels of N-GAL (14.31 [28.34] ng/mL vs 13.41 [38.24] ng/mL, neuron-specific enolase (5.40 [0.41] ng/mL vs 4.32 [0.61] ng

  15. Evaluation of left ventricular function by cardiac CT

    International Nuclear Information System (INIS)

    Naito, Hiroaki; Kozuka, Takahiro

    1982-01-01

    Left ventricular function was evaluated by CT, which was compared with the data of left ventriculography for various cardiac diseases. The end diastolic volume of the left ventricle can be readily computed from CT, with a satisfactory correlation with that of left ventriculography (r = 0.95). The left ventricular ejection fraction, calculated from the areal ratio of the left ventricular lumen in end-diastolic imaging to that in end-sytolic imaging, also roughly reflects left ventricular contractile function, but shows correlation with left ventriculography by only r = 0.79. Although the cardiac output is not sensitive for functional evaluation, it can be directly calculated by means of dynamic scanning and shows a satisfactory correlation with the ear piece pigment dilution (r = 0.85). Evaluation of left ventricular function by CT shows a high precision in comparison with left ventriculography, but still lacks temporal resolving power. (Chiba, N.)

  16. Autonomic cardiac innervation

    Science.gov (United States)

    Hasan, Wohaib

    2013-01-01

    Autonomic cardiac neurons have a common origin in the neural crest but undergo distinct developmental differentiation as they mature toward their adult phenotype. Progenitor cells respond to repulsive cues during migration, followed by differentiation cues from paracrine sources that promote neurochemistry and differentiation. When autonomic axons start to innervate cardiac tissue, neurotrophic factors from vascular tissue are essential for maintenance of neurons before they reach their targets, upon which target-derived trophic factors take over final maturation, synaptic strength and postnatal survival. Although target-derived neurotrophins have a central role to play in development, alternative sources of neurotrophins may also modulate innervation. Both developing and adult sympathetic neurons express proNGF, and adult parasympathetic cardiac ganglion neurons also synthesize and release NGF. The physiological function of these “non-classical” cardiac sources of neurotrophins remains to be determined, especially in relation to autocrine/paracrine sustenance during development.   Cardiac autonomic nerves are closely spatially associated in cardiac plexuses, ganglia and pacemaker regions and so are sensitive to release of neurotransmitter, neuropeptides and trophic factors from adjacent nerves. As such, in many cardiac pathologies, it is an imbalance within the two arms of the autonomic system that is critical for disease progression. Although this crosstalk between sympathetic and parasympathetic nerves has been well established for adult nerves, it is unclear whether a degree of paracrine regulation occurs across the autonomic limbs during development. Aberrant nerve remodeling is a common occurrence in many adult cardiovascular pathologies, and the mechanisms regulating outgrowth or denervation are disparate. However, autonomic neurons display considerable plasticity in this regard with neurotrophins and inflammatory cytokines having a central regulatory

  17. Extracting neuronal functional network dynamics via adaptive Granger causality analysis.

    Science.gov (United States)

    Sheikhattar, Alireza; Miran, Sina; Liu, Ji; Fritz, Jonathan B; Shamma, Shihab A; Kanold, Patrick O; Babadi, Behtash

    2018-04-24

    Quantifying the functional relations between the nodes in a network based on local observations is a key challenge in studying complex systems. Most existing time series analysis techniques for this purpose provide static estimates of the network properties, pertain to stationary Gaussian data, or do not take into account the ubiquitous sparsity in the underlying functional networks. When applied to spike recordings from neuronal ensembles undergoing rapid task-dependent dynamics, they thus hinder a precise statistical characterization of the dynamic neuronal functional networks underlying adaptive behavior. We develop a dynamic estimation and inference paradigm for extracting functional neuronal network dynamics in the sense of Granger, by integrating techniques from adaptive filtering, compressed sensing, point process theory, and high-dimensional statistics. We demonstrate the utility of our proposed paradigm through theoretical analysis, algorithm development, and application to synthetic and real data. Application of our techniques to two-photon Ca 2+ imaging experiments from the mouse auditory cortex reveals unique features of the functional neuronal network structures underlying spontaneous activity at unprecedented spatiotemporal resolution. Our analysis of simultaneous recordings from the ferret auditory and prefrontal cortical areas suggests evidence for the role of rapid top-down and bottom-up functional dynamics across these areas involved in robust attentive behavior.

  18. Serial measurement of neuron specific enolase improves prognostication in cardiac arrest patients treated with hypothermia: A prospective study

    Directory of Open Access Journals (Sweden)

    Storm Christian

    2012-01-01

    Full Text Available Abstract Background Neuron specific enolase (NSE has repeatedly been evaluated for neurological prognostication in patients after cardiac arrest. However, it is unclear whether current guidelines for NSE cutoff levels also apply to cardiac arrest patients treated with hypothermia. Thus, we investigated the prognostic significance of absolute NSE levels and NSE kinetics in cardiac arrest patients treated with hypothermia. Methods In a prospective study of 35 patients resuscitated from cardiac arrest, NSE was measured daily for four days following admission. Outcome was assessed at ICU discharge using the CPC score. All patients received hypothermia treatment for 24 hours at 33°C with a surface cooling device according to current guidelines. Results The cutoff for absolute NSE levels in patients with unfavourable outcome (CPC 3-5 72 hours after cardiac arrest was 57 μg/l with an area under the curve (AUC of 0.82 (sensitivity 47%, specificity 100%. The cutoff level for NSE kinetics in patients with unfavourable outcome (CPC 3-5 was an absolute increase of 7.9 μg/l (AUC 0.78, sensitivity 63%, specificity 100% and a relative increase of 33.1% (AUC 0.803, sensitivity 67%, specificity 100% at 48 hours compared to admission. Conclusion In cardiac arrest patients treated with hypothermia, prognostication of unfavourable outcome by NSE kinetics between admission and 48 hours after resuscitation may be superior to prognostication by absolute NSE levels.

  19. Hypertrophy of Neurons Within Cardiac Ganglia in Human, Canine, and Rat Heart Failure: The Potential Role of Nerve Growth Factor

    OpenAIRE

    Singh, Sanjay; Sayers, Scott; Walter, James S.; Thomas, Donald; Dieter, Robert S.; Nee, Lisa M.; Wurster, Robert D.

    2013-01-01

    Background Autonomic imbalances including parasympathetic withdrawal and sympathetic overactivity are cardinal features of heart failure regardless of etiology; however, mechanisms underlying these imbalances remain unknown. Animal model studies of heart and visceral organ hypertrophy predict that nerve growth factor levels should be elevated in heart failure; whether this is so in human heart failure, though, remains unclear. We tested the hypotheses that neurons in cardiac ganglia are hyper...

  20. Functional characterisation of filamentous actin probe expression in neuronal cells.

    Directory of Open Access Journals (Sweden)

    Shrujna Patel

    Full Text Available Genetically encoded filamentous actin probes, Lifeact, Utrophin and F-tractin, are used as tools to label the actin cytoskeleton. Recent evidence in several different cell types indicates that these probes can cause changes in filamentous actin dynamics, altering cell morphology and function. Although these probes are commonly used to visualise actin dynamics in neurons, their effects on axonal and dendritic morphology has not been systematically characterised. In this study, we quantitatively analysed the effect of Lifeact, Utrophin and F-tractin on neuronal morphogenesis in primary hippocampal neurons. Our data show that the expression of actin-tracking probes significantly impacts on axonal and dendrite growth these neurons. Lifeact-GFP expression, under the control of a pBABE promoter, caused a significant decrease in total axon length, while another Lifeact-GFP expression, under the control of a CAG promoter, decreased the length and complexity of dendritic trees. Utr261-EGFP resulted in increased dendritic branching but Utr230-EGFP only accumulated in cell soma, without labelling any neurites. Lifeact-7-mEGFP and F-tractin-EGFP in a pEGFP-C1 vector, under the control of a CMV promoter, caused only minor changes in neuronal morphology as detected by Sholl analysis. The results of this study demonstrate the effects that filamentous actin tracking probes can have on the axonal and dendritic compartments of neuronal cells and emphasise the care that must be taken when interpreting data from experiments using these probes.

  1. Cardiac structure and function in Cushing's syndrome: a cardiac magnetic resonance imaging study.

    Science.gov (United States)

    Kamenický, Peter; Redheuil, Alban; Roux, Charles; Salenave, Sylvie; Kachenoura, Nadjia; Raissouni, Zainab; Macron, Laurent; Guignat, Laurence; Jublanc, Christel; Azarine, Arshid; Brailly, Sylvie; Young, Jacques; Mousseaux, Elie; Chanson, Philippe

    2014-11-01

    Patients with Cushing's syndrome have left ventricular (LV) hypertrophy and dysfunction on echocardiography, but echo-based measurements may have limited accuracy in obese patients. No data are available on right ventricular (RV) and left atrial (LA) size and function in these patients. The objective of the study was to evaluate LV, RV, and LA structure and function in patients with Cushing's syndrome by means of cardiac magnetic resonance, currently the reference modality in assessment of cardiac geometry and function. Eighteen patients with active Cushing's syndrome and 18 volunteers matched for age, sex, and body mass index were studied by cardiac magnetic resonance. The imaging was repeated in the patients 6 months (range 2-12 mo) after the treatment of hypercortisolism. Compared with controls, patients with Cushing's syndrome had lower LV, RV, and LA ejection fractions (P Cushing's syndrome is associated with subclinical biventricular and LA systolic dysfunctions that are reversible after treatment. Despite skeletal muscle atrophy, Cushing's syndrome patients have an increased LV mass, reversible upon correction of hypercortisolism.

  2. Cardiac Autonomic Function Is Associated With the Coronary Microcirculatory Function in Patients With Type 2 Diabetes

    DEFF Research Database (Denmark)

    von Scholten, Bernt Johan; Hansen, Christian Stevns; Hasbak, Philip

    2016-01-01

    Cardiac autonomic dysfunction and cardiac microvascular dysfunction are diabetic complications associated with increased mortality, but the association between these has been difficult to assess. We applied new and sensitive methods to assess this in patients with type 2 diabetes mellitus (T2DM......). In a cross-sectional design, coronary flow reserve (CFR) assessed by cardiac (82)Rb-positron emission tomography/computed tomography, cardiac autonomic reflex tests, and heart rate variability indices were performed in 55 patients with T2DM, without cardiovascular disease, and in 28 control subjects. Cardiac....... A heart rate variability index, reflecting sympathetic and parasympathetic function (low-frequency power), and the late heart-to-mediastinum ratio, reflecting the function of adrenergic receptors and sympathetic activity, were positively correlated with CFR after adjustment for age and heart rate...

  3. Pituitary adenylate cyclase 1 receptor internalization and endosomal signaling mediate the pituitary adenylate cyclase activating polypeptide-induced increase in guinea pig cardiac neuron excitability.

    Science.gov (United States)

    Merriam, Laura A; Baran, Caitlin N; Girard, Beatrice M; Hardwick, Jean C; May, Victor; Parsons, Rodney L

    2013-03-06

    After G-protein-coupled receptor activation and signaling at the plasma membrane, the receptor complex is often rapidly internalized via endocytic vesicles for trafficking into various intracellular compartments and pathways. The formation of signaling endosomes is recognized as a mechanism that produces sustained intracellular signals that may be distinct from those generated at the cell surface for cellular responses including growth, differentiation, and survival. Pituitary adenylate cyclase activating polypeptide (PACAP; Adcyap1) is a potent neurotransmitter/neurotrophic peptide and mediates its diverse cellular functions in part through internalization of its cognate G-protein-coupled PAC1 receptor (PAC1R; Adcyap1r1). In the present study, we examined whether PAC1R endocytosis participates in the regulation of neuronal excitability. Although PACAP increased excitability in 90% of guinea pig cardiac neurons, pretreatment with Pitstop 2 or dynasore to inhibit clathrin and dynamin I/II, respectively, suppressed the PACAP effect. Subsequent addition of inhibitor after the PACAP-induced increase in excitability developed gradually attenuated excitability with no changes in action potential properties. Likewise, the PACAP-induced increase in excitability was markedly decreased at ambient temperature. Receptor trafficking studies with GFP-PAC1 cell lines demonstrated the efficacy of Pitstop 2, dynasore, and low temperatures at suppressing PAC1R endocytosis. In contrast, brefeldin A pretreatments to disrupt Golgi vesicle trafficking did not blunt the PACAP effect, and PACAP/PAC1R signaling still increased neuronal cAMP production even with endocytic blockade. Our results demonstrate that PACAP/PAC1R complex endocytosis is a key step for the PACAP modulation of cardiac neuron excitability.

  4. Sleep, Neuronal Plasticity and Brain Function

    NARCIS (Netherlands)

    Meerlo, Peter; Benca, Ruth M.; Abel, Ted

    2015-01-01

    Sleep is truly one of the biggest mysteries in behavioral neuroscience. Humans spend a substantial portion of their lives asleep, as do all other mammalian and bird species that have been studied to date, yet the functions of sleep remain elusive and continue to be a topic of debate among sleep

  5. Confounding the origin and function of mirror neurons.

    Science.gov (United States)

    Rizzolatti, Giacomo

    2014-04-01

    Cook et al. argue that mirror neurons originate in sensorimotor associative learning and that their function is determined by their origin. Both these claims are hard to accept. It is here suggested that a major role in the origin of the mirror mechanism is played by top-down connections rather than by associative learning.

  6. Relating neuronal firing patterns to functional differentiation of cerebral cortex.

    Directory of Open Access Journals (Sweden)

    Shigeru Shinomoto

    2009-07-01

    Full Text Available It has been empirically established that the cerebral cortical areas defined by Brodmann one hundred years ago solely on the basis of cellular organization are closely correlated to their function, such as sensation, association, and motion. Cytoarchitectonically distinct cortical areas have different densities and types of neurons. Thus, signaling patterns may also vary among cytoarchitectonically unique cortical areas. To examine how neuronal signaling patterns are related to innate cortical functions, we detected intrinsic features of cortical firing by devising a metric that efficiently isolates non-Poisson irregular characteristics, independent of spike rate fluctuations that are caused extrinsically by ever-changing behavioral conditions. Using the new metric, we analyzed spike trains from over 1,000 neurons in 15 cortical areas sampled by eight independent neurophysiological laboratories. Analysis of firing-pattern dissimilarities across cortical areas revealed a gradient of firing regularity that corresponded closely to the functional category of the cortical area; neuronal spiking patterns are regular in motor areas, random in the visual areas, and bursty in the prefrontal area. Thus, signaling patterns may play an important role in function-specific cerebral cortical computation.

  7. Decreased function of survival motor neuron protein impairs endocytic pathways.

    Science.gov (United States)

    Dimitriadi, Maria; Derdowski, Aaron; Kalloo, Geetika; Maginnis, Melissa S; O'Hern, Patrick; Bliska, Bryn; Sorkaç, Altar; Nguyen, Ken C Q; Cook, Steven J; Poulogiannis, George; Atwood, Walter J; Hall, David H; Hart, Anne C

    2016-07-26

    Spinal muscular atrophy (SMA) is caused by depletion of the ubiquitously expressed survival motor neuron (SMN) protein, with 1 in 40 Caucasians being heterozygous for a disease allele. SMN is critical for the assembly of numerous ribonucleoprotein complexes, yet it is still unclear how reduced SMN levels affect motor neuron function. Here, we examined the impact of SMN depletion in Caenorhabditis elegans and found that decreased function of the SMN ortholog SMN-1 perturbed endocytic pathways at motor neuron synapses and in other tissues. Diminished SMN-1 levels caused defects in C. elegans neuromuscular function, and smn-1 genetic interactions were consistent with an endocytic defect. Changes were observed in synaptic endocytic proteins when SMN-1 levels decreased. At the ultrastructural level, defects were observed in endosomal compartments, including significantly fewer docked synaptic vesicles. Finally, endocytosis-dependent infection by JC polyomavirus (JCPyV) was reduced in human cells with decreased SMN levels. Collectively, these results demonstrate for the first time, to our knowledge, that SMN depletion causes defects in endosomal trafficking that impair synaptic function, even in the absence of motor neuron cell death.

  8. Exercise improves cardiac autonomic function in obesity and diabetes.

    Science.gov (United States)

    Voulgari, Christina; Pagoni, Stamatina; Vinik, Aaron; Poirier, Paul

    2013-05-01

    Physical activity is a key element in the prevention and management of obesity and diabetes. Regular physical activity efficiently supports diet-induced weight loss, improves glycemic control, and can prevent or delay type 2 diabetes diagnosis. Furthermore, physical activity positively affects lipid profile, blood pressure, reduces the rate of cardiovascular events and associated mortality, and restores the quality of life in type 2 diabetes. However, recent studies have documented that a high percentage of the cardiovascular benefits of exercise cannot be attributed solely to enhanced cardiovascular risk factor modulation. Obesity in concert with diabetes is characterized by sympathetic overactivity and the progressive loss of cardiac parasympathetic influx. These are manifested via different pathogenetic mechanisms, including hyperinsulinemia, visceral obesity, subclinical inflammation and increased thrombosis. Cardiac autonomic neuropathy is an underestimated risk factor for the increased cardiovascular morbidity and mortality associated with obesity and diabetes. The same is true for the role of physical exercise in the restoration of the heart cardioprotective autonomic modulation in these individuals. This review addresses the interplay of cardiac autonomic function in obesity and diabetes, and focuses on the importance of exercise in improving cardiac autonomic dysfunction. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Proangiogenic scaffolds as functional templates for cardiac tissue engineering

    OpenAIRE

    Madden, Lauran R.; Mortisen, Derek J.; Sussman, Eric M.; Dupras, Sarah K.; Fugate, James A.; Cuy, Janet L.; Hauch, Kip D.; Laflamme, Michael A.; Murry, Charles E.; Ratner, Buddy D.

    2010-01-01

    We demonstrate here a cardiac tissue-engineering strategy addressing multicellular organization, integration into host myocardium, and directional cues to reconstruct the functional architecture of heart muscle. Microtemplating is used to shape poly(2-hydroxyethyl methacrylate-co-methacrylic acid) hydrogel into a tissue-engineering scaffold with architectures driving heart tissue integration. The construct contains parallel channels to organize cardiomyocyte bundles, supported by micrometer-s...

  10. Functionalized anatomical models for EM-neuron Interaction modeling

    Science.gov (United States)

    Neufeld, Esra; Cassará, Antonino Mario; Montanaro, Hazael; Kuster, Niels; Kainz, Wolfgang

    2016-06-01

    The understanding of interactions between electromagnetic (EM) fields and nerves are crucial in contexts ranging from therapeutic neurostimulation to low frequency EM exposure safety. To properly consider the impact of in vivo induced field inhomogeneity on non-linear neuronal dynamics, coupled EM-neuronal dynamics modeling is required. For that purpose, novel functionalized computable human phantoms have been developed. Their implementation and the systematic verification of the integrated anisotropic quasi-static EM solver and neuronal dynamics modeling functionality, based on the method of manufactured solutions and numerical reference data, is described. Electric and magnetic stimulation of the ulnar and sciatic nerve were modeled to help understanding a range of controversial issues related to the magnitude and optimal determination of strength-duration (SD) time constants. The results indicate the importance of considering the stimulation-specific inhomogeneous field distributions (especially at tissue interfaces), realistic models of non-linear neuronal dynamics, very short pulses, and suitable SD extrapolation models. These results and the functionalized computable phantom will influence and support the development of safe and effective neuroprosthetic devices and novel electroceuticals. Furthermore they will assist the evaluation of existing low frequency exposure standards for the entire population under all exposure conditions.

  11. Optogenetic Stimulation of Locus Ceruleus Neurons Augments Inhibitory Transmission to Parasympathetic Cardiac Vagal Neurons via Activation of Brainstem α1 and β1 Receptors

    OpenAIRE

    Wang, Xin; Piñol, Ramón A.; Byrne, Peter; Mendelowitz, David

    2014-01-01

    Locus ceruleus (LC) noradrenergic neurons are critical in generating alertness. In addition to inducing cortical arousal, the LC also orchestrates changes in accompanying autonomic system function that compliments increased attention, such as during stress, excitation, and/or exposure to averse or novel stimuli. Although the association between arousal and increased heart rate is well accepted, the neurobiological link between the LC and parasympathetic neurons that control heart rate has not...

  12. Functional discriminant method and neuronal net

    International Nuclear Information System (INIS)

    Minh-Quan Tran.

    1993-02-01

    The ZEUS detector at the ep storage ring HERA at DESY is equipped with a 3 level trigger system. This enormous effort is necessary to fight against the high proton beamgas background that was estimated to be at the level of 100 kHz. In this thesis two methods were investigated to calculate a trigger decision from a set of various trigger parameters. The Functional Discriminant Analysis evalutes a decision parameter that is optimized by means of a linear algebra technic. A method is shown how to determine the most important trigger parameters. A 'feed forward' neuralnetwork was analyzed in order to allow none lineare cuts in the n dimensinal configuration space spanned by the trigger parameters. The error back propagation method was used to teach the neural network. It is shown that both decision methods are able to abstract the important characteristics of event samples. As soon as they are tought they will seperate events from these classes even though they were not part of the training sample. (orig.) [de

  13. Chronic intermittent hypoxia-hypercapnia blunts heart rate responses and alters neurotransmission to cardiac vagal neurons.

    Science.gov (United States)

    Dyavanapalli, Jhansi; Jameson, Heather; Dergacheva, Olga; Jain, Vivek; Alhusayyen, Mona; Mendelowitz, David

    2014-07-01

    Patients with obstructive sleep apnoea experience chronic intermittent hypoxia-hypercapnia (CIHH) during sleep that elicit sympathetic overactivity and diminished parasympathetic activity to the heart, leading to hypertension and depressed baroreflex sensitivity. The parasympathetic control of heart rate arises from pre-motor cardiac vagal neurons (CVNs) located in nucleus ambiguus (NA) and dorsal motor nucleus of the vagus (DMNX). The mechanisms underlying diminished vagal control of heart rate were investigated by studying the changes in blood pressure, heart rate, and neurotransmission to CVNs evoked by acute hypoxia-hypercapnia (H-H) and CIHH. In vivo telemetry recordings of blood pressure and heart rate were obtained in adult rats during 4 weeks of CIHH exposure. Retrogradely labelled CVNs were identified in an in vitro brainstem slice preparation obtained from adult rats exposed either to air or CIHH for 4 weeks. Postsynaptic inhibitory or excitatory currents were recorded using whole cell voltage clamp techniques. Rats exposed to CIHH had increases in blood pressure, leading to hypertension, and blunted heart rate responses to acute H-H. CIHH induced an increase in GABAergic and glycinergic neurotransmission to CVNs in NA and DMNX, respectively; and a reduction in glutamatergic neurotransmission to CVNs in both nuclei. CIHH blunted the bradycardia evoked by acute H-H and abolished the acute H-H evoked inhibition of GABAergic transmission while enhancing glycinergic neurotransmission to CVNs in NA. These changes with CIHH inhibit CVNs and vagal outflow to the heart, both in acute and chronic exposures to H-H, resulting in diminished levels of cardioprotective parasympathetic activity to the heart as seen in OSA patients. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

  14. Novel axolotl cardiac function analysis method using magnetic resonance imaging.

    Directory of Open Access Journals (Sweden)

    Pedro Gomes Sanches

    Full Text Available The salamander axolotl is capable of complete regeneration of amputated heart tissue. However, non-invasive imaging tools for assessing its cardiac function were so far not employed. In this study, cardiac magnetic resonance imaging is introduced as a non-invasive technique to image heart function of axolotls. Three axolotls were imaged with magnetic resonance imaging using a retrospectively gated Fast Low Angle Shot cine sequence. Within one scanning session the axolotl heart was imaged three times in all planes, consecutively. Heart rate, ejection fraction, stroke volume and cardiac output were calculated using three techniques: (1 combined long-axis, (2 short-axis series, and (3 ultrasound (control for heart rate only. All values are presented as mean ± standard deviation. Heart rate (beats per minute among different animals was 32.2±6.0 (long axis, 30.4±5.5 (short axis and 32.7±4.9 (ultrasound and statistically similar regardless of the imaging method (p > 0.05. Ejection fraction (% was 59.6±10.8 (long axis and 48.1±11.3 (short axis and it differed significantly (p = 0.019. Stroke volume (μl/beat was 133.7±33.7 (long axis and 93.2±31.2 (short axis, also differed significantly (p = 0.015. Calculations were consistent among the animals and over three repeated measurements. The heart rate varied depending on depth of anaesthesia. We described a new method for defining and imaging the anatomical planes of the axolotl heart and propose one of our techniques (long axis analysis may prove useful in defining cardiac function in regenerating axolotl hearts.

  15. Pim-1 Kinase Phosphorylates Cardiac Troponin I and Regulates Cardiac Myofilament Function

    Directory of Open Access Journals (Sweden)

    Ni Zhu

    2018-03-01

    Full Text Available Background/Aims: Pim-1 is a serine/threonine kinase that is highly expressed in the heart, and exerts potent cardiac protective effects through enhancing survival, proliferation, and regeneration of cardiomyocytes. Its myocardial specific substrates, however, remain unknown. In the present study, we aim to investigate whether Pim-1 modulates myofilament activity through phosphorylation of cardiac troponin I (cTnI, a key component in regulating myofilament function in the heart. Methods: Coimmunoprecipitation and immunofluorescent assays were employed to investigate the interaction of Pim-1 with cTnI in cardiomyocytes. Biochemical, site directed mutagenesis, and mass spectrometric analyses were utilized to identify the phosphorylation sites of Pim1 in cTnI. Myofilament functional assay using skinned cardiac fiber was used to assess the effect of Pim1-mediated phosphorylation on cardiac myofilament activity. Lastly, the functional significance of Pim1-mediated cTnI in heart disease was determined in diabetic mice. Results: We found that Pim-1 specifically interacts with cTnI in cardiomyocytes and this interaction leads to Pim1-mediated cTnI phosphorylation, predominantly at Ser23/24 and Ser150. Furthermore, our functional assay demonstrated that Pim-1 induces a robust phosphorylation of cTnI within the troponin complex, thus leading to a decreased Ca2+ sensitivity. Insulin-like growth factor 1 (IGF-1, a peptide growth factor that has been shown to stimulate myocardial contractility, markedly induces cTnI phosphorylation at Ser23/24 and Ser150 through increasing Pim-1 expression in cardiomyocytes. In a high-fat diabetic mice model, the expression of Pim1 in the heart is significantly decreased, which is accompanied by a decreased phosphorylation of cTnI at Ser23/24 and Ser150, further implicating the pathological significance of the Pim1/cTnI axis in the development of diabetic cardiomyopathy. Conclusion: Our results demonstrate that Pim-1 is a

  16. Purinergic modulation of adult guinea pig cardiomyocytes in long term cultures and co-cultures with extracardiac or intrinsic cardiac neurones.

    Science.gov (United States)

    Horackova, M; Huang, M H; Armour, J A

    1994-05-01

    To determine the capacity of ATP to modify cardiomyocytes directly or indirectly via peripheral autonomic neurones, the effects of various purinergic agents were studied on long term cultures of adult guinea pig ventricular myocytes and their co-cultures with extracardiac (stellate ganglion) or intrinsic cardiac neurones. Ventricular myocytes and cardiac neurones were enzymatically dissociated and plated together or alone (myocytes only). Myocyte cultures were used for experiments after three to six weeks. The electrical and contractile properties of cultured myocytes and myocyte-neuronal networks were investigated. The spontaneous beating frequency of ventricular myocytes co-cultured with stellate ganglion neurones increased by approximately 140% (p under control conditions, but when beta adrenergic receptors of tetrodotoxin sensitive neural responses were blocked, ATP induced greater augmentation (> 100%). In contrast, ATP induced much smaller effects in non-innervated myocyte cultures (approximately 26%, p UTP > MSATP > beta gamma ATP > alpha beta ATP. Adenosine (10(-4) M) attenuated the beating frequency of myocytes in both types of co-culture, while not significantly affecting non-innervated myocyte cultures. The experimental model used in this study showed that extrinsic and intrinsic cardiac neurones which possess P2 receptors can greatly enhance cardiac myocyte contractile rate when activated by ATP. Since adenosine reduced contractile rate in both types of co-cultures while not affecting non-innervated myocytes, it is concluded that some of these neurones possess P1 receptors.

  17. Identification and functional characterization of cardiac pacemaker cells in zebrafish.

    Directory of Open Access Journals (Sweden)

    Federico Tessadori

    Full Text Available In the mammalian heart a conduction system of nodes and conducting cells generates and transduces the electrical signals evoking myocardial contractions. Specialized pacemaker cells initiating and controlling cardiac contraction rhythmicity are localized in an anatomically identifiable structure of myocardial origin, the sinus node. We previously showed that in mammalian embryos sinus node cells originate from cardiac progenitors expressing the transcription factors T-box transcription factor 3 (Tbx3 and Islet-1 (Isl1. Although cardiac development and function are strikingly conserved amongst animal classes, in lower vertebrates neither structural nor molecular distinguishable components of a conduction system have been identified, questioning its evolutionary origin. Here we show that zebrafish embryos lacking the LIM/homeodomain-containing transcription factor Isl1 display heart rate defects related to pacemaker dysfunction. Moreover, 3D reconstructions of gene expression patterns in the embryonic and adult zebrafish heart led us to uncover a previously unidentified, Isl1-positive and Tbx2b-positive region in the myocardium at the junction of the sinus venosus and atrium. Through their long interconnecting cellular protrusions the identified Isl1-positive cells form a ring-shaped structure. In vivo labeling of the Isl1-positive cells by transgenic technology allowed their isolation and electrophysiological characterization, revealing their unique pacemaker activity. In conclusion we demonstrate that Isl1-expressing cells, organized as a ring-shaped structure around the venous pole, hold the pacemaker function in the adult zebrafish heart. We have thereby identified an evolutionary conserved, structural and molecular distinguishable component of the cardiac conduction system in a lower vertebrate.

  18. Complete functional characterization of sensory neurons by system identification.

    Science.gov (United States)

    Wu, Michael C-K; David, Stephen V; Gallant, Jack L

    2006-01-01

    System identification is a growing approach to sensory neurophysiology that facilitates the development of quantitative functional models of sensory processing. This approach provides a clear set of guidelines for combining experimental data with other knowledge about sensory function to obtain a description that optimally predicts the way that neurons process sensory information. This prediction paradigm provides an objective method for evaluating and comparing computational models. In this chapter we review many of the system identification algorithms that have been used in sensory neurophysiology, and we show how they can be viewed as variants of a single statistical inference problem. We then review many of the practical issues that arise when applying these methods to neurophysiological experiments: stimulus selection, behavioral control, model visualization, and validation. Finally we discuss several problems to which system identification has been applied recently, including one important long-term goal of sensory neuroscience: developing models of sensory systems that accurately predict neuronal responses under completely natural conditions.

  19. Stimulation of neuronal neurite outgrowth using functionalized carbon nanotubes

    Energy Technology Data Exchange (ETDEWEB)

    Matsumoto, K; Sato, C; Shimizu, N [Graduate School of Life Sciences, Toyo University, 1-1-1 Izumino, Itakura-machi, Ora-gun, Gunma 374-0193 (Japan); Naka, Y [Bio-Nano Electronics Research Center, Toyo University, 2100 Kujirai, Kawagoe-shi, Saitama 350-8585 (Japan); Whitby, R, E-mail: shimizu@toyonet.toyo.ac.jp [School of Pharmacy and Biomolecular Sciences, University of Brighton, Cockroft Building, Lewes Road, Brighton BN2 4GJ (United Kingdom)

    2010-03-19

    Low concentrations (0.11-1.7 {mu}g ml{sup -1}) of functionalized carbon nanotubes (CNTs), which are multi-walled CNTs modified by amino groups, when added with nerve growth factor (NGF), promoted outgrowth of neuronal neurites in dorsal root ganglion (DRG) neurons and rat pheochromocytoma cell line PC12h cells in culture media. The quantity of active extracellular signal-regulated kinase (ERK) was higher after the addition of both 0.85 {mu}g ml{sup -1} CNTs and NGF than that with NGF alone. CNTs increased the number of cells with neurite outgrowth in DRG neurons and PC12h cells after the inhibition of the ERK signaling pathway using a mitogen-activated protein kinase (MAPK)/ERK kinase (MEK) inhibitor. Active ERK proteins were detected in MEK inhibitor-treated neurons after the addition of CNTs to the culture medium. These results demonstrate that CNTs may stimulate neurite outgrowth by activation of the ERK signaling pathway. Thus, CNTs are biocompatible and are promising candidates for biological applications and devices.

  20. Proangiogenic scaffolds as functional templates for cardiac tissue engineering.

    Science.gov (United States)

    Madden, Lauran R; Mortisen, Derek J; Sussman, Eric M; Dupras, Sarah K; Fugate, James A; Cuy, Janet L; Hauch, Kip D; Laflamme, Michael A; Murry, Charles E; Ratner, Buddy D

    2010-08-24

    We demonstrate here a cardiac tissue-engineering strategy addressing multicellular organization, integration into host myocardium, and directional cues to reconstruct the functional architecture of heart muscle. Microtemplating is used to shape poly(2-hydroxyethyl methacrylate-co-methacrylic acid) hydrogel into a tissue-engineering scaffold with architectures driving heart tissue integration. The construct contains parallel channels to organize cardiomyocyte bundles, supported by micrometer-sized, spherical, interconnected pores that enhance angiogenesis while reducing scarring. Surface-modified scaffolds were seeded with human ES cell-derived cardiomyocytes and cultured in vitro. Cardiomyocytes survived and proliferated for 2 wk in scaffolds, reaching adult heart densities. Cardiac implantation of acellular scaffolds with pore diameters of 30-40 microm showed angiogenesis and reduced fibrotic response, coinciding with a shift in macrophage phenotype toward the M2 state. This work establishes a foundation for spatially controlled cardiac tissue engineering by providing discrete compartments for cardiomyocytes and stroma in a scaffold that enhances vascularization and integration while controlling the inflammatory response.

  1. Functional capacity and mental state of patients undergoing cardiac surgery

    Directory of Open Access Journals (Sweden)

    Bruna Corrêa

    Full Text Available Abstract Introduction: Cardiovascular diseases are a serious public health problem in Brazil. Myocardial revascularization surgery (MRS as well as cardiac valve replacement and repair are procedures indicated to treat them. Thus, extracorporeal circulation (ECC is still widely used in these surgeries, in which patients with long ECC times may have greater neurological deficits. Neurological damage resulting from MRS can have devastating consequences such as loss of independence and worsening of quality of life. Objective: To assess the effect of cardiac surgery on a patient’s mental state and functional capacity in both the pre- and postoperative periods. Methods: We conducted a cross-sectional study with convenience sampling of subjects undergoing MRS and valve replacement. Participants were administered the Mini-Mental State Exam (MMSE and the Duke Activity Status Index (DASI in the pre- and postoperative periods, as well as before their hospital discharge. Results: This study assessed nine patients (eight males aged 62.4 ± 6.3 years with a BMI of 29.5 ± 2.3 kg/m2. There was a significant decrease in DASI scores and VO2 from preoperative to postoperative status (p = 0.003 and p = 0.003, respectively. Conclusion: This study revealed a loss of cognitive and exercise capacity after cardiac surgery. A larger sample however is needed to consolidate these findings.

  2. Effect of prolonged space flight on cardiac function and dimensions

    Science.gov (United States)

    Henry, W. L.; Epstein, S. E.; Griffith, J. M.; Goldstein, R. E.; Redwood, D. R.

    1974-01-01

    Echocardiographic studies were performed preflight 5 days before launch and on recovery day and 1, 2, 4, 11, 31 and 68 days postflight. From these echocardiograms measurements were made. From these primary measurements, left ventricular end-diastolic volume, end-systolic volume, stroke volume, and mass were derived using the accepted assumptions. Findings in the Scientist Pilot and Pilot resemble those seen in trained distance runners. Wall thickness measurements were normal in all three crewmembers preflight. Postflight basal studies were unchanged in the Commander on recovery day through 68 days postflight in both the Scientist Pilot and Pilot, however, the left ventricular end-diastolic volume, stroke volume, and mass were decreased slightly. Left ventricular function curves were constructed for the Commander and Pilot by plotting stroke volume versus end-diastolic volume. In both astronauts, preflight and postflight data fell on the same straight line demonstrating that no deterioration in cardiac function had occurred. These data indicate that the cardiovascular system adapts well to prolonged weightlessness and suggest that alterations in cardiac dimensions and function are unlikely to limit man's future in space.

  3. Cardiac effects of 3-iodothyronamine: a new aminergic system modulating cardiac function.

    Science.gov (United States)

    Chiellini, Grazia; Frascarelli, Sabina; Ghelardoni, Sandra; Carnicelli, Vittoria; Tobias, Sandra C; DeBarber, Andrea; Brogioni, Simona; Ronca-Testoni, Simonetta; Cerbai, Elisabetta; Grandy, David K; Scanlan, Thomas S; Zucchi, Riccardo

    2007-05-01

    3-Iodothyronamine T1AM is a novel endogenous thyroid hormone derivative that activates the G protein-coupled receptor known as trace anime-associated receptor 1 (TAAR1). In the isolated working rat heart and in rat cardiomyocytes, T1AM produced a reversible, dose-dependent negative inotropic effect (e.g., 27+/-5, 51+/-3, and 65+/-2% decrease in cardiac output at 19, 25, and 38 microM concentration, respectively). An independent negative chronotropic effect was also observed. The hemodynamic effects of T1AM were remarkably increased in the presence of the tyrosine kinase inhibitor genistein, whereas they were attenuated in the presence of the tyrosine phosphatase inhibitor vanadate. No effect was produced by inhibitors of protein kinase A, protein kinase C, calcium-calmodulin kinase II, phosphatidylinositol-3-kinase, or MAP kinases. Tissue cAMP levels were unchanged. In rat ventricular tissue, Western blot experiments with antiphosphotyrosine antibodies showed reduced phosphorylation of microsomal and cytosolic proteins after perfusion with synthetic T1AM; reverse transcriptase-polymerase chain reaction experiments revealed the presence of transcripts for at least 5 TAAR subtypes; specific and saturable binding of [125I]T1AM was observed, with a dissociation constant in the low micromolar range (5 microM); and endogenous T1AM was detectable by tandem mass spectrometry. In conclusion, our findings provide evidence for the existence of a novel aminergic system modulating cardiac function.

  4. Engineered hybrid cardiac patches with multifunctional electronics for online monitoring and regulation of tissue function

    Science.gov (United States)

    Feiner, Ron; Engel, Leeya; Fleischer, Sharon; Malki, Maayan; Gal, Idan; Shapira, Assaf; Shacham-Diamand, Yosi; Dvir, Tal

    2016-06-01

    In cardiac tissue engineering approaches to treat myocardial infarction, cardiac cells are seeded within three-dimensional porous scaffolds to create functional cardiac patches. However, current cardiac patches do not allow for online monitoring and reporting of engineered-tissue performance, and do not interfere to deliver signals for patch activation or to enable its integration with the host. Here, we report an engineered cardiac patch that integrates cardiac cells with flexible, freestanding electronics and a 3D nanocomposite scaffold. The patch exhibited robust electronic properties, enabling the recording of cellular electrical activities and the on-demand provision of electrical stimulation for synchronizing cell contraction. We also show that electroactive polymers containing biological factors can be deposited on designated electrodes to release drugs in the patch microenvironment on demand. We expect that the integration of complex electronics within cardiac patches will eventually provide therapeutic control and regulation of cardiac function.

  5. Engineered hybrid cardiac patches with multifunctional electronics for online monitoring and regulation of tissue function

    Science.gov (United States)

    Feiner, Ron; Engel, Leeya; Fleischer, Sharon; Malki, Maayan; Gal, Idan; Shapira, Assaf; Shacham-Diamand, Yosi; Dvir, Tal

    2016-01-01

    In cardiac tissue engineering approaches to treat myocardial infarction, cardiac cells are seeded within three-dimensional porous scaffolds to create functional cardiac patches. However, current cardiac patches do not allow for online monitoring and reporting of engineered-tissue performance, and do not interfere to deliver signals for patch activation or to enable its integration with the host. Here, we report an engineered cardiac patch that integrates cardiac cells with flexible, free-standing electronics and a 3D nanocomposite scaffold. The patch exhibited robust electronic properties, enabling the recording of cellular electrical activities and the on-demand provision of electrical stimulation for synchronizing cell contraction. We also show that electroactive polymers containing biological factors can be deposited on designated electrodes to release drugs in the patch microenvironment on-demand. We expect that the integration of complex electronics within cardiac patches will eventually provide therapeutic control and regulation of cardiac function. PMID:26974408

  6. Functional diversity of supragranular GABAergic neurons in the barrel cortex

    Directory of Open Access Journals (Sweden)

    Luc J Gentet

    2012-08-01

    Full Text Available Although the neocortex forms a distributed system comprised of several functional areas, its vertical columnar organization is largely conserved across areas and species, suggesting the existence of a canonical neocortical microcircuit. In order to elucidate the principles governing the organization of such a cortical diagram, a detailed understanding of the dynamics binding different types of cortical neurons into a coherent algorithm is essential. Within this complex circuitry, GABAergic interneurons, while forming approximately only 15-20% of all cortical neurons, appear critical in maintaining a dynamic balance between excitation and inhibition. Despite their importance, cortical GABAergic neurons have not been extensively studied in vivo and their precise role in shaping the local microcircuit sensory response still remains to be determined. Their paucity, combined with their molecular, anatomical and physiological diversity, has made it difficult to even establish a consensual nomenclature.However, recent technological advances in microscopy and mouse genetics have fostered a renewed interest in neocortical interneurons by putting them within visible reach of experimenters. The anatomically well-defined whisker-to-barrel pathway of the rodent is particularly amenable to studies attempting to link cortical circuit dynamics to behavior. To each whisker corresponds a discrete cortical unit equivalent to a single column, specialized in the encoding and processing of the sensory information it receives. In this review, we will focus on the functional role that each subtype of supragranular GABAergic neuron embedded within such a single neocortical unit may play in shaping the dynamics of the local circuit during somatosensory integration.

  7. The effect of childhood obesity on cardiac functions.

    Science.gov (United States)

    Üner, Abdurrahman; Doğan, Murat; Epcacan, Zerrin; Epçaçan, Serdar

    2014-03-01

    Obesity is a metabolic disorder defined as excessive accumulation of body fat, which is made up of genetic, environmental, and hormonal factors and has various social, psychological, and medical complications. Childhood obesity is a major indicator of adult obesity. The aim of this study is to evaluate the cardiac functions via electrocardiography (ECG), echocardiography (ECHO), and treadmill test in childhood obesity. A patient group consisting of 30 obese children and a control group consisting of 30 non-obese children were included in the study. The age range was between 8 and 17 years. Anthropometric measurements, physical examination, ECG, ECHO, and treadmill test were done in all patients. P-wave dispersion (PD) was found to be statistically significantly high in obese patients. In ECHO analysis, we found that end-diastolic diameter, end-systolic diameter, left ventricle posterior wall thickness, and interventricular septum were significantly greater in obese children. In treadmill test, exercise capacity was found to be significantly lower and the hemodynamic response to exercise was found to be defective in obese children. Various cardiac structural and functional changes occur in childhood obesity and this condition includes important cardiovascular risks. PD, left ventricle end-systolic and end-diastolic diameter, left ventricle posterior wall thickness, interventricular septum thickness, exercise capacity, and hemodynamic and ECG measurements during exercise testing are useful tests to determine cardiac dysfunctions and potential arrhythmias even in early stages of childhood obesity. Early recognition and taking precautions for obesity during childhood is very important to intercept complications that will occur in adulthood.

  8. Cardiac structure and function and dependency in the oldest old.

    Science.gov (United States)

    Leibowitz, David; Jacobs, Jeremy M; Stessman-Lande, Irit; Cohen, Aharon; Gilon, Dan; Ein-Mor, Eliana; Stessman, Jochanan

    2011-08-01

    To examine the association between cardiac function and activities of daily living (ADLs) in an age-homogenous, community-dwelling population born in 1920 and 1921. Cross-sectional analysis of a prospective cohort study. Community-dwelling elderly population. Participants were recruited from the Jerusalem Longitudinal Cohort Study, which has followed an age-homogenous cohort of Jerusalem residents born in 1920 and 1921. Four hundred eighty-nine of the participants (228 male, 261 female) from the most recent set of data collection in 2005 and 2006 underwent echocardiography at their place of residence in addition to structured interviews and physical examination. A home-based comprehensive assessment was performed to assess health and functional status, including performance of ADLs. Dependence was defined as needing assistance with one or more basic ADLs. Standard echocardiographic assessment of cardiac structure and function, including ejection fraction (EF) and diastolic function as assessed using early diastolic mitral annular tissue velocity measurements obtained using tissue Doppler, was performed. Of the participants with limitation in at least one ADL, significantly more had low EF (dependence in ADL had higher left ventricular mass index (LVMI) (129.3 vs 119.7 g/m²) and left atrial volume index (LAVI) (41.3 vs 36.7 mL/m²). There were no differences between the groups in percentage of participants with impaired diastolic function or average ratio of early diastolic transmitral flow velocity to early diastolic mitral annular tissue velocity (11.5 vs 11.8; P=.64). In this age-homogenous cohort of the oldest old, high LVMI and LAVI and indices of systolic but not diastolic function as assessed according to Doppler were associated with limitations in ADLs. © 2011, Copyright the Authors. Journal compilation © 2011, The American Geriatrics Society.

  9. Intrinsic cardiac nervous system in tachycardia induced heart failure.

    Science.gov (United States)

    Arora, Rakesh C; Cardinal, Rene; Smith, Frank M; Ardell, Jeffrey L; Dell'Italia, Louis J; Armour, J Andrew

    2003-11-01

    The purpose of this study was to test the hypothesis that early-stage heart failure differentially affects the intrinsic cardiac nervous system's capacity to regulate cardiac function. After 2 wk of rapid ventricular pacing in nine anesthetized canines, cardiac and right atrial neuronal function were evaluated in situ in response to enhanced cardiac sensory inputs, stimulation of extracardiac autonomic efferent neuronal inputs, and close coronary arterial administration of neurochemicals that included nicotine. Right atrial neuronal intracellular electrophysiological properties were then evaluated in vitro in response to synaptic activation and nicotine. Intrinsic cardiac nicotine-sensitive, neuronally induced cardiac responses were also evaluated in eight sham-operated, unpaced animals. Two weeks of rapid ventricular pacing reduced the cardiac index by 54%. Intrinsic cardiac neurons of paced hearts maintained their cardiac mechano- and chemosensory transduction properties in vivo. They also responded normally to sympathetic and parasympathetic preganglionic efferent neuronal inputs, as well as to locally administered alpha-or beta-adrenergic agonists or angiotensin II. The dose of nicotine needed to modify intrinsic cardiac neurons was 50 times greater in failure compared with normal preparations. That dose failed to alter monitored cardiovascular indexes in failing preparations. Phasic and accommodating neurons identified in vitro displayed altered intracellular membrane properties compared with control, including decreased membrane resistance, indicative of reduced excitability. Early-stage heart failure differentially affects the intrinsic cardiac nervous system's capacity to regulate cardiodynamics. While maintaining its capacity to transduce cardiac mechano- and chemosensory inputs, as well as inputs from extracardiac autonomic efferent neurons, intrinsic cardiac nicotine-sensitive, local-circuit neurons differentially remodel such that their capacity to

  10. Neurotransmission to parasympathetic cardiac vagal neurons in the brain stem is altered with left ventricular hypertrophy-induced heart failure.

    Science.gov (United States)

    Cauley, Edmund; Wang, Xin; Dyavanapalli, Jhansi; Sun, Ke; Garrott, Kara; Kuzmiak-Glancy, Sarah; Kay, Matthew W; Mendelowitz, David

    2015-10-01

    Hypertension, cardiac hypertrophy, and heart failure (HF) are widespread and debilitating cardiovascular diseases that affect nearly 23 million people worldwide. A distinctive hallmark of these cardiovascular diseases is autonomic imbalance, with increased sympathetic activity and decreased parasympathetic vagal tone. Recent device-based approaches, such as implantable vagal stimulators that stimulate a multitude of visceral sensory and motor fibers in the vagus nerve, are being evaluated as new therapeutic approaches for these and other diseases. However, little is known about how parasympathetic activity to the heart is altered with these diseases, and this lack of knowledge is an obstacle in the goal of devising selective interventions that can target and selectively restore parasympathetic activity to the heart. To identify the changes that occur within the brain stem to diminish the parasympathetic cardiac activity, left ventricular hypertrophy was elicited in rats by aortic pressure overload using a transaortic constriction approach. Cardiac vagal neurons (CVNs) in the brain stem that generate parasympathetic activity to the heart were identified with a retrograde tracer and studied using patch-clamp electrophysiological recordings in vitro. Animals with left cardiac hypertrophy had diminished excitation of CVNs, which was mediated both by an augmented frequency of spontaneous inhibitory GABAergic neurotransmission (with no alteration of inhibitory glycinergic activity) as well as a diminished amplitude and frequency of excitatory neurotransmission to CVNs. Opportunities to alter these network pathways and neurotransmitter receptors provide future targets of intervention in the goal to restore parasympathetic activity and autonomic balance to the heart in cardiac hypertrophy and other cardiovascular diseases. Copyright © 2015 the American Physiological Society.

  11. Metaiodobenzylguanidine [131I] scintigraphy detects impaired myocardial sympathetic neuronal transport function of canine mechanical-overload heart failure

    International Nuclear Information System (INIS)

    Rabinovitch, M.A.; Rose, C.P.; Rouleau, J.L.

    1987-01-01

    In heart failure secondary to chronic mechanical overload, cardiac sympathetic neurons demonstrate depressed catecholamine synthetic and transport function. To assess the potential of sympathetic neuronal imaging for detection of depressed transport function, serial scintigrams were acquired after the intravenous administration of metaiodobenzylguanidine [ 131 I] to 13 normal dogs, 3 autotransplanted (denervated) dogs, 5 dogs with left ventricular failure, and 5 dogs with compensated left ventricular hypertrophy due to a surgical arteriovenous shunt. Nine dogs were killed at 14 hours postinjection for determination of metaiodobenzylguanidine [ 131 I] and endogenous norepinephrine content in left atrium, left ventricle, liver, and spleen. By 4 hours postinjection, autotransplanted dogs had a 39% reduction in mean left ventricular tracer accumulation, reflecting an absent intraneuronal tracer pool. Failure dogs demonstrated an accelerated early mean left ventricular tracer efflux rate (26.0%/hour versus 13.7%/hour in normals), reflecting a disproportionately increased extraneuronal tracer pool. They also showed reduced late left ventricular and left atrial concentrations of tracer, consistent with a reduced intraneuronal tracer pool. By contrast, compensated hypertrophy dogs demonstrated a normal early mean left ventricular tracer efflux rate (16.4%/hour) and essentially normal late left ventricular and left atrial concentrations of tracer. Metaiodobenzylguanidine [ 131 I] scintigraphic findings reflect the integrity of the cardiac sympathetic neuronal transport system in canine mechanical-overload heart failure. Metaiodobenzylguanidine [ 123 I] scintigraphy should be explored as a means of early detection of mechanical-overload heart failure in patients

  12. Longstanding Hyperthyroidism Is Associated with Normal or Enhanced Intrinsic Cardiomyocyte Function despite Decline in Global Cardiac Function

    Science.gov (United States)

    Redetzke, Rebecca A.; Gerdes, A. Martin

    2012-01-01

    Thyroid hormones (THs) play a pivotal role in cardiac homeostasis. TH imbalances alter cardiac performance and ultimately cause cardiac dysfunction. Although short-term hyperthyroidism typically leads to heightened left ventricular (LV) contractility and improved hemodynamic parameters, chronic hyperthyroidism is associated with deleterious cardiac consequences including increased risk of arrhythmia, impaired cardiac reserve and exercise capacity, myocardial remodeling, and occasionally heart failure. To evaluate the long-term consequences of chronic hyperthyroidism on LV remodeling and function, we examined LV isolated myocyte function, chamber function, and whole tissue remodeling in a hamster model. Three-month-old F1b hamsters were randomized to control or 10 months TH treatment (0.1% grade I desiccated TH). LV chamber remodeling and function was assessed by echocardiography at 1, 2, 4, 6, 8, and 10 months of treatment. After 10 months, terminal cardiac function was assessed by echocardiography and LV hemodynamics. Hyperthyroid hamsters exhibited significant cardiac hypertrophy and deleterious cardiac remodeling characterized by myocyte lengthening, chamber dilatation, decreased relative wall thickness, increased wall stress, and increased LV interstitial fibrotic deposition. Importantly, hyperthyroid hamsters demonstrated significant LV systolic and diastolic dysfunction. Despite the aforementioned remodeling and global cardiac decline, individual isolated cardiac myocytes from chronically hyperthyroid hamsters had enhanced function when compared with myocytes from untreated age-matched controls. Thus, it appears that long-term hyperthyroidism may impair global LV function, at least in part by increasing interstitial ventricular fibrosis, in spite of normal or enhanced intrinsic cardiomyocyte function. PMID:23056390

  13. Longstanding hyperthyroidism is associated with normal or enhanced intrinsic cardiomyocyte function despite decline in global cardiac function.

    Directory of Open Access Journals (Sweden)

    Nathan Y Weltman

    Full Text Available Thyroid hormones (THs play a pivotal role in cardiac homeostasis. TH imbalances alter cardiac performance and ultimately cause cardiac dysfunction. Although short-term hyperthyroidism typically leads to heightened left ventricular (LV contractility and improved hemodynamic parameters, chronic hyperthyroidism is associated with deleterious cardiac consequences including increased risk of arrhythmia, impaired cardiac reserve and exercise capacity, myocardial remodeling, and occasionally heart failure. To evaluate the long-term consequences of chronic hyperthyroidism on LV remodeling and function, we examined LV isolated myocyte function, chamber function, and whole tissue remodeling in a hamster model. Three-month-old F1b hamsters were randomized to control or 10 months TH treatment (0.1% grade I desiccated TH. LV chamber remodeling and function was assessed by echocardiography at 1, 2, 4, 6, 8, and 10 months of treatment. After 10 months, terminal cardiac function was assessed by echocardiography and LV hemodynamics. Hyperthyroid hamsters exhibited significant cardiac hypertrophy and deleterious cardiac remodeling characterized by myocyte lengthening, chamber dilatation, decreased relative wall thickness, increased wall stress, and increased LV interstitial fibrotic deposition. Importantly, hyperthyroid hamsters demonstrated significant LV systolic and diastolic dysfunction. Despite the aforementioned remodeling and global cardiac decline, individual isolated cardiac myocytes from chronically hyperthyroid hamsters had enhanced function when compared with myocytes from untreated age-matched controls. Thus, it appears that long-term hyperthyroidism may impair global LV function, at least in part by increasing interstitial ventricular fibrosis, in spite of normal or enhanced intrinsic cardiomyocyte function.

  14. Functional significance of cardiac reinnervation in heart transplant recipients.

    Science.gov (United States)

    Schwaiblmair, M; von Scheidt, W; Uberfuhr, P; Ziegler, S; Schwaiger, M; Reichart, B; Vogelmeier, C

    1999-09-01

    There is accumulating evidence of structural sympathetic reinnervation after human cardiac transplantation. However, the functional significance of reinnervation in terms of exercise capacity has not been established as yet; we therefore investigated the influence of reinnervation on cardiopulmonary exercise testing. After orthotopic heart transplantation 35 patients (mean age, 49.1 +/- 8.4 years) underwent positron emission tomography with scintigraphically measured uptake of C11-hydroxyephedrine (HED), lung function testing, and cardiopulmonary exercise testing. Two groups were defined based on scintigraphic findings, indicating a denervated group (n = 15) with a HED uptake of 5.45%/min and a reinnervated group (n = 20) with a HED uptake of 10.59%/min. The two study groups did not show significant differences with regard to anthropometric data, number of rejection episodes, preoperative hemodynamics, and postoperative lung function data. The reinnervated group had a significant longer time interval from transplantation (1625 +/- 1069 versus 800 +/- 1316 days, p exercise (137 +/- 15 versus 120 +/- 20 beats/min, p = .012), peak oxygen uptake (21.0 +/- 4 versus 16.1 +/- 5 mL/min/kg, p = .006), peak oxygen pulse (12.4 +/- 2.9 versus 10.2 +/- 2.7 mL/min/beat, p = .031), and anaerobic threshold (11.2 +/- 1.8 versus 9.5 +/- 2.1 mL/min, p = .046) were significantly increased in comparison to denervated transplant recipients. Additionally, a decreased functional dead space ventilation (0.24 +/- 0.05 versus 0.30 +/- 0.05, p = .004) was observed in the reinnervated group. Our study results support the hypothesis that partial sympathetic reinnervation after cardiac transplantation is of functional significance. Sympathetic reinnervation enables an increased peak oxygen uptake. This is most probably due to partial restoration of the chronotropic and inotropic competence of the heart as well as an improved oxygen delivery to the exercising muscles and a reduced ventilation

  15. Toxic effects of lead on neuronal development and function

    International Nuclear Information System (INIS)

    Freedman, R.; Olson, L.; Hoffer, B.J.

    1990-01-01

    The effects of lead on the development of the nervous system are of immediate concern to human health. While it is clear that lead can affect neuronal development at levels of exposure within the range found in the environment, the particular mechanism of the disruption is not readily ascertained. The goal of the authors research is to develop a model system in which the effects of lead on central nervous system development can be demonstrated. To study neuronal development in a system that minimizes such difficulties, the authors have grafted discrete brain regions derived from rat fetuses into the anterior chamber of the eye of adult hosts. The brain pieces continue organotypic development in the eye, but are isolated from possible secondary changes due to alterations in the development of the endocrine and other somatic systems because the adult host has these systems already fully developed. Using this system, they have discovered that lead induces a hypernoradrenergic innervation of central nervous system tissue. The increased innervation is observed not only structurally, but also functionally. Since norepinephrine is an inhibitory neurotransmitter, this ingrowth may explain the profound slowing of discharge of cerebellar neurons recorded in grafts of lead-treated animals. Studies in other tissues suggest that increased axonal ingrowth may be a general problem of lead intoxication that encompasses many brain areas, as well as peripheral sympathetic systems

  16. Myocardial ischaemia and the cardiac nervous system.

    Science.gov (United States)

    Armour, J A

    1999-01-01

    The intrinsic cardiac nervous system has been classically considered to contain only parasympathetic efferent postganglionic neurones which receive inputs from medullary parasympathetic efferent preganglionic neurones. In such a view, intrinsic cardiac ganglia act as simple relay stations of parasympathetic efferent neuronal input to the heart, the major autonomic control of the heart purported to reside solely in the brainstem and spinal cord. Data collected over the past two decades indicate that processing occurs within the mammalian intrinsic cardiac nervous system which involves afferent neurones, local circuit neurones (interconnecting neurones) as well as both sympathetic and parasympathetic efferent postganglionic neurones. As such, intrinsic cardiac ganglionic interactions represent the organ component of the hierarchy of intrathoracic nested feedback control loops which provide rapid and appropriate reflex coordination of efferent autonomic neuronal outflow to the heart. In such a concept, the intrinsic cardiac nervous system acts as a distributive processor, integrating parasympathetic and sympathetic efferent centrifugal information to the heart in addition to centripetal information arising from cardiac sensory neurites. A number of neurochemicals have been shown to influence the interneuronal interactions which occur within the intrathoracic cardiac nervous system. For instance, pharmacological interventions that modify beta-adrenergic or angiotensin II receptors affect cardiomyocyte function not only directly, but indirectly by influencing the capacity of intrathoracic neurones to regulate cardiomyocytes. Thus, current pharmacological management of heart disease may influence cardiomyocyte function directly as well as indirectly secondary to modifying the cardiac nervous system. This review presents a brief summary of developing concepts about the role of the cardiac nervous system in regulating the normal heart. In addition, it provides some

  17. Sympathetic neurons are a powerful driver of myocyte function in cardiovascular disease.

    Science.gov (United States)

    Larsen, Hege E; Lefkimmiatis, Konstantinos; Paterson, David J

    2016-12-14

    Many therapeutic interventions in disease states of heightened cardiac sympathetic activity are targeted to the myocytes. However, emerging clinical data highlights a dominant role in disease progression by the neurons themselves. Here we describe a novel experimental model of the peripheral neuro-cardiac axis to study the neuron's ability to drive a myocyte cAMP phenotype. We employed a co-culture of neonatal ventricular myocytes and sympathetic stellate neurons from normal (WKY) and pro-hypertensive (SHR) rats that are sympathetically hyper-responsive and measured nicotine evoked cAMP responses in the myocytes using a fourth generation FRET cAMP sensor. We demonstrated the dominant role of neurons in driving the myocyte ß-adrenergic phenotype, where SHR cultures elicited heightened myocyte cAMP responses during neural activation. Moreover, cross-culturing healthy neurons onto diseased myocytes rescued the diseased cAMP response of the myocyte. Conversely, healthy myocytes developed a diseased cAMP response if diseased neurons were introduced. Our results provide evidence for a dominant role played by the neuron in driving the adrenergic phenotype seen in cardiovascular disease. We also highlight the potential of using healthy neurons to turn down the gain of neurotransmission, akin to a smart pre-synaptic ß-blocker.

  18. Heterogeneous response of cardiac sympathetic function to cardiac resynchronization therapy in heart failure documented by 11[C]-hydroxy-ephedrine and PET/CT

    International Nuclear Information System (INIS)

    Capitanio, Selene; Nanni, Cristina; Marini, Cecilia; Bonfiglioli, Rachele; Martignani, Cristian; Dib, Bassam; Fuccio, Chiara; Boriani, Giuseppe; Picori, Lorena; Boschi, Stefano; Morbelli, Silvia

    2015-01-01

    Introduction: Cardiac resynchronization therapy (CRT) is an accepted treatment in patients with end-stage heart failure. PET permits the absolute quantification of global and regional homogeneity in cardiac sympathetic innervation. We evaluated the variation of cardiac adrenergic activity in patients with idiopathic heart failure (IHF) disease (NYHA III–IV) after CRT using 11 C-hydroxyephedrine (HED) PET/CT. Methods: Ten IHF patients (mean age = 68; range = 55–81; average left ventricular ejection fraction 26 ± 4%) implanted with a resynchronization device underwent three HED PET/CT studies: PET 1 one week after inactive device implantation; PET 2, one week after PET 1 under stimulated rhythm; PET 3, at 3 months under active CRT. A dedicated software (PMOD 3.4 version) was used to estimate global and regional cardiac uptake of HED through 17 segment polar maps. Results: At baseline, HED uptake was heterogeneously distributed throughout the left ventricle with a variation coefficient of 18 ± 5%. This variable markedly decreased after three months CRT (12 ± 5%, p < 0.01). Interestingly, subdividing the 170 myocardial segments (17 segments of each patient multiplied by the number of patients) into two groups, according to the median value of tracer uptake expressed as % of maximal myocardial uptake (76%), we observed a different behaviour depending on baseline innervation: HED uptake significantly increased only in segments with “impaired innervation” (SUV 2.61 ± 0.92 at PET1 and 3.05 ± 1.67 at three months, p < 0.01). Conclusion: As shown by HED PET/CT uptake and distribution, improvement in homogeneity of myocardial neuronal function reflected a selective improvement of tracer uptake in regions with more severe neuronal damage. Advances in Knowledge: These finding supported the presence of a myocardial regional variability in response of cardiac sympathetic system to CRT and a systemic response involving remote tissues with rich adrenergic innervation

  19. Stimulus-response functions of single avian olfactory bulb neurones.

    Science.gov (United States)

    McKeegan, Dorothy E F; Demmers, Theodorus G M; Wathes, Christopher M; Jones, R Bryan; Gentle, Michael J

    2002-10-25

    This study investigated olfactory processing in a functional context by examining the responses of single avian olfactory bulb neurones to two biologically important gases over relevant concentration ranges. Recordings of extracellular spike activity were made from 80 single units in the left olfactory bulb of 11 anaesthetised, freely breathing adult hens (Gallus domesticus). The units were spontaneously active, exhibiting widely variable firing rates (0.07-47.28 spikes/s) and variable temporal firing patterns. Single units were tested for their response to an ascending concentration series of either ammonia (2.5-100 ppm) or hydrogen sulphide (1-50 ppm), delivered directly to the olfactory epithelium. Stimulation with a calibrated gas delivery system resulted in modification of spontaneous activity causing either inhibition (47% of units) or excitation (53%) of firing. For ammonia, 20 of the 35 units tested exhibited a response, while for hydrogen sulphide, 25 of the 45 units tested were responsive. Approximate response thresholds for ammonia (median threshold 3.75 ppm (range 2.5-60 ppm, n=20)) and hydrogen sulphide (median threshold 1 ppm (range 1-10 ppm, n=25)) were determined with most units exhibiting thresholds near the lower end of these ranges. Stimulus response curves were constructed for 23 units; 16 (the most complete) were subjected to a linear regression analysis to determine whether they were best fitted by a linear, log or power function. No single function provided the best fit for all the curves (seven were linear, eight were log, one was power). These findings show that avian units respond to changes in stimulus concentration in a manner generally consistent with reported responses in mammalian olfactory bulb neurones. However, this study illustrates a level of fine-tuning to small step changes in concentration (<5 ppm) not previously demonstrated in vertebrate single olfactory bulb neurones.

  20. Cardiac function adaptations in hibernating grizzly bears (Ursus arctos horribilis).

    Science.gov (United States)

    Nelson, O Lynne; Robbins, Charles T

    2010-03-01

    Research on the cardiovascular physiology of hibernating mammals may provide insight into evolutionary adaptations; however, anesthesia used to handle wild animals may affect the cardiovascular parameters of interest. To overcome these potential biases, we investigated the functional cardiac phenotype of the hibernating grizzly bear (Ursus arctos horribilis) during the active, transitional and hibernating phases over a 4 year period in conscious rather than anesthetized bears. The bears were captive born and serially studied from the age of 5 months to 4 years. Heart rate was significantly different from active (82.6 +/- 7.7 beats/min) to hibernating states (17.8 +/- 2.8 beats/min). There was no difference from the active to the hibernating state in diastolic and stroke volume parameters or in left atrial area. Left ventricular volume:mass was significantly increased during hibernation indicating decreased ventricular mass. Ejection fraction of the left ventricle was not different between active and hibernating states. In contrast, total left atrial emptying fraction was significantly reduced during hibernation (17.8 +/- 2.8%) as compared to the active state (40.8 +/- 1.9%). Reduced atrial chamber function was also supported by reduced atrial contraction blood flow velocities and atrial contraction ejection fraction during hibernation; 7.1 +/- 2.8% as compared to 20.7 +/- 3% during the active state. Changes in the diastolic cardiac filling cycle, especially atrial chamber contribution to ventricular filling, appear to be the most prominent macroscopic functional change during hibernation. Thus, we propose that these changes in atrial chamber function constitute a major adaptation during hibernation which allows the myocardium to conserve energy, avoid chamber dilation and remain healthy during a period of extremely low heart rates. These findings will aid in rational approaches to identifying underlying molecular mechanisms.

  1. Neurons the decision makers, Part I: The firing function of a single neuron.

    Science.gov (United States)

    Saaty, Thomas

    2017-02-01

    This paper is concerned with understanding synthesis of electric signals in the neural system based on making pairwise comparisons. Fundamentally, every person and every animal are born with the talent to compare stimuli from things that share properties in space or over time. Comparisons always need experience to distinguish among things. Pairwise comparisons are numerically reciprocal. If a value is assigned to the larger of two elements that have a given property when compared with the smaller one, then the smaller has the reciprocal of that value when compared with the larger. Because making comparisons requires the reciprocal property, we need mathematics that can cope with division. There are four division algebras that would allow us to use our reciprocals arising from comparisons: The real numbers, the complex numbers, the non-commutative quaternions and the non-associative octonions. Rather than inferring function as from electric flow in a network, in this paper we infer the flow from function. Neurons fire in response to stimuli and their firings vary relative to the intensities of the stimuli. We believe neurons use some kind of pairwise comparison mechanism to determine when to fire based on the stimuli they receive. The ideas we develop here about flows are used to deduce how a system based on this kind of firing determination works and can be described. Furthermore the firing of neurons requires continuous comparisons. To develop a formula describing the output of these pairwise comparisons requires solving Fredholm's equation of the second kind which is satisfied if and only if a simple functional equation has solutions. The Fourier transform of the real solution of this equation leads to inverse square laws like those that are common in physics. The Fourier transform applied to a complex valued solution leads to Dirac type of firings. Such firings are dense in the very general fields of functions known as Sobolev spaces and thus can be used to

  2. Neuronal Function in Male Sprague Dawley Rats During Normal Ageing.

    Science.gov (United States)

    Idowu, A J; Olatunji-Bello, I I; Olagunju, J A

    2017-03-06

    During normal ageing, there are physiological changes especially in high energy demanding tissues including the brain and skeletal muscles. Ageing may disrupt homeostasis and allow tissue vulnerability to disease. To establish an appropriate animal model which is readily available and will be useful to test therapeutic strategies during normal ageing, we applied behavioral approaches to study age-related changes in memory and motor function as a basis for neuronal function in ageing in male Sprague Dawley rats. 3 months, n=5; 6 months, n=5 and 18 months, n=5 male Sprague Dawley Rats were tested using the Novel Object Recognition Task (NORT) and the Elevated plus Maze (EPM) Test. Data was analyzed by ANOVA and the Newman-Keuls post hoc test. The results showed an age-related gradual decline in exploratory behavior and locomotor activity with increasing age in 3 months, 6 months and 18 months old rats, although the values were not statistically significant, but grooming activity significantly increased with increasing age. Importantly, we established a novel finding that the minimum distance from the novel object was statistically significant between 3 months and 18 months old rats and this may be an index for age-related memory impairment in the NORT. Altogether, we conclude that the male Sprague Dawley rat show age-related changes in neuronal function and may be a useful model for carrying out investigations into the mechanisms involved in normal ageing.

  3. Cardiac structure and functions in patients with asymptomatic primary hyperparathyroidism.

    Science.gov (United States)

    Aktas Yılmaz, B; Akyel, A; Kan, E; Ercin, U; Tavil, Y; Bilgihan, A; Cakır, N; Arslan, M; Balos Toruner, F

    2013-11-01

    The data about cardiovascular (CV) changes in patients with asymptomatic primary hyperparathyroidism (PHPT) are scarce. The aim of this study is to compare cardiac structure and functions in patients with asymptomatic PHPT and controls by using tissue Doppler echocardiography. Thirty-eight patients with asymptomatic PHPT and 31 sex- and age-matched controls with similar cardiac risk factors were evaluated. There was no significant difference in ejection fraction (EF) between the patients and the controls [64±5.95 vs 62±3.25% (p=0.094)]. Left ventricular mass index (LVMI) was significantly higher in patients than controls [105.96 (66.45-167.24) vs 93.79 (64.25- 139.25) g/m2, p=0.014]. There was a significant correlation between LVMI and serum calcium (Ca) (r=0.240, p<0.005). Myocardial performance index (MPI) was significantly higher in patients than controls [0.49 (0.35-0.60) vs 0.39 (0.33-0.62), p<0.001]. There was positive correlation between theMPI and serumCa levels (r=0.505, p<0.001), parathyroid hormone (PTH) levels (r=0.464, p<0.001) and LVMI (r=0.270, p<0.005). When the normotensive patients and controls were evaluated, the difference between the groups remained statistically significant considering LVMI and MPI [109 (66.45-167.24) g/m2 vs 94.17 (64.25-75.10) g/m2, p=0.03; and 0.49 (0.35-0.60) vs 0.39 (0.33-0.62), p<0.01, respectively]. There were significant correlations between MPI and Ca (r=0.566, p<0.001), and PTH (r=0.472, p<0.001). Our study results showed that cardiacmorphology and diastolic functions are altered in the patients with asymptomatic PHPT. High serum PTH and Ca levels may have an impact on these CV changes. Whether these subtle CV changes would affect cardiac systolic functions and mortality in patients with asymptomatic PHPT should be investigated in further prospective studies.

  4. Relationship between quantitative cardiac neuronal imaging with {sup 123}I-meta-iodobenzylguanidine and hospitalization in patients with heart failure

    Energy Technology Data Exchange (ETDEWEB)

    Parker, Matthew W.; Sood, Nitesh [University of Connecticut, School of Medicine Department of Medicine, Farmington, CT (United States); Hartford Hospital, Division of Cardiology, Hartford, CT (United States); Ahlberg, Alan W. [Hartford Hospital, Division of Cardiology, Hartford, CT (United States); Jacobson, Arnold F. [GE Healthcare, Princeton, NJ (United States); Heller, Gary V. [The Intersocietal Accreditation Commission, Ellicott City, MD (United States); Lundbye, Justin B. [University of Connecticut, School of Medicine Department of Medicine, Farmington, CT (United States); The Hospital of Central Connecticut, Division of Cardiology, New Britain, CT (United States)

    2014-09-15

    Hospitalization in patients with systolic heart failure is associated with morbidity, mortality, and cost. Myocardial sympathetic innervation, imaged by {sup 123}I-meta-iodobenzylguanidine ({sup 123}I-mIBG), has been associated with cardiac events in a recent multicenter study. The present analysis explored the relationship between {sup 123}I-mIBG imaging findings and hospitalization. Source documents from the ADMIRE-HF trial were reviewed to identify hospitalization events in patients with systolic heart failure following cardiac neuronal imaging using {sup 123}I-mIBG. Time to hospitalization was analyzed with the Kaplan-Meier method and compared to the mIBG heart-to-mediastinum (H/M) ratio using multiple-failure Cox regression. During 1.4 years of median follow-up, 362 end-point hospitalizations occurred in 207 of 961 subjects, 79 % of whom had H/M ratio <1.6. Among subjects hospitalized for any cause, 88 % had H/M ratio <1.6 and subjects with H/M ratio <1.6 experienced hospitalization earlier than subjects with higher H/M ratios (log-rank p = 0.003). After adjusting for elevated brain natriuretic peptide (BNP) and time since heart failure diagnosis, a low mIBG H/M ratio was associated with cardiac-related hospitalization (HR 1.48, 95 % CI 1.05 - 2.0; p = 0.02). The mIBG H/M ratio may risk-stratify patients with heart failure for cardiac-related hospitalization, especially when used in conjunction with BNP. Further studies are warranted to examine these relationships. (orig.)

  5. Relationship between quantitative cardiac neuronal imaging with 123I-meta-iodobenzylguanidine and hospitalization in patients with heart failure

    International Nuclear Information System (INIS)

    Parker, Matthew W.; Sood, Nitesh; Ahlberg, Alan W.; Jacobson, Arnold F.; Heller, Gary V.; Lundbye, Justin B.

    2014-01-01

    Hospitalization in patients with systolic heart failure is associated with morbidity, mortality, and cost. Myocardial sympathetic innervation, imaged by 123 I-meta-iodobenzylguanidine ( 123 I-mIBG), has been associated with cardiac events in a recent multicenter study. The present analysis explored the relationship between 123 I-mIBG imaging findings and hospitalization. Source documents from the ADMIRE-HF trial were reviewed to identify hospitalization events in patients with systolic heart failure following cardiac neuronal imaging using 123 I-mIBG. Time to hospitalization was analyzed with the Kaplan-Meier method and compared to the mIBG heart-to-mediastinum (H/M) ratio using multiple-failure Cox regression. During 1.4 years of median follow-up, 362 end-point hospitalizations occurred in 207 of 961 subjects, 79 % of whom had H/M ratio <1.6. Among subjects hospitalized for any cause, 88 % had H/M ratio <1.6 and subjects with H/M ratio <1.6 experienced hospitalization earlier than subjects with higher H/M ratios (log-rank p = 0.003). After adjusting for elevated brain natriuretic peptide (BNP) and time since heart failure diagnosis, a low mIBG H/M ratio was associated with cardiac-related hospitalization (HR 1.48, 95 % CI 1.05 - 2.0; p = 0.02). The mIBG H/M ratio may risk-stratify patients with heart failure for cardiac-related hospitalization, especially when used in conjunction with BNP. Further studies are warranted to examine these relationships. (orig.)

  6. Sex differences in cardiac function after prolonged strenuous exercise.

    Science.gov (United States)

    Cote, Anita T; Phillips, Aaron A; Foulds, Heather J; Charlesworth, Sarah A; Bredin, Shannon S D; Burr, Jamie F; Koehle, Michael S; Warburton, Darren E R

    2015-05-01

    To evaluate sex differences in left ventricular (LV) function after an ultramarathon, and the association of vascular and training indices with the magnitude of exercise-induced cardiac fatigue. Descriptive field study. Fat Dog 100 Ultramarathon Trail Race, Canada. Thirty-four (13 women) recreational runners (aged 28-56 years). A 100-km or 160-km mountain marathon. Baseline baroreceptor sensitivity, heart rate variability, and arterial compliance; Pre-exercise and postexercise echocardiographic evaluations of LV dimensions, volumes, Doppler flow velocities, tissue velocities, strain, and strain rate. Finishers represented 17 men (44.8 ± 6.6 years) and 8 women (45.9 ± 10.2 years; P = 0.758). After ultraendurance exercise, significant reductions (P training status/experience. These findings suggest that vascular health is an important contributor to the degree of cardiovascular strain incurred as the result of an acute bout of prolonged strenuous exercise.

  7. Cardiac diastolic function after recovery from pre-eclampsia.

    Science.gov (United States)

    Soma-Pillay, P; Louw, M C; Adeyemo, A O; Makin, J; Pattinson, R C

    Pre-eclampsia is associated with significant changes to the cardiovascular system during pregnancy. Eccentric and concentric remodelling of the left ventricle occurs, resulting in impaired contractility and diastolic dysfunction. It is unclear whether these structural and functional changes resolve completely after delivery. The objective of the study was to determine cardiac diastolic function at delivery and one year post-partum in women with severe pre-eclampsia, and to determine possible future cardiovascular risk. This was a descriptive study performed at Steve Biko Academic Hospital, a tertiary referral hospital in Pretoria, South Africa. Ninety-six women with severe preeclampsia and 45 normotensive women with uncomplicated pregnancies were recruited during the delivery admission. Seventy-four (77.1%) women in the pre-eclamptic group were classified as a maternal near miss. Transthoracic Doppler echocardiography was performed at delivery and one year post-partum. At one year post-partum, women with pre-eclampsia had a higher diastolic blood pressure (p = 0.001) and body mass index (p = 0.02) than women in the normotensive control group. Women with early onset pre-eclampsia requiring delivery prior to 34 weeks' gestation had an increased risk of diastolic dysfunction at one year post-partum (RR 3.41, 95% CI: 1.11-10.5, p = 0.04) and this was irrespective of whether the patient had chronic hypertension or not. Women who develop early-onset pre-eclampsia requiring delivery before 34 weeks are at a significant risk of developing cardiac diastolic dysfunction one year after delivery compared to normotensive women with a history of a low-risk pregnancy.

  8. Comparative functional expression of nAChR subtypes in rodent DRG neurons.

    Science.gov (United States)

    Smith, Nathan J; Hone, Arik J; Memon, Tosifa; Bossi, Simon; Smith, Thomas E; McIntosh, J Michael; Olivera, Baldomero M; Teichert, Russell W

    2013-01-01

    We investigated the functional expression of nicotinic acetylcholine receptors (nAChRs) in heterogeneous populations of dissociated rat and mouse lumbar dorsal root ganglion (DRG) neurons by calcium imaging. By this experimental approach, it is possible to investigate the functional expression of multiple receptor and ion-channel subtypes across more than 100 neuronal and glial cells simultaneously. Based on nAChR expression, DRG neurons could be divided into four subclasses: (1) neurons that express predominantly α3β4 and α6β4 nAChRs; (2) neurons that express predominantly α7 nAChRs; (3) neurons that express a combination of α3β4/α6β4 and α7 nAChRs; and (4) neurons that do not express nAChRs. In this comparative study, the same four neuronal subclasses were observed in mouse and rat DRG. However, the expression frequency differed between species: substantially more rat DRG neurons were in the first three subclasses than mouse DRG neurons, at all developmental time points tested in our study. Approximately 70-80% of rat DRG neurons expressed functional nAChRs, in contrast to only ~15-30% of mouse DRG neurons. Our study also demonstrated functional coupling between nAChRs, voltage-gated calcium channels, and mitochondrial Ca(2) (+) transport in discrete subsets of DRG neurons. In contrast to the expression of nAChRs in DRG neurons, we demonstrated that a subset of non-neuronal DRG cells expressed muscarinic acetylcholine receptors and not nAChRs. The general approach to comparative cellular neurobiology outlined in this paper has the potential to better integrate molecular and systems neuroscience by uncovering the spectrum of neuronal subclasses present in a given cell population and the functionally integrated signaling components expressed in each subclass.

  9. Catenin-dependent cadherin function drives divisional segregation of spinal motor neurons.

    Science.gov (United States)

    Bello, Sanusi M; Millo, Hadas; Rajebhosale, Manisha; Price, Stephen R

    2012-01-11

    Motor neurons that control limb movements are organized as a neuronal nucleus in the developing ventral horn of the spinal cord called the lateral motor column. Neuronal migration segregates motor neurons into distinct lateral and medial divisions within the lateral motor column that project axons to dorsal or ventral limb targets, respectively. This migratory phase is followed by an aggregation phase whereby motor neurons within a division that project to the same muscle cluster together. These later phases of motor neuron organization depend on limb-regulated differential cadherin expression within motor neurons. Initially, all motor neurons display the same cadherin expression profile, which coincides with the migratory phase of motor neuron segregation. Here, we show that this early, pan-motor neuron cadherin function drives the divisional segregation of spinal motor neurons in the chicken embryo by controlling motor neuron migration. We manipulated pan-motor neuron cadherin function through dissociation of cadherin binding to their intracellular partners. We found that of the major intracellular transducers of cadherin signaling, γ-catenin and α-catenin predominate in the lateral motor column. In vivo manipulations that uncouple cadherin-catenin binding disrupt divisional segregation via deficits in motor neuron migration. Additionally, reduction of the expression of cadherin-7, a cadherin predominantly expressed in motor neurons only during their migration, also perturbs divisional segregation. Our results show that γ-catenin-dependent cadherin function is required for spinal motor neuron migration and divisional segregation and suggest a prolonged role for cadherin expression in all phases of motor neuron organization.

  10. Functional Effects of Hyperthyroidism on Cardiac Papillary Muscle in Rats

    Directory of Open Access Journals (Sweden)

    Fabricio Furtado Vieira

    Full Text Available Abstract Background: Hyperthyroidism is currently recognized to affect the cardiovascular system, leading to a series of molecular and functional changes. However, little is known about the functional influence of hyperthyroidism in the regulation of cytoplasmic calcium and on the sodium/calcium exchanger (NCX in the cardiac muscle. Objectives: To evaluate the functional changes in papillary muscles isolated from animals with induced hyperthyroidism. Methods: We divided 36 Wistar rats into a group of controls and another of animals with hyperthyroidism induced by intraperitoneal T3 injection. We measured in the animals' papillary muscles the maximum contraction force, speed of contraction (+df/dt and relaxation (-df/dt, contraction and relaxation time, contraction force at different concentrations of extracellular sodium, post-rest potentiation (PRP, and contraction force induced by caffeine. Results: In hyperthyroid animals, we observed decreased PRP at all rest times (p < 0.05, increased +df/dt and -df/dt (p < 0.001, low positive inotropic response to decreased concentration of extracellular sodium (p < 0.001, reduction of the maximum force in caffeine-induced contraction (p < 0.003, and decreased total contraction time (p < 0.001. The maximal contraction force did not differ significantly between groups (p = 0.973. Conclusion: We hypothesize that the changes observed are likely due to a decrease in calcium content in the sarcoplasmic reticulum, caused by calcium leakage, decreased expression of NCX, and increased expression of a-MHC and SERCA2.

  11. Cardiac microvascular endothelial cells express a functional Ca+ -sensing receptor.

    Science.gov (United States)

    Berra Romani, Roberto; Raqeeb, Abdul; Laforenza, Umberto; Scaffino, Manuela Federica; Moccia, Francesco; Avelino-Cruz, Josè Everardo; Oldani, Amanda; Coltrini, Daniela; Milesi, Veronica; Taglietti, Vanni; Tanzi, Franco

    2009-01-01

    The mechanism whereby extracellular Ca(2+) exerts the endothelium-dependent control of vascular tone is still unclear. In this study, we assessed whether cardiac microvascular endothelial cells (CMEC) express a functional extracellular Ca(2+)-sensing receptor (CaSR) using a variety of techniques. CaSR mRNA was detected using RT-PCR, and CaSR protein was identified by immunocytochemical analysis. In order to assess the functionality of the receptor, CMEC were loaded with the Ca(2+)-sensitive fluorochrome, Fura-2/AM. A number of CaSR agonists, such as spermine, Gd(3+), La(3+) and neomycin, elicited a heterogeneous intracellular Ca(2+) signal, which was abolished by disruption of inositol 1,4,5-trisphosphate (InsP(3)) signaling and by depletion of intracellular stores with cyclopiazonic acid. The inhibition of the Na(+)/Ca(2+) exchanger upon substitution of extracellular Na(+) unmasked the Ca(2+) signal triggered by an increase in extracellular Ca(2+) levels. Finally, aromatic amino acids, which function as allosteric activators of CaSR, potentiated the Ca(2+) response to the CaSR agonist La(3+). These data provide evidence that CMEC express CaSR, which is able to respond to physiological agonists by mobilizing Ca(2+) from intracellular InsP(3)-sensitive stores. Copyright 2008 S. Karger AG, Basel.

  12. Functional Effects of Hyperthyroidism on Cardiac Papillary Muscle in Rats.

    Science.gov (United States)

    Vieira, Fabricio Furtado; Olivoto, Robson Ruiz; Silva, Priscyla Oliveira da; Francisco, Julio Cesar; Fogaça, Rosalvo Tadeu Hochmuller

    2016-12-01

    Hyperthyroidism is currently recognized to affect the cardiovascular system, leading to a series of molecular and functional changes. However, little is known about the functional influence of hyperthyroidism in the regulation of cytoplasmic calcium and on the sodium/calcium exchanger (NCX) in the cardiac muscle. To evaluate the functional changes in papillary muscles isolated from animals with induced hyperthyroidism. We divided 36 Wistar rats into a group of controls and another of animals with hyperthyroidism induced by intraperitoneal T3 injection. We measured in the animals' papillary muscles the maximum contraction force, speed of contraction (+df/dt) and relaxation (-df/dt), contraction and relaxation time, contraction force at different concentrations of extracellular sodium, post-rest potentiation (PRP), and contraction force induced by caffeine. In hyperthyroid animals, we observed decreased PRP at all rest times (p < 0.05), increased +df/dt and -df/dt (p < 0.001), low positive inotropic response to decreased concentration of extracellular sodium (p < 0.001), reduction of the maximum force in caffeine-induced contraction (p < 0.003), and decreased total contraction time (p < 0.001). The maximal contraction force did not differ significantly between groups (p = 0.973). We hypothesize that the changes observed are likely due to a decrease in calcium content in the sarcoplasmic reticulum, caused by calcium leakage, decreased expression of NCX, and increased expression of a-MHC and SERCA2.

  13. Social interaction in robotic agents emulating the mirror neuron function

    NARCIS (Netherlands)

    Barakova, E.I.; Mira, J.; Álvarez, J.R.

    2007-01-01

    Emergent interactions that are expressed by the movements of two agents are discussed in this paper. The common coding principle is used to show how the mirror neuron system may facilitate interaction behaviour. Synchronization between neuron groups in different structures of the mirror neuron

  14. Relationship between cardiac function and resting cerebral blood flow

    DEFF Research Database (Denmark)

    Henriksen, Otto M; Jensen, Lars T; Krabbe, Katja

    2014-01-01

    ) and 2.4 l min(-1) m(-2), respectively, in females. No effects of cardiac output or cardiac index on CBF or structural signs of brain ageing were observed. However, fractional brain flow defined as the ratio of total brain flow to cardiac output was inversely correlated with cardiac index (r(2) = 0.22, P...... = 0.008) and furthermore lower in males than in females (8.6% versus 12.5%, P = 0.003). Fractional brain flow was also inversely correlated with cerebral white matter lesion grade, although this effect was not significant when adjusted for age. Frequency analysis of heart rate variability showed...

  15. Efficacy of B-Type Natriuretic Peptide Is Coupled to Phosphodiesterase 2A in Cardiac Sympathetic Neurons.

    Science.gov (United States)

    Li, Dan; Lu, Chieh-Ju; Hao, Guoliang; Wright, Hannah; Woodward, Lavinia; Liu, Kun; Vergari, Elisa; Surdo, Nicoletta C; Herring, Neil; Zaccolo, Manuela; Paterson, David J

    2015-07-01

    Elevated B-type natriuretic peptide (BNP) regulates cGMP-phosphodiesterase activity. Its elevation is regarded as an early compensatory response to cardiac failure where it can facilitate sympathovagal balance and cardiorenal homeostasis. However, recent reports suggest a paradoxical proadrenergic action of BNP. Because phosphodiesterase activity is altered in cardiovascular disease, we tested the hypothesis that BNP might lose its efficacy by minimizing the action of cGMP on downstream pathways coupled to neurotransmission. BNP decreased norepinephrine release from atrial preparations in response to field stimulation and also significantly reduced the heart rate responses to sympathetic nerve stimulation in vitro. Using electrophysiological recording and fluorescence imaging, BNP also reduced the depolarization evoked calcium current and intracellular calcium transient in isolated cardiac sympathetic neurons. Pharmacological manipulations suggested that the reduction in the calcium transient was regulated by a cGMP/protein kinase G pathway. Fluorescence resonance energy transfer measurements for cAMP, and an immunoassay for cGMP, showed that BNP increased cGMP, but not cAMP. In addition, overexpression of phosphodiesterase 2A after adenoviral gene transfer markedly decreased BNP stimulation of cGMP and abrogated the BNP responses to the calcium current, intracellular calcium transient, and neurotransmitter release. These effects were reversed on inhibition of phosphodiesterase 2A. Moreover, phosphodiesterase 2A activity was significantly elevated in stellate neurons from the prohypertensive rat compared with the normotensive control. Our data suggest that abnormally high levels of phosphodiesterase 2A may provide a brake against the inhibitory action of BNP on sympathetic transmission. © 2015 American Heart Association, Inc.

  16. Leptin signaling in GABA neurons, but not glutamate neurons, is required for reproductive function.

    Science.gov (United States)

    Zuure, Wieteke A; Roberts, Amy L; Quennell, Janette H; Anderson, Greg M

    2013-11-06

    The adipocyte-derived hormone leptin acts in the brain to modulate the central driver of fertility: the gonadotropin releasing hormone (GnRH) neuronal system. This effect is indirect, as GnRH neurons do not express leptin receptors (LEPRs). Here we test whether GABAergic or glutamatergic neurons provide the intermediate pathway between the site of leptin action and the GnRH neurons. Leptin receptors were deleted from GABA and glutamate neurons using Cre-Lox transgenics, and the downstream effects on puberty onset and reproduction were examined. Both mouse lines displayed the expected increase in body weight and region-specific loss of leptin signaling in the hypothalamus. The GABA neuron-specific LEPR knock-out females and males showed significantly delayed puberty onset. Adult fertility observations revealed that these knock-out animals have decreased fecundity. In contrast, glutamate neuron-specific LEPR knock-out mice displayed normal fertility. Assessment of the estrogenic hypothalamic-pituitary-gonadal axis regulation in females showed that leptin action on GABA neurons is not necessary for estradiol-mediated suppression of tonic luteinizing hormone secretion (an indirect measure of GnRH neuron activity) but is required for regulation of a full preovulatory-like luteinizing hormone surge. In conclusion, leptin signaling in GABAergic (but not glutamatergic neurons) plays a critical role in the timing of puberty onset and is involved in fertility regulation throughout adulthood in both sexes. These results form an important step in explaining the role of central leptin signaling in the reproductive system. Limiting the leptin-to-GnRH mediators to GABAergic cells will enable future research to focus on a few specific types of neurons.

  17. Interoception across modalities: on the relationship between cardiac awareness and the sensitivity for gastric functions.

    Directory of Open Access Journals (Sweden)

    Beate M Herbert

    Full Text Available The individual sensitivity for ones internal bodily signals ("interoceptive awareness" has been shown to be of relevance for a broad range of cognitive and affective functions. Interoceptive awareness has been primarily assessed via measuring the sensitivity for ones cardiac signals ("cardiac awareness" which can be non-invasively measured by heartbeat perception tasks. It is an open question whether cardiac awareness is related to the sensitivity for other bodily, visceral functions. This study investigated the relationship between cardiac awareness and the sensitivity for gastric functions in healthy female persons by using non-invasive methods. Heartbeat perception as a measure for cardiac awareness was assessed by a heartbeat tracking task and gastric sensitivity was assessed by a water load test. Gastric myoelectrical activity was measured by electrogastrography (EGG and subjective feelings of fullness, valence, arousal and nausea were assessed. The results show that cardiac awareness was inversely correlated with ingested water volume and with normogastric activity after water load. However, persons with good and poor cardiac awareness did not differ in their subjective ratings of fullness, nausea and affective feelings after drinking. This suggests that good heartbeat perceivers ingested less water because they subjectively felt more intense signals of fullness during this lower amount of water intake compared to poor heartbeat perceivers who ingested more water until feeling the same signs of fullness. These findings demonstrate that cardiac awareness is related to greater sensitivity for gastric functions, suggesting that there is a general sensitivity for interoceptive processes across the gastric and cardiac modality.

  18. Nonenzymatic glucosylation of neuronal calmodulin and its functional consequences

    International Nuclear Information System (INIS)

    Kowluru, R.A.; Kowluru, A.; Bitensky, M.W.

    1986-01-01

    Glucosylation (NEG) (nonenzymatic) of proteins is a posttranslational protein modification that occurs readily in the diabetic environment. As a consequence of NEG some proteins are known to undergo a change in function. Their studies of red blood cell (RBC) cytoskeletal proteins indicate that calmodulin is glucosylated in the diabetic RBC and this is followed by a change in function. Here they present new data in support of their earlier findings. Purified bovine brain calmodulin was glucosylated in vitro in the presence of 28 mM glucose. After six days of incubation at room temperature 2.75 moles of glucose were incorporated per mole of calmodulin. Glucosylated calmodulin exhibited a marked reduction in calcium dependent functions. Its ability to stimulate neuronal phosphodiesterase (PDE) and adenylate cyclase was reduced by 65 and 80% respectively. Its ability to stimulate rat brain protein kinase was reduced by 40%. Glucosylated calmodulin exhibited a 56% drop in its 45 Ca binding as compared with unmodified calmodulin. These data provide an additional example in which NEG markedly alters protein function

  19. Reduced Right Ventricular Function Predicts Long-Term Cardiac Re-Hospitalization after Cardiac Surgery.

    Directory of Open Access Journals (Sweden)

    Leela K Lella

    Full Text Available The significance of right ventricular ejection fraction (RVEF, independent of left ventricular ejection fraction (LVEF, following isolated coronary artery bypass grafting (CABG and valve procedures remains unknown. The aim of this study is to examine the significance of abnormal RVEF by cardiac magnetic resonance (CMR, independent of LVEF in predicting outcomes of patients undergoing isolated CABG and valve surgery.From 2007 to 2009, 109 consecutive patients (mean age, 66 years; 38% female were referred for pre-operative CMR. Abnormal RVEF and LVEF were considered 30 days outcomes included, cardiac re-hospitalization, worsening congestive heart failure and mortality. Mean clinical follow up was 14 months.Forty-eight patients had reduced RVEF (mean 25% and 61 patients had normal RVEF (mean 50% (p<0.001. Fifty-four patients had reduced LVEF (mean 30% and 55 patients had normal LVEF (mean 59% (p<0.001. Patients with reduced RVEF had a higher incidence of long-term cardiac re-hospitalization vs. patients with normal RVEF (31% vs.13%, p<0.05. Abnormal RVEF was a predictor for long-term cardiac re-hospitalization (HR 3.01 [CI 1.5-7.9], p<0.03. Reduced LVEF did not influence long-term cardiac re-hospitalization.Abnormal RVEF is a stronger predictor for long-term cardiac re-hospitalization than abnormal LVEF in patients undergoing isolated CABG and valve procedures.

  20. Spironolactone in chronic hemodialysis patients improves cardiac function

    International Nuclear Information System (INIS)

    Taheri, Shahram; Mortazavi, Mojhgan; Shahidi Shahrzad; Seirafian, Shiva; Pourmoghadas, Ali; Garakyaraghi, Mohammad; Eshaghian, Afrooz; Ghassami, Maryam

    2009-01-01

    We performed this study to assess whether low dose spironolactone could be administered in hemodialysis (HD) patients with moderate to severe heart failure to improve cardiovascular function and reduce hospitalization without inducing hyperkalemia. We enrolled 16 chronic HD patients with moderate to severe heart failure and left ventricle ejection fraction :5 45%. In a double blinded randomized placebo controlled study, one group of 8 patients received 25 mg of spironolactone after each dialysis session within six months, and the rest received a placebo. Echocardiography was performed on all the patients to assess ejection fraction and left ventricular mass during 12 hours after completion of hemodialysis at the beginning and the end of study. Serum potassium was measured predialysis every 4 weeks. The mean ejection fraction increased significantly more in spironolactone group during the study period than in the placebo group (6.2 + - 1.64 vs. 0.83 + - 4.9, P0.046). The mean left ventricular mass decreased in the spironolactone group, but increased significantly in the placebo group during the period (-8.4 + - 4.72 vs. 3 + -7.97. 95%, P= 0.021). The incidence of hyperkalemia was not significantly increased in the study or controlled groups. In conclusion, we found in this study that administration of spironolactone in chronic HD patients with moderate to severe heart failure substantially improved their cardiac function and decreases left ventricular mass without development of significant hyperkalemia. (author)

  1. Sodium Channel (Dys)Function and Cardiac Arrhythmias

    NARCIS (Netherlands)

    Remme, Carol Ann; Bezzina, Connie R.

    2010-01-01

    P>Cardiac voltage-gated sodium channels are transmembrane proteins located in the cell membrane of cardiomyocytes. Influx of sodium ions through these ion channels is responsible for the initial fast upstroke of the cardiac action potential. This inward sodium current thus triggers the initiation

  2. Evaluation of the cardiac efficiency by means of functional radiocardiography

    Energy Technology Data Exchange (ETDEWEB)

    Scheibe, J; Stoll, W [Friedrich-Schiller-Universitaet, Jena (German Democratic Republic). Bereich Medizin

    1982-01-01

    A new method of evaluating the cardiac efficiency by means of radiocardiography performed on exertion with /sup 113m/InCl is reported. Analysis of stroke volume, end diastolic volume and of the quotient of cardiac output to end diastolic volume on exertion enables an adequate evaluation of the actual myocardial efficiency.

  3. ABC of the cardiac magnetic resonance. Part 1: anatomy and function

    International Nuclear Information System (INIS)

    Loureiro, Ricardo; Rached, Heron; Castro, Claudio C.; Cerri, Giovanni G.; Favaro, Daniele; Baptista, Luciana; Andrade, Joalbo; Rochitte, Carlos E.; Parga Filho, Jose; Avila, Luiz F.; Piva, Rosa M.V.

    2003-01-01

    The objective of this work is to demonstrate the fundamental concepts, the basic sequences and the clinical and potential applications of cardiac magnetic resonance as a diagnostic technique in updated radiology and cardiology practices. In this first part, we present the basic planning of the cardiac image acquisition, the nomenclature and standardized myocardial segmentation, image synchronization principles for electrocardiogram and the heart functional and anatomical evaluation by cardiac magnetic resonance. (author)

  4. Relationship between cardiac function and resting cerebral blood flow: MRI measurements in healthy elderly subjects.

    Science.gov (United States)

    Henriksen, Otto M; Jensen, Lars T; Krabbe, Katja; Larsson, Henrik B W; Rostrup, Egill

    2014-11-01

    Although both impaired cardiac function and reduced cerebral blood flow are associated with ageing, current knowledge of the influence of cardiac function on resting cerebral blood flow (CBF) is limited. The aim of this study was to investigate the potential effects of cardiac function on CBF. CBF and cardiac output were measured in 31 healthy subjects 50-75 years old using magnetic resonance imaging techniques. Mean values of CBF, cardiac output and cardiac index were 43.6 ml per 100 g min(-1), 5.5 l min(-1) and 2.7 l min(-1) m(-2), respectively, in males, and 53.4 ml per 100 g min(-1), 4.3 l min(-1) and 2.4 l min(-1) m(-2), respectively, in females. No effects of cardiac output or cardiac index on CBF or structural signs of brain ageing were observed. However, fractional brain flow defined as the ratio of total brain flow to cardiac output was inversely correlated with cardiac index (r(2) = 0.22, P = 0.008) and furthermore lower in males than in females (8.6% versus 12.5%, P = 0.003). Fractional brain flow was also inversely correlated with cerebral white matter lesion grade, although this effect was not significant when adjusted for age. Frequency analysis of heart rate variability showed a gender-related inverse association of increased low-to-high-frequency power ratio with CBF and fractional brain flow. The findings do not support a direct effect of cardiac function on CBF, but demonstrates gender-related differences in cardiac output distribution. We propose fractional brain flow as a novel index that may be a useful marker of adequate brain perfusion in the context of ageing as well as cardiovascular disease. © 2013 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

  5. [Functional organization and structure of the serotonergic neuronal network of terrestrial snail].

    Science.gov (United States)

    Nikitin, E S; Balaban, P M

    2011-01-01

    The extension of knowledge how the brain works requires permanent improvement of methods of recording of neuronal activity and increase in the number of neurons recorded simultaneously to better understand the collective work of neuronal networks and assemblies. Conventional methods allow simultaneous intracellular recording up to 2-5 neurons and their membrane potentials, currents or monosynaptic connections or observation of spiking of neuronal groups with subsequent discrimination of individual spikes with loss of details of the dynamics of membrane potential. We recorded activity of a compact group of serotonergic neurons (up to 56 simultaneously) in the ganglion of a terrestrial mollusk using the method of optical recording of membrane potential that allowed to record individual action potentials in details with action potential parameters and to reveal morphology of the neurons rcorded. We demonstrated clear clustering in the group in relation with the dynamics of action potentials and phasic or tonic components in the neuronal responses to external electrophysiological and tactile stimuli. Also, we showed that identified neuron Pd2 could induce activation of a significant number of neurons in the group whereas neuron Pd4 did not induce any activation. However, its activation is delayed with regard to activation of the reacting group of neurons. Our data strongly support the concept of possible delegation of the integrative function by the network to a single neuron.

  6. The effects of levosimendan in cardiac surgery patients with poor left ventricular function

    NARCIS (Netherlands)

    de Hert, Stefan G.; Lorsomradee, Suraphong; Cromheecke, Stefanie; van der Linden, Philippe J.

    2007-01-01

    BACKGROUND: Patients with poor left ventricular function often require inotropic drug support immediately after cardiopulmonary bypass. Levosimendan improves cardiac function by a novel mechanism of action compared to currently available drugs. We hypothesized that, in patients with severely

  7. Cardiac Alpha1-Adrenergic Receptors: Novel Aspects of Expression, Signaling Mechanisms, Physiologic Function, and Clinical Importance

    Science.gov (United States)

    O’Connell, Timothy D.; Jensen, Brian C.; Baker, Anthony J.

    2014-01-01

    Adrenergic receptors (AR) are G-protein-coupled receptors (GPCRs) that have a crucial role in cardiac physiology in health and disease. Alpha1-ARs signal through Gαq, and signaling through Gq, for example, by endothelin and angiotensin receptors, is thought to be detrimental to the heart. In contrast, cardiac alpha1-ARs mediate important protective and adaptive functions in the heart, although alpha1-ARs are only a minor fraction of total cardiac ARs. Cardiac alpha1-ARs activate pleiotropic downstream signaling to prevent pathologic remodeling in heart failure. Mechanisms defined in animal and cell models include activation of adaptive hypertrophy, prevention of cardiac myocyte death, augmentation of contractility, and induction of ischemic preconditioning. Surprisingly, at the molecular level, alpha1-ARs localize to and signal at the nucleus in cardiac myocytes, and, unlike most GPCRs, activate “inside-out” signaling to cause cardioprotection. Contrary to past opinion, human cardiac alpha1-AR expression is similar to that in the mouse, where alpha1-AR effects are seen most convincingly in knockout models. Human clinical studies show that alpha1-blockade worsens heart failure in hypertension and does not improve outcomes in heart failure, implying a cardioprotective role for human alpha1-ARs. In summary, these findings identify novel functional and mechanistic aspects of cardiac alpha1-AR function and suggest that activation of cardiac alpha1-AR might be a viable therapeutic strategy in heart failure. PMID:24368739

  8. Cardiac function of the naked mole-rat: ecophysiological responses to working underground.

    Science.gov (United States)

    Grimes, Kelly M; Voorhees, Andrew; Chiao, Ying Ann; Han, Hai-Chao; Lindsey, Merry L; Buffenstein, Rochelle

    2014-03-01

    The naked mole-rat (NMR) is a strictly subterranean rodent with a low resting metabolic rate. Nevertheless, it can greatly increase its metabolic activity to meet the high energetic demands associated with digging through compacted soils in its xeric natural habitat where food is patchily distributed. We hypothesized that the NMR heart would naturally have low basal function and exhibit a large cardiac reserve, thereby mirroring the species' low basal metabolism and large metabolic scope. Echocardiography showed that young (2-4 yr old) healthy NMRs have low fractional shortening (28 ± 2%), ejection fraction (43 ± 2%), and cardiac output (6.5 ± 0.4 ml/min), indicating low basal cardiac function. Histology revealed large NMR cardiomyocyte cross-sectional area (216 ± 10 μm(2)) and cardiac collagen deposition of 2.2 ± 0.4%. Neither of these histomorphometric traits was considered pathological, since biaxial tensile testing showed no increase in passive ventricular stiffness. NMR cardiomyocyte fibers showed a low degree of rotation, contributing to the observed low NMR cardiac contractility. Interestingly, when the exercise mimetic dobutamine (3 μg/g ip) was administered, NMRs showed pronounced increases in fractional shortening, ejection fraction, cardiac output, and stroke volume, indicating an increased cardiac reserve. The relatively low basal cardiac function and enhanced cardiac reserve of NMRs are likely to be ecophysiological adaptations to life in an energetically taxing environment.

  9. New developments in paediatric cardiac functional ultrasound imaging.

    Science.gov (United States)

    de Korte, Chris L; Nillesen, Maartje M; Saris, Anne E C M; Lopata, Richard G P; Thijssen, Johan M; Kapusta, Livia

    2014-07-01

    Ultrasound imaging can be used to estimate the morphology as well as the motion and deformation of tissues. If the interrogated tissue is actively deforming, this deformation is directly related to its function and quantification of this deformation is normally referred as 'strain imaging'. Tissue can also be deformed by applying an internal or external force and the resulting, induced deformation is a function of the mechanical tissue characteristics. In combination with the load applied, these strain maps can be used to estimate or reconstruct the mechanical properties of tissue. This technique was named 'elastography' by Ophir et al. in 1991. Elastography can be used for atherosclerotic plaque characterisation, while the contractility of the heart or skeletal muscles can be assessed with strain imaging. Rather than using the conventional video format (DICOM) image information, radio frequency (RF)-based ultrasound methods enable estimation of the deformation at higher resolution and with higher precision than commercial methods using Doppler (tissue Doppler imaging) or video image data (2D speckle tracking methods). However, the improvement in accuracy is mainly achieved when measuring strain along the ultrasound beam direction, so it has to be considered a 1D technique. Recently, this method has been extended to multiple directions and precision further improved by using spatial compounding of data acquired at multiple beam steered angles. Using similar techniques, the blood velocity and flow can be determined. RF-based techniques are also beneficial for automated segmentation of the ventricular cavities. In this paper, new developments in different techniques of quantifying cardiac function by strain imaging, automated segmentation, and methods of performing blood flow imaging are reviewed and their application in paediatric cardiology is discussed.

  10. Cardiac neuronal imaging with 123I-meta-iodobenzylguanidine in heart failure: implications of endpoint selection and quantitative analysis on clinical decisions

    International Nuclear Information System (INIS)

    Petretta, Mario; Pellegrino, Teresa; Cuocolo, Alberto

    2014-01-01

    There are a number of radiopharmaceuticals that can be used to investigate autonomic neuronal functions. Among these, the norepinephrine analogue meta-iodobenzylguanidine (MIBG) labelled with 123 I has been widely used and validated as a marker of adrenergic neuron function. The first study addressing the prognostic value of 123 I-MIBG imaging in heart failure (HF) was that of Merlet et al. in 90 patients suffering from either ischaemic or idiopathic cardiomyopathy. After publication of this study, more recent studies have indicated that patients with HF and decreased late heart-to-mediastinum (H/M) ratio or increased myocardial MIBG washout have a worse prognosis than those with normal quantitative myocardial MIBG parameters. However, MIBG scintigraphy has still to reach widespread clinical application mainly because of the value of other cheaper variables such as left ventricular (LV) ejection fraction and brain natriuretic peptide (BNP) plasma levels. The possibility that the detection of mechanical dyssynchrony by innervation imaging might identify patients who would benefit from resynchronization pacing is another area of research interest. In 2010, the landmark AdreView Myocardial Imaging for Risk Evaluation in Heart Failure (ADMIRE-HF) study was published. This trial consisted of two identical open-label phase III studies enrolling patients in 96 sites in North America and Europe to provide prospective validation of the prognostic role of quantitation of sympathetic cardiac innervation using MIBG. The primary endpoint was the relationship between late HIM ratio and time-to-occurrence of the first event among a combination of HF progression, potentially life-threatening arrhythmic event, and cardiac death. The authors found that a HIM ratio <1.6 provided prognostic information beyond LV ejection fraction, BNP, and New York Heart Association (NYHA) functional class at the time of enrolment. In a recent article in this journal, Parker et al. present the results

  11. Cardiac neuronal imaging with {sup 123}I-meta-iodobenzylguanidine in heart failure: implications of endpoint selection and quantitative analysis on clinical decisions

    Energy Technology Data Exchange (ETDEWEB)

    Petretta, Mario [University Federico II, Department of Translational Medicine, Naples (Italy); Pellegrino, Teresa [National Council of Research, Institute of Biostructure and Bioimaging, Naples (Italy); Cuocolo, Alberto [University Federico II, Department of Advanced Biomedical Sciences, Naples (Italy)

    2014-09-15

    There are a number of radiopharmaceuticals that can be used to investigate autonomic neuronal functions. Among these, the norepinephrine analogue meta-iodobenzylguanidine (MIBG) labelled with {sup 123}I has been widely used and validated as a marker of adrenergic neuron function. The first study addressing the prognostic value of {sup 123}I-MIBG imaging in heart failure (HF) was that of Merlet et al. in 90 patients suffering from either ischaemic or idiopathic cardiomyopathy. After publication of this study, more recent studies have indicated that patients with HF and decreased late heart-to-mediastinum (H/M) ratio or increased myocardial MIBG washout have a worse prognosis than those with normal quantitative myocardial MIBG parameters. However, MIBG scintigraphy has still to reach widespread clinical application mainly because of the value of other cheaper variables such as left ventricular (LV) ejection fraction and brain natriuretic peptide (BNP) plasma levels. The possibility that the detection of mechanical dyssynchrony by innervation imaging might identify patients who would benefit from resynchronization pacing is another area of research interest. In 2010, the landmark AdreView Myocardial Imaging for Risk Evaluation in Heart Failure (ADMIRE-HF) study was published. This trial consisted of two identical open-label phase III studies enrolling patients in 96 sites in North America and Europe to provide prospective validation of the prognostic role of quantitation of sympathetic cardiac innervation using MIBG. The primary endpoint was the relationship between late HIM ratio and time-to-occurrence of the first event among a combination of HF progression, potentially life-threatening arrhythmic event, and cardiac death. The authors found that a HIM ratio <1.6 provided prognostic information beyond LV ejection fraction, BNP, and New York Heart Association (NYHA) functional class at the time of enrolment. In a recent article in this journal, Parker et al. present

  12. Neuronal spike sorting based on radial basis function neural networks

    Directory of Open Access Journals (Sweden)

    Taghavi Kani M

    2011-02-01

    Full Text Available "nBackground: Studying the behavior of a society of neurons, extracting the communication mechanisms of brain with other tissues, finding treatment for some nervous system diseases and designing neuroprosthetic devices, require an algorithm to sort neuralspikes automatically. However, sorting neural spikes is a challenging task because of the low signal to noise ratio (SNR of the spikes. The main purpose of this study was to design an automatic algorithm for classifying neuronal spikes that are emitted from a specific region of the nervous system."n "nMethods: The spike sorting process usually consists of three stages: detection, feature extraction and sorting. We initially used signal statistics to detect neural spikes. Then, we chose a limited number of typical spikes as features and finally used them to train a radial basis function (RBF neural network to sort the spikes. In most spike sorting devices, these signals are not linearly discriminative. In order to solve this problem, the aforesaid RBF neural network was used."n "nResults: After the learning process, our proposed algorithm classified any arbitrary spike. The obtained results showed that even though the proposed Radial Basis Spike Sorter (RBSS reached to the same error as the previous methods, however, the computational costs were much lower compared to other algorithms. Moreover, the competitive points of the proposed algorithm were its good speed and low computational complexity."n "nConclusion: Regarding the results of this study, the proposed algorithm seems to serve the purpose of procedures that require real-time processing and spike sorting.

  13. The function of mirror neurons in the learning process

    OpenAIRE

    Mara Daniel

    2017-01-01

    In the last years, Neurosciences have developed very much, being elaborated many important theories scientific research in the field. The main goal of neuroscience is to understand how groups of neurons interact to create the behavior. Neuroscientists studying the action of molecules, genes and cells. It also explores the complex interactions involved in motion perception, thoughts, emotions and learning. Brick fundamental nervous system is the nerve cell, neuron. Neurons exchange information...

  14. Changes of cardiac function in hyperthyroidism and hypothyroidism

    International Nuclear Information System (INIS)

    Morishita, Takeshi; Kawamura, Yasuaki; Yamazaki, Junichi; Okuzumi, Ichio; Muto, Toshinori; Wakakura, Manabu; Okamoto, Kiyoshi; Irie, Minoru; Inoue, Kazuko.

    1988-01-01

    Changes of cardiac parameters in patients with 21 hyperthyroidisms and 11 primary hypothyroidisms were studied administered by methimazole or 1-thyroxine using radionuclide method. In hyperthyroidisms, cardiac parameter (CI, EF, PEP/LVET, PEP) normalized 4 - 6 week delayed compared with hormonal level (T 3 , T 4 ) recovery period. On the other hand, in hypothyroidism PEP/LVET delayed about 2 weeks compared with hormonal level, however, other cardiac parameters were maintained within normal level, relatively. Correlation between T 3 and LVET was significant statistically (r = -0.59, p 3 and PEP was significant (r = -0.60, p < 0.01) in hypothyroidisms, respectively. (author)

  15. Evaluation of cardiac functions in patients with thalassemia major

    International Nuclear Information System (INIS)

    Kucuk, N.O.; Aras, G.; Sipahi, T.; Ibis, E.; Akar, N.; Soylu, A.; Erbay, G.

    1999-01-01

    It is known that a blood transfusion is necessary for survival in patients with thalassemia, but it may cause myocardial dysfunction due to myocardial siderosis as in other organs. The aim of this study was to evaluate myocardial perfusion by means of stress thallium scanning (MPS) and left ventricular functions by rest radionuclide ventriculography (RNV). Twenty-one patients at ages 9-16 (mean 12.1±3.2) who have been diagnosed with thalassemia for 4-15 years mean 12.7±4.8) were included in the study. They had blood transfusion 78-318 times (mean 162.1±71). MPS and RNV was performed within two days after the any transfusion. MPS showed ischemia in 3 patients and normal perfusion in 18 patients. RNV revealed normal systolic parameters (wall motion, EF, PER, TPE) but diminished diastolic parameters (TPF, PFR) compared with normal values (p<0.05). We conclude that ischemia or fixed defects may be seen in stress MPS as results of cardiac involvement in patients with thalassemia. But, RNV is an important and preferable test for the early detection of subclinic cardiomyopathy. RNV may therefore show diastolic abnormalities before the systolic abnormalities show up. (author)

  16. Evaluation of cardiac functions in patients with thalassemia major

    Energy Technology Data Exchange (ETDEWEB)

    Kucuk, N.O.; Aras, G.; Sipahi, T.; Ibis, E.; Akar, N.; Soylu, A.; Erbay, G. [Ankara Univ. (Turkey). Medical School

    1999-06-01

    It is known that a blood transfusion is necessary for survival in patients with thalassemia, but it may cause myocardial dysfunction due to myocardial siderosis as in other organs. The aim of this study was to evaluate myocardial perfusion by means of stress thallium scanning (MPS) and left ventricular functions by rest radionuclide ventriculography (RNV). Twenty-one patients at ages 9-16 (mean 12.1{+-}3.2) who have been diagnosed with thalassemia for 4-15 years mean 12.7{+-}4.8) were included in the study. They had blood transfusion 78-318 times (mean 162.1{+-}71). MPS and RNV was performed within two days after the any transfusion. MPS showed ischemia in 3 patients and normal perfusion in 18 patients. RNV revealed normal systolic parameters (wall motion, EF, PER, TPE) but diminished diastolic parameters (TPF, PFR) compared with normal values (p<0.05). We conclude that ischemia or fixed defects may be seen in stress MPS as results of cardiac involvement in patients with thalassemia. But, RNV is an important and preferable test for the early detection of subclinic cardiomyopathy. RNV may therefore show diastolic abnormalities before the systolic abnormalities show up. (author)

  17. Overexpression of survival motor neuron improves neuromuscular function and motor neuron survival in mutant SOD1 mice.

    Science.gov (United States)

    Turner, Bradley J; Alfazema, Neza; Sheean, Rebecca K; Sleigh, James N; Davies, Kay E; Horne, Malcolm K; Talbot, Kevin

    2014-04-01

    Spinal muscular atrophy results from diminished levels of survival motor neuron (SMN) protein in spinal motor neurons. Low levels of SMN also occur in models of amyotrophic lateral sclerosis (ALS) caused by mutant superoxide dismutase 1 (SOD1) and genetic reduction of SMN levels exacerbates the phenotype of transgenic SOD1(G93A) mice. Here, we demonstrate that SMN protein is significantly reduced in the spinal cords of patients with sporadic ALS. To test the potential of SMN as a modifier of ALS, we overexpressed SMN in 2 different strains of SOD1(G93A) mice. Neuronal overexpression of SMN significantly preserved locomotor function, rescued motor neurons, and attenuated astrogliosis in spinal cords of SOD1(G93A) mice. Despite this, survival was not prolonged, most likely resulting from SMN mislocalization and depletion of gems in motor neurons of symptomatic mice. Our results reveal that SMN upregulation slows locomotor deficit onset and motor neuron loss in this mouse model of ALS. However, disruption of SMN nuclear complexes by high levels of mutant SOD1, even in the presence of SMN overexpression, might limit its survival promoting effects in this specific mouse model. Studies in emerging mouse models of ALS are therefore warranted to further explore the potential of SMN as a modifier of ALS. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Cardiac Function in 7-8-Year-Old Offspring of Women with Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Maarten Rijpert

    2011-01-01

    Full Text Available Offspring of type 1 diabetic mothers (ODMs are at risk of short-term and long-term complications, such as neonatal macrosomia (birth weight >90th percentile, hypertrophic cardiomyopathy, and cardiovascular morbidity in later life. However, no studies have been performed regarding cardiac outcome. In this study, we investigated cardiac dimensions and function in 30 ODMs at 7-8 years of age in relation to neonatal macrosomia and maternal glycemic control during pregnancy and compared these with those in a control group of 30 children of nondiabetic women. We found that cardiac dimensions and systolic and diastolic function parameters in ODMs were comparable with those in controls. Neonatal macrosomia and poorer maternal glycemic control during pregnancy were not related to worse cardiac outcome in ODM. We conclude that cardiac function at 7-8 years of age in offspring of women with type 1 diabetes is reassuring and comparable with that in controls.

  19. Assessment of Cardiac Function in Fetuses of Gestational Diabetic Mothers During the Second Trimester.

    Science.gov (United States)

    Atiq, Mehnaz; Ikram, Anum; Hussain, Batool M; Saleem, Bakhtawar

    2017-06-01

    Fetuses of diabetic mothers may have structural or functional cardiac abnormalities which increase morbidity and mortality. Isolated functional abnormalities have been identified in the third trimester. The aim of the present study was to assess fetal cardiac function (systolic, diastolic, and global myocardial performance) in the second trimester in mothers with gestational diabetes, and also to relate cardiac function with glycemic control. Mothers with gestational diabetes mellitus referred for fetal cardiac evaluation in the second trimester (between 19 and 24 weeks) from March 2015 to February 2016 were enrolled as case subjects in this study. Non-diabetic mothers who had a fetal echocardiogram done between 19 and 24 weeks for other indications were enrolled as controls. Functional cardiac variables showed a statistically significant difference in isovolumetric relaxation and contraction times and the myocardial performance index and mitral E/A ratios in the gestational diabetic group (p = 0.003). Mitral annular plane systolic excursion was significantly less in the diabetic group (p = 0.01). The only functional cardiac variable found abnormal in mothers with poor glycemic control was the prolonged isovolumetric relaxation time. Functional cardiac abnormalities can be detected in the second trimester in fetuses of gestational diabetic mothers and timely intervention can improve postnatal outcomes.

  20. Neuron-specific feeding RNAi in C. elegans and its use in a screen for essential genes required for GABA neuron function.

    Science.gov (United States)

    Firnhaber, Christopher; Hammarlund, Marc

    2013-11-01

    Forward genetic screens are important tools for exploring the genetic requirements for neuronal function. However, conventional forward screens often have difficulty identifying genes whose relevant functions are masked by pleiotropy. In particular, if loss of gene function results in sterility, lethality, or other severe pleiotropy, neuronal-specific functions cannot be readily analyzed. Here we describe a method in C. elegans for generating cell-specific knockdown in neurons using feeding RNAi and its application in a screen for the role of essential genes in GABAergic neurons. We combine manipulations that increase the sensitivity of select neurons to RNAi with manipulations that block RNAi in other cells. We produce animal strains in which feeding RNAi results in restricted gene knockdown in either GABA-, acetylcholine-, dopamine-, or glutamate-releasing neurons. In these strains, we observe neuron cell-type specific behavioral changes when we knock down genes required for these neurons to function, including genes encoding the basal neurotransmission machinery. These reagents enable high-throughput, cell-specific knockdown in the nervous system, facilitating rapid dissection of the site of gene action and screening for neuronal functions of essential genes. Using the GABA-specific RNAi strain, we screened 1,320 RNAi clones targeting essential genes on chromosomes I, II, and III for their effect on GABA neuron function. We identified 48 genes whose GABA cell-specific knockdown resulted in reduced GABA motor output. This screen extends our understanding of the genetic requirements for continued neuronal function in a mature organism.

  1. Age-related normal structural and functional ventricular values in cardiac function assessed by magnetic resonance

    International Nuclear Information System (INIS)

    Fiechter, Michael; Gaemperli, Oliver; Kaufmann, Philipp A; Fuchs, Tobias A; Gebhard, Catherine; Stehli, Julia; Klaeser, Bernd; Stähli, Barbara E; Manka, Robert; Manes, Costantina; Tanner, Felix C

    2013-01-01

    The heart is subject to structural and functional changes with advancing age. However, the magnitude of cardiac age-dependent transformation has not been conclusively elucidated. This retrospective cardiac magnetic resonance (CMR) study included 183 subjects with normal structural and functional ventricular values. End systolic volume (ESV), end diastolic volume (EDV), and ejection fraction (EF) were obtained from the left and the right ventricle in breath-hold cine CMR. Patients were classified into four age groups (20–29, 30–49, 50–69, and ≥70 years) and cardiac measurements were compared using Pearson’s rank correlation over the four different groups. With advanced age a slight but significant decrease in ESV (r=−0.41 for both ventricles, P<0.001) and EDV (r=−0.39 for left ventricle, r=−0.35 for right ventricle, P<0.001) were observed associated with a significant increase in left (r=0.28, P<0.001) and right (r=0.27, P<0.01) ventricular EF reaching a maximal increase in EF of +8.4% (P<0.001) for the left and +6.1% (P<0.01) for the right ventricle in the oldest compared to the youngest patient group. Left ventricular myocardial mass significantly decreased over the four different age groups (P<0.05). The aging process is associated with significant changes in left and right ventricular EF, ESV and EDV in subjects with no cardiac functional and structural abnormalities. These findings underline the importance of using age adapted values as standard of reference when evaluating CMR studies

  2. Inhalation of Simulated Smog Atmospheres Affects Cardiac Function in Mice

    Science.gov (United States)

    The health effects of individual criteria air pollutants have been well investigated. However, little is known about the health effects of air pollutant mixtures that more realistically represent environmental exposures. The present study was designed to evaluate the cardiac eff...

  3. Investigation of synapse formation and function in a glutamatergic-GABAergic two-neuron microcircuit.

    Science.gov (United States)

    Chang, Chia-Ling; Trimbuch, Thorsten; Chao, Hsiao-Tuan; Jordan, Julia-Christine; Herman, Melissa A; Rosenmund, Christian

    2014-01-15

    Neural circuits are composed of mainly glutamatergic and GABAergic neurons, which communicate through synaptic connections. Many factors instruct the formation and function of these synapses; however, it is difficult to dissect the contribution of intrinsic cell programs from that of extrinsic environmental effects in an intact network. Here, we perform paired recordings from two-neuron microculture preparations of mouse hippocampal glutamatergic and GABAergic neurons to investigate how synaptic input and output of these two principal cells develop. In our reduced preparation, we found that glutamatergic neurons showed no change in synaptic output or input regardless of partner neuron cell type or neuronal activity level. In contrast, we found that glutamatergic input caused the GABAergic neuron to modify its output by way of an increase in synapse formation and a decrease in synaptic release efficiency. These findings are consistent with aspects of GABAergic synapse maturation observed in many brain regions. In addition, changes in GABAergic output are cell wide and not target-cell specific. We also found that glutamatergic neuronal activity determined the AMPA receptor properties of synapses on the partner GABAergic neuron. All modifications of GABAergic input and output required activity of the glutamatergic neuron. Because our system has reduced extrinsic factors, the changes we saw in the GABAergic neuron due to glutamatergic input may reflect initiation of maturation programs that underlie the formation and function of in vivo neural circuits.

  4. Chronic Cardiac-Targeted RNA Interference for the Treatment of Heart Failure Restores Cardiac Function and Reduces Pathological Hypertrophy

    Science.gov (United States)

    Suckau, Lennart; Fechner, Henry; Chemaly, Elie; Krohn, Stefanie; Hadri, Lahouaria; Kockskämper, Jens; Westermann, Dirk; Bisping, Egbert; Ly, Hung; Wang, Xiaomin; Kawase, Yoshiaki; Chen, Jiqiu; Liang, Lifan; Sipo, Isaac; Vetter, Roland; Weger, Stefan; Kurreck, Jens; Erdmann, Volker; Tschope, Carsten; Pieske, Burkert; Lebeche, Djamel; Schultheiss, Heinz-Peter; Hajjar, Roger J.; Poller, Wolfgang Ch.

    2009-01-01

    Background RNA interference (RNAi) has the potential to be a novel therapeutic strategy in diverse areas of medicine. We report on targeted RNAi for the treatment of heart failure (HF), an important disorder in humans resulting from multiple etiologies. Successful treatment of HF is demonstrated in a rat model of transaortic banding by RNAi targeting of phospholamban (PLB), a key regulator of cardiac Ca2+ homeostasis. Whereas gene therapy rests on recombinant protein expression as its basic principle, RNAi therapy employs regulatory RNAs to achieve its effect. Methods and Results We describe structural requirements to obtain high RNAi activity from adenoviral (AdV) and adeno-associated virus (AAV9) vectors and show that an AdV short hairpin RNA vector (AdV-shRNA) silenced PLB in cardiomyocytes (NRCMs) and improved hemodynamics in HF rats 1 month after aortic root injection. For simplified long-term therapy we developed a dimeric cardiotropic AAV vector (rAAV9-shPLB) delivering RNAi activity to the heart via intravenous injection. Cardiac PLB protein was reduced to 25% and SERCA2a suppression in the HF groups was rescued. In contrast to traditional vectors rAAV9 shows high affinity for myocardium, but low affinity for liver and other organs. rAAV9-shPLB therapy restored diastolic (LVEDP, dp/dtmin, Tau) and systolic (fractional shortening) functional parameters to normal range. The massive cardiac dilation was normalized and the cardiac hypertrophy, cardiomyocyte diameter and cardiac fibrosis significantly reduced. Importantly, there was no evidence of microRNA deregulation or hepatotoxicity during these RNAi therapies. Conclusion Our data show, for the first time, high efficacy of an RNAi therapeutic strategy in a cardiac disease. PMID:19237664

  5. Functional Connectome Analysis of Dopamine Neuron Glutamatergic Connections in Forebrain Regions.

    Science.gov (United States)

    Mingote, Susana; Chuhma, Nao; Kusnoor, Sheila V; Field, Bianca; Deutch, Ariel Y; Rayport, Stephen

    2015-12-09

    In the ventral tegmental area (VTA), a subpopulation of dopamine neurons express vesicular glutamate transporter 2 and make glutamatergic connections to nucleus accumbens (NAc) and olfactory tubercle (OT) neurons. However, their glutamatergic connections across the forebrain have not been explored systematically. To visualize dopamine neuron forebrain projections and to enable photostimulation of their axons independent of transmitter status, we virally transfected VTA neurons with channelrhodopsin-2 fused to enhanced yellow fluorescent protein (ChR2-EYFP) and used DAT(IREScre) mice to restrict expression to dopamine neurons. ChR2-EYFP-expressing neurons almost invariably stained for tyrosine hydroxylase, identifying them as dopaminergic. Dopamine neuron axons visualized by ChR2-EYFP fluorescence projected most densely to the striatum, moderately to the amygdala and entorhinal cortex (ERC), sparsely to prefrontal and cingulate cortices, and rarely to the hippocampus. Guided by ChR2-EYFP fluorescence, we recorded systematically from putative principal neurons in target areas and determined the incidence and strength of glutamatergic connections by activating all dopamine neuron terminals impinging on recorded neurons with wide-field photostimulation. This revealed strong glutamatergic connections in the NAc, OT, and ERC; moderate strength connections in the central amygdala; and weak connections in the cingulate cortex. No glutamatergic connections were found in the dorsal striatum, hippocampus, basolateral amygdala, or prefrontal cortex. These results indicate that VTA dopamine neurons elicit widespread, but regionally distinct, glutamatergic signals in the forebrain and begin to define the dopamine neuron excitatory functional connectome. Dopamine neurons are important for the control of motivated behavior and are involved in the pathophysiology of several major neuropsychiatric disorders. Recent studies have shown that some ventral midbrain dopamine neurons are

  6. Direct evidence of impaired neuronal Na/K-ATPase pump function in alternating hemiplegia of childhood.

    Science.gov (United States)

    Simmons, Christine Q; Thompson, Christopher H; Cawthon, Bryan E; Westlake, Grant; Swoboda, Kathryn J; Kiskinis, Evangelos; Ess, Kevin C; George, Alfred L

    2018-03-19

    Mutations in ATP1A3 encoding the catalytic subunit of the Na/K-ATPase expressed in mammalian neurons cause alternating hemiplegia of childhood (AHC) as well as an expanding spectrum of other neurodevelopmental syndromes and neurological phenotypes. Most AHC cases are explained by de novo heterozygous ATP1A3 mutations, but the fundamental molecular and cellular consequences of these mutations in human neurons are not known. In this study, we investigated the electrophysiological properties of neurons generated from AHC patient-specific induced pluripotent stem cells (iPSCs) to ascertain functional disturbances underlying this neurological disease. Fibroblasts derived from two subjects with AHC, a male and a female, both heterozygous for the common ATP1A3 mutation G947R, were reprogrammed to iPSCs. Neuronal differentiation of iPSCs was initiated by neurogenin-2 (NGN2) induction followed by co-culture with mouse glial cells to promote maturation of cortical excitatory neurons. Whole-cell current clamp recording demonstrated that, compared with control iPSC-derived neurons, neurons differentiated from AHC iPSCs exhibited a significantly lower level of ouabain-sensitive outward current ('pump current'). This finding correlated with significantly depolarized potassium equilibrium potential and depolarized resting membrane potential in AHC neurons compared with control neurons. In this cellular model, we also observed a lower evoked action potential firing frequency when neurons were held at their resting potential. However, evoked action potential firing frequencies were not different between AHC and control neurons when the membrane potential was clamped to -80 mV. Impaired neuronal excitability could be explained by lower voltage-gated sodium channel availability at the depolarized membrane potential observed in AHC neurons. Our findings provide direct evidence of impaired neuronal Na/K-ATPase ion transport activity in human AHC neurons and demonstrate the potential

  7. Myocardin-related transcription factors are required for cardiac development and function

    Science.gov (United States)

    Mokalled, Mayssa H.; Carroll, Kelli J.; Cenik, Bercin K.; Chen, Beibei; Liu, Ning; Olson, Eric N.; Bassel-Duby, Rhonda

    2016-01-01

    Myocardin-Related Transcription Factors A and B (MRTF-A and MRTF-B) are highly homologous proteins that function as powerful coactivators of serum response factor (SRF), a ubiquitously expressed transcription factor essential for cardiac development. The SRF/MRTF complex binds to CArG boxes found in the control regions of genes that regulate cytoskeletal dynamics and muscle contraction, among other processes. While SRF is required for heart development and function, the role of MRTFs in the developing or adult heart has not been explored. Through cardiac-specific deletion of MRTF alleles in mice, we show that either MRTF-A or MRTF-B is dispensable for cardiac development and function, whereas deletion of both MRTF-A and MRTF-B causes a spectrum of structural and functional cardiac abnormalities. Defects observed in MRTF-A/B null mice ranged from reduced cardiac contractility and adult onset heart failure to neonatal lethality accompanied by sarcomere disarray. RNA-seq analysis on neonatal hearts identified the most altered pathways in MRTF double knockout hearts as being involved in cytoskeletal organization. Together, these findings demonstrate redundant but essential roles of the MRTFs in maintenance of cardiac structure and function and as indispensible links in cardiac cytoskeletal gene regulatory networks. PMID:26386146

  8. Simultaneous determination of dynamic cardiac metabolism and function using PET/MRI.

    Science.gov (United States)

    Barton, Gregory P; Vildberg, Lauren; Goss, Kara; Aggarwal, Niti; Eldridge, Marlowe; McMillan, Alan B

    2018-05-01

    Cardiac metabolic changes in heart disease precede overt contractile dysfunction. However, metabolism and function are not typically assessed together in clinical practice. The purpose of this study was to develop a cardiac positron emission tomography/magnetic resonance (PET/MR) stress test to assess the dynamic relationship between contractile function and metabolism in a preclinical model. Following an overnight fast, healthy pigs (45-50 kg) were anesthetized and mechanically ventilated. 18 F-fluorodeoxyglucose ( 18 F-FDG) solution was administered intravenously at a constant rate of 0.01 mL/s for 60 minutes. A cardiac PET/MR stress test was performed using normoxic gas (F I O 2  = .209) and hypoxic gas (F I O 2  = .12). Simultaneous cardiac imaging was performed on an integrated 3T PET/MR scanner. Hypoxic stress induced a significant increase in heart rate, cardiac output, left ventricular (LV) ejection fraction (EF), and peak torsion. There was a significant decline in arterial SpO 2 , LV end-diastolic and end-systolic volumes in hypoxia. Increased LV systolic function was coupled with an increase in myocardial FDG uptake (Ki) during hypoxic stress. PET/MR with continuous FDG infusion captures dynamic changes in both cardiac metabolism and contractile function. This technique warrants evaluation in human cardiac disease for assessment of subtle functional and metabolic abnormalities.

  9. Functional Relevance of Coronary Artery Disease by Cardiac Magnetic Resonance and Cardiac Computed Tomography: Myocardial Perfusion and Fractional Flow Reserve

    Directory of Open Access Journals (Sweden)

    Gianluca Pontone

    2015-01-01

    Full Text Available Coronary artery disease (CAD is one of the leading causes of morbidity and mortality and it is responsible for an increasing resource burden. The identification of patients at high risk for adverse events is crucial to select those who will receive the greatest benefit from revascularization. To this aim, several non-invasive functional imaging modalities are usually used as gatekeeper to invasive coronary angiography, but the diagnostic yield of elective invasive coronary angiography remains unfortunately low. Stress myocardial perfusion imaging by cardiac magnetic resonance (stress-CMR has emerged as an accurate technique for diagnosis and prognostic stratification of the patients with known or suspected CAD thanks to high spatial and temporal resolution, absence of ionizing radiation, and the multiparametric value including the assessment of cardiac anatomy, function, and viability. On the other side, cardiac computed tomography (CCT has emerged as unique technique providing coronary arteries anatomy and more recently, due to the introduction of stress-CCT and noninvasive fractional flow reserve (FFR-CT, functional relevance of CAD in a single shot scan. The current review evaluates the technical aspects and clinical experience of stress-CMR and CCT in the evaluation of functional relevance of CAD discussing the strength and weakness of each approach.

  10. Nebivolol: impact on cardiac and endothelial function and clinical utility

    Directory of Open Access Journals (Sweden)

    Toblli JE

    2012-03-01

    Full Text Available Jorge Eduardo Toblli1, Federico DiGennaro1, Jorge Fernando Giani2, Fernando Pablo Dominici21Hospital Aleman, 2Instituto de Química y Fisicoquímica Biológicas (IQUIFIB, Facultad de Farmacia y Bioquímica, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, ArgentinaAbstract: Endothelial dysfunction is a systemic pathological state of the endothelium characterized by a reduction in the bioavailability of vasodilators, essentially nitric oxide, leading to impaired endothelium-dependent vasodilation, as well as disarrangement in vascular wall metabolism and function. One of the key factors in endothelial dysfunction is overproduction of reactive oxygen species which participate in the development of hypertension, atherosclerosis, diabetes, cardiac hypertrophy, heart failure, ischemia-reperfusion injury, and stroke. Because impaired endothelial activity is believed to have a major causal role in the pathophysiology of vascular disease, hypertension, and heart failure, therapeutic agents which modify this condition are of clinical interest. Nebivolol is a third-generation β-blocker with high selectivity for β1-adrenergic receptors and causes vasodilation by interaction with the endothelial L-arginine/nitric oxide pathway. This dual mechanism of action underscores several hemodynamic qualities of nebivolol, which include reductions in heart rate and blood pressure and improvements in systolic and diastolic function. Although nebivolol reduces blood pressure to a degree similar to that of conventional β-blockers and other types of antihypertensive drugs, it may have advantages in populations with difficult-to-treat hypertension, such as patients with heart failure along with other comorbidities, like diabetes and obesity, and elderly patients in whom nitric oxide-mediated endothelial dysfunction may be more pronounced. Furthermore, recent data indicate that nebivolol appears to be a cost-effective treatment for elderly patients with

  11. Voltage imaging to understand connections and functions of neuronal circuits

    Science.gov (United States)

    Antic, Srdjan D.; Empson, Ruth M.

    2016-01-01

    Understanding of the cellular mechanisms underlying brain functions such as cognition and emotions requires monitoring of membrane voltage at the cellular, circuit, and system levels. Seminal voltage-sensitive dye and calcium-sensitive dye imaging studies have demonstrated parallel detection of electrical activity across populations of interconnected neurons in a variety of preparations. A game-changing advance made in recent years has been the conceptualization and development of optogenetic tools, including genetically encoded indicators of voltage (GEVIs) or calcium (GECIs) and genetically encoded light-gated ion channels (actuators, e.g., channelrhodopsin2). Compared with low-molecular-weight calcium and voltage indicators (dyes), the optogenetic imaging approaches are 1) cell type specific, 2) less invasive, 3) able to relate activity and anatomy, and 4) facilitate long-term recordings of individual cells' activities over weeks, thereby allowing direct monitoring of the emergence of learned behaviors and underlying circuit mechanisms. We highlight the potential of novel approaches based on GEVIs and compare those to calcium imaging approaches. We also discuss how novel approaches based on GEVIs (and GECIs) coupled with genetically encoded actuators will promote progress in our knowledge of brain circuits and systems. PMID:27075539

  12. Functional Characterization of Lamina X Neurons in ex-Vivo Spinal Cord Preparation

    Directory of Open Access Journals (Sweden)

    Volodymyr Krotov

    2017-11-01

    Full Text Available Functional properties of lamina X neurons in the spinal cord remain unknown despite the established role of this area for somatosensory integration, visceral nociception, autonomic regulation and motoneuron output modulation. Investigations of neuronal functioning in the lamina X have been hampered by technical challenges. Here we introduce an ex-vivo spinal cord preparation with both dorsal and ventral roots still attached for functional studies of the lamina X neurons and their connectivity using an oblique LED illumination for resolved visualization of lamina X neurons in a thick tissue. With the elaborated approach, we demonstrate electrophysiological characteristics of lamina X neurons by their membrane properties, firing pattern discharge and fiber innervation (either afferent or efferent. The tissue preparation has been also probed using Ca2+ imaging with fluorescent Ca2+ dyes (membrane-impermeable or -permeable to demonstrate the depolarization-induced changes in intracellular calcium concentration in lamina X neurons. Finally, we performed visualization of subpopulations of lamina X neurons stained by retrograde labeling with aminostilbamidine dye to identify sympathetic preganglionic and projection neurons in the lamina X. Thus, the elaborated approach provides a reliable tool for investigation of functional properties and connectivity in specific neuronal subpopulations, boosting research of lamina X of the spinal cord.

  13. The function of mirror neurons in the learning process

    Directory of Open Access Journals (Sweden)

    Mara Daniel

    2017-01-01

    Full Text Available In the last years, Neurosciences have developed very much, being elaborated many important theories scientific research in the field. The main goal of neuroscience is to understand how groups of neurons interact to create the behavior. Neuroscientists studying the action of molecules, genes and cells. It also explores the complex interactions involved in motion perception, thoughts, emotions and learning. Brick fundamental nervous system is the nerve cell, neuron. Neurons exchange information by sending electrical signals and chemical through connections called synapses. Discovered by a group of Italian researchers from the University of Parma, neurons - mirror are a special class of nerve cells played an important role in the direct knowledge, automatic and unconscious environment. These cortical neurons are activated not only when an action is fulfilled, but when we see how the same action is performed by someone else, they represent neural mechanism by which the actions, intentions and emotions of others can be understood automatically. In childhood neurons - mirror are extremely important. Thanks to them we learned a lot in the early years: smile, to ask for help and, in fact, all the behaviors and family and group norms. People learn by what they see and sense the others. Neurons - mirror are important to understanding the actions and intentions of other people and learn new skills through mirror image. They are involved in planning and controlling actions, abstract thinking and memory. If a child observes an action, neurons - mirror is activated and forming new neural pathways as if even he takes that action. Efficient activity of mirror neurons leads to good development in all areas at a higher emotional intelligence and the ability to empathize with others.

  14. Cardiac function in survivors of childhood acute myeloid leukemia treated with chemotherapy only

    DEFF Research Database (Denmark)

    Jarfelt, Marianne; Andersen, Niels Holmark; Glosli, Heidi

    2015-01-01

    OBJECTIVES: We report cardiac function of patients treated for Childhood acute myeloid leukemia with chemotherapy only according to three consecutive Nordic protocols. METHODS: Ninety-eight of 138 eligible patients accepted examination with standardized echocardiography. Results were compared...

  15. Effect of Cardiac Rehabilitation on Heart Rate and Functional Capacity in Patients After Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Mandana Parvand

    2016-09-01

    Discussion: Cardiac rehabilitation can increase the performance of blood circulation and uptake of oxygen in body. Due to these changes, there was a significant increase in the functional capacity and an insignificant reduction in the heart rate.

  16. Functions of PDE3 Isoforms in Cardiac Muscle

    Science.gov (United States)

    Movsesian, Matthew; Ahmad, Faiyaz

    2018-01-01

    Isoforms in the PDE3 family of cyclic nucleotide phosphodiesterases have important roles in cyclic nucleotide-mediated signalling in cardiac myocytes. These enzymes are targeted by inhibitors used to increase contractility in patients with heart failure, with a combination of beneficial and adverse effects on clinical outcomes. This review covers relevant aspects of the molecular biology of the isoforms that have been identified in cardiac myocytes; the roles of these enzymes in modulating cAMP-mediated signalling and the processes mediated thereby; and the potential for targeting these enzymes to improve the profile of clinical responses. PMID:29415428

  17. Functional properties of human neuronal Kv11 channels

    DEFF Research Database (Denmark)

    Einarsen, Karoline; Calloe, Kirstine; Grunnet, Morten

    2009-01-01

    Kv11 potassium channels are important for regulation of the membrane potential. Kv11.2 and Kv11.3 are primarily found in the nervous system, where they most likely are involved in the regulation of neuronal excitability. Two isoforms of human Kv11.2 have been published so far. Here, we present...... current characteristics of the isoforms presented in this work may contribute to the regulation of neuronal excitability....

  18. Histological and functional benefit following transplantation of motor neuron progenitors to the injured rat spinal cord.

    Directory of Open Access Journals (Sweden)

    Sharyn L Rossi

    2010-07-01

    Full Text Available Motor neuron loss is characteristic of cervical spinal cord injury (SCI and contributes to functional deficit.In order to investigate the amenability of the injured adult spinal cord to motor neuron differentiation, we transplanted spinal cord injured animals with a high purity population of human motor neuron progenitors (hMNP derived from human embryonic stem cells (hESCs. In vitro, hMNPs displayed characteristic motor neuron-specific markers, a typical electrophysiological profile, functionally innervated human or rodent muscle, and secreted physiologically active growth factors that caused neurite branching and neuronal survival. hMNP transplantation into cervical SCI sites in adult rats resulted in suppression of intracellular signaling pathways associated with SCI pathogenesis, which correlated with greater endogenous neuronal survival and neurite branching. These neurotrophic effects were accompanied by significantly enhanced performance on all parameters of the balance beam task, as compared to controls. Interestingly, hMNP transplantation resulted in survival, differentiation, and site-specific integration of hMNPs distal to the SCI site within ventral horns, but hMNPs near the SCI site reverted to a neuronal progenitor state, suggesting an environmental deficiency for neuronal maturation associated with SCI.These findings underscore the barriers imposed on neuronal differentiation of transplanted cells by the gliogenic nature of the injured spinal cord, and the physiological relevance of transplant-derived neurotrophic support to functional recovery.

  19. Challenging the neuronal MIBG uptake by pharmacological intervention: effect of a single dose of oral amitriptyline on regional cardiac MIBG uptake

    Energy Technology Data Exchange (ETDEWEB)

    Estorch, Montserrat; Carrio, Ignasi; Mena, Esther; Flotats, Albert; Camacho, Valle; Fuertes, Jordi [Autonomous University of Barcelona, Department of Nuclear Medicine, Hospital Sant Pau, Barcelona (Spain); Kulisewsky, Jaume [Autonomous University of Barcelona, Department of Neurology, Hospital Sant Pau, Barcelona (Spain); Narula, Jagat [Irvine College of Medicine, Division of Cardiology, University of California, Irvine, CA (United States)

    2004-12-01

    Imaging with metaiodobenzylguanidine (MIBG) is used for the assessment of neuronal dysfunction in various cardiovascular disorders. Although valuable information is obtained by resting MIBG imaging, it is conceivable that competitive interference with the re-uptake mechanism would exaggerate MIBG defects and might unmask subclinical neuronal dysfunction. Tricyclic antidepressants, such as amitriptyline, have been reported to significantly increase cardiac MIBG washout and inhibit uptake into presynaptic neurons. This study was undertaken to assess whether a single oral dose of amitriptyline could influence cardiac MIBG distribution. Six patients (aged 62-81 years; four males, two females) who had demonstrated a normal cardiac MIBG scan during work-up for movement disorders were studied. The patients underwent a second {sup 123}I-MIBG study after oral administration of 25 mg amitriptyline within 1 week. Single-photon emission computed tomography images were acquired at 4 h to assess the regional distribution of MIBG, after generation of polar maps and employing a 20-segment model. Mean percentage of peak activity was calculated for each segment at rest and after amitriptyline administration. After amitriptyline administration, there was a decrease in regional MIBG uptake in 10{+-}4 segments per patient [62/120 segments (52%): 37 segments with a 5-10% decrease, 25 segments with a >10% decrease]. This change was statistically significant in lateral (P=0.003), apical (P<0.0001) and inferior (P=0.03) regions. A single oral dose of amitriptyline can induce changes in the uptake and retention of cardiac MIBG, indicating the feasibility of use of pharmacological intervention in cardiac neurotransmission imaging. (orig.)

  20. Comparative Toxicity of Different Crude Oils on the Cardiac Function of Marine Medaka (Oryzias melastigma Embryo

    Directory of Open Access Journals (Sweden)

    Zhendong Zhang

    2014-12-01

    Full Text Available The acute toxic effect of different crude oils (heavy crude oil and bonny light crude oil on embryos of marine medaka Oryzias melastigma was measured and evaluated by exposure to the water-accommodated fraction (WAF in the present study. The cardiac function of medaka embryos was used as target organ of ecotoxicological effect induced by oil exposure. Results showed that the developing marine medaka heart was a sensitive target organ to crude oil exposure the heavy crude oil WAF was more toxic to cardiac function of medaka embryos than bonny light cured oil one. Cardiac function of medaka embryos was clearly affected by exposure to heavy crude oil WAF after 24 hours exposure and showed a dose-dependent slowing of heart rate. Furthermore, swelled and enlarged heart morphology, lowered blood circulation and accumulation of blood cells around the heart area were found. However, the toxic effect of bonny light crude oil on cardiac function of medaka embryos was comparatively low. Statistical results showed that the cardiac function was only affected by highest bonny light crude oil WAF (9.8 mg/L exposure treatment. These findings indicated that cardiac function of marine medaka embryo was a good toxicity model for oil pollution and could be used to compare and evaluate the toxicity of different crude oils. The heart rate was an appropriate endpoint in the acute toxicity test.

  1. A portable cadmium telluride multidetector probe for cardiac function monitoring

    Energy Technology Data Exchange (ETDEWEB)

    Arntz, Y.; Chambron, J.; Dumitresco, B.; Eclancher, B. E-mail: eclan@alsace.u-strasbg.fr; Prat, V

    1999-06-01

    A new nuclear stethoscope based on a matrix of small CdTe semiconductor detectors has been developed for studying the cardiac performance by gamma ventriculography at the equilibrium, in rest and stress conditions, in the early and recovery phases of the coronary disease and to follow the long-term therapy. The light-weight probe consists of an array of 64 detectors 5x5x2 mm grouped in 16 independent units in a lead shielded aluminum box including 16 preamplifiers. The probe is connected to an electronic box containing DC power supply, 16 channel amplifiers, discriminators and counters, two analog-triggering ECG channels, and interface to a PC. The left ventricle activity is, preferentially, detected by using a low-resolution matching convergent collimator. A physical evaluation of the probe has been performed, both with static tests and dynamically with a hydraulic home-built model of beating heart ventricle paced by a rhythm simulator. The sum of the 16 detectors activity provided a radiocardiogram (RCG) which well depicted the filling and ejection of the cardiac beats, allowing to compare the clinically relevant parameters of the cardiac performance, proportional variables of the stroke volume (SV), ejection fraction (EF) and ventricular flow-rate with the known absolute values programmed on the model. The portable system is now in operation for clinical assessment of cardiac patients.

  2. A portable cadmium telluride multidetector probe for cardiac function monitoring

    International Nuclear Information System (INIS)

    Arntz, Y.; Chambron, J.; Dumitresco, B.; Eclancher, B.; Prat, V.

    1999-01-01

    A new nuclear stethoscope based on a matrix of small CdTe semiconductor detectors has been developed for studying the cardiac performance by gamma ventriculography at the equilibrium, in rest and stress conditions, in the early and recovery phases of the coronary disease and to follow the long-term therapy. The light-weight probe consists of an array of 64 detectors 5x5x2 mm grouped in 16 independent units in a lead shielded aluminum box including 16 preamplifiers. The probe is connected to an electronic box containing DC power supply, 16 channel amplifiers, discriminators and counters, two analog-triggering ECG channels, and interface to a PC. The left ventricle activity is, preferentially, detected by using a low-resolution matching convergent collimator. A physical evaluation of the probe has been performed, both with static tests and dynamically with a hydraulic home-built model of beating heart ventricle paced by a rhythm simulator. The sum of the 16 detectors activity provided a radiocardiogram (RCG) which well depicted the filling and ejection of the cardiac beats, allowing to compare the clinically relevant parameters of the cardiac performance, proportional variables of the stroke volume (SV), ejection fraction (EF) and ventricular flow-rate with the known absolute values programmed on the model. The portable system is now in operation for clinical assessment of cardiac patients

  3. Cardiac structure and function predicts functional decline in the oldest old.

    Science.gov (United States)

    Leibowitz, David; Jacobs, Jeremy M; Lande-Stessman, Irit; Gilon, Dan; Stessman, Jochanan

    2018-02-01

    Background This study examined the association between cardiac structure and function and the deterioration in activities of daily living (ADLs) in an age-homogenous, community-dwelling population of patients born in 1920-1921 over a five-year follow-up period. Design Longitudinal cohort study. Methods Patients were recruited from the Jerusalem Longitudinal Cohort Study, which has followed an age-homogenous cohort of Jerusalem residents born in 1920-1921. Patients underwent home echocardiography and were followed up for five years. Dependence was defined as needing assistance with one or more basic ADL. Standard echocardiographic assessment of cardiac structure and function, including systolic and diastolic function, was performed. Reassessment of ADLs was performed at the five-year follow-up. Results A total of 459 patients were included in the study. Of these, 362 (79%) showed a deterioration in at least one ADL at follow-up. Patients with functional deterioration had a significantly higher left ventricular mass index and left atrial volume with a lower ejection fraction. There was no significant difference between the diastolic parameters the groups in examined. When the data were examined categorically, a significantly larger percentage of patients with functional decline had an abnormal left ventricular ejection fraction and left ventricular hypertrophy. The association between left ventricular mass index and functional decline remained significant in all multivariate models. Conclusions In this cohort of the oldest old, an elevated left ventricular mass index, higher left atrial volumes and systolic, but not diastolic dysfunction, were predictive of functional disability.

  4. Adrenergic Blockade Bi-directionally and Asymmetrically Alters Functional Brain-Heart Communication and Prolongs Electrical Activities of the Brain and Heart during Asphyxic Cardiac Arrest

    Science.gov (United States)

    Tian, Fangyun; Liu, Tiecheng; Xu, Gang; Li, Duan; Ghazi, Talha; Shick, Trevor; Sajjad, Azeem; Wang, Michael M.; Farrehi, Peter; Borjigin, Jimo

    2018-01-01

    Sudden cardiac arrest is a leading cause of death in the United States. The neurophysiological mechanism underlying sudden death is not well understood. Previously we have shown that the brain is highly stimulated in dying animals and that asphyxia-induced death could be delayed by blocking the intact brain-heart neuronal connection. These studies suggest that the autonomic nervous system plays an important role in mediating sudden cardiac arrest. In this study, we tested the effectiveness of phentolamine and atenolol, individually or combined, in prolonging functionality of the vital organs in CO2-mediated asphyxic cardiac arrest model. Rats received either saline, phentolamine, atenolol, or phentolamine plus atenolol, 30 min before the onset of asphyxia. Electrocardiogram (ECG) and electroencephalogram (EEG) signals were simultaneously collected from each rat during the entire process and investigated for cardiac and brain functions using a battery of analytic tools. We found that adrenergic blockade significantly suppressed the initial decline of cardiac output, prolonged electrical activities of both brain and heart, asymmetrically altered functional connectivity within the brain, and altered, bi-directionally and asymmetrically, functional, and effective connectivity between the brain and heart. The protective effects of adrenergic blockers paralleled the suppression of brain and heart connectivity, especially in the right hemisphere associated with central regulation of sympathetic function. Collectively, our results demonstrate that blockade of brain-heart connection via alpha- and beta-adrenergic blockers significantly prolonged the detectable activities of both the heart and the brain in asphyxic rat. The beneficial effects of combined alpha and beta blockers may help extend the survival of cardiac arrest patients. PMID:29487541

  5. Adrenergic Blockade Bi-directionally and Asymmetrically Alters Functional Brain-Heart Communication and Prolongs Electrical Activities of the Brain and Heart during Asphyxic Cardiac Arrest

    Directory of Open Access Journals (Sweden)

    Fangyun Tian

    2018-02-01

    Full Text Available Sudden cardiac arrest is a leading cause of death in the United States. The neurophysiological mechanism underlying sudden death is not well understood. Previously we have shown that the brain is highly stimulated in dying animals and that asphyxia-induced death could be delayed by blocking the intact brain-heart neuronal connection. These studies suggest that the autonomic nervous system plays an important role in mediating sudden cardiac arrest. In this study, we tested the effectiveness of phentolamine and atenolol, individually or combined, in prolonging functionality of the vital organs in CO2-mediated asphyxic cardiac arrest model. Rats received either saline, phentolamine, atenolol, or phentolamine plus atenolol, 30 min before the onset of asphyxia. Electrocardiogram (ECG and electroencephalogram (EEG signals were simultaneously collected from each rat during the entire process and investigated for cardiac and brain functions using a battery of analytic tools. We found that adrenergic blockade significantly suppressed the initial decline of cardiac output, prolonged electrical activities of both brain and heart, asymmetrically altered functional connectivity within the brain, and altered, bi-directionally and asymmetrically, functional, and effective connectivity between the brain and heart. The protective effects of adrenergic blockers paralleled the suppression of brain and heart connectivity, especially in the right hemisphere associated with central regulation of sympathetic function. Collectively, our results demonstrate that blockade of brain-heart connection via alpha- and beta-adrenergic blockers significantly prolonged the detectable activities of both the heart and the brain in asphyxic rat. The beneficial effects of combined alpha and beta blockers may help extend the survival of cardiac arrest patients.

  6. Overhydration, Cardiac Function and Survival in Hemodialysis Patients.

    Science.gov (United States)

    Onofriescu, Mihai; Siriopol, Dimitrie; Voroneanu, Luminita; Hogas, Simona; Nistor, Ionut; Apetrii, Mugurel; Florea, Laura; Veisa, Gabriel; Mititiuc, Irina; Kanbay, Mehmet; Sascau, Radu; Covic, Adrian

    2015-01-01

    .29-5.89 for RFO >17.4%) and multivariate (HR = 2.31, 95%CI = 1.42-3.77 for RFO >15% and HR = 4.17, 95%CI = 2.48-7.02 for RFO >17.4%) Cox regression analysis. The study shows that the hydration status is associated with the mortality risk in a HD population, independently of cardiac morphology and function. We also describe and propose a new cut-off for RFO, in order to better define the relationship between overhydration and mortality risk. Further studies are needed to properly validate this new cut-off in other HD populations.

  7. Overhydration, Cardiac Function and Survival in Hemodialysis Patients.

    Directory of Open Access Journals (Sweden)

    Mihai Onofriescu

    .67, 95%CI = 2.29-5.89 for RFO >17.4% and multivariate (HR = 2.31, 95%CI = 1.42-3.77 for RFO >15% and HR = 4.17, 95%CI = 2.48-7.02 for RFO >17.4% Cox regression analysis.The study shows that the hydration status is associated with the mortality risk in a HD population, independently of cardiac morphology and function. We also describe and propose a new cut-off for RFO, in order to better define the relationship between overhydration and mortality risk. Further studies are needed to properly validate this new cut-off in other HD populations.

  8. Unique functional properties of somatostatin-expressing GABAergic neurons in mouse barrel cortex.

    NARCIS (Netherlands)

    Gentet, L.J.; Kremer, Y.; Taniguchi, H.; Huang, Z.J.; Staiger, J.F.; Petersen, C.C.H.

    2012-01-01

    Neocortical GABAergic neurons have diverse molecular, structural and electrophysiological features, but the functional correlates of this diversity are largely unknown. We found unique membrane potential dynamics of somatostatin-expressing (SOM) neurons in layer 2/3 of the primary somatosensory

  9. Dynamical patterns of calcium signaling in a functional model of neuron-astrocyte networks

    DEFF Research Database (Denmark)

    Postnov, D.E.; Koreshkov, R.N.; Brazhe, N.A.

    2009-01-01

    We propose a functional mathematical model for neuron-astrocyte networks. The model incorporates elements of the tripartite synapse and the spatial branching structure of coupled astrocytes. We consider glutamate-induced calcium signaling as a specific mode of excitability and transmission...... in astrocytic-neuronal networks. We reproduce local and global dynamical patterns observed experimentally....

  10. Effects of vildagliptin versus sitagliptin, on cardiac function, heart rate variability and mitochondrial function in obese insulin-resistant rats

    Science.gov (United States)

    Apaijai, Nattayaporn; Pintana, Hiranya; Chattipakorn, Siriporn C; Chattipakorn, Nipon

    2013-01-01

    Background and Purpose Long-term high-fat diet (HFD) consumption has been shown to cause insulin resistance, which is characterized by hyperinsulinaemia with metabolic inflexibility. Insulin resistance is associated with cardiac sympathovagal imbalance, cardiac dysfunction and cardiac mitochondrial dysfunction. Dipeptidyl peptidase-4 (DPP-4) inhibitors, vildagliptin and sitagliptin, are oral anti-diabetic drugs often prescribed in patients with cardiovascular disease. Therefore, in this study, we sought to determine the effects of vildagliptin and sitagliptin in a murine model of insulin resistance. Experimental Approach Male Wistar rats weighing 180–200 g, were fed either a normal diet (20% energy from fat) or a HFD (59% energy from fat) for 12 weeks. These rats were then divided into three subgroups to receive vildagliptin (3 mg·kg−1·day−1), sitagliptin (30 mg·kg−1·day−1) or vehicle for another 21 days. Metabolic parameters, oxidative stress, heart rate variability (HRV), cardiac function and cardiac mitochondrial function were determined. Key Results Rats that received HFD developed insulin resistance characterized by increased body weight, plasma insulin, total cholesterol and oxidative stress levels along with a decreased high-density lipoprotein (HDL) level. Moreover, cardiac dysfunction, depressed HRV, cardiac mitochondrial dysfunction and cardiac mitochondrial morphology changes were observed in HFD rats. Both vildagliptin and sitagliptin decreased plasma insulin, total cholesterol and oxidative stress as well as increased HDL level. Furthermore, vildagliptin and sitagliptin attenuated cardiac dysfunction, prevented cardiac mitochondrial dysfunction and completely restored HRV. Conclusions and Implications Both vildagliptin and sitagliptin share similar efficacy in cardioprotection in obese insulin-resistant rats. PMID:23488656

  11. α-Synuclein fibril-induced paradoxical structural and functional defects in hippocampal neurons.

    Science.gov (United States)

    Froula, Jessica M; Henderson, Benjamin W; Gonzalez, Jose Carlos; Vaden, Jada H; Mclean, John W; Wu, Yumei; Banumurthy, Gokulakrishna; Overstreet-Wadiche, Linda; Herskowitz, Jeremy H; Volpicelli-Daley, Laura A

    2018-05-01

    Neuronal inclusions composed of α-synuclein (α-syn) characterize Parkinson's Disease (PD) and Dementia with Lewy bodies (DLB). Cognitive dysfunction defines DLB, and up to 80% of PD patients develop dementia. α-Syn inclusions are abundant in the hippocampus, yet functional consequences are unclear. To determine if pathologic α-syn causes neuronal defects, we induced endogenous α-syn to form inclusions resembling those found in diseased brains by treating hippocampal neurons with α-syn fibrils. At seven days after adding fibrils, α-syn inclusions are abundant in axons, but there is no cell death at this time point, allowing us to assess for potential alterations in neuronal function that are not caused by neuron death. We found that exposure of neurons to fibrils caused a significant reduction in mushroom spine densities, adding to the growing body of literature showing that altered spine morphology is a major pathologic phenotype in synucleinopathies. The reduction in spine densities occurred only in wild type neurons and not in neurons from α-syn knockout mice, suggesting that the changes in spine morphology result from fibril-induced corruption of endogenously expressed α-syn. Paradoxically, reduced postsynaptic spine density was accompanied by increased frequency of miniature excitatory postsynaptic currents (EPSCs) and presynaptic docked vesicles, suggesting enhanced presynaptic function. Action-potential dependent activity was unchanged, suggesting compensatory mechanisms responding to synaptic defects. Although activity at the level of the synapse was unchanged, neurons exposed to α-syn fibrils, showed reduced frequency and amplitudes of spontaneous Ca 2+ transients. These findings open areas of research to determine the mechanisms that alter neuronal function in brain regions critical for cognition at time points before neuron death.

  12. Stochastic nanoroughness modulates neuron-astrocyte interactions and function via mechanosensing cation channels.

    Science.gov (United States)

    Blumenthal, Nils R; Hermanson, Ola; Heimrich, Bernd; Shastri, V Prasad

    2014-11-11

    Extracellular soluble signals are known to play a critical role in maintaining neuronal function and homeostasis in the CNS. However, the CNS is also composed of extracellular matrix macromolecules and glia support cells, and the contribution of the physical attributes of these components in maintenance and regulation of neuronal function is not well understood. Because these components possess well-defined topography, we theorize a role for topography in neuronal development and we demonstrate that survival and function of hippocampal neurons and differentiation of telencephalic neural stem cells is modulated by nanoroughness. At roughnesses corresponding to that of healthy astrocytes, hippocampal neurons dissociated and survived independent from astrocytes and showed superior functional traits (increased polarity and calcium flux). Furthermore, telencephalic neural stem cells differentiated into neurons even under exogenous signals that favor astrocytic differentiation. The decoupling of neurons from astrocytes seemed to be triggered by changes to astrocyte apical-surface topography in response to nanoroughness. Blocking signaling through mechanosensing cation channels using GsMTx4 negated the ability of neurons to sense the nanoroughness and promoted decoupling of neurons from astrocytes, thus providing direct evidence for the role of nanotopography in neuron-astrocyte interactions. We extrapolate the role of topography to neurodegenerative conditions and show that regions of amyloid plaque buildup in brain tissue of Alzheimer's patients are accompanied by detrimental changes in tissue roughness. These findings suggest a role for astrocyte and ECM-induced topographical changes in neuronal pathologies and provide new insights for developing therapeutic targets and engineering of neural biomaterials.

  13. Dopaminergic Neurons Controlling Anterior Pituitary Functions: Anatomy and Ontogenesis in Zebrafish.

    Science.gov (United States)

    Fontaine, Romain; Affaticati, Pierre; Bureau, Charlotte; Colin, Ingrid; Demarque, Michaël; Dufour, Sylvie; Vernier, Philippe; Yamamoto, Kei; Pasqualini, Catherine

    2015-08-01

    Dopaminergic (DA) neurons located in the preoptico-hypothalamic region of the brain exert a major neuroendocrine control on reproduction, growth, and homeostasis by regulating the secretion of anterior pituitary (or adenohypophysis) hormones. Here, using a retrograde tract tracing experiment, we identified the neurons playing this role in the zebrafish. The DA cells projecting directly to the anterior pituitary are localized in the most anteroventral part of the preoptic area, and we named them preoptico-hypophyseal DA (POHDA) neurons. During development, these neurons do not appear before 72 hours postfertilization (hpf) and are the last dopaminergic cell group to differentiate. We found that the number of neurons in this cell population continues to increase throughout life proportionally to the growth of the fish. 5-Bromo-2'-deoxyuridine incorporation analysis suggested that this increase is due to continuous neurogenesis and not due to a phenotypic change in already-existing neurons. Finally, expression profiles of several genes (foxg1a, dlx2a, and nr4a2a/b) were different in the POHDA compared with the adjacent suprachiasmatic DA neurons, suggesting that POHDA neurons develop as a distinct DA cell population in the preoptic area. This study offers some insights into the regional identity of the preoptic area and provides the first bases for future functional genetic studies on the development of DA neurons controlling anterior pituitary functions.

  14. Circadian Activators Are Expressed Days before They Initiate Clock Function in Late Pacemaker Neurons from Drosophila.

    Science.gov (United States)

    Liu, Tianxin; Mahesh, Guruswamy; Houl, Jerry H; Hardin, Paul E

    2015-06-03

    Circadian pacemaker neurons in the Drosophila brain control daily rhythms in locomotor activity. These pacemaker neurons can be subdivided into early or late groups depending on whether rhythms in period (per) and timeless (tim) expression are initiated at the first instar (L1) larval stage or during metamorphosis, respectively. Because CLOCK-CYCLE (CLK-CYC) heterodimers initiate circadian oscillator function by activating per and tim transcription, a Clk-GFP transgene was used to mark when late pacemaker neurons begin to develop. We were surprised to see that CLK-GFP was already expressed in four of five clusters of late pacemaker neurons during the third instar (L3) larval stage. CLK-GFP is only detected in postmitotic neurons from L3 larvae, suggesting that these four late pacemaker neuron clusters are formed before the L3 larval stage. A GFP-cyc transgene was used to show that CYC, like CLK, is also expressed exclusively in pacemaker neurons from L3 larval brains, demonstrating that CLK-CYC is not sufficient to activate per and tim in late pacemaker neurons at the L3 larval stage. These results suggest that most late pacemaker neurons develop days before novel factors activate circadian oscillator function during metamorphosis. Copyright © 2015 the authors 0270-6474/15/358662-10$15.00/0.

  15. Maternal creatine supplementation affects the morpho-functional development of hippocampal neurons in rat offspring.

    Science.gov (United States)

    Sartini, S; Lattanzi, D; Ambrogini, P; Di Palma, M; Galati, C; Savelli, D; Polidori, E; Calcabrini, C; Rocchi, M B L; Sestili, P; Cuppini, R

    2016-01-15

    Creatine supplementation has been shown to protect neurons from oxidative damage due to its antioxidant and ergogenic functions. These features have led to the hypothesis of creatine supplementation use during pregnancy as prophylactic treatment to prevent CNS damage, such as hypoxic-ischemic encephalopathy. Unfortunately, very little is known on the effects of creatine supplementation during neuron differentiation, while in vitro studies revealed an influence on neuron excitability, leaving the possibility of creatine supplementation during the CNS development an open question. Using a multiple approach, we studied the hippocampal neuron morphological and functional development in neonatal rats born by dams supplemented with 1% creatine in drinking water during pregnancy. CA1 pyramidal neurons of supplemented newborn rats showed enhanced dendritic tree development, increased LTP maintenance, larger evoked-synaptic responses, and higher intrinsic excitability in comparison to controls. Moreover, a faster repolarizing phase of action potential with the appearance of a hyperpolarization were recorded in neurons of the creatine-treated group. Consistently, CA1 neurons of creatine exposed pups exhibited a higher maximum firing frequency than controls. In summary, we found that creatine supplementation during pregnancy positively affects morphological and electrophysiological development of CA1 neurons in offspring rats, increasing neuronal excitability. Altogether, these findings emphasize the need to evaluate the benefits and the safety of maternal intake of creatine in humans. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  16. Multimodality Cardiac Imaging for the Assessment of Left Atrial Function and the Association With Atrial Arrhythmias

    DEFF Research Database (Denmark)

    Olsen, Flemming Javier; Bertelsen, Litten; de Knegt, Martina Chantal

    2016-01-01

    Several cardiac imaging modalities are able to visualize the left atrium (LA) and, therefore, allow for quantification of both structural and functional properties of this cardiac chamber. In echocardiography, only the maximal LA volume is included in the assessment of diastolic function at the c......Several cardiac imaging modalities are able to visualize the left atrium (LA) and, therefore, allow for quantification of both structural and functional properties of this cardiac chamber. In echocardiography, only the maximal LA volume is included in the assessment of diastolic function...... atrial fibrillation, which will be a point of focus in this review. Pivotal cardiac magnetic resonance imaging studies have revealed high correlation between LA fibrosis and risk of atrial fibrillation recurrence after catheter ablation, and subsequent multimodality imaging studies have uncovered...... an inverse relationship between LA reservoir function and degree of LA fibrosis. This has sparked an increased interest into the application of advanced imaging modalities, including both speckle tracking echocardiography and tissue tracking by cardiac magnetic resonance imaging. Even though increasing...

  17. Moderate-Intensity Exercise Affects Gut Microbiome Composition and Influences Cardiac Function in Myocardial Infarction Mice

    Directory of Open Access Journals (Sweden)

    Zuheng Liu

    2017-09-01

    Full Text Available Physical exercise is commonly regarded as protective against cardiovascular disease (CVD. Recent studies have reported that exercise alters the gut microbiota and that modification of the gut microbiota can influence cardiac function. Here, we focused on the relationships among exercise, the gut microbiota and cardiac function after myocardial infarction (MI. Four-week-old C57BL/6J mice were exercised on a treadmill for 4 weeks before undergoing left coronary artery ligation. Cardiac function was assessed using echocardiography. Gut microbiomes were evaluated post-exercise and post-MI using 16S rRNA gene sequencing on an Illumina HiSeq platform. Exercise training inhibited declines in cardiac output and stroke volume in post-MI mice. In addition, physical exercise and MI led to alterations in gut microbial composition. Exercise training increased the relative abundance of Butyricimonas and Akkermansia. Additionally, key operational taxonomic units were identified, including 24 lineages (mainly from Bacteroidetes, Barnesiella, Helicobacter, Parabacteroides, Porphyromonadaceae, Ruminococcaceae, and Ureaplasma that were closely related to exercise and cardiac function. These results suggested that exercise training improved cardiac function to some extent in addition to altering the gut microbiota; therefore, they could provide new insights into the use of exercise training for the treatment of CVD.

  18. elPBN neurons regulate rVLM activity through elPBN-rVLM projections during activation of cardiac sympathetic afferent nerves.

    Science.gov (United States)

    Guo, Zhi-Ling; Longhurst, John C; Tjen-A-Looi, Stephanie C; Fu, Liang-Wu

    2016-08-01

    The external lateral parabrachial nucleus (elPBN) within the pons and rostral ventrolateral medulla (rVLM) contributes to central processing of excitatory cardiovascular reflexes during stimulation of cardiac sympathetic afferent nerves (CSAN). However, the importance of elPBN cardiovascular neurons in regulation of rVLM activity during CSAN activation remains unclear. We hypothesized that CSAN stimulation excites the elPBN cardiovascular neurons and, in turn, increases rVLM activity through elPBN-rVLM projections. Compared with controls, in rats subjected to microinjection of retrograde tracer into the rVLM, the numbers of elPBN neurons double-labeled with c-Fos (an immediate early gene) and the tracer were increased after CSAN stimulation (P neurons contain vesicular glutamate transporter 3. In cats, epicardial bradykinin and electrical stimulation of CSAN increased the activity of elPBN cardiovascular neurons, which was attenuated (n = 6, P neurons in the elPBN and rVLM sequentially through a monosynaptic (glutamatergic) excitatory elPBN-rVLM pathway. Copyright © 2016 the American Physiological Society.

  19. The changes in beta-adrenoceptor-mediated cardiac function in experimental hypothyroidism: the possible contribution of cardiac beta3-adrenoceptors.

    Science.gov (United States)

    Arioglu, E; Guner, S; Ozakca, I; Altan, V M; Ozcelikay, A T

    2010-02-01

    Thyroid hormone deficiency has been reported to decrease expression and function of both beta(1)- and beta(2)-adrenoceptor in different tissues including heart. The purpose of this study was to examine the possible contribution of beta(3)-adrenoceptors to cardiac dysfunction in hypothyroidism. In addition, effect of this pathology on beta(1)- and beta(2)-adrenoceptor was investigated. Hypothyroidism was induced by adding methimazole (300 mg/l) to drinking water of rats for 8 weeks. Cardiac hemodynamic parameters were measured in anesthetised rats in vivo. Responses to beta-adrenoceptor agonists were examined in rat papillary muscle in vitro. We also studied the effect of hypotyroidism on mRNA expression of beta-adrenoceptors, Gialpha, GRK, and eNOS in rat heart. All of the hemodynamic parameters (systolic, diastolic and mean arterial pressure, left ventricular pressure, heart rate, +dp/dt, and -dp/dt) were significantly reduced by the methimazole treatment. The negative inotropic effect elicited by BRL 37344 (a beta(3)-adrenoceptor preferential agonist) and positive inotropic effects produced by isoprenaline and noradrenaline, respectively, were significantly decreased in papillary muscle of hypothyroid rats as compared to those of controls. On the other hand, hypothyroidism resulted in increased cardiac beta(2)- and beta(3)-adrenoceptor, Gialpha(2), Gialpha(3), GRK3, and eNOS mRNA expressions. However, beta(1)-adrenoceptor and GRK2 mRNA expressions were not changed significantly in this pathology. These results show that mRNA expression of beta(3)-adrenoceptors as well as the signalling pathway components mediated through beta(3)-adrenoceptors are significantly increased in hypothyroid rat heart. Since we could not correlate these alternates with the decreased negative inotropic response mediated by this receptor subtype, it is not clear whether these changes are important for hypothyroid induced reduction in cardiac function.

  20. Control of neuronal network organization by chemical surface functionalization of multi-walled carbon nanotube arrays

    International Nuclear Information System (INIS)

    Liu Jie; Bibari, Olivier; Marchand, Gilles; Benabid, Alim-Louis; Sauter-Starace, Fabien; Appaix, Florence; De Waard, Michel

    2011-01-01

    Carbon nanotube substrates are promising candidates for biological applications and devices. Interfacing of these carbon nanotubes with neurons can be controlled by chemical modifications. In this study, we investigated how chemical surface functionalization of multi-walled carbon nanotube arrays (MWNT-A) influences neuronal adhesion and network organization. Functionalization of MWNT-A dramatically modifies the length of neurite fascicles, cluster inter-connection success rate, and the percentage of neurites that escape from the clusters. We propose that chemical functionalization represents a method of choice for developing applications in which neuronal patterning on MWNT-A substrates is required.

  1. Control of neuronal network organization by chemical surface functionalization of multi-walled carbon nanotube arrays

    Energy Technology Data Exchange (ETDEWEB)

    Liu Jie; Bibari, Olivier; Marchand, Gilles; Benabid, Alim-Louis; Sauter-Starace, Fabien [CEA, LETI-Minatec, 17 Rue des Martyrs, 38054 Grenoble Cedex 9 (France); Appaix, Florence; De Waard, Michel, E-mail: fabien.sauter@cea.fr, E-mail: michel.dewaard@ujf-grenoble.fr [Inserm U836, Grenoble Institute of Neuroscience, Site Sante la Tronche, Batiment Edmond J Safra, Chemin Fortune Ferrini, BP170, 38042 Grenoble Cedex 09 (France)

    2011-05-13

    Carbon nanotube substrates are promising candidates for biological applications and devices. Interfacing of these carbon nanotubes with neurons can be controlled by chemical modifications. In this study, we investigated how chemical surface functionalization of multi-walled carbon nanotube arrays (MWNT-A) influences neuronal adhesion and network organization. Functionalization of MWNT-A dramatically modifies the length of neurite fascicles, cluster inter-connection success rate, and the percentage of neurites that escape from the clusters. We propose that chemical functionalization represents a method of choice for developing applications in which neuronal patterning on MWNT-A substrates is required.

  2. Therapeutic Inhibition of miR-208a Improves Cardiac Function and Survival During Heart Failure

    Science.gov (United States)

    Montgomery, Rusty L.; Hullinger, Thomas G.; Semus, Hillary M.; Dickinson, Brent A.; Seto, Anita G.; Lynch, Joshua M.; Stack, Christianna; Latimer, Paul A.; Olson, Eric N.; van Rooij, Eva

    2012-01-01

    Background Diastolic dysfunction in response to hypertrophy is a major clinical syndrome with few therapeutic options. MicroRNAs act as negative regulators of gene expression by inhibiting translation or promoting degradation of target mRNAs. Previously, we reported that genetic deletion of the cardiac-specific miR-208a prevents pathological cardiac remodeling and upregulation of Myh7 in response to pressure overload. Whether this miRNA might contribute to diastolic dysfunction or other forms of heart disease is currently unknown. Methods and Results Here, we show that systemic delivery of an antisense oligonucleotide induces potent and sustained silencing of miR-208a in the heart. Therapeutic inhibition of miR-208a by subcutaneous delivery of antimiR-208a during hypertension-induced heart failure in Dahl hypertensive rats dose-dependently prevents pathological myosin switching and cardiac remodeling while improving cardiac function, overall health, and survival. Transcriptional profiling indicates that antimiR-208a evokes prominent effects on cardiac gene expression; plasma analysis indicates significant changes in circulating levels of miRNAs on antimiR-208a treatment. Conclusions These studies indicate the potential of oligonucleotide-based therapies for modulating cardiac miRNAs and validate miR-208 as a potent therapeutic target for the modulation of cardiac function and remodeling during heart disease progression. PMID:21900086

  3. elPBN neurons regulate rVLM activity through elPBN-rVLM projections during activation of cardiac sympathetic afferent nerves

    Science.gov (United States)

    Longhurst, John C.; Tjen-A-Looi, Stephanie C.; Fu, Liang-Wu

    2016-01-01

    The external lateral parabrachial nucleus (elPBN) within the pons and rostral ventrolateral medulla (rVLM) contributes to central processing of excitatory cardiovascular reflexes during stimulation of cardiac sympathetic afferent nerves (CSAN). However, the importance of elPBN cardiovascular neurons in regulation of rVLM activity during CSAN activation remains unclear. We hypothesized that CSAN stimulation excites the elPBN cardiovascular neurons and, in turn, increases rVLM activity through elPBN-rVLM projections. Compared with controls, in rats subjected to microinjection of retrograde tracer into the rVLM, the numbers of elPBN neurons double-labeled with c-Fos (an immediate early gene) and the tracer were increased after CSAN stimulation (P < 0.05). The majority of these elPBN neurons contain vesicular glutamate transporter 3. In cats, epicardial bradykinin and electrical stimulation of CSAN increased the activity of elPBN cardiovascular neurons, which was attenuated (n = 6, P < 0.05) after blockade of glutamate receptors with iontophoresis of kynurenic acid (Kyn, 25 mM). In separate cats, microinjection of Kyn (1.25 nmol/50 nl) into the elPBN reduced rVLM activity evoked by both bradykinin and electrical stimulation (n = 5, P < 0.05). Excitation of the elPBN with microinjection of dl-homocysteic acid (2 nmol/50 nl) significantly increased basal and CSAN-evoked rVLM activity. However, the enhanced rVLM activity induced by dl-homocysteic acid injected into the elPBN was reversed following iontophoresis of Kyn into the rVLM (n = 7, P < 0.05). These data suggest that cardiac sympathetic afferent stimulation activates cardiovascular neurons in the elPBN and rVLM sequentially through a monosynaptic (glutamatergic) excitatory elPBN-rVLM pathway. PMID:27225950

  4. Diverse Roles of Axonemal Dyneins in Drosophila Auditory Neuron Function and Mechanical Amplification in Hearing.

    Science.gov (United States)

    Karak, Somdatta; Jacobs, Julie S; Kittelmann, Maike; Spalthoff, Christian; Katana, Radoslaw; Sivan-Loukianova, Elena; Schon, Michael A; Kernan, Maurice J; Eberl, Daniel F; Göpfert, Martin C

    2015-11-26

    Much like vertebrate hair cells, the chordotonal sensory neurons that mediate hearing in Drosophila are motile and amplify the mechanical input of the ear. Because the neurons bear mechanosensory primary cilia whose microtubule axonemes display dynein arms, we hypothesized that their motility is powered by dyneins. Here, we describe two axonemal dynein proteins that are required for Drosophila auditory neuron function, localize to their primary cilia, and differently contribute to mechanical amplification in hearing. Promoter fusions revealed that the two axonemal dynein genes Dmdnah3 (=CG17150) and Dmdnai2 (=CG6053) are expressed in chordotonal neurons, including the auditory ones in the fly's ear. Null alleles of both dyneins equally abolished electrical auditory neuron responses, yet whereas mutations in Dmdnah3 facilitated mechanical amplification, amplification was abolished by mutations in Dmdnai2. Epistasis analysis revealed that Dmdnah3 acts downstream of Nan-Iav channels in controlling the amplificatory gain. Dmdnai2, in addition to being required for amplification, was essential for outer dynein arms in auditory neuron cilia. This establishes diverse roles of axonemal dyneins in Drosophila auditory neuron function and links auditory neuron motility to primary cilia and axonemal dyneins. Mutant defects in sperm competition suggest that both dyneins also function in sperm motility.

  5. Autonomous CaMKII Activity as a Drug Target for Histological and Functional Neuroprotection after Resuscitation from Cardiac Arrest

    Directory of Open Access Journals (Sweden)

    Guiying Deng

    2017-01-01

    Full Text Available The Ca2+/calmodulin-dependent protein kinase II (CaMKII is a major mediator of physiological glutamate signaling, but its role in pathological glutamate signaling (excitotoxicity remains less clear, with indications for both neuro-toxic and neuro-protective functions. Here, the role of CaMKII in ischemic injury is assessed utilizing our mouse model of cardiac arrest and cardiopulmonary resuscitation (CA/CPR. CaMKII inhibition (with tatCN21 or tatCN19o at clinically relevant time points (30 min after resuscitation greatly reduces neuronal injury. Importantly, CaMKII inhibition also works in combination with mild hypothermia, the current standard of care. The relevant drug target is specifically Ca2+-independent “autonomous” CaMKII activity generated by T286 autophosphorylation, as indicated by substantial reduction in injury in autonomy-incompetent T286A mutant mice. In addition to reducing cell death, tatCN19o also protects the surviving neurons from functional plasticity impairments and prevents behavioral learning deficits, even at extremely low doses (0.01 mg/kg, further highlighting the clinical potential of our findings.

  6. Spatiotemporal intracellular dynamics of neurotrophin and its receptors. Implications for neurotrophin signaling and neuronal function.

    Science.gov (United States)

    Bronfman, F C; Lazo, O M; Flores, C; Escudero, C A

    2014-01-01

    Neurons possess a polarized morphology specialized to contribute to neuronal networks, and this morphology imposes an important challenge for neuronal signaling and communication. The physiology of the network is regulated by neurotrophic factors that are secreted in an activity-dependent manner modulating neuronal connectivity. Neurotrophins are a well-known family of neurotrophic factors that, together with their cognate receptors, the Trks and the p75 neurotrophin receptor, regulate neuronal plasticity and survival and determine the neuronal phenotype in healthy and regenerating neurons. Is it now becoming clear that neurotrophin signaling and vesicular transport are coordinated to modify neuronal function because disturbances of vesicular transport mechanisms lead to disturbed neurotrophin signaling and to diseases of the nervous system. This chapter summarizes our current understanding of how the regulated secretion of neurotrophin, the distribution of neurotrophin receptors in different locations of neurons, and the intracellular transport of neurotrophin-induced signaling in distal processes are achieved to allow coordinated neurotrophin signaling in the cell body and axons.

  7. Polysensory response characteristics of dorsal root ganglion neurones that may serve sensory functions during myocardial ischaemia.

    Science.gov (United States)

    Huang, M H; Horackova, M; Negoescu, R M; Wolf, S; Armour, J A

    1996-09-01

    To determine the response characteristics of dorsal root ganglion neurones that may serve sensory functions during myocardial ischaemia. Extracellular recordings were made from 54 spontaneously active and 5 normally quiescent dorsal root ganglion neurones (T2-T5) in 22 anaesthetized open-chest dogs under control conditions and during epicardial mechanical or chemical stimulation and myocardial ischaemia. The activity of 78% of spontaneously active and all quiescent neurones with left ventricular sensory fields was modified by left ventricular ischaemia. Forty-six spontaneously active neurones (85%) were polysensory with respect to mechanical and chemical stimuli. The 5 quiescent neurones responded only to chemical stimuli. Spontaneously active neurones associated with left ventricular mechanosensory endings (37 neurones) generated four different activity patterns in response to similar mechanical stimuli (high or low pressure active, high-low pressure active, high-low pressure inactive). A fifth group generated activity which was not related to chamber dynamics. Adenosine, adenosine 5'-triphosphate, substance P and bradykinin modified 72, 61, 65 and 63% of the spontaneously active neurones, respectively. Maximum local mechanical or chemical stimuli enhanced activity to similar degrees, as did ischaemia. Each ischaemia-sensitive neurone displayed unique activity patterns in response to similar mechanical or chemical stimuli. Most myocardial ischemia-sensitive dorsal root ganglion neurones associated with epicardial neurites sense mechanical and multiple chemical stimuli, a small population sensing only mechanical or chemical stimuli. Activity patterns generated by these neurones depend on their primary sensory characteristics or those of other neurones that may converge on them, as well as the type and magnitude of the stimuli that impinge upon their sensory fields, both normally and during ischaemia.

  8. Engineered hybrid cardiac patches with multifunctional electronics for online monitoring and regulation of tissue function.

    Science.gov (United States)

    Feiner, Ron; Engel, Leeya; Fleischer, Sharon; Malki, Maayan; Gal, Idan; Shapira, Assaf; Shacham-Diamand, Yosi; Dvir, Tal

    2016-06-01

    In cardiac tissue engineering approaches to treat myocardial infarction, cardiac cells are seeded within three-dimensional porous scaffolds to create functional cardiac patches. However, current cardiac patches do not allow for online monitoring and reporting of engineered-tissue performance, and do not interfere to deliver signals for patch activation or to enable its integration with the host. Here, we report an engineered cardiac patch that integrates cardiac cells with flexible, freestanding electronics and a 3D nanocomposite scaffold. The patch exhibited robust electronic properties, enabling the recording of cellular electrical activities and the on-demand provision of electrical stimulation for synchronizing cell contraction. We also show that electroactive polymers containing biological factors can be deposited on designated electrodes to release drugs in the patch microenvironment on demand. We expect that the integration of complex electronics within cardiac patches will eventually provide therapeutic control and regulation of cardiac function.

  9. The profound effects of microcystin on cardiac antioxidant enzymes, mitochondrial function and cardiac toxicity in rat

    International Nuclear Information System (INIS)

    Qiu Tong; Xie Ping; Liu Ying; Li Guangyu; Xiong Qian; Hao Le; Li Huiying

    2009-01-01

    Deaths from microcystin toxication have widely been attributed to hypovolemic shock due to hepatic interstitial hemorrhage, while some recent studies suggest that cardiogenic complication is also involved. So far, information on cardiotoxic effects of MC has been rare and the underlying mechanism is still puzzling. The present study examined toxic effects of microcystins on heart muscle of rats intravenously injected with extracted MC at two doses, 0.16LD 50 (14 μg MC-LReq kg -1 body weight) and 1LD 50 (87 μg MC-LReq kg -1 body weight). In the dead rats, both TTC staining and maximum elevations of troponin I levels confirmed myocardial infarction after MC exposure, besides a serious interstitial hemorrhage in liver. In the 1LD 50 dose group, the coincident falls in heart rate and blood pressure were related to mitochondria dysfunction in heart, while increases in creatine kinase and troponin I levels indicated cardiac cell injury. The corresponding pathological alterations were mainly characterized as loss of adherence between cardiac myocytes and swollen or ruptured mitochondria at the ultrastructural level. MC administration at a dose of 1LD 50 not only enhanced activities and up-regulated mRNA transcription levels of antioxidant enzymes, but also increased GSH content. At both doses, level of lipid peroxides increased obviously, suggesting serious oxidative stress in mitochondria. Simultaneously, complex I and III were significantly inhibited, indicating blocks in electron flow along the mitochondrial respiratory chain in heart. In conclusion, the findings of this study implicate a role for MC-induced cardiotoxicity as a potential factor that should be considered when evaluating the mechanisms of death associated with microcystin intoxication in Brazil

  10. Cardiac autonomic function in patients with diabetes improves with practice of comprehensive yogic breathing program

    Directory of Open Access Journals (Sweden)

    Viveka P Jyotsna

    2013-01-01

    Full Text Available Background: The aim of this study was to observe the effect comprehensive yogic breathing (Sudarshan Kriya Yoga [SKY] and Pranayam had on cardiac autonomic functions in patients with diabetes. Materials and Methods: This is a prospective randomized controlled intervention trial. Cardiac autonomic functions were assessed in 64 diabetics. Patients were randomized into two groups, one group receiving standard therapy for diabetes and the other group receiving standard therapy for diabetes and comprehensive yogic breathing program. Standard therapy included dietary advice, brisk walking for 45 min daily, and administration of oral antidiabetic drugs. Comprehensive yogic breathing program was introduced to the participants through a course of 12 h spread over 3 days. It was an interactive session in which SKY, a rhythmic cyclical breathing, preceded by Pranayam is taught under the guidance of a certified teacher. Cardiac autonomic function tests were done before and after 6 months of intervention. Results: In the intervention group, after practicing the breathing techniques for 6 months, the improvement in sympathetic functions was statistically significant (P 0.04. The change in sympathetic functions in the standard therapy group was not significant (P 0.75.Parasympathetic functions did not show any significant change in either group. When both parasympathetic and sympathetic cardiac autonomic functions were considered, there was a trend toward improvement in patients following comprehensive yogic breathing program (P 0.06. In the standard therapy group, no change in cardiac autonomic functions was noted (P 0.99. Conclusion: Cardiac autonomic functions improved in patients with diabetes on standard treatment who followed the comprehensive yogic breathing program compared to patients who were on standard therapy alone.

  11. Regulatory effects of phospholamban on cardiac sarcoplasmic reticulum function

    International Nuclear Information System (INIS)

    Kim, Hae Won.

    1989-01-01

    In this thesis, the author reports the effect of phospholamban on: (a) Ca 2+ release by cardiac SR and (b) the Ca 2+ -ATPase activity in a purified reconstituted system. Phosphorylation of phospholamban by Ca 2+ · calmodulin-dependent protein kinase had no appreciable effect on the initial rates of Ca 2+ release from cardiac SR vesicles loaded under passive conditions and on the apparent 45 Ca 2+ - 40 Ca 2+ exchange from cardiac SR vesicles loaded under active conditions. us, it appears that Ca 2+ · calmodulin-dependent phosphorylation of phospholamban is not involved in the regulation of Ca 2+ release and 45 Ca 2+-40 Ca 2+ exchange. To determine the molecular mechanism by which phospholamban regulates the Ca 2+ pump, a reconstituted system was developed, using a freeze-thaw sonication procedure. The Ca 2+ -ATPase was purified by a method which yields an active enzyme preparation essentially free of phospholamban. The best rates of Ca 2+ uptake were obtained when cholate and phosphatidylcholine (PC) were used at a ratio of cholate/PC/Ca 2 + -ATPase of 2/80/1. The maximal rates of Ca 2+ Uptake were 700 nmol/min/mg reconstituted vesicles compared to 800 nmol/min/mg SR vesicles. The EC 50 values for Ca 2+ were 0.05 μM for both Ca 2+ uptake and Ca 2+ -ATPase activity in the reconstituted vesicles compared to 0.63 μM Ca 2+ in native SR vesicles. To determine the effect of phospholamban on the Ca + -ATPase activity in the reconstituted vesicles, purified phospholamban was added to the cholate/Ca 2+ -ATPase mixture prior to combining it with liposomes

  12. Importance of circulating IGF-1 for normal cardiac morphology, function and post infarction remodeling.

    Science.gov (United States)

    Scharin Täng, M; Redfors, B; Lindbom, M; Svensson, J; Ramunddal, T; Ohlsson, C; Shao, Y; Omerovic, E

    2012-12-01

    IGF-1 plays an important role in cardiovascular homeostasis, and plasma levels of IGF-1 correlate inversely with systolic function in heart failure. It is not known to what extent circulating IGF-1 secreted by the liver and local autocrine/paracrine IGF-1 expressed in the myocardium contribute to these beneficial effects on cardiac function and morphology. In the present study, we used a mouse model of liver-specific inducible deletion of the IGF-1 gene (LI-IGF-1 -/- mouse) in an attempt to evaluate the importance of circulating IGF-I on cardiac morphology and function under normal and pathological conditions, with an emphasis on its regulatory role in myocardial phosphocreatine metabolism. Echocardiography was performed in LI-IGF-1 -/- and control mice at rest and during dobutamine stress, both at baseline and post myocardial infarction (MI). High-energy phosphate metabolites were compared between LI-IGF-1 -/- and control mice at 4 weeks post MI. We found that LI-IGF-1 -/- mice had significantly greater left ventricular dimensions at baseline and showed a greater relative increase in cardiac dimensions, as well as deterioration of cardiac function, post MI. Myocardial creatine content was 17.9% lower in LI-IGF-1 -/- mice, whereas there was no detectable difference in high-energy nucleotides. These findings indicate an important role of circulating IGF-1 in preserving cardiac structure and function both in physiological settings and post MI. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Endothelial Function as a Possible Significant Determinant of Cardiac Function during Exercise in Patients with Structural Heart Disease

    Directory of Open Access Journals (Sweden)

    Bonpei Takase

    2009-01-01

    Full Text Available This study was investigated the role that endothelial function and systemic vascular resistance (SVR play in determining cardiac function reserve during exercise by a new ambulatory radionuclide monitoring system (VEST in patients with heart disease. The study population consisted of 32 patients. The patients had cardiopulmonary stress testing using the treadmill Ramp protocol and the VEST. The anaerobic threshold (AT was autodetermined using the V-slope method. The SVR was calculated by determining the mean blood pressure/cardiac output. Flow-mediated vasodilation (FMD was measured in the brachial artery to evaluate endotheilial function. FMD and the percent change f'rom rest to AT in SVR correlated with those from rest to AT in ejection fraction and peak ejection ratio by VEST, respectively. Our findings suggest that FMD in the brachial artery and the SVR determined by VEST in patients with heart disease can possibly reflect cardiac function reserve during aerobic exercise.

  14. Neuronal Functions of Activators of G Protein Signaling

    Directory of Open Access Journals (Sweden)

    Man K. Tse

    2012-05-01

    Full Text Available G protein-coupled receptors (GPCRs are one of the most important gateways for signal transduction across the plasma membrane. Over the past decade, several classes of alternative regulators of G protein signaling have been identified and reported to activate the G proteins independent of the GPCRs. One group of such regulators is the activator of G protein signaling (AGS family which comprises of AGS1-10. They have entirely different activation mechanisms for G proteins as compared to the classic model of GPCR-mediated signaling and confer upon cells new avenues of signal transduction. As GPCRs are widely expressed in our nervous system, it is believed that the AGS family plays a major role in modulating the G protein signaling in neurons. In this article, we will review the current knowledge on AGS proteins in relation to their potential roles in neuronal regulations.

  15. Osmosensation in vasopressin neurons: changing actin density to optimize function.

    Science.gov (United States)

    Prager-Khoutorsky, Masha; Bourque, Charles W

    2010-02-01

    The proportional relation between circulating vasopressin concentration and plasma osmolality is fundamental for body fluid homeostasis. Although changes in the sensitivity of this relation are associated with pathophysiological conditions, central mechanisms modulating osmoregulatory gain are unknown. Here, we review recent data that sheds important light on this process. The cell autonomous osmosensitivity of vasopressin neurons depends on cation channels comprising a variant of the transient receptor potential vanilloid 1 (TRPV1) channel. Hyperosmotic activation is mediated by a mechanical process where sensitivity increases in proportion with actin filament density. Moreover, angiotensin II amplifies osmotic activation by a rapid stimulation of actin polymerization, suggesting that neurotransmitter-induced changes in cytoskeletal organization in osmosensory neurons can mediate central changes in osmoregulatory gain. (c) 2009 Elsevier Ltd. All rights reserved.

  16. Two Aspects of ASIC Function: Synaptic Plasticity and Neuronal Injury.

    Science.gov (United States)

    Huang, Yan; Jiang, Nan; Li, Jun; Ji, Yong-Hua; Xiong, Zhi-Gang; Zha, Xiang-ming

    2015-01-01

    Extracellular brain pH fluctuates in both physiological and disease conditions. The main postsynaptic proton receptor is the acid-sensing ion channels (ASICs). During the past decade, much progress has been made on protons, ASICs, and neurological disease. This review summarizes the recent progress on synaptic role of protons and our current understanding of how ASICs contribute to various types of neuronal injury in the brain. PMID:25582290

  17. The Intrinsic Electrophysiological Properties of Mammalian Neurons: Insights into Central Nervous System Function

    Science.gov (United States)

    Llinas, Rodolfo R.

    1988-12-01

    This article reviews the electroresponsive properties of single neurons in the mammalian central nervous system (CNS). In some of these cells the ionic conductances responsible for their excitability also endow them with autorhythmic electrical oscillatory properties. Chemical or electrical synaptic contacts between these neurons often result in network oscillations. In such networks, autorhytmic neurons may act as true oscillators (as pacemakers) or as resonators (responding preferentially to certain firing frequencies). Oscillations and resonance in the CNS are proposed to have diverse functional roles, such as (i) determining global functional states (for example, sleep-wakefulness or attention), (ii) timing in motor coordination, and (iii) specifying connectivity during development. Also, oscillation, especially in the thalamo-cortical circuits, may be related to certain neurological and psychiatric disorders. This review proposes that the autorhythmic electrical properties of central neurons and their connectivity form the basis for an intrinsic functional coordinate system that provides internal context to sensory input.

  18. Stable xenon CT measurement of cerebral blood flow in cardiac transplantation candidates: Correlation with cognitive function

    International Nuclear Information System (INIS)

    Bello, J.A.; Fink, M.E.; Hilal, S.K.; Rose, E.A.; Reemtsma, K.

    1987-01-01

    Thirteen consecutive unselected patients with NYHA class 4 cardiac failure referred for cardiac transplantation underwent neurologic examination and cerebral blood flow measurement (rCBF) using the stable xenon enhanced CT method on a GE9800 system. Eleven men and two women were studied (mean age = 43.8 +- 6.1). On neurological examination, six of the patients demonstrated normal mental function; the remaining seven patients demonstrated memory, language, or learning impairment. There was no difference in mean cardiac output between the groups (4.9 L/min +- 1.68 vs. 4.2L/min +- 1.57). rCBF was significantly reduced in the impaired group. Cognitive impairment in patients with cardiac failure can be correlated with cerebral ischemia. Stable xenon CT measurement of rCBF in transplant candidates may help identify patients requiring more rapid transplantation to prevent permanent cerebral injury

  19. Niche-dependent development of functional neuronal networks from embryonic stem cell-derived neural populations

    Directory of Open Access Journals (Sweden)

    Siebler Mario

    2009-08-01

    Full Text Available Abstract Background The present work was performed to investigate the ability of two different embryonic stem (ES cell-derived neural precursor populations to generate functional neuronal networks in vitro. The first ES cell-derived neural precursor population was cultivated as free-floating neural aggregates which are known to form a developmental niche comprising different types of neural cells, including neural precursor cells (NPCs, progenitor cells and even further matured cells. This niche provides by itself a variety of different growth factors and extracellular matrix proteins that influence the proliferation and differentiation of neural precursor and progenitor cells. The second population was cultivated adherently in monolayer cultures to control most stringently the extracellular environment. This population comprises highly homogeneous NPCs which are supposed to represent an attractive way to provide well-defined neuronal progeny. However, the ability of these different ES cell-derived immature neural cell populations to generate functional neuronal networks has not been assessed so far. Results While both precursor populations were shown to differentiate into sufficient quantities of mature NeuN+ neurons that also express GABA or vesicular-glutamate-transporter-2 (vGlut2, only aggregate-derived neuronal populations exhibited a synchronously oscillating network activity 2–4 weeks after initiating the differentiation as detected by the microelectrode array technology. Neurons derived from homogeneous NPCs within monolayer cultures did merely show uncorrelated spiking activity even when differentiated for up to 12 weeks. We demonstrated that these neurons exhibited sparsely ramified neurites and an embryonic vGlut2 distribution suggesting an inhibited terminal neuronal maturation. In comparison, neurons derived from heterogeneous populations within neural aggregates appeared as fully mature with a dense neurite network and punctuated

  20. A Cell Model to Evaluate Chemical Effects on Adult Human Cardiac Progenitor Cell Differentiation and Function

    Science.gov (United States)

    Adult cardiac stem cells (CSC) and progenitor cells (CPC) represent a population of cells in the heart critical for its regeneration and function over a lifetime. The impact of chemicals on adult human CSC/CPC differentiation and function is unknown. Research was conducted to dev...

  1. Network control principles predict neuron function in the Caenorhabditis elegans connectome

    Science.gov (United States)

    Yan, Gang; Vértes, Petra E.; Towlson, Emma K.; Chew, Yee Lian; Walker, Denise S.; Schafer, William R.; Barabási, Albert-László

    2017-10-01

    Recent studies on the controllability of complex systems offer a powerful mathematical framework to systematically explore the structure-function relationship in biological, social, and technological networks. Despite theoretical advances, we lack direct experimental proof of the validity of these widely used control principles. Here we fill this gap by applying a control framework to the connectome of the nematode Caenorhabditis elegans, allowing us to predict the involvement of each C. elegans neuron in locomotor behaviours. We predict that control of the muscles or motor neurons requires 12 neuronal classes, which include neuronal groups previously implicated in locomotion by laser ablation, as well as one previously uncharacterized neuron, PDB. We validate this prediction experimentally, finding that the ablation of PDB leads to a significant loss of dorsoventral polarity in large body bends. Importantly, control principles also allow us to investigate the involvement of individual neurons within each neuronal class. For example, we predict that, within the class of DD motor neurons, only three (DD04, DD05, or DD06) should affect locomotion when ablated individually. This prediction is also confirmed; single cell ablations of DD04 or DD05 specifically affect posterior body movements, whereas ablations of DD02 or DD03 do not. Our predictions are robust to deletions of weak connections, missing connections, and rewired connections in the current connectome, indicating the potential applicability of this analytical framework to larger and less well-characterized connectomes.

  2. Three Types of Cortical L5 Neurons that Differ in Brain-Wide Connectivity and Function

    Science.gov (United States)

    Kim, Euiseok J.; Juavinett, Ashley L.; Kyubwa, Espoir M.; Jacobs, Matthew W.; Callaway, Edward M.

    2015-01-01

    SUMMARY Cortical layer 5 (L5) pyramidal neurons integrate inputs from many sources and distribute outputs to cortical and subcortical structures. Previous studies demonstrate two L5 pyramid types: cortico-cortical (CC) and cortico-subcortical (CS). We characterize connectivity and function of these cell types in mouse primary visual cortex and reveal a new subtype. Unlike previously described L5 CC and CS neurons, this new subtype does not project to striatum [cortico-cortical, non-striatal (CC-NS)] and has distinct morphology, physiology and visual responses. Monosynaptic rabies tracing reveals that CC neurons preferentially receive input from higher visual areas, while CS neurons receive more input from structures implicated in top-down modulation of brain states. CS neurons are also more direction-selective and prefer faster stimuli than CC neurons. These differences suggest distinct roles as specialized output channels, with CS neurons integrating information and generating responses more relevant to movement control and CC neurons being more important in visual perception. PMID:26671462

  3. Three Types of Cortical Layer 5 Neurons That Differ in Brain-wide Connectivity and Function.

    Science.gov (United States)

    Kim, Euiseok J; Juavinett, Ashley L; Kyubwa, Espoir M; Jacobs, Matthew W; Callaway, Edward M

    2015-12-16

    Cortical layer 5 (L5) pyramidal neurons integrate inputs from many sources and distribute outputs to cortical and subcortical structures. Previous studies demonstrate two L5 pyramid types: cortico-cortical (CC) and cortico-subcortical (CS). We characterize connectivity and function of these cell types in mouse primary visual cortex and reveal a new subtype. Unlike previously described L5 CC and CS neurons, this new subtype does not project to striatum [cortico-cortical, non-striatal (CC-NS)] and has distinct morphology, physiology, and visual responses. Monosynaptic rabies tracing reveals that CC neurons preferentially receive input from higher visual areas, while CS neurons receive more input from structures implicated in top-down modulation of brain states. CS neurons are also more direction-selective and prefer faster stimuli than CC neurons. These differences suggest distinct roles as specialized output channels, with CS neurons integrating information and generating responses more relevant to movement control and CC neurons being more important in visual perception. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Network control principles predict neuron function in the Caenorhabditis elegans connectome.

    Science.gov (United States)

    Yan, Gang; Vértes, Petra E; Towlson, Emma K; Chew, Yee Lian; Walker, Denise S; Schafer, William R; Barabási, Albert-László

    2017-10-26

    Recent studies on the controllability of complex systems offer a powerful mathematical framework to systematically explore the structure-function relationship in biological, social, and technological networks. Despite theoretical advances, we lack direct experimental proof of the validity of these widely used control principles. Here we fill this gap by applying a control framework to the connectome of the nematode Caenorhabditis elegans, allowing us to predict the involvement of each C. elegans neuron in locomotor behaviours. We predict that control of the muscles or motor neurons requires 12 neuronal classes, which include neuronal groups previously implicated in locomotion by laser ablation, as well as one previously uncharacterized neuron, PDB. We validate this prediction experimentally, finding that the ablation of PDB leads to a significant loss of dorsoventral polarity in large body bends. Importantly, control principles also allow us to investigate the involvement of individual neurons within each neuronal class. For example, we predict that, within the class of DD motor neurons, only three (DD04, DD05, or DD06) should affect locomotion when ablated individually. This prediction is also confirmed; single cell ablations of DD04 or DD05 specifically affect posterior body movements, whereas ablations of DD02 or DD03 do not. Our predictions are robust to deletions of weak connections, missing connections, and rewired connections in the current connectome, indicating the potential applicability of this analytical framework to larger and less well-characterized connectomes.

  5. Vascular calcification and cardiac function according to residual renal function in patients on hemodialysis with urination.

    Directory of Open Access Journals (Sweden)

    Dong Ho Shin

    Full Text Available Vascular calcification is common and may affect cardiac function in patients with end-stage renal disease (ESRD. However, little is known about the effect of residual renal function on vascular calcification and cardiac function in patients on hemodialysis.This study was conducted between January 2014 and January 2017. One hundred six patients with residual renal function on maintenance hemodialysis for 3 months were recruited. We used residual renal urea clearance (KRU to measure residual renal function. First, abdominal aortic calcification score (AACS and brachial-ankle pulse wave velocity (baPWV were measured in patients on hemodialysis. Second, we performed echocardiography and investigated new cardiovascular events after study enrollment.The median KRU was 0.9 (0.3-2.5 mL/min/1.73m2. AACS (4.0 [1.0-10.0] vs. 3.0 [0.0-8.0], p = 0.05 and baPWV (1836.1 ± 250.4 vs. 1676.8 ± 311.0 cm/s, p = 0.01 were significantly higher in patients with a KRU < 0.9 mL/min/1.73m2 than a KRU ≥ 0.9 mL/min/1.73m2. Log-KRU significantly negatively correlated with log-AACS (ß = -0.29, p = 0.002 and baPWV (ß = -0.19, P = 0.05 after factor adjustment. The proportion of left ventricular diastolic dysfunction was significantly higher in patients with a KRU < 0.9 mL/min/1.73m2 than with a KRU ≥ 0.9 mL/min/1.73m2 (67.9% vs. 49.1%, p = 0.05. Patients with a KRU < 0.9 mL/min/1.73m2 showed a higher tendency of cumulative cardiovascular events compared to those with a KRU ≥ 0.9 ml/min/1.73m2 (P = 0.08.Residual renal function was significantly associated with vascular calcification and left ventricular diastolic dysfunction in patients on hemodialysis.

  6. PET measures of pre- and post-synaptic cardiac beta adrenergic function

    Energy Technology Data Exchange (ETDEWEB)

    Link, Jeanne M.; Stratton, John R.; Levy, Wayne; Poole, Jeanne E.; Shoner, Steven C.; Stuetzle, Werner; Caldwell, James H. E-mail: jcald@u.washington.edu

    2003-11-01

    Positron Emission Tomography was used to measure global and regional cardiac {beta}-adrenergic function in 19 normal subjects and 9 congestive heart failure patients. [{sup 11}C]-meta-hydroxyephedrine was used to image norepinephrine transporter function as an indicator of pre-synaptic function and [{sup 11}C]-CGP12177 was used to measure cell surface {beta}-receptor density as an indicator of post-synaptic function. Pre-synaptic, but not post-synaptic, function was significantly different between normals and CHF patients. Pre-synaptic function was well matched to post-synaptic function in the normal hearts but significantly different and poorly matched in the CHF patients studied. This imaging technique can help us understand regional sympathetic function in cardiac disease.

  7. Differentiation of Spermatogonia Stem Cells into Functional Mature Neurons Characterized with Differential Gene Expression.

    Science.gov (United States)

    Bojnordi, Maryam Nazm; Azizi, Hossein; Skutella, Thomas; Movahedin, Mansoureh; Pourabdolhossein, Fereshteh; Shojaei, Amir; Hamidabadi, Hatef Ghasemi

    2017-09-01

    Transplantation of embryonic stem cells (ESCs) is a promising therapeutic approach for the treatment of neurodegenerative diseases. However, ESCs are not usable clinically due to immunological and ethical limitations. The identification of an alternative safe cell source opens novel options via autologous transplantation in neuro-regeneration circumventing these problems. Here, we examined the neurogenic capacity of embryonic stem-like cells (ES-like cells) derived from the testis using neural growth factor inducers and utilized them to generate functional mature neurons. The neuronal differentiation of ES-like cells is induced in three stages. Stage 1 is related to embryoid body (EB) formation. To induce neuroprogenitor cells, EBs were cultured in the presence of retinoic acid, N 2 supplement and fibroblast growth factor followed by culturing in a neurobasal medium containing B 27 , N 2 supplements for additional 10 days, to allow the maturation and development of neuronal progenitor cells. The neurogenic differentiation was confirmed by immunostaining for markers of mature neurons. The differentiated neurons were positive for Tuj1 and Tau1. Real-time PCR dates indicated the expression of Nestin and Neuro D (neuroprogenitor markers) in induced cells at the second stage of the differentiation protocol. The differentiated mature neurons exhibited the specific neuron markers Map2 and β-tubulin. The functional maturity of neurons was confirmed by an electrophysiological analysis of passive and active neural membrane properties. These findings indicated a differentiation capacity of ES-like cells derived from the testis to functionally mature neurons, which proposes them as a novel cell source for neuroregenerative medicine.

  8. Focusing on neuronal cell-type specific mechanisms for brain circuit organization, function and dysfunction

    Institute of Scientific and Technical Information of China (English)

    Lu Li

    2017-01-01

    Mammalian brain circuits consist of dynamically interconnected neurons with characteristic morphology, physiology, connectivity and genetics which are often called neuronal cell types. Neuronal cell types have been considered as building blocks of brain circuits, but knowledge of how neuron types or subtypes connect to and interact with each other to perform neural computation is still lacking. Such mechanistic insights are critical not only to our understanding of normal brain functions, such as perception, motion and cognition, but also to brain disorders including Alzheimer's disease, Schizophrenia and epilepsy, to name a few. Thus it is necessary to carry out systematic and standardized studies on neuronal cell-type specific mechanisms for brain circuit organization and function, which will provide good opportunities to bridge basic and clinical research. Here based on recent technology advancements, we discuss the strategy to target and manipulate specific populations of neuronsin vivo to provide unique insights on how neuron types or subtypes behave, interact, and generate emergent properties in a fully connected brain network. Our approach is highlighted by combining transgenic animal models, targeted electrophysiology and imaging with robotics, thus complete and standardized mapping ofin vivo properties of genetically defined neuron populations can be achieved in transgenic mouse models, which will facilitate the development of novel therapeutic strategies for brain disorders.

  9. The functional significance of newly born neurons integrated into olfactory bulb circuits.

    Science.gov (United States)

    Sakamoto, Masayuki; Kageyama, Ryoichiro; Imayoshi, Itaru

    2014-01-01

    The olfactory bulb (OB) is the first central processing center for olfactory information connecting with higher areas in the brain, and this neuronal circuitry mediates a variety of odor-evoked behavioral responses. In the adult mammalian brain, continuous neurogenesis occurs in two restricted regions, the subventricular zone (SVZ) of the lateral ventricle and the hippocampal dentate gyrus. New neurons born in the SVZ migrate through the rostral migratory stream and are integrated into the neuronal circuits of the OB throughout life. The significance of this continuous supply of new neurons in the OB has been implicated in plasticity and memory regulation. Two decades of huge investigation in adult neurogenesis revealed the biological importance of integration of new neurons into the olfactory circuits. In this review, we highlight the recent findings about the physiological functions of newly generated neurons in rodent OB circuits and then discuss the contribution of neurogenesis in the brain function. Finally, we introduce cutting edge technologies to monitor and manipulate the activity of new neurons.

  10. The functional significance of newly born neurons integrated into olfactory bulb circuits

    Directory of Open Access Journals (Sweden)

    Masayuki eSakamoto

    2014-05-01

    Full Text Available The olfactory bulb (OB is the first central processing center for olfactory information connecting with higher areas in the brain, and this neuronal circuitry mediates a variety of odor-evoked behavioral responses. In the adult mammalian brain, continuous neurogenesis occurs in two restricted regions, the subventricular zone (SVZ of the lateral ventricle and the hippocampal dentate gyrus. New neurons born in the SVZ migrate through the rostral migratory stream and are integrated into the neuronal circuits of the OB throughout life. The significance of this continuous supply of new neurons in the OB has been implicated in plasticity and memory regulation. Two decades of huge investigation in adult neurogenesis revealed the biological importance of integration of new neurons into the olfactory circuits. In this review, we highlight the recent findings about the physiological functions of newly generated neurons in rodent OB circuits and then discuss the contribution of neurogenesis in the brain function. Finally, we introduce cutting edge technologies to monitor and manipulate the activity of new neurons.

  11. Gravity Reception and Cardiac Function in the Spider

    Science.gov (United States)

    Finck, A.

    1985-01-01

    The following features of the arachnid gravity system were studied. (1) the absolute threshold to hyper-gz is quite low indicating fine proprioreceptive properties of the lyriform organ, the Gz/vibration detector; (2) the neurogenic heart of the spider is a good dependent variable for assessing its behavior to Gz and other stimuli which produce mechanical effects on the exoskeleton; (3) Not only is the cardiac response useful but it is now understood to be an integral part of the system which compensates for the consequences of gravity in the spider (an hydraulic leg extension); and (4) a theoretical model was proposed in which a mechanical amplifier, the leg lever, converts a weak force (at the tarsus) to a strong force (at the patella), capable of compressing the exoskeleton and consequently the lyriform receptor.

  12. Mitochondrial function in engineered cardiac tissues is regulated by extracellular matrix elasticity and tissue alignment.

    Science.gov (United States)

    Lyra-Leite, Davi M; Andres, Allen M; Petersen, Andrew P; Ariyasinghe, Nethika R; Cho, Nathan; Lee, Jezell A; Gottlieb, Roberta A; McCain, Megan L

    2017-10-01

    Mitochondria in cardiac myocytes are critical for generating ATP to meet the high metabolic demands associated with sarcomere shortening. Distinct remodeling of mitochondrial structure and function occur in cardiac myocytes in both developmental and pathological settings. However, the factors that underlie these changes are poorly understood. Because remodeling of tissue architecture and extracellular matrix (ECM) elasticity are also hallmarks of ventricular development and disease, we hypothesize that these environmental factors regulate mitochondrial function in cardiac myocytes. To test this, we developed a new procedure to transfer tunable polydimethylsiloxane disks microcontact-printed with fibronectin into cell culture microplates. We cultured Sprague-Dawley neonatal rat ventricular myocytes within the wells, which consistently formed tissues following the printed fibronectin, and measured oxygen consumption rate using a Seahorse extracellular flux analyzer. Our data indicate that parameters associated with baseline metabolism are predominantly regulated by ECM elasticity, whereas the ability of tissues to adapt to metabolic stress is regulated by both ECM elasticity and tissue alignment. Furthermore, bioenergetic health index, which reflects both the positive and negative aspects of oxygen consumption, was highest in aligned tissues on the most rigid substrate, suggesting that overall mitochondrial function is regulated by both ECM elasticity and tissue alignment. Our results demonstrate that mitochondrial function is regulated by both ECM elasticity and myofibril architecture in cardiac myocytes. This provides novel insight into how extracellular cues impact mitochondrial function in the context of cardiac development and disease. NEW & NOTEWORTHY A new methodology has been developed to measure O 2 consumption rates in engineered cardiac tissues with independent control over tissue alignment and matrix elasticity. This led to the findings that matrix

  13. Cortical Bone Stem Cell Therapy Preserves Cardiac Structure and Function After Myocardial Infarction.

    Science.gov (United States)

    Sharp, Thomas E; Schena, Giana J; Hobby, Alexander R; Starosta, Timothy; Berretta, Remus M; Wallner, Markus; Borghetti, Giulia; Gross, Polina; Yu, Daohai; Johnson, Jaslyn; Feldsott, Eric; Trappanese, Danielle M; Toib, Amir; Rabinowitz, Joseph E; George, Jon C; Kubo, Hajime; Mohsin, Sadia; Houser, Steven R

    2017-11-10

    Cortical bone stem cells (CBSCs) have been shown to reduce ventricular remodeling and improve cardiac function in a murine myocardial infarction (MI) model. These effects were superior to other stem cell types that have been used in recent early-stage clinical trials. However, CBSC efficacy has not been tested in a preclinical large animal model using approaches that could be applied to patients. To determine whether post-MI transendocardial injection of allogeneic CBSCs reduces pathological structural and functional remodeling and prevents the development of heart failure in a swine MI model. Female Göttingen swine underwent left anterior descending coronary artery occlusion, followed by reperfusion (ischemia-reperfusion MI). Animals received, in a randomized, blinded manner, 1:1 ratio, CBSCs (n=9; 2×10 7 cells total) or placebo (vehicle; n=9) through NOGA-guided transendocardial injections. 5-ethynyl-2'deoxyuridine (EdU)-a thymidine analog-containing minipumps were inserted at the time of MI induction. At 72 hours (n=8), initial injury and cell retention were assessed. At 3 months post-MI, cardiac structure and function were evaluated by serial echocardiography and terminal invasive hemodynamics. CBSCs were present in the MI border zone and proliferating at 72 hours post-MI but had no effect on initial cardiac injury or structure. At 3 months, CBSC-treated hearts had significantly reduced scar size, smaller myocytes, and increased myocyte nuclear density. Noninvasive echocardiographic measurements showed that left ventricular volumes and ejection fraction were significantly more preserved in CBSC-treated hearts, and invasive hemodynamic measurements documented improved cardiac structure and functional reserve. The number of EdU + cardiac myocytes was increased in CBSC- versus vehicle- treated animals. CBSC administration into the MI border zone reduces pathological cardiac structural and functional remodeling and improves left ventricular functional reserve

  14. Relationship between quantitative cardiac neuronal imaging with ¹²³I-meta-iodobenzylguanidine and hospitalization in patients with heart failure.

    Science.gov (United States)

    Parker, Matthew W; Sood, Nitesh; Ahlberg, Alan W; Jacobson, Arnold F; Heller, Gary V; Lundbye, Justin B

    2014-09-01

    Hospitalization in patients with systolic heart failure is associated with morbidity, mortality, and cost. Myocardial sympathetic innervation, imaged by (123)I-meta-iodobenzylguanidine ((123)I-mIBG), has been associated with cardiac events in a recent multicenter study. The present analysis explored the relationship between (123)I-mIBG imaging findings and hospitalization. Source documents from the ADMIRE-HF trial were reviewed to identify hospitalization events in patients with systolic heart failure following cardiac neuronal imaging using (123)I-mIBG. Time to hospitalization was analyzed with the Kaplan-Meier method and compared to the mIBG heart-to-mediastinum (H/M) ratio using multiple-failure Cox regression. During 1.4 years of median follow-up, 362 end-point hospitalizations occurred in 207 of 961 subjects, 79 % of whom had H/M ratio heart failure diagnosis, a low mIBG H/M ratio was associated with cardiac-related hospitalization (HR 1.48, 95 % CI 1.05 - 2.0; p = 0.02). The mIBG H/M ratio may risk-stratify patients with heart failure for cardiac-related hospitalization, especially when used in conjunction with BNP. Further studies are warranted to examine these relationships.

  15. Pattern separation: a common function for new neurons in hippocampus and olfactory bulb.

    Science.gov (United States)

    Sahay, Amar; Wilson, Donald A; Hen, René

    2011-05-26

    While adult-born neurons in the olfactory bulb (OB) and the dentate gyrus (DG) subregion of the hippocampus have fundamentally different properties, they may have more in common than meets the eye. Here, we propose that new granule cells in the OB and DG may function as modulators of principal neurons to influence pattern separation and that adult neurogenesis constitutes an adaptive mechanism to optimally encode contextual or olfactory information. See the related Perspective from Aimone, Deng, and Gage, "Resolving New Memories: A Critical Look at the Dentate Gyrus, Adult Neurogenesis, and Pattern Separation," in this issue of Neuron. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Two aspects of ASIC function: Synaptic plasticity and neuronal injury.

    Science.gov (United States)

    Huang, Yan; Jiang, Nan; Li, Jun; Ji, Yong-Hua; Xiong, Zhi-Gang; Zha, Xiang-ming

    2015-07-01

    Extracellular brain pH fluctuates in both physiological and disease conditions. The main postsynaptic proton receptor is the acid-sensing ion channels (ASICs). During the past decade, much progress has been made on protons, ASICs, and neurological disease. This review summarizes the recent progress on synaptic role of protons and our current understanding of how ASICs contribute to various types of neuronal injury in the brain. This article is part of the Special Issue entitled 'Acid-Sensing Ion Channels in the Nervous System'. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Microglia Dictate the Impact of Saturated Fat Consumption on Hypothalamic Inflammation and Neuronal Function

    Directory of Open Access Journals (Sweden)

    Martin Valdearcos

    2014-12-01

    Full Text Available Diets rich in saturated fat produce inflammation, gliosis, and neuronal stress in the mediobasal hypothalamus (MBH. Here, we show that microglia mediate this process and its functional impact. Although microglia and astrocytes accumulate in the MBH of mice fed a diet rich in saturated fatty acids (SFAs, only the microglia undergo inflammatory activation, along with a buildup of hypothalamic SFAs. Enteric gavage specifically with SFAs reproduces microglial activation and neuronal stress in the MBH, and SFA treatment activates murine microglia, but not astrocytes, in culture. Moreover, depleting microglia abrogates SFA-induced inflammation in hypothalamic slices. Remarkably, depleting microglia from the MBH of mice abolishes inflammation and neuronal stress induced by excess SFA consumption, and in this context, microglial depletion enhances leptin signaling and reduces food intake. We thus show that microglia sense SFAs and orchestrate an inflammatory process in the MBH that alters neuronal function when SFA consumption is high.

  18. Functional properties and synaptic integration of genetically labelled dopaminergic neurons in intrastriatal grafts

    DEFF Research Database (Denmark)

    Sørensen, Andreas Toft; Thompson, Lachlan; Kirik, Deniz

    2005-01-01

    in the dopamine-depleted striatum than of those in the intact striatum. Our findings define specific electrophysiological characteristics of transplanted fetal dopaminergic neurons, and we provide the first direct evidence of functional synaptic integration of these neurons into host neural circuitries......., the electrophysiological properties grafted cells need to have in order to induce substantial functional recovery are poorly defined. It has not been possible to prospectively identify and record from dopaminergic neurons in fetal transplants. Here we used transgenic mice expressing green fluorescent protein under control...... of the rat tyrosine hydroxylase promoter for whole-cell patch-clamp recordings of endogenous and grafted dopaminergic neurons. We transplanted ventral mesencephalic tissue from E12.5 transgenic mice into striatum of neonatal rats with or without lesions of the nigrostriatal dopamine system. The transplanted...

  19. Functional architecture of reward learning in mushroom body extrinsic neurons of larval Drosophila.

    Science.gov (United States)

    Saumweber, Timo; Rohwedder, Astrid; Schleyer, Michael; Eichler, Katharina; Chen, Yi-Chun; Aso, Yoshinori; Cardona, Albert; Eschbach, Claire; Kobler, Oliver; Voigt, Anne; Durairaja, Archana; Mancini, Nino; Zlatic, Marta; Truman, James W; Thum, Andreas S; Gerber, Bertram

    2018-03-16

    The brain adaptively integrates present sensory input, past experience, and options for future action. The insect mushroom body exemplifies how a central brain structure brings about such integration. Here we use a combination of systematic single-cell labeling, connectomics, transgenic silencing, and activation experiments to study the mushroom body at single-cell resolution, focusing on the behavioral architecture of its input and output neurons (MBINs and MBONs), and of the mushroom body intrinsic APL neuron. Our results reveal the identity and morphology of almost all of these 44 neurons in stage 3 Drosophila larvae. Upon an initial screen, functional analyses focusing on the mushroom body medial lobe uncover sparse and specific functions of its dopaminergic MBINs, its MBONs, and of the GABAergic APL neuron across three behavioral tasks, namely odor preference, taste preference, and associative learning between odor and taste. Our results thus provide a cellular-resolution study case of how brains organize behavior.

  20. ALS-associated mutant FUS induces selective motor neuron degeneration through toxic gain of function.

    Science.gov (United States)

    Sharma, Aarti; Lyashchenko, Alexander K; Lu, Lei; Nasrabady, Sara Ebrahimi; Elmaleh, Margot; Mendelsohn, Monica; Nemes, Adriana; Tapia, Juan Carlos; Mentis, George Z; Shneider, Neil A

    2016-02-04

    Mutations in FUS cause amyotrophic lateral sclerosis (ALS), including some of the most aggressive, juvenile-onset forms of the disease. FUS loss-of-function and toxic gain-of-function mechanisms have been proposed to explain how mutant FUS leads to motor neuron degeneration, but neither has been firmly established in the pathogenesis of ALS. Here we characterize a series of transgenic FUS mouse lines that manifest progressive, mutant-dependent motor neuron degeneration preceded by early, structural and functional abnormalities at the neuromuscular junction. A novel, conditional FUS knockout mutant reveals that postnatal elimination of FUS has no effect on motor neuron survival or function. Moreover, endogenous FUS does not contribute to the onset of the ALS phenotype induced by mutant FUS. These findings demonstrate that FUS-dependent motor degeneration is not due to loss of FUS function, but to the gain of toxic properties conferred by ALS mutations.

  1. Effects of a single terlipressin administration on cardiac function and perfusion in cirrhosis

    DEFF Research Database (Denmark)

    Krag, Aleksander; Bendtsen, Flemming; Mortensen, Christian

    2010-01-01

    BACKGROUND: The vasoconstrictor terlipressin is widely used in the treatment of the hepatorenal syndrome and variceal bleeding. However, terlipressin may compromise cardiac function and induce ischemia. AIM: Therefore, we aimed to assess the effects of terlipressin on cardiac function and perfusion...... with nonrefractory ascites, both at baseline and after terlipressin treatment. The decrease in the left ventricular wall thickening and wall motion correlated with the Child--Pugh score, r=-0.59, P=0.005 and r=-0.48, P=0.03. CONCLUSION: In advanced cirrhosis, the increase in afterload and EDV after terlipressin...

  2. Evaluating the cardiac function of duchenne muscular dystrophy with Doppler Tei index

    International Nuclear Information System (INIS)

    Yao Fengjuan; Zheng Ju; Lu Kun; Liu Donghong; Wu Miaoling; Lin Hong; Zhang Cheng; Yu Hongkui

    2007-01-01

    Objective: To evaluate the cardiac function of early Duchenne muscular dystrophy (DMD) by left ventricular ejection fraction (LVEF) and pulse Doppler Tei index. Methods: Twenty-eight DMD patients and fifteen normal people were studied. LVEF, E/A and Tei index were measured and calculated by M-mode and Pulse wave Doppler respectively. Results: Compared with control group, Tei index and IRT were significantly high, and there were not significant difference in LVEF(%) and E/A. Conclusion: Tei index was valuable in assessing cardiac function of early DMD. (authors)

  3. Inspiration from heart development: Biomimetic development of functional human cardiac organoids.

    Science.gov (United States)

    Richards, Dylan J; Coyle, Robert C; Tan, Yu; Jia, Jia; Wong, Kerri; Toomer, Katelynn; Menick, Donald R; Mei, Ying

    2017-10-01

    Recent progress in human organoids has provided 3D tissue systems to model human development, diseases, as well as develop cell delivery systems for regenerative therapies. While direct differentiation of human embryoid bodies holds great promise for cardiac organoid production, intramyocardial cell organization during heart development provides biological foundation to fabricate human cardiac organoids with defined cell types. Inspired by the intramyocardial organization events in coronary vasculogenesis, where a diverse, yet defined, mixture of cardiac cell types self-organizes into functional myocardium in the absence of blood flow, we have developed a defined method to produce scaffold-free human cardiac organoids that structurally and functionally resembled the lumenized vascular network in the developing myocardium, supported hiPSC-CM development and possessed fundamental cardiac tissue-level functions. In particular, this development-driven strategy offers a robust, tunable system to examine the contributions of individual cell types, matrix materials and additional factors for developmental insight, biomimetic matrix composition to advance biomaterial design, tissue/organ-level drug screening, and cell therapy for heart repair. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. The lateral paragigantocellular nucleus modulates parasympathetic cardiac neurons: a mechanism for rapid eye movement sleep-dependent changes in heart rate.

    Science.gov (United States)

    Dergacheva, Olga; Wang, Xin; Lovett-Barr, Mary R; Jameson, Heather; Mendelowitz, David

    2010-08-01

    Rapid eye movement (REM) sleep is generally associated with a withdrawal of parasympathetic activity and heart rate increases; however, episodic vagally mediated heart rate decelerations also occur during REM sleep. This alternating pattern of autonomic activation provides a physiological basis for REM sleep-induced cardiac arrhythmias. Medullary neurons within the lateral paragigantocellular nucleus (LPGi) are thought to be active after REM sleep recovery and play a role in REM sleep control. In proximity to the LPGi are parasympathetic cardiac vagal neurons (CVNs) within the nucleus ambiguus (NA), which are critical for controlling heart rate. This study examined brain stem pathways that may mediate REM sleep-related reductions in parasympathetic cardiac activity. Electrical stimulation of the LPGi evoked inhibitory GABAergic postsynaptic currents in CVNs in an in vitro brain stem slice preparation in rats. Because brain stem cholinergic mechanisms are involved in REM sleep regulation, we also studied the role of nicotinic neurotransmission in modulation of GABAergic pathway from the LGPi to CVNs. Application of nicotine diminished the GABAergic responses evoked by electrical stimulation. This inhibitory effect of nicotine was prevented by the alpha7 nicotinic receptor antagonist alpha-bungarotoxin. Moreover, hypoxia/hypercapnia (H/H) diminished LPGi-evoked GABAergic current in CVNs, and this inhibitory effect was also prevented by alpha-bungarotoxin. In conclusion, stimulation of the LPGi evokes an inhibitory pathway to CVNs, which may constitute a mechanism for the reduced parasympathetic cardiac activity and increase in heart rate during REM sleep. Inhibition of this pathway by nicotinic receptor activation and H/H may play a role in REM sleep-related and apnea-associated bradyarrhythmias.

  5. Diverse Intrinsic Properties Shape Functional Phenotype of Low-Frequency Neurons in the Auditory Brainstem

    Directory of Open Access Journals (Sweden)

    Hui Hong

    2018-06-01

    Full Text Available In the auditory system, tonotopy is the spatial arrangement of where sounds of different frequencies are processed. Defined by the organization of neurons and their inputs, tonotopy emphasizes distinctions in neuronal structure and function across topographic gradients and is a common feature shared among vertebrates. In this study we characterized action potential firing patterns and ion channel properties from neurons located in the extremely low-frequency region of the chicken nucleus magnocellularis (NM, an auditory brainstem structure. We found that NM neurons responsible for encoding the lowest sound frequencies (termed NMc neurons have enhanced excitability and fired bursts of action potentials to sinusoidal inputs ≤10 Hz; a distinct firing pattern compared to higher-frequency neurons. This response property was due to lower amounts of voltage dependent potassium (KV conductances, unique combination of KV subunits and specialized sodium (NaV channel properties. Particularly, NMc neurons had significantly lower KV1 and KV3 currents, but higher KV2 current. NMc neurons also showed larger and faster transient NaV current (INaT with different voltage dependence of inactivation from higher-frequency neurons. In contrast, significantly smaller resurgent sodium current (INaR was present in NMc with kinetics and voltage dependence that differed from higher-frequency neurons. Immunohistochemistry showed expression of NaV1.6 channel subtypes across the tonotopic axis. However, various immunoreactive patterns were observed between regions, likely underlying some tonotopic differences in INaT and INaR. Finally, using pharmacology and computational modeling, we concluded that KV3, KV2 channels and INaR work synergistically to regulate burst firing in NMc.

  6. An electronic implementation for Liao's chaotic delayed neuron model with non-monotonous activation function

    International Nuclear Information System (INIS)

    Duan Shukai; Liao Xiaofeng

    2007-01-01

    A new chaotic delayed neuron model with non-monotonously increasing transfer function, called as chaotic Liao's delayed neuron model, was recently reported and analyzed. An electronic implementation of this model is described in detail. At the same time, some methods in circuit design, especially for circuit with time delayed unit and non-monotonously increasing activation unit, are also considered carefully. We find that the dynamical behaviors of the designed circuits are closely similar to the results predicted by numerical experiments

  7. Prediction of rat behavior outcomes in memory tasks using functional connections among neurons.

    Directory of Open Access Journals (Sweden)

    Hu Lu

    Full Text Available BACKGROUND: Analyzing the neuronal organizational structures and studying the changes in the behavior of the organism is key to understanding cognitive functions of the brain. Although some studies have indicated that spatiotemporal firing patterns of neuronal populations have a certain relationship with the behavioral responses, the issues of whether there are any relationships between the functional networks comprised of these cortical neurons and behavioral tasks and whether it is possible to take advantage of these networks to predict correct and incorrect outcomes of single trials of animals are still unresolved. METHODOLOGY/PRINCIPAL FINDINGS: This paper presents a new method of analyzing the structures of whole-recorded neuronal functional networks (WNFNs and local neuronal circuit groups (LNCGs. The activity of these neurons was recorded in several rats. The rats performed two different behavioral tasks, the Y-maze task and the U-maze task. Using the results of the assessment of the WNFNs and LNCGs, this paper describes a realization procedure for predicting the behavioral outcomes of single trials. The methodology consists of four main parts: construction of WNFNs from recorded neuronal spike trains, partitioning the WNFNs into the optimal LNCGs using social community analysis, unsupervised clustering of all trials from each dataset into two different clusters, and predicting the behavioral outcomes of single trials. The results show that WNFNs and LNCGs correlate with the behavior of the animal. The U-maze datasets show higher accuracy for unsupervised clustering results than those from the Y-maze task, and these datasets can be used to predict behavioral responses effectively. CONCLUSIONS/SIGNIFICANCE: The results of the present study suggest that a methodology proposed in this paper is suitable for analysis of the characteristics of neuronal functional networks and the prediction of rat behavior. These types of structures in cortical

  8. PINK1 is necessary for long term survival and mitochondrial function in human dopaminergic neurons.

    Directory of Open Access Journals (Sweden)

    Alison Wood-Kaczmar

    2008-06-01

    Full Text Available Parkinson's disease (PD is a common age-related neurodegenerative disease and it is critical to develop models which recapitulate the pathogenic process including the effect of the ageing process. Although the pathogenesis of sporadic PD is unknown, the identification of the mendelian genetic factor PINK1 has provided new mechanistic insights. In order to investigate the role of PINK1 in Parkinson's disease, we studied PINK1 loss of function in human and primary mouse neurons. Using RNAi, we created stable PINK1 knockdown in human dopaminergic neurons differentiated from foetal ventral mesencephalon stem cells, as well as in an immortalised human neuroblastoma cell line. We sought to validate our findings in primary neurons derived from a transgenic PINK1 knockout mouse. For the first time we demonstrate an age dependent neurodegenerative phenotype in human and mouse neurons. PINK1 deficiency leads to reduced long-term viability in human neurons, which die via the mitochondrial apoptosis pathway. Human neurons lacking PINK1 demonstrate features of marked oxidative stress with widespread mitochondrial dysfunction and abnormal mitochondrial morphology. We report that PINK1 plays a neuroprotective role in the mitochondria of mammalian neurons, especially against stress such as staurosporine. In addition we provide evidence that cellular compensatory mechanisms such as mitochondrial biogenesis and upregulation of lysosomal degradation pathways occur in PINK1 deficiency. The phenotypic effects of PINK1 loss-of-function described here in mammalian neurons provides mechanistic insight into the age-related degeneration of nigral dopaminergic neurons seen in PD.

  9. Multiple functional attributes of glucose-monitoring neurons in the medial orbitofrontal (ventrolateral prefrontal) cortex.

    Science.gov (United States)

    Szabó, István; Hormay, Edina; Csetényi, Bettina; Nagy, Bernadett; Lénárd, László; Karádi, Zoltán

    2018-02-01

    Multiple functional attributes of glucose-monitoring neurons in the medial orbitofrontal (ventrolateral prefrontal) cortex. NEUROSCI BIOBEHAV REV 73(1) XXX-XXX, 2017.- Special chemosensory cells, the glucose-monitoring (GM) neurons, reportedly involved in the central feeding control, exist in the medial orbitofrontal (ventrolateral prefrontal) cortex (mVLPFC). Electrophysiological, metabolic and behavioral studies reveal complex functional attributes of these cells and raise their homeostatic significance. Single neuron recordings, by means of the multibarreled microelectrophoretic technique, elucidate differential sensitivities of limbic forebrain neurons in the rat and the rhesus monkey to glucose and other chemicals, whereas gustatory stimulations demonstrate their distinct taste responsiveness. Metabolic examinations provide evidence for alteration of blood glucose level in glucose tolerance test and elevation of plasma triglyceride concentration after destruction of the local GM cells by streptozotocin (STZ). In behavioral studies, STZ microinjection into the mVLPFC fails to interfere with the acquisition of saccharin conditioned taste avoidance, does cause, however, taste perception deficit in taste reactivity tests. Multiple functional attributes of GM neurons in the mVLPFC, within the frame of the hierarchically organized central GM neuronal network, appear to play important role in the maintenance of the homeostatic balance. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Investigations of new cardiac functional imaging using Fourier analysis of gated blood-pool study

    International Nuclear Information System (INIS)

    Maeda, H.; Takeda, K.; Nakagawa, T.; Yamaguchi, N.; Taguchi, M.; Konishi, T.; Hamada, M.

    1982-01-01

    A new cardiac functional imaging, using temporal Fourier analysis of 28-frame gated cardiac blood-pool studies, was developed. A time-activity curve of each pixel was approximated by its Fourier series. Approximation by the sum for terms to the 3rd frequency of its Fourier series was considered to be most reasonable because of having the least aberration due to statistical fluctuation and close agreement between the global left ventricular curve and the regional fitted curves in normal subjects. To evaluate the ventricular systolic and diastolic performances, 9 parameters were analyzed from thus fitted curves on a pixel-by-pixel basis and displayed on a colour CRT in 64x64 matrix form. In patients with hypertrophic obstructive cardiomyopathy and other cardiac lesions, detailed information on the regional ventricular systolic and diastolic performances was clearly visualized by this method, which was difficult to obtain from the usual functional images of phase and amplitude at the fundamental frequency alone

  11. Engineering the heart: Evaluation of conductive nanomaterials for improving implant integration and cardiac function

    Science.gov (United States)

    Zhou, Jin; Chen, Jun; Sun, Hongyu; Qiu, Xiaozhong; Mou, Yongchao; Liu, Zhiqiang; Zhao, Yuwei; Li, Xia; Han, Yao; Duan, Cuimi; Tang, Rongyu; Wang, Chunlan; Zhong, Wen; Liu, Jie; Luo, Ying; (Mengqiu) Xing, Malcolm; Wang, Changyong

    2014-01-01

    Recently, carbon nanotubes together with other types of conductive materials have been used to enhance the viability and function of cardiomyocytes in vitro. Here we demonstrated a paradigm to construct ECTs for cardiac repair using conductive nanomaterials. Single walled carbon nanotubes (SWNTs) were incorporated into gelatin hydrogel scaffolds to construct three-dimensional ECTs. We found that SWNTs could provide cellular microenvironment in vitro favorable for cardiac contraction and the expression of electrochemical associated proteins. Upon implantation into the infarct hearts in rats, ECTs structurally integrated with the host myocardium, with different types of cells observed to mutually invade into implants and host tissues. The functional measurements showed that SWNTs were essential to improve the performance of ECTs in inhibiting pathological deterioration of myocardium. This work suggested that conductive nanomaterials hold therapeutic potential in engineering cardiac tissues to repair myocardial infarction. PMID:24429673

  12. Corazonin neurons function in sexually dimorphic circuitry that shape behavioral responses to stress in Drosophila.

    Directory of Open Access Journals (Sweden)

    Yan Zhao

    Full Text Available All organisms are confronted with dynamic environmental changes that challenge homeostasis, which is the operational definition of stress. Stress produces adaptive behavioral and physiological responses, which, in the Metazoa, are mediated through the actions of various hormones. Based on its associated phenotypes and its expression profiles, a candidate stress hormone in Drosophila is the corazonin neuropeptide. We evaluated the potential roles of corazonin in mediating stress-related changes in target behaviors and physiologies through genetic alteration of corazonin neuronal excitability. Ablation of corazonin neurons confers resistance to metabolic, osmotic, and oxidative stress, as measured by survival. Silencing and activation of corazonin neurons lead to differential lifespan under stress, and these effects showed a strong dependence on sex. Additionally, altered corazonin neuron physiology leads to fundamental differences in locomotor activity, and these effects were also sex-dependent. The dynamics of altered locomotor behavior accompanying stress was likewise altered in flies with altered corazonin neuronal function. We report that corazonin transcript expression is altered under starvation and osmotic stress, and that triglyceride and dopamine levels are equally impacted in corazonin neuronal alterations and these phenotypes similarly show significant sexual dimorphisms. Notably, these sexual dimorphisms map to corazonin neurons. These results underscore the importance of central peptidergic processing within the context of stress and place corazonin signaling as a critical feature of neuroendocrine events that shape stress responses and may underlie the inherent sexual dimorphic differences in stress responses.

  13. The Role of Diacylglycerol Acyltransferase (DGAT) 1 and 2 in Cardiac Metabolism and Function.

    Science.gov (United States)

    Roe, Nathan D; Handzlik, Michal K; Li, Tao; Tian, Rong

    2018-03-21

    It is increasingly recognized that synthesis and turnover of cardiac triglyceride (TG) play a pivotal role in the regulation of lipid metabolism and function of the heart. The last step in TG synthesis is catalyzed by diacylglycerol:acyltransferase (DGAT) which esterifies the diacylglycerol with a fatty acid. Mammalian heart has two DGAT isoforms, DGAT1 and DGAT2, yet their roles in cardiac metabolism and function remain poorly defined. Here, we show that inactivation of DGAT1 or DGAT2 in adult mouse heart results in a moderate suppression of TG synthesis and turnover. Partial inhibition of DGAT activity increases cardiac fatty acid oxidation without affecting PPARα signaling, myocardial energetics or contractile function. Moreover, coinhibition of DGAT1/2 in the heart abrogates TG turnover and protects the heart against high fat diet-induced lipid accumulation with no adverse effects on basal or dobutamine-stimulated cardiac function. Thus, the two DGAT isoforms in the heart have partially redundant function, and pharmacological inhibition of one DGAT isoform is well tolerated in adult hearts.

  14. Exercise and type 2 diabetes mellitus: changes in tissue-specific fat distribution and cardiac function.

    Science.gov (United States)

    Jonker, Jacqueline T; de Mol, Pieter; de Vries, Suzanna T; Widya, Ralph L; Hammer, Sebastiaan; van Schinkel, Linda D; van der Meer, Rutger W; Gans, Rijk O B; Webb, Andrew G; Kan, Hermien E; de Koning, Eelco J P; Bilo, Henk J G; Lamb, Hildo J

    2013-11-01

    To prospectively assess the effects of an exercise intervention on organ-specific fat accumulation and cardiac function in type 2 diabetes mellitus. Written informed consent was obtained from all participants, and the study protocol was approved by the medical ethics committee. The study followed 12 patients with type 2 diabetes mellitus (seven men; mean age, 46 years ± 2 [standard error]) before and after 6 months of moderate-intensity exercise, followed by a high-altitude trekking expedition with exercise of long duration. Abdominal, epicardial, and paracardial fat volume were measured by using magnetic resonance (MR) imaging. Cardiac function was quantified with cardiac MR, and images were analyzed by a researcher who was supervised by a senior researcher (4 and 21 years of respective experience in cardiac MR). Hepatic, myocardial, and intramyocellular triglyceride (TG) content relative to water were measured with proton MR spectroscopy at 1.5 and 7 T. Two-tailed paired t tests were used for statistical analysis. Exercise reduced visceral abdominal fat volume from 348 mL ± 57 to 219 mL ± 33 (P Exercise decreased hepatic TG content from 6.8% ± 2.3 to 4.6% ± 1.6 (P Exercise did not change epicardial fat volume (P = .9), myocardial TG content (P = .9), intramyocellular lipid content (P = .3), or cardiac function (P = .5). A 6-month exercise intervention in type 2 diabetes mellitus decreased hepatic TG content and visceral abdominal and paracardial fat volume, which are associated with increased cardiovascular risk, but cardiac function was unaffected. Tissue-specific exercise-induced changes in body fat distribution in type 2 diabetes mellitus were demonstrated in this study. RSNA, 2013

  15. A portable cadmium telluride multidetector probe for cardiac function monitoring

    CERN Document Server

    Arntz, Y; Dumitresco, B; Eclancher, B; Prat, V

    1999-01-01

    A new nuclear stethoscope based on a matrix of small CdTe semiconductor detectors has been developed for studying the cardiac performance by gamma ventriculography at the equilibrium, in rest and stress conditions, in the early and recovery phases of the coronary disease and to follow the long-term therapy. The light-weight probe consists of an array of 64 detectors 5x5x2 mm grouped in 16 independent units in a lead shielded aluminum box including 16 preamplifiers. The probe is connected to an electronic box containing DC power supply, 16 channel amplifiers, discriminators and counters, two analog-triggering ECG channels, and interface to a PC. The left ventricle activity is, preferentially, detected by using a low-resolution matching convergent collimator. A physical evaluation of the probe has been performed, both with static tests and dynamically with a hydraulic home-built model of beating heart ventricle paced by a rhythm simulator. The sum of the 16 detectors activity provided a radiocardiogram (RCG) wh...

  16. Analysis of cardiac diastolic function: application in coronary artery disease

    International Nuclear Information System (INIS)

    Miller, T.R.; Goldman, K.J.; Sampathkumaran, K.S.; Biello, D.R.; Ludbrook, P.A.; Sobel, B.E.

    1983-01-01

    Separation of systolic and diastolic parameters in gated cardiac blood-pool imaging (RVG) was achieved with the retention of two harmonics in the Fourier-series representation of the time-activity curve. Regional and global analysis of left-ventricular peak filling rate (PFR) and time to peak filling (TPF) was performed in 18 control subjects, 20 patients with coronary artery disease (CAD) but with normal RVG (normal regional wall motion and ejection fraction, and 16 CAD patients with abnormal RVG. In regional analysis of CAD patients, the standard deviation of the TPF histogram identified 13/20 (65%) of normal RVG patients and 12/16 (75%) of abnormal RVG patients as abnormal. In global analysis of CAD patients, PFR values identified 10/20 (50%) of normal RVG patients and 11/16 (69%) of abnormal RVG patients as abnormal. Thus, left-ventricular systolic and diastolic parameters can be separately measured with retention of higher-order harmonics in the Fourier transform, and regional inhomogeneity of diastolic filling can be detected in CAD patients with normal resting ejection fraction and wall motion

  17. Functional Organization of Neuronal and Humoral Signals Regulating Feeding Behavior

    Science.gov (United States)

    Schwartz, Gary J.; Zeltser, Lori M.

    2014-01-01

    Energy homeostasis- ensuring that energy availability matches energy requirements- is essential for survival. One way that energy balance is achieved is through coordinated action of neural and neuroendocrine feeding circuits, which promote energy intake when energy supply is limited. Feeding behavior engages multiple somatic and visceral tissues distributed throughout the body – contraction of skeletal and smooth muscles in the head and along the upper digestive tract required to consume and digest food, as well as stimulation of endocrine and exocrine secretions from a wide range of organs. Accordingly, neurons that contribute to feeding behaviors are localized to central, peripheral and enteric nervous systems. To promote energy balance, feeding circuits must be able to identify and respond to energy requirements, as well as the amount of energy available from internal and external sources, and then direct appropriate coordinated responses throughout the body. PMID:23642202

  18. Alteration of protein folding and degradation in motor neuron diseases : Implications and protective functions of small heat shock proteins

    NARCIS (Netherlands)

    Carra, Serena; Crippa, Valeria; Rusmini, Paola; Boncoraglio, Alessandra; Minoia, Melania; Giorgetti, Elisa; Kampinga, Harm H.; Poletti, Angelo

    Motor neuron diseases (MNDs) are neurodegenerative disorders that specifically affect the survival and function of upper and/or lower motor neurons. Since motor neurons are responsible for the control of voluntary muscular movement, MNDs are characterized by muscle spasticity, weakness and atrophy.

  19. Organization of Functional Long-Range Circuits Controlling the Activity of Serotonergic Neurons in the Dorsal Raphe Nucleus

    Directory of Open Access Journals (Sweden)

    Li Zhou

    2017-03-01

    Full Text Available Serotonergic neurons play key roles in various biological processes. However, circuit mechanisms underlying tight control of serotonergic neurons remain largely unknown. Here, we systematically investigated the organization of long-range synaptic inputs to serotonergic neurons and GABAergic neurons in the dorsal raphe nucleus (DRN of mice with a combination of viral tracing, slice electrophysiological, and optogenetic techniques. We found that DRN serotonergic neurons and GABAergic neurons receive largely comparable synaptic inputs from six major upstream brain areas. Upon further analysis of the fine functional circuit structures, we found both bilateral and ipsilateral patterns of topographic connectivity in the DRN for the axons from different inputs. Moreover, the upstream brain areas were found to bidirectionally control the activity of DRN serotonergic neurons by recruiting feedforward inhibition or via a push-pull mechanism. Our study provides a framework for further deciphering the functional roles of long-range circuits controlling the activity of serotonergic neurons in the DRN.

  20. Inflammatory mediator bradykinin increases population of sensory neurons expressing functional T-type Ca(2+) channels.

    Science.gov (United States)

    Huang, Dongyang; Liang, Ce; Zhang, Fan; Men, Hongchao; Du, Xiaona; Gamper, Nikita; Zhang, Hailin

    2016-04-29

    T-type Ca(2+) channels are important regulators of peripheral sensory neuron excitability. Accordingly, T-type Ca(2+) currents are often increased in various pathological pain conditions, such as inflammation or nerve injury. Here we investigated effects of inflammation on functional expression of T-type Ca(2+) channels in small-diameter cultured dorsal root ganglion (DRG) neurons. We found that overnight treatment of DRG cultures with a cocktail of inflammatory mediators bradykinin (BK), adenosine triphosphate (ATP), norepinephrine (NE) and prostaglandin E2 (PGE2) strongly increased the population size of the small-diameter neurons displaying low-voltage activated (LVA, T-type) Ca(2+) currents while having no effect on the peak LVA current amplitude. When applied individually, BK and ATP also increased the population size of LVA-positive neurons while NE and PGE2 had no effect. The PLC inhibitor U-73122 and B2 receptor antagonist, Hoe-140, both abolished the increase of the population of LVA-positive DRG neurons. Inflammatory treatment did not affect CaV3.2 mRNA or protein levels in DRG cultures. Furthermore, an ubiquitination inhibitor, MG132, did not increase the population of LVA-positive neurons. Our data suggest that inflammatory mediators BK and ATP increase the abundance of LVA-positive DRG neurons in total neuronal population by stimulating the recruitment of a 'reserve pool' of CaV3.2 channels, particularly in neurons that do not display measurable LVA currents under control conditions. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  1. The Effects of NAD+ on Apoptotic Neuronal Death and Mitochondrial Biogenesis and Function after Glutamate Excitotoxicity

    Science.gov (United States)

    Wang, Xiaowan; Li, Hailong; Ding, Shinghua

    2014-01-01

    NAD+ is an essential co-enzyme for cellular energy metabolism and is also involved as a substrate for many cellular enzymatic reactions. It has been shown that NAD+ has a beneficial effect on neuronal survival and brain injury in in vitro and in vivo ischemic models. However, the effect of NAD+ on mitochondrial biogenesis and function in ischemia has not been well investigated. In the present study, we used an in vitro glutamate excitotoxicity model of primary cultured cortical neurons to study the effect of NAD+ on apoptotic neuronal death and mitochondrial biogenesis and function. Our results show that supplementation of NAD+ could effectively reduce apoptotic neuronal death, and apoptotic inducing factor translocation after neurons were challenged with excitotoxic glutamate stimulation. Using different approaches including confocal imaging, mitochondrial DNA measurement and Western blot analysis of PGC-1 and NRF-1, we also found that NAD+ could significantly attenuate glutamate-induced mitochondrial fragmentation and the impairment of mitochondrial biogenesis. Furthermore, NAD+ treatment effectively inhibited mitochondrial membrane potential depolarization and NADH redistribution after excitotoxic glutamate stimulation. Taken together, our results demonstrated that NAD+ is capable of inhibiting apoptotic neuronal death after glutamate excitotoxicity via preserving mitochondrial biogenesis and integrity. Our findings provide insights into potential neuroprotective strategies in ischemic stroke. PMID:25387075

  2. Neuron-NG2 Cell Synapses: Novel Functions for Regulating NG2 Cell Proliferation and Differentiation

    Directory of Open Access Journals (Sweden)

    Qian-Kun Yang

    2013-01-01

    Full Text Available NG2 cells are a population of CNS cells that are distinct from neurons, mature oligodendrocytes, astrocytes, and microglia. These cells can be identified by their NG2 proteoglycan expression. NG2 cells have a highly branched morphology, with abundant processes radiating from the cell body, and express a complex set of voltage-gated channels, AMPA/kainate, and GABA receptors. Neurons notably form classical and nonclassical synapses with NG2 cells, which have varied characteristics and functions. Neuron-NG2 cell synapses could fine-tune NG2 cell activities, including the NG2 cell cycle, differentiation, migration, and myelination, and may be a novel potential therapeutic target for NG2 cell-related diseases, such as hypoxia-ischemia injury and periventricular leukomalacia. Furthermore, neuron-NG2 cell synapses may be correlated with the plasticity of CNS in adulthood with the synaptic contacts passing onto their progenies during proliferation, and synaptic contacts decrease rapidly upon NG2 cell differentiation. In this review, we highlight the characteristics of classical and nonclassical neuron-NG2 cell synapses, the potential functions, and the fate of synaptic contacts during proliferation and differentiation, with the emphasis on the regulation of the NG2 cell cycle by neuron-NG2 cell synapses and their potential underlying mechanisms.

  3. Regulator of G protein signaling 5 (RGS5) inhibits sonic hedgehog function in mouse cortical neurons.

    Science.gov (United States)

    Liu, Chuanliang; Hu, Qiongqiong; Jing, Jia; Zhang, Yun; Jin, Jing; Zhang, Liulei; Mu, Lili; Liu, Yumei; Sun, Bo; Zhang, Tongshuai; Kong, Qingfei; Wang, Guangyou; Wang, Dandan; Zhang, Yao; Liu, Xijun; Zhao, Wei; Wang, Jinghua; Feng, Tao; Li, Hulun

    2017-09-01

    Regulator of G protein signaling 5 (RGS5) acts as a GTPase-activating protein (GAP) for the Gαi subunit and negatively regulates G protein-coupled receptor signaling. However, its presence and function in postmitotic differentiated primary neurons remains largely uncharacterized. During neural development, sonic hedgehog (Shh) signaling is involved in cell signaling pathways via Gαi activity. In particular, Shh signaling is essential for embryonic neural tube patterning, which has been implicated in neuronal polarization involving neurite outgrowth. Here, we examined whether RGS5 regulates Shh signaling in neurons. RGS5 transcripts were found to be expressed in cortical neurons and their expression gradually declined in a time-dependent manner in culture system. When an adenovirus expressing RGS5 was introduced into an in vitro cell culture model of cortical neurons, RGS5 overexpression significantly reduced neurite outgrowth and FM4-64 uptake, while cAMP-PKA signaling was also affected. These findings suggest that RGS5 inhibits Shh function during neurite outgrowth and the presynaptic terminals of primary cortical neurons mature via modulation of cAMP. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Different requirements of functional telomeres in neural stem cells and terminally differentiated neurons.

    Science.gov (United States)

    Lobanova, Anastasia; She, Robert; Pieraut, Simon; Clapp, Charlie; Maximov, Anton; Denchi, Eros Lazzerini

    2017-04-01

    Telomeres have been studied extensively in peripheral tissues, but their relevance in the nervous system remains poorly understood. Here, we examine the roles of telomeres at distinct stages of murine brain development by using lineage-specific genetic ablation of TRF2, an essential component of the shelterin complex that protects chromosome ends from the DNA damage response machinery. We found that functional telomeres are required for embryonic and adult neurogenesis, but their uncapping has surprisingly no detectable consequences on terminally differentiated neurons. Conditional knockout of TRF2 in post-mitotic immature neurons had virtually no detectable effect on circuit assembly, neuronal gene expression, and the behavior of adult animals despite triggering massive end-to-end chromosome fusions across the brain. These results suggest that telomeres are dispensable in terminally differentiated neurons and provide mechanistic insight into cognitive abnormalities associated with aberrant telomere length in humans. © 2017 Lobanova et al.; Published by Cold Spring Harbor Laboratory Press.

  5. Structural and functional cardiac adaptations to 6 months of football training in untrained hypertensive men

    DEFF Research Database (Denmark)

    Andersen, L. J.; Randers, M. B.; Hansen, P. R.

    2014-01-01

    We investigated the effects of 3 and 6 months of regular football training on cardiac structure and function in hypertensive men. Thirty-one untrained males with mild-to-moderate hypertension were randomized 2:1 to a football training group (n = 20) and a control group receiving traditional...... training improves LV diastolic function in untrained men with mild-to-moderate arterial hypertension. Furthermore, it may improve longitudinal systolic function of both ventricles. The results suggest that football training has favorable effects on cardiac function in hypertensive men....... function improved with respect to tricuspid annular plane systolic excursion (21.8 ± 3.2 to 24.5 ± 3.7 mm). Arterial blood pressure decreased in both groups, but significantly more in the football training group. No significant changes were observed in the control group. In conclusion, short-term football...

  6. Cardiac Morphology and Function, and Blood Gas Transport in Aquaporin-1 Knockout Mice.

    Directory of Open Access Journals (Sweden)

    Samer eAl-Samir

    2016-05-01

    Full Text Available We have studied cardiac and respiratory functions of aquaporin- 1-deficient mice by the Pressure-Volume-loop technique and by blood gas analysis. In addition, the morphological properties of the animals’ hearts were analysed. In anesthesia under maximal dobutamine stimulation, the mice exhibit a moderately elevated heart rate of < 600 min-1 and an O2 consumption of ~0.6 ml/min/g, which is about twice the basal rate. In this state, which is similar to the resting state of the conscious animal, all cardiac functions including stroke volume and cardiac output exhibited resting values and were identical between deficient and wildtype animals. Likewise, pulmonary and peripheral exchange of O2 and CO2 were normal. In contrast, several morphological parameters of the heart tissue of deficient mice were altered: 1 left ventricular wall thickness was reduced by 12%, 2 left ventricular mass, normalized to tibia length, was reduced by 10-20%, 3 cardiac muscle fiber cross sectional area was decreased by 17%, and 4 capillary density was diminished by 10%. As the P-V-loop technique yielded normal end-diastolic and end-systolic left ventricular volumes, the deficient hearts are characterized by thin ventricular walls in combination with normal intraventricular volumes. The aquaporin-1-deficient heart thus seems to be at a disadvantage compared to the wildtype heart by a reduced left-ventricular wall thickness and an increased diffusion distance between blood capillaries and muscle mitochondria. While under the present quasi-resting conditions these morphological alterations have no consequences for cardiac function, we expect that the deficient hearts will show a reduced maximal cardiac output.

  7. Survivors of cardiac arrest with good neurological outcome show considerable impairments of memory functioning.

    Science.gov (United States)

    Sulzgruber, Patrick; Kliegel, Andreas; Wandaller, Cosima; Uray, Thomas; Losert, Heidrun; Laggner, Anton N; Sterz, Fritz; Kliegel, Matthias

    2015-03-01

    Deficits in cognitive function are a well-known dysfunction in survivors of cardiac arrest. However, data concerning memory function in this neurological vulnerable patient collective remain scarce and inconclusive. Therefore, we aimed to assess multiple aspects of retrospective and prospective memory performance in patients after cardiac arrest. We prospectively enrolled 33 survivors of cardiac arrest, with cerebral performance categories (CPC) 1 and 2 and a control-group (n=33) matched in sex, age and educational-level. To assess retrospective and prospective memory performance we administrated 4 weeks after cardiac arrest the "Rey Adult Learning Test" (RAVLT), the "Digit-Span-Backwards Test", the "Logic-Memory Test" and the "Red-Pencil Test". Results indicate an impairment in immediate and delayed free recall, but not in recognition. However, the overall impairment in immediate recall was qualified by analyzing RAVLT performance, showing that patients were only impaired in trials 4 and 5 of the learning sequence. Moreover, working and prospective memory as well as prose recall were worse in cardiac arrest survivors. Cranial computed tomography was available in 61% of all patients (n=20) but there was no specific neurological damage detectable that could be linked to this cognitive impairment. Episodic long-term memory functioning appears to be particularly impaired after cardiac arrest. In contrast, short-term memory storage, even tested via free-call, seems not to be affected. Based on cranial computed tomography we suggest that global brain ischemia rather than focal brain lesions appear to underlie these effects. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  8. Single versus Serial Measurements of Neuron-Specific Enolase and Prediction of Poor Neurological Outcome in Persistently Unconscious Patients after Out-Of-Hospital Cardiac Arrest - A TTM-Trial Substudy

    DEFF Research Database (Denmark)

    Wiberg, Sebastian; Hassager, Christian; Stammet, Pascal

    2017-01-01

    were included from sites participating in the TTM-trial biobank sub study. NSE was measured at 24, 48 and 72 hours after ROSC and follow-up was concluded after 180 days. The primary end point was poor neurological function or death defined by a cerebral performance category score (CPC-score) of 3 to 5...... of the biomarker neuron-specific enolase (NSE) in combination with other predictors of outcome in patients admitted after out-of-hospital cardiac arrest (OHCA). This study sought to investigate the ability of NSE to predict poor outcome in patients remaining unconscious at day three after OHCA. In addition....... RESULTS: A total of 685 (73%) patients participated in the study. At day three after OHCA 63 (9%) patients had died and 473 (69%) patients were not awake. In these patients, a single NSE measurement at 48 hours predicted poor outcome with an area under the receiver operating characteristics curve (AUC...

  9. Exercise and Type 2 Diabetes Mellitus : Changes in Tissue-specific Fat Distribution and Cardiac Function

    NARCIS (Netherlands)

    Jonker, Jacqueline T.; de Mol, Pieter; de Vries, Suzanna T.; Widya, Ralph L.; Hammer, Sebastiaan; van Schinkel, Linda D.; van der Meer, Rutger W.; Gans, Rijk O. B.; Webb, Andrew G.; Kan, Hermien E.; de Koning, Eelco J. P.; Bilo, Henk J. G.; Lamb, Hildo J.

    2013-01-01

    Purpose: To prospectively assess the effects of an exercise intervention on organ-specific fat accumulation and cardiac function in type 2 diabetes mellitus. Materials and Methods: Written informed consent was obtained from all participants, and the study protocol was approved by the medical ethics

  10. The diagnostic and therapeutic aspects of loss-of-function cardiac sodium channelopathies in children

    NARCIS (Netherlands)

    Chockalingam, Priya; Clur, Sally-Ann B.; Breur, Johannes M. P. J.; Kriebel, Thomas; Paul, Thomas; Rammeloo, Lukas A.; Wilde, Arthur A. M.; Blom, Nico A.

    2012-01-01

    BACKGROUND Loss-of-function sodium channelopathies manifest as a spectrum of diseases including Brugada syndrome (BrS) and cardiac conduction disease. OBJECTIVE To analyze the diagnostic and therapeutic aspects of these disorders in children. METHODS Patients aged <= 16 years with genetically

  11. Tei index in determination of fetal cardiac function in pregnant women with gestational diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Guo-Dong Li

    2016-09-01

    Full Text Available Objective: To explore the application value of Tei index in determination of fetal cardiac function in pregnant women with gestational diabetes mellitus (GDM. Methods: A total of 60 gestational diabetes mellitus pregnant women with single birth were included in the study and served as GDM group, while 60 healthy pregnant women with single birth were served as the control group. The fetal echocardiography was performed. The cardiac structure, function, and other related indicators were detected and compared. Results: IVSs, LVWT, RVWT, LVEF, LVFS, and RVFS in GDM group were significantly greater than those in the control group (P<0.05. E/A MV and E/A TV in GDM group were significantly lower than those in the control group (P<0.05. The left and right ventricular Tei index in GDM group was significantly higher than that in the control group (P<0.05. Conclusions: The fetal cardiac structure and function in GDM pregnant women can cause damage to a different degree. Tei index is an important indicator to evaluate the fetal cardiac function in GDM pregnant women, and can be applied in the early diagnosis and treatment; therefore, it deserved to be widely recommended in the clinic.

  12. Cardiac Autonomic Function during Submaximal Treadmill Exercise in Adults with Down Syndrome

    Science.gov (United States)

    Mendonca, Goncalo V.; Pereira, Fernando D.; Fernhall, Bo

    2011-01-01

    This study determined whether the cardiac autonomic function of adults with Down syndrome (DS) differs from that of nondisabled persons during submaximal dynamic exercise. Thirteen participants with DS and 12 nondisabled individuals performed maximal and submaximal treadmill tests with metabolic and heart rate (HR) measurements. Spectral analysis…

  13. In Vivo Neuromechanics: Decoding Causal Motor Neuron Behavior with Resulting Musculoskeletal Function.

    Science.gov (United States)

    Sartori, Massimo; Yavuz, Utku Ş; Farina, Dario

    2017-10-18

    Human motor function emerges from the interaction between the neuromuscular and the musculoskeletal systems. Despite the knowledge of the mechanisms underlying neural and mechanical functions, there is no relevant understanding of the neuro-mechanical interplay in the neuro-musculo-skeletal system. This currently represents the major challenge to the understanding of human movement. We address this challenge by proposing a paradigm for investigating spinal motor neuron contribution to skeletal joint mechanical function in the intact human in vivo. We employ multi-muscle spatial sampling and deconvolution of high-density fiber electrical activity to decode accurate α-motor neuron discharges across five lumbosacral segments in the human spinal cord. We use complete α-motor neuron discharge series to drive forward subject-specific models of the musculoskeletal system in open-loop with no corrective feedback. We perform validation tests where mechanical moments are estimated with no knowledge of reference data over unseen conditions. This enables accurate blinded estimation of ankle function purely from motor neuron information. Remarkably, this enables observing causal associations between spinal motor neuron activity and joint moment control. We provide a new class of neural data-driven musculoskeletal modeling formulations for bridging between movement neural and mechanical levels in vivo with implications for understanding motor physiology, pathology, and recovery.

  14. Regulated appearance of NMDA receptor subunits and channel functions during in vitro neuronal differentiation.

    Science.gov (United States)

    Jelitai, Márta; Schlett, Katalin; Varju, Patrícia; Eisel, Ulrich; Madarász, Emília

    2002-04-01

    The schedule of NMDA receptor subunit expression and the appearance of functional NMDA-gated ion channels were investigated during the retinoic acid (RA) induced neuronal differentiation of NE-4C, a p53-deficient mouse neuroectodermal progenitor cell line. NR2A, NR2B, and NR2D subunit transcripts were present in both nondifferentiated and neuronally differentiated cultures, while NR2C subunits were expressed only transiently, during the early period of neural differentiation. Several splice variants of NR1 were detected in noninduced progenitors and in RA-induced cells, except the N1 exon containing transcripts that appeared after the fourth day of induction, when neuronal processes were already formed. NR1 and NR2A subunit proteins were detected both in nondifferentiated progenitor cells and in neurons, while the mature form of NR2B subunit protein appeared only at the time of neuronal process elongation. Despite the early presence of NR1 and NR2A subunits, NMDA-evoked responses could be detected in NE-4C neurons only after the sixth day of induction, coinciding in time with the expression of the mature NR2B subunit. The formation of functional NMDA receptors also coincided with the appearance of synapsin I and synaptophysin. The lag period between the production of the subunits and the onset of channel function suggests that subunits capable of channel formation cannot form functional NMDA receptors until a certain stage of neuronal commitment. Thus, the in vitro neurogenesis by NE-4C cells provides a suitable tool to investigate some inherent regulatory processes involved in the initial maturation of NMDA receptor complexes. Copyright 2002 Wiley Periodicals, Inc.

  15. Action Potential Shortening and Impairment of Cardiac Function by Ablation of Slc26a6.

    Science.gov (United States)

    Sirish, Padmini; Ledford, Hannah A; Timofeyev, Valeriy; Thai, Phung N; Ren, Lu; Kim, Hyo Jeong; Park, Seojin; Lee, Jeong Han; Dai, Gu; Moshref, Maryam; Sihn, Choong-Ryoul; Chen, Wei Chun; Timofeyeva, Maria Valeryevna; Jian, Zhong; Shimkunas, Rafael; Izu, Leighton T; Chiamvimonvat, Nipavan; Chen-Izu, Ye; Yamoah, Ebenezer N; Zhang, Xiao-Dong

    2017-10-01

    Intracellular pH (pH i ) is critical to cardiac excitation and contraction; uncompensated changes in pH i impair cardiac function and trigger arrhythmia. Several ion transporters participate in cardiac pH i regulation. Our previous studies identified several isoforms of a solute carrier Slc26a6 to be highly expressed in cardiomyocytes. We show that Slc26a6 mediates electrogenic Cl - /HCO 3 - exchange activities in cardiomyocytes, suggesting the potential role of Slc26a6 in regulation of not only pH i , but also cardiac excitability. To test the mechanistic role of Slc26a6 in the heart, we took advantage of Slc26a6 knockout ( Slc26a6 -/ - ) mice using both in vivo and in vitro analyses. Consistent with our prediction of its electrogenic activities, ablation of Slc26a6 results in action potential shortening. There are reduced Ca 2+ transient and sarcoplasmic reticulum Ca 2+ load, together with decreased sarcomere shortening in Slc26a6 -/ - cardiomyocytes. These abnormalities translate into reduced fractional shortening and cardiac contractility at the in vivo level. Additionally, pH i is elevated in Slc26a6 -/ - cardiomyocytes with slower recovery kinetics from intracellular alkalization, consistent with the Cl - /HCO 3 - exchange activities of Slc26a6. Moreover, Slc26a6 -/ - mice show evidence of sinus bradycardia and fragmented QRS complex, supporting the critical role of Slc26a6 in cardiac conduction system. Our study provides mechanistic insights into Slc26a6, a unique cardiac electrogenic Cl - /HCO 3 - transporter in ventricular myocytes, linking the critical roles of Slc26a6 in regulation of pH i , excitability, and contractility. pH i is a critical regulator of other membrane and contractile proteins. Future studies are needed to investigate possible changes in these proteins in Slc26a6 -/ - mice. © 2017 American Heart Association, Inc.

  16. Adaptive servo ventilation improves Cheyne-Stokes respiration, cardiac function, and prognosis in chronic heart failure patients with cardiac resynchronization therapy.

    Science.gov (United States)

    Miyata, Makiko; Yoshihisa, Akiomi; Suzuki, Satoshi; Yamada, Shinya; Kamioka, Masashi; Kamiyama, Yoshiyuki; Yamaki, Takayoshi; Sugimoto, Koichi; Kunii, Hiroyuki; Nakazato, Kazuhiko; Suzuki, Hitoshi; Saitoh, Shu-ichi; Takeishi, Yasuchika

    2012-09-01

    Cheyne-Stokes respiration (CSR-CSA) is often observed in patients with chronic heart failure (CHF). Although cardiac resynchronization therapy (CRT) is effective for CHF patients with left ventricular dyssynchrony, it is still unclear whether adaptive servo ventilation (ASV) improves cardiac function and prognosis of CHF patients with CSR-CSA after CRT. Twenty two patients with CHF and CSR-CSA after CRT defibrillator (CRTD) implantation were enrolled in the present study and randomly assigned into two groups: 11 patients treated with ASV (ASV group) and 11 patients treated without ASV (non-ASV group). Measurement of plasma B-type natriuretic peptide (BNP) levels (before 3, and 6 months later) and echocardiography (before and 6 months) were performed in each group. Patients were followed up to register cardiac events (cardiac death and re-hospitalization) after discharge. In the ASV group, indices for apnea-hypopnea, central apnea, and oxyhemoglobin saturation were improved on ASV. BNP levels, cardiac systolic and diastolic function were improved with ASV treatment for 6 months. Importantly, the event-free rate was significantly higher in the ASV group than in the non-ASV group. ASV improves CSR-CSA, cardiac function, and prognosis in CHF patients with CRTD. Patients with CSR-CSA and post CRTD implantation would get benefits by treatment with ASV. Copyright © 2012 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  17. Neuronal damage biomarkers in the identification of patients at risk of long-term postoperative cognitive dysfunction after cardiac surgery

    NARCIS (Netherlands)

    Kok, W F; Koerts, Janneke; Tucha, O; Scheeren, T W L; Absalom, A R

    Biomarkers of neurological injury can potentially predict postoperative cognitive dysfunction. We aimed to identify whether classical neuronal damage-specific biomarkers, including brain fatty acid-binding protein, neuron-specific enolase and S100 calcium-binding protein β, as well as plasma-free

  18. Ultrasonographic assessment of maternal cardiac function and peripheral circulation during normal gestation in dogs.

    Science.gov (United States)

    Blanco, Paula G; Tórtora, Mariana; Rodríguez, Raúl; Arias, Daniel O; Gobello, Cristina

    2011-10-01

    The aim of this study was to describe changes in cardiac morphology, systolic function and some peripheral hemodynamic parameters during normal pregnancy in dogs. Twenty healthy bitches, 10 pregnant (PG) and 10 non-pregnant controls (CG), were evaluated every 10 days using echocardiography from day 0 of the estrus cycle to parturition or to day 65 for the PG and CG groups, respectively. Systolic blood pressure (SBP) and uterine artery resistance index (RI) were also assessed. Throughout the study, the shortening fraction and cardiac output increased up to 30% vs. 5% (Pdogs. Copyright © 2010 Elsevier Ltd. All rights reserved.

  19. Effects of the angiotensin-converting enzyme inhibitor enalapril on sympathetic neuronal function and {beta}-adrenergic desensitization in heart failure after myocardial infarction in rats

    Energy Technology Data Exchange (ETDEWEB)

    Igawa, Akihiko; Nozawa, Takashi; Yoshida, Naohiro [Toyama Medical and Pharmaceutical Univ. (Japan)] [and others

    2002-11-01

    One of the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors in the treatment of heart failure may derive from sympathoinhibition and the prevention of {beta}-adrenergic desensitization. However, the roles of these properties in the overall effects of ACE inhibitor are not clear. We studied the effects of chronic enalapril treatment (20 mg/L in drinking water for 12 weeks) on left ventricular (LV) function, cardiac norepinephrine (NE), sympathetic neuronal function assessed by {sup 131}I-metaiodobenzylguanidine (MIBG), {beta}-receptors, and isometric contraction of papillary muscle in rats with myocardial infarction (MI) induced by coronary artery ligation. Decreased LV function in the MI rats was associated with reduced cardiac NE content and MIBG uptake, and severely blunted responses of non-infarcted papillary muscle to isoproterenol, forskolin, and calcium. Enalapril attenuated LV remodeling in association with a reduction of the ventricular loading condition and restored baseline developed tension of non-infarcted papillary muscle to the level of sham-operated rats. However, enalapril did not improve cardiac NE content, MIBG uptake, or inotropic responsiveness to {beta}-agonists. These results suggest that the major effect of the ACE inhibitor enalapril in the treatment of heart failure is not due to sympathoinhibition or restoration of {beta}-adrenergic pathway in this model of heart failure. (author)

  20. Effects of the angiotensin-converting enzyme inhibitor enalapril on sympathetic neuronal function and β-adrenergic desensitization in heart failure after myocardial infarction in rats

    International Nuclear Information System (INIS)

    Igawa, Akihiko; Nozawa, Takashi; Yoshida, Naohiro

    2002-01-01

    One of the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors in the treatment of heart failure may derive from sympathoinhibition and the prevention of β-adrenergic desensitization. However, the roles of these properties in the overall effects of ACE inhibitor are not clear. We studied the effects of chronic enalapril treatment (20 mg/L in drinking water for 12 weeks) on left ventricular (LV) function, cardiac norepinephrine (NE), sympathetic neuronal function assessed by 131 I-metaiodobenzylguanidine (MIBG), β-receptors, and isometric contraction of papillary muscle in rats with myocardial infarction (MI) induced by coronary artery ligation. Decreased LV function in the MI rats was associated with reduced cardiac NE content and MIBG uptake, and severely blunted responses of non-infarcted papillary muscle to isoproterenol, forskolin, and calcium. Enalapril attenuated LV remodeling in association with a reduction of the ventricular loading condition and restored baseline developed tension of non-infarcted papillary muscle to the level of sham-operated rats. However, enalapril did not improve cardiac NE content, MIBG uptake, or inotropic responsiveness to β-agonists. These results suggest that the major effect of the ACE inhibitor enalapril in the treatment of heart failure is not due to sympathoinhibition or restoration of β-adrenergic pathway in this model of heart failure. (author)

  1. The Role of Levosimendan in Patients with Decreased Left Ventricular Function Undergoing Cardiac Surgery

    Directory of Open Access Journals (Sweden)

    Marija Bozhinovska

    2016-06-01

    Full Text Available The postoperative low cardiac output is one of the most important complications following cardiac surgery and is associated with increased morbidity and mortality. The condition requires inotropic support to achieve adequate hemodynamic status and tissue perfusion. While catecholamines are utilised as a standard therapy in cardiac surgery, their use is limited due to increased oxygen consumption. Levosimendan is calcium sensitising inodilatator expressing positive inotropic effect by binding with cardiac troponin C without increasing oxygen demand. Furthermore, the drug opens potassium ATP (KATP channels in cardiac mitochondria and in the vascular muscle cells, showing cardioprotective and vasodilator properties, respectively. In the past decade, levosimendan demonstrated promising results in treating patients with reduced left ventricular function when administered in peri- or post- operative settings. In addition, pre-operative use of levosimendan in patients with severely reduced left ventricular ejection fraction may reduce the requirements for postoperative inotropic support, mechanical support, duration of intensive care unit stay as well as hospital stay and a decrease in post-operative mortality. However, larger studies are needed to clarify clinical advantages of levosimendan versus conventional inotropes.

  2. Use of the cardiopulmonary flow index to evaluate cardiac function in thoroughbred horses

    International Nuclear Information System (INIS)

    Guthrie, A.J.; Killeen, V.M.; Grosskopf, J.F.W.

    1991-01-01

    The ratio of the cardiopulmonary blood volume to stroke volume is called the cardiopulmonary flow index (CPFI). The CPFI can be determined indirectly from the simultaneous recording of a radiocardiogram and an electrocardiogram. The CPFI and cardiac output were measured simultaneously in horses that were diagnosed as having cardiac disease. The results obtained from these subjects were compared with those from control animals and significant differences were found between the mean CPFI of the control horses and those with macroscopically visible myocardial fibrosis on post mortem examination. No significant differences were found between the means of the cardiac output measured in either of the groups of horses. The effect of pharmacological acceleration of the heart rate on the CPFI was also studied. Significant differences were found between the mean CPFI and the slopes of the regression lines of CPFI on heart rate of the control and principal groups of horses. These differences were greatest at heart rates near to the resting heart rates of the individuals. The CPFI was found to be a more sensitive measure of cardiac function than cardiac output, in the horses. 16 refs., 2 figs., 2 tabs

  3. Retinal function in patients with the neuronal ceroid lipofuscinosis phenotype

    Directory of Open Access Journals (Sweden)

    Elizabeth Maria Aparecida Barasnevicius Quagliato

    Full Text Available ABSTRACT Purpose: To analyze the clinical features, visual acuity, and full-field electroretinogram (ERG findings of 15 patients with the neuronal ceroid lipofuscinosis (NCL phenotype and to establish the role of ERG testing in NCL diagnosis. Methods: The medical records of five patients with infantile NCL, five with Jansky-Bielschowsky disease, and five with juvenile NCL who underwent full-field ERG testing were retrospectively analyzed. Results: Progressive vision loss was the initial symptom in 66.7% of patients and was isolated or associated with ataxia, epilepsy, and neurodevelopmental involution. Epilepsy was present in 93.3% of patients, of whom 86.6% presented with neurodevelopmental involution. Fundus findings ranged from normal to pigmentary/atrophic abnormalities. Cone-rod, rod-cone, and both types of dysfunction were observed in six, one, and eight patients, respectively. Conclusion: In our study, all patients with the NCL phenotype had abnormal ERG findings, and the majority exhibited both cone-rod and rod-cone dysfunction. We conclude that ERG is a valuable tool for the characterization of visual dysfunction in patients with the NCL phenotype and is useful for diagnosis.

  4. Morphological and functional correlates of VIP neurons in cerebral cortex

    International Nuclear Information System (INIS)

    Magistretti, P.J.; Morrison, J.H.; Shoemaker, W.J.; Bloom, F.E.

    1984-01-01

    Vasoactive Intestinal Polypeptide (VIP) promotes the hydrolysis of 3H-glycogen newly synthesized from 3H-glucose by mouse cortical slices. This effect occurs rapidly, approximately 50% of the maximal effect being reached within one minute. The maximal effect is achieved after 5 minutes and maintained for at least 25 minutes. Furthermore the glycogenolytic effect of VIP is reversible, and pharmacologically specific. Thus several neuropeptides present in cerebral cortex such as cholecystokinin-8, somatostatin-28, somatostatin-14, met-enkephalin, leu-enkephalin, do not affect 3H-glycogen levels. VIP fragments 6-28, 16-28 and 21-28 are similarly inactive. Furthermore, among the peptides which share structural homologies with VIP, such as glucagon, secretin, PHI-27 and Gastric Inhibitory Peptide, only secretin and PHI-27 promote 3H-glycogen hydrolysis, with EC50 of 500 and 300 nM respectively, compared to an EC50 of 25 nM for VIP. Immunohistochemical observations indicate that each VIP-containing bipolar cell is identified with a unique radical cortical volume, which is generally between 15-60 micrograms in diameter and overlaps with the contiguous domains of neighbouring VIP-containing bipolar cells. Thus this set of biochemical and morphological observations support the notion that VIP neurons have the capacity to regulate the availability of energy substrates in cerebral cortex locally, within circumscribed, contiguous, radial domains

  5. Update on the slow delayed rectifier potassium current (I(Ks)): role in modulating cardiac function.

    Science.gov (United States)

    Liu, Zhenzhen; Du, Lupei; Li, Minyong

    2012-01-01

    The slow delayed rectifier current (I(Ks)) is the slow component of cardiac delayed rectifier current and is critical for the late phase repolarization of cardiac action potential. This current is also an important target for Sympathetic Nervous System (SNS) to regulate the cardiac electivity to accommodate to heart rate alterations in response to exercise or emotional stress and can be up-regulated by β- adrenergic or other signal molecules. I(Ks) channel is originated by the co-assembly of pore-forming KCNQ1 α-subunit and accessory KCNE1 β-subunit. Mutations in any subunit can bring about severe long QT syndrome (LQT-1, LQT-5) as characterized by deliquium, seizures and sudden death. This review summarizes the normal physiological functions and molecular basis of I(Ks) channels, as well as illustrates up-to-date development on its blockers and activators. Therefore, the current extensive survey should generate fundamental understanding of the role of I(Ks) channel in modulating cardiac function and donate some instructions to the progression of I(Ks) blockers and activators as potential antiarrhythmic agents or pharmacological tools to determine the physiological and pathological function of I(Ks).

  6. Gamma Radiation (5-10 Gy) Impairs Neuronal Function in the Guinea Pig Hippocampus

    Science.gov (United States)

    1993-01-01

    Radiation (5-10 Gy) Impairs Neuronal Function in the Guinea Pig Hippocampus TERRY C. PELLMAR AND DENNIS L. LEPINSKI Ph.vsiology Department..Irmned Forces...L. Gamma Radiation ioral effects. Within hours of irradiation with 10 Gy and (5- 10 Gy) Impairs Neuronal Function in the Guinea Pig Hippo- less...acti v- Guinea pigs were exposed to 5 and 10 Gy ’y radiation. Hippo- ity (9) are evident. campal brain slices were isolated 30 min, I day, 3 days and 5

  7. Assessment of cardiac morphology and ventricular function in healthy Chinese individuals using MRI

    International Nuclear Information System (INIS)

    Lu Minjie; Zhao Shihua; Jiang Shiliang

    2011-01-01

    Objective: To investigate reproducibility of cardiac MRI for assessment of cardiac morphology and ventricular function in selected normal Chinese Han population. Methods: Two hundred and sixty-nine normal volunteers underwent cardiac MRI using a 1.5 T MR system. HASTE and steady state free precession imaging were performed with long and short axis images and cine mode through the ventricle with wireless vector cardiac gating. The images were reviewed by two independent observers. The dimensions of cardiac chambers and ventricular function including ejection fraction (EF), end diastolic volume (EDV) , end systolic volume (ESV) and myocardial mass were evaluated. The data between male and female were compared by using two-tailed unpaired t test. Results: Total imaging time was (15±3) min. The anteroposterior diameter of the left atrium was (2.87±0.77) cm, the right atrial diameter perpendicular to the atrial septum was (3.61±0.57) cm, the end diastolic diameter of the left ventricle was (4.97± 0.52) cm, the end diastolic diameter of the right ventricle was (2.65±0.48) cm. On the left ventricle, EF was (60.62±7.08)%, EDV was (115.37±26.71) ml, ESV was (46.02±15.72) ml and LV mass was (82.97±24.03) g. On the right ventricle, EF was (47.73±6.50)%, EDV was (128.27±32.16) ml, ESV was (67.7±21.07) ml and RV mass was (48.24±13.42) g. There were no statistically significant differences in LVESV (P=0.144), LVEDV index (P=0.714), LVESV index (P=0.113), LVCI (P=0.199), RVEF (P=0.296) and RV mass (P=0.093), and statistically significant differences in other cardiac parameters between male and female. Conclusion: Cardiac MRI can provide useful information about cardiac function and morphology with a high level of reproducibility in normal Chinese Han population. (authors)

  8. Iron insufficiency compromises motor neurons and their mitochondrial function in Irp2-null mice

    KAUST Repository

    Jeong, Suh Young; Crooks, Daniel R.; Wilson-Ollivierre, Hayden; Ghosh, Manik C.; Sougrat, Rachid; Lee, Jaekwon; Cooperman, Sharon; Mitchell, James B.; Beaumont, Carole; Rouault, Tracey A.

    2011-01-01

    Genetic ablation of Iron Regulatory Protein 2 (Irp2, Ireb2), which post-transcriptionally regulates iron metabolism genes, causes a gait disorder in mice that progresses to hind-limb paralysis. Here we have demonstrated that misregulation of iron metabolism from loss of Irp2 causes lower motor neuronal degeneration with significant spinal cord axonopathy. Mitochondria in the lumbar spinal cord showed significantly decreased Complex I and II activities, and abnormal morphology. Lower motor neurons appeared to be the most adversely affected neurons, and we show that functional iron starvation due to misregulation of iron import and storage proteins, including transferrin receptor 1 and ferritin, may have a causal role in disease. We demonstrated that two therapeutic approaches were beneficial for motor neuron survival. First, we activated a homologous protein, IRP1, by oral Tempol treatment and found that axons were partially spared from degeneration. Secondly, we genetically decreased expression of the iron storage protein, ferritin, to diminish functional iron starvation. These data suggest that functional iron deficiency may constitute a previously unrecognized molecular basis for degeneration of motor neurons in mice.

  9. Iron insufficiency compromises motor neurons and their mitochondrial function in Irp2-null mice

    KAUST Repository

    Jeong, Suh Young

    2011-10-07

    Genetic ablation of Iron Regulatory Protein 2 (Irp2, Ireb2), which post-transcriptionally regulates iron metabolism genes, causes a gait disorder in mice that progresses to hind-limb paralysis. Here we have demonstrated that misregulation of iron metabolism from loss of Irp2 causes lower motor neuronal degeneration with significant spinal cord axonopathy. Mitochondria in the lumbar spinal cord showed significantly decreased Complex I and II activities, and abnormal morphology. Lower motor neurons appeared to be the most adversely affected neurons, and we show that functional iron starvation due to misregulation of iron import and storage proteins, including transferrin receptor 1 and ferritin, may have a causal role in disease. We demonstrated that two therapeutic approaches were beneficial for motor neuron survival. First, we activated a homologous protein, IRP1, by oral Tempol treatment and found that axons were partially spared from degeneration. Secondly, we genetically decreased expression of the iron storage protein, ferritin, to diminish functional iron starvation. These data suggest that functional iron deficiency may constitute a previously unrecognized molecular basis for degeneration of motor neurons in mice.

  10. Iron insufficiency compromises motor neurons and their mitochondrial function in Irp2-null mice.

    Directory of Open Access Journals (Sweden)

    Suh Young Jeong

    Full Text Available Genetic ablation of Iron Regulatory Protein 2 (Irp2, Ireb2, which post-transcriptionally regulates iron metabolism genes, causes a gait disorder in mice that progresses to hind-limb paralysis. Here we have demonstrated that misregulation of iron metabolism from loss of Irp2 causes lower motor neuronal degeneration with significant spinal cord axonopathy. Mitochondria in the lumbar spinal cord showed significantly decreased Complex I and II activities, and abnormal morphology. Lower motor neurons appeared to be the most adversely affected neurons, and we show that functional iron starvation due to misregulation of iron import and storage proteins, including transferrin receptor 1 and ferritin, may have a causal role in disease. We demonstrated that two therapeutic approaches were beneficial for motor neuron survival. First, we activated a homologous protein, IRP1, by oral Tempol treatment and found that axons were partially spared from degeneration. Secondly, we genetically decreased expression of the iron storage protein, ferritin, to diminish functional iron starvation. These data suggest that functional iron deficiency may constitute a previously unrecognized molecular basis for degeneration of motor neurons in mice.

  11. Linking Neurons to Network Function and Behavior by Two-Photon Holographic Optogenetics and Volumetric Imaging.

    Science.gov (United States)

    Dal Maschio, Marco; Donovan, Joseph C; Helmbrecht, Thomas O; Baier, Herwig

    2017-05-17

    We introduce a flexible method for high-resolution interrogation of circuit function, which combines simultaneous 3D two-photon stimulation of multiple targeted neurons, volumetric functional imaging, and quantitative behavioral tracking. This integrated approach was applied to dissect how an ensemble of premotor neurons in the larval zebrafish brain drives a basic motor program, the bending of the tail. We developed an iterative photostimulation strategy to identify minimal subsets of channelrhodopsin (ChR2)-expressing neurons that are sufficient to initiate tail movements. At the same time, the induced network activity was recorded by multiplane GCaMP6 imaging across the brain. From this dataset, we computationally identified activity patterns associated with distinct components of the elicited behavior and characterized the contributions of individual neurons. Using photoactivatable GFP (paGFP), we extended our protocol to visualize single functionally identified neurons and reconstruct their morphologies. Together, this toolkit enables linking behavior to circuit activity with unprecedented resolution. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Determinants of functional coupling between astrocytes and respiratory neurons in the pre-Bötzinger complex.

    Directory of Open Access Journals (Sweden)

    Christian Schnell

    Full Text Available Respiratory neuronal network activity is thought to require efficient functioning of astrocytes. Here, we analyzed neuron-astrocyte communication in the pre-Bötzinger Complex (preBötC of rhythmic slice preparations from neonatal mice. In astrocytes that exhibited rhythmic potassium fluxes and glutamate transporter currents, we did not find a translation of respiratory neuronal activity into phase-locked astroglial calcium signals. In up to 20% of astrocytes, 2-photon calcium imaging revealed spontaneous calcium fluctuations, although with no correlation to neuronal activity. Calcium signals could be elicited in preBötC astrocytes by metabotropic glutamate receptor activation or after inhibition of glial glutamate uptake. In the latter case, astrocyte calcium elevation preceded a surge of respiratory neuron discharge activity followed by network failure. We conclude that astrocytes do not exhibit respiratory-rhythmic calcium fluctuations when they are able to prevent synaptic glutamate accumulation. Calcium signaling is, however, observed when glutamate transport processes in astrocytes are suppressed or neuronal discharge activity is excessive.

  13. Myocardin-related transcription factors are required for cardiac development and function

    OpenAIRE

    Mokalled, Mayssa H.; Carroll, Kelli J.; Cenik, Bercin K.; Chen, Beibei; Liu, Ning; Olson, Eric N.; Bassel-Duby, Rhonda

    2015-01-01

    Myocardin-Related Transcription Factors A and B (MRTF-A and MRTF-B) are highly homologous proteins that function as powerful coactivators of serum response factor (SRF), a ubiquitously expressed transcription factor essential for cardiac development. The SRF/MRTF complex binds to CArG boxes found in the control regions of genes that regulate cytoskeletal dynamics and muscle contraction, among other processes. While SRF is required for heart development and function, the role of MRTFs in the d...

  14. TNNI3K is a novel mediator of myofilament function and phosphorylates cardiac troponin I

    International Nuclear Information System (INIS)

    Wang, Hui; Wang, Lin; Song, Li; Zhang, Yan-Wan; Ye, Jue; Xu, Rui-Xia; Shi, Na; Meng, Xian-Min

    2013-01-01

    The phosphorylation of cardiac troponin I (cTnI) plays an important role in the contractile dysfunction associated with heart failure. Human cardiac troponin I-interacting kinase (TNNI3K) is a novel cardiac-specific functional kinase that can bind to cTnI in a yeast two-hybrid screen. The purpose of this study was to investigate whether TNNI3K can phosphorylate cTnI at specific sites and to examine whether the phosphorylation of cTnI caused by TNNI3K can regulate cardiac myofilament contractile function. Co-immunoprecipitation was performed to confirm that TNNI3K could interact with cTnI. Kinase assays further indicated that TNNI3K did not phosphorylate cTnI at Ser23/24 and Ser44, but directly phosphorylated Ser43 and Thr143 in vitro. The results obtained for adult rat cardiomyocytes also indicated that enhanced phosphorylation of cTnI at Ser43 and Thr143 correlated with rTNNI3K (rat TNNI3K) overexpression, and phosphorylation was reduced when rTNNI3K was knocked down. To determine the contractile function modulated by TNNI3K-mediated phosphorylation of cTnI, cardiomyocyte contraction was studied in adult rat ventricular myocytes. The contraction of cardiomyocytes increased with rTNNI3K overexpression and decreased with rTNNI3K knockdown. We conclude that TNNI3K may be a novel mediator of cTnI phosphorylation and contribute to the regulation of cardiac myofilament contraction function

  15. Effects of plasma viscosity modulation on cardiac function during moderate hemodilution

    Directory of Open Access Journals (Sweden)

    Chatpun Surapong

    2010-01-01

    Full Text Available Background : Previous studies have found that increasing plasma viscosity as whole blood viscosity decrease has beneficial effects in microvascular hemodynamics. As the heart couples with systemic vascular network, changes in plasma and blood viscosity during hemodilution determine vascular pressure drop and flow rate, which influence cardiac function. This study aimed to investigate how changes in plasma viscosity affect on cardiac function during acute isovolemic hemodilution. Materials and Methods: Plasma viscosity was modulated by hemodilution of 40% of blood volume with three different plasma expanders (PEs. Dextran 2000 kDa (Dx2M, 6.3 cP and dextran 70 kDa (Dx70, 3.0 cP were used as high and moderate viscogenic PEs, respectively. Polyethylene glycol conjugated with human serum albumin (PEG-HSA, 2.2 cP was used as low viscogenic PE. The cardiac function was assessed using a miniaturized pressure-volume conductance catheter. Results: After hemodilution, pressure dropped to 84%, 79%, and 78% of baseline for Dx2M, Dx70 and PEG-HSA, respectively. Cardiac output markedly increased for Dx2M and PEG-HSA. Dx2M significantly produced higher stroke work relative to baseline and compared to Dx70. Conclusion: Acute hemodilution with PEG-HSA without increasing plasma viscosity provided beneficial effects on cardiac function compared to Dx70, and similar to those measured with Dx2M. Potentially negative effects of increasing peripheral vascular resistance due to the increase in plasma viscosity were prevented.

  16. Neuronal Function in Male Sprague Dawley Rats During Normal ...

    African Journals Online (AJOL)

    olayemitoyin

    Summary: During normal ageing, there are physiological changes especially in high energy ... science and technology (U.S. Bureau of the Census ... strategies that can be applied to preserve function with ..... Intelligent Technology for an.

  17. Cardiac function associated with home ventilator care in Duchenne muscular dystrophy.

    Science.gov (United States)

    Lee, Sangheun; Lee, Heeyoung; Eun, Lucy Youngmin; Gang, Seung Woong

    2018-02-01

    Cardiomyopathy is becoming the leading cause of death in patients with Duchenne muscular dystrophy because mechanically assisted lung ventilation and assisted coughing have helped resolve respiratory complications. To clarify cardiopulmonary function, we compared cardiac function between the home ventilator-assisted and non-ventilator-assisted groups. We retrospectively reviewed patients with Duchenne muscular dystrophy from January 2010 to March 2016 at Gangnam Severance Hospital. Demographic characteristics, pulmonary function, and echocardiography data were investigated. Fifty-four patients with Duchenne muscular dystrophy were divided into 2 groups: home ventilator-assisted and non-ventilator-assisted. The patients in the home ventilator group were older (16.25±1.85 years) than those in the nonventilator group (14.73±1.36 years) ( P =0.001). Height, weight, and body surface area did not differ significantly between groups. The home ventilator group had a lower seated functional vital capacity (1,038±620.41 mL) than the nonventilator group (1,455±603.12 mL). Mean left ventricular ejection fraction and fractional shortening were greater in the home ventilator group, but the data did not show any statistical difference. The early ventricular filling velocity/late ventricular filling velocity ratio (1.7±0.44) was lower in the home ventilator group than in the nonventilator group (2.02±0.62). The mitral valve annular systolic velocity was higher in the home ventilator group (estimated β, 1.06; standard error, 0.48). Patients with Duchenne muscular dystrophy on a ventilator may have better systolic and diastolic cardiac functions. Noninvasive ventilator assistance can help preserve cardiac function. Therefore, early utilization of noninvasive ventilation or oxygen may positively influence cardiac function in patients with Duchenne muscular dystrophy.

  18. [Cardiac Synchronization Function Estimation Based on ASM Level Set Segmentation Method].

    Science.gov (United States)

    Zhang, Yaonan; Gao, Yuan; Tang, Liang; He, Ying; Zhang, Huie

    At present, there is no accurate and quantitative methods for the determination of cardiac mechanical synchronism, and quantitative determination of the synchronization function of the four cardiac cavities with medical images has a great clinical value. This paper uses the whole heart ultrasound image sequence, and segments the left & right atriums and left & right ventricles of each frame. After the segmentation, the number of pixels in each cavity and in each frame is recorded, and the areas of the four cavities of the image sequence are therefore obtained. The area change curves of the four cavities are further extracted, and the synchronous information of the four cavities is obtained. Because of the low SNR of Ultrasound images, the boundary lines of cardiac cavities are vague, so the extraction of cardiac contours is still a challenging problem. Therefore, the ASM model information is added to the traditional level set method to force the curve evolution process. According to the experimental results, the improved method improves the accuracy of the segmentation. Furthermore, based on the ventricular segmentation, the right and left ventricular systolic functions are evaluated, mainly according to the area changes. The synchronization of the four cavities of the heart is estimated based on the area changes and the volume changes.

  19. Establishing Early Functional Perfusion and Structure in Tissue Engineered Cardiac Constructs.

    Science.gov (United States)

    Wang, Bo; Patnaik, Sourav S; Brazile, Bryn; Butler, J Ryan; Claude, Andrew; Zhang, Ge; Guan, Jianjun; Hong, Yi; Liao, Jun

    2015-01-01

    Myocardial infarction (MI) causes massive heart muscle death and remains a leading cause of death in the world. Cardiac tissue engineering aims to replace the infarcted tissues with functional engineered heart muscles or revitalize the infarcted heart by delivering cells, bioactive factors, and/or biomaterials. One major challenge of cardiac tissue engineering and regeneration is the establishment of functional perfusion and structure to achieve timely angiogenesis and effective vascularization, which are essential to the survival of thick implants and the integration of repaired tissue with host heart. In this paper, we review four major approaches to promoting angiogenesis and vascularization in cardiac tissue engineering and regeneration: delivery of pro-angiogenic factors/molecules, direct cell implantation/cell sheet grafting, fabrication of prevascularized cardiac constructs, and the use of bioreactors to promote angiogenesis and vascularization. We further provide a detailed review and discussion on the early perfusion design in nature-derived biomaterials, synthetic biodegradable polymers, tissue-derived acellular scaffolds/whole hearts, and hydrogel derived from extracellular matrix. A better understanding of the current approaches and their advantages, limitations, and hurdles could be useful for developing better materials for future clinical applications.

  20. The effects of pleural fluid drainage on respiratory function in mechanically ventilated patients after cardiac surgery.

    Science.gov (United States)

    Brims, Fraser J H; Davies, Michael G; Elia, Andy; Griffiths, Mark J D

    2015-01-01

    Pleural effusions occur commonly after cardiac surgery and the effects of drainage on gas exchange in this population are not well established. We examined pulmonary function indices following drainage of pleural effusions in cardiac surgery patients. We performed a retrospective study examining the effects of pleural fluid drainage on the lung function indices of patients recovering from cardiac surgery requiring mechanical ventilation for more than 7 days. We specifically analysed patients who had pleural fluid removed via an intercostal tube (ICT: drain group) compared with those of a control group (no effusion, no ICT). In the drain group, 52 ICTs were sited in 45 patients. The mean (SD) volume of fluid drained was 1180 (634) mL. Indices of oxygenation were significantly worse in the drain group compared with controls prior to drainage. The arterial oxygen tension (PaO2)/fractional inspired oxygen (FiO2) (P/F) ratio improved on day 1 after ICT placement (mean (SD), day 0: 31.01 (8.92) vs 37.18 (10.7); pdrain group patients were more likely to have an improved mode of ventilation on day 1 compared with controls (p=0.028). Pleural effusion after cardiac surgery may impair oxygenation. Drainage of pleural fluid is associated with a rapid and sustained improvement in oxygenation.

  1. The effects of pleural fluid drainage on respiratory function in mechanically ventilated patients after cardiac surgery

    Science.gov (United States)

    Brims, Fraser J H; Davies, Michael G; Elia, Andy; Griffiths, Mark J D

    2015-01-01

    Background Pleural effusions occur commonly after cardiac surgery and the effects of drainage on gas exchange in this population are not well established. We examined pulmonary function indices following drainage of pleural effusions in cardiac surgery patients. Methods We performed a retrospective study examining the effects of pleural fluid drainage on the lung function indices of patients recovering from cardiac surgery requiring mechanical ventilation for more than 7 days. We specifically analysed patients who had pleural fluid removed via an intercostal tube (ICT: drain group) compared with those of a control group (no effusion, no ICT). Results In the drain group, 52 ICTs were sited in 45 patients. The mean (SD) volume of fluid drained was 1180 (634) mL. Indices of oxygenation were significantly worse in the drain group compared with controls prior to drainage. The arterial oxygen tension (PaO2)/fractional inspired oxygen (FiO2) (P/F) ratio improved on day 1 after ICT placement (mean (SD), day 0: 31.01 (8.92) vs 37.18 (10.7); pdrain group patients were more likely to have an improved mode of ventilation on day 1 compared with controls (p=0.028). Conclusions Pleural effusion after cardiac surgery may impair oxygenation. Drainage of pleural fluid is associated with a rapid and sustained improvement in oxygenation. PMID:26339492

  2. Awareness of cardiac function in anxious, phobic and hypochondriacal patients.

    Science.gov (United States)

    Tyrer, P; Lee, I; Alexander, J

    1980-02-01

    Awareness of pulse rate was tested in 60 psychiatric out-patients with anxiety, phobic or hypochondriacal neuroses by asking them to record how fast their hearts were beating during exposure to short film sequences. Correlations between subjective and objective heart rate (ECG) were significantly higher in anxious and hypochondriacal patients than in phobic ones. The results suggest that somatic symptoms in hypochondriacal and anxiety neurosis reflect increased awareness of bodily function.

  3. Clinical research on correlation between BNP and left cardiac function in patients with heart failure

    International Nuclear Information System (INIS)

    Yin Xin; Xu Dandan; Wu Chunxu

    2005-01-01

    To investigate the correlation between brain natriuretic peptide (BNP) and the cardiac function in patients with heart failure(HF), the plasma level of BNP was determined by IRMA and the left cardiac function parameters were measured on echocardiogram in patients with different grade of HF. The results showed that the plasma level of BNP elevated with the worsening of heart failure (NYHA classification). The plasma levels of BNP were negatively correlated with left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVDd). The plasma level of BNP increases significantly along with the severity of HF classified by NYHA, and might be a biochemical parameter for evaluating the left ventricular function. (authors)

  4. Functional adaptation to loading of a single bone is neuronally regulated and involves multiple bones.

    Science.gov (United States)

    Sample, Susannah J; Behan, Mary; Smith, Lesley; Oldenhoff, William E; Markel, Mark D; Kalscheur, Vicki L; Hao, Zhengling; Miletic, Vjekoslav; Muir, Peter

    2008-09-01

    Regulation of load-induced bone formation is considered a local phenomenon controlled by osteocytes, although it has also been hypothesized that functional adaptation may be neuronally regulated. The aim of this study was to examine bone formation in multiple bones, in response to loading of a single bone, and to determine whether adaptation may be neuronally regulated. Load-induced responses in the left and right ulnas and humeri were determined after loading of the right ulna in male Sprague-Dawley rats (69 +/- 16 days of age). After a single period of loading at -760-, -2000-, or -3750-microepsilon initial peak strain, rats were given calcein to label new bone formation. Bone formation and bone neuropeptide concentrations were determined at 10 days. In one group, temporary neuronal blocking was achieved by perineural anesthesia of the brachial plexus with bupivicaine during loading. We found right ulna loading induces adaptive responses in other bones in both thoracic limbs compared with Sham controls and that neuronal blocking during loading abrogated bone formation in the loaded ulna and other thoracic limb bones. Skeletal adaptation was more evident in distal long bones compared with proximal long bones. We also found that the single period of loading modulated bone neuropeptide concentrations persistently for 10 days. We conclude that functional adaptation to loading of a single bone in young rapidly growing rats is neuronally regulated and involves multiple bones. Persistent changes in bone neuropeptide concentrations after a single loading period suggest that plasticity exists in the innervation of bone.

  5. Functional Properties of Human Stem Cell-Derived Neurons in Health and Disease

    Directory of Open Access Journals (Sweden)

    Jason P. Weick

    2016-01-01

    Full Text Available Stem cell-derived neurons from various source materials present unique model systems to examine the fundamental properties of central nervous system (CNS development as well as the molecular underpinnings of disease phenotypes. In order to more accurately assess potential therapies for neurological disorders, multiple strategies have been employed in recent years to produce neuronal populations that accurately represent in vivo regional and transmitter phenotypes. These include new technologies such as direct conversion of somatic cell types into neurons and glia which may accelerate maturation and retain genetic hallmarks of aging. In addition, novel forms of genetic manipulations have brought human stem cells nearly on par with those of rodent with respect to gene targeting. For neurons of the CNS, the ultimate phenotypic characterization lies with their ability to recapitulate functional properties such as passive and active membrane characteristics, synaptic activity, and plasticity. These features critically depend on the coordinated expression and localization of hundreds of ion channels and receptors, as well as scaffolding and signaling molecules. In this review I will highlight the current state of knowledge regarding functional properties of human stem cell-derived neurons, with a primary focus on pluripotent stem cells. While significant advances have been made, critical hurdles must be overcome in order for this technology to support progression toward clinical applications.

  6. The design of a new spiking neuron using dual work function silicon nanowire transistors

    International Nuclear Information System (INIS)

    Bindal, Ahmet; Hamedi-Hagh, Sotoudeh

    2007-01-01

    A new spike neuron cell is designed using vertically grown, undoped silicon nanowire transistors. This study presents an entire design cycle from designing and optimizing vertical nanowire transistors for minimal power dissipation to realizing a neuron cell and measuring its dynamic power consumption, performance and layout area. The design cycle starts with determining individual metal gate work functions for NMOS and PMOS transistors as a function of wire radius to produce a 300 mV threshold voltage. The wire radius and effective channel length are subsequently varied to find a common body geometry for both transistors that yields smaller than 1 pA OFF current while producing maximum drive currents. A spike neuron cell is subsequently built using these transistors to measure its transient performance, power dissipation and layout area. Post-layout simulation results indicate that the neuron consumes 0.397 μW to generate a +1 V and 1.12 μW to generate a -1 V output pulse for a fan-out of five synapses at 500 MHz; the power dissipation increases by approximately 3 nW for each additional synapse at the output for generating either pulse. The neuron circuit occupies approximately 0.27 μm 2

  7. Snapin-regulated late endosomal transport is critical for efficient autophagy-lysosomal function in neurons.

    Science.gov (United States)

    Cai, Qian; Lu, Li; Tian, Jin-Hua; Zhu, Yi-Bing; Qiao, Haifa; Sheng, Zu-Hang

    2010-10-06

    Neuron maintenance and survival require late endocytic transport from distal processes to the soma where lysosomes are predominantly localized. Here, we report a role for Snapin in attaching dynein to late endosomes through its intermediate chain (DIC). snapin(-/-) neurons exhibit aberrant accumulation of immature lysosomes, clustering and impaired retrograde transport of late endosomes along processes, reduced lysosomal proteolysis due to impaired delivery of internalized proteins and hydrolase precursors from late endosomes to lysosomes, and impaired clearance of autolysosomes, combined with reduced neuron viability and neurodegeneration. The phenotypes are rescued by expressing the snapin transgene, but not the DIC-binding-defective Snapin-L99K mutant. Snapin overexpression in wild-type neurons enhances late endocytic transport and lysosomal function, whereas expressing the mutant defective in Snapin-DIC coupling shows a dominant-negative effect. Altogether, our study highlights new mechanistic insights into how Snapin-DIC coordinates retrograde transport and late endosomal-lysosomal trafficking critical for autophagy-lysosomal function, and thus neuronal homeostasis. Copyright © 2010 Elsevier Inc. All rights reserved.

  8. Improved cardiac function and exercise capacity following correction of pectus excavatum: a review of current literature.

    Science.gov (United States)

    Maagaard, Marie; Heiberg, Johan

    2016-09-01

    Patients with pectus excavatum (PE) often describe improvements in exercise stamina following corrective surgery. Studies have investigated the surgical effect on physiological parameters; still, no consensus has yet been reached. Therefore, the aim of this literature review was to describe the cardiac outcome after surgical correction, both at rest and during exercise. In February 2016, a detailed search of the databases PubMed, Medline, and EMBASE was performed. We assessed clinical studies that described cardiac outcomes both before and after surgical correction of PE. We only included studies reporting either pre-defined echocardiographic or exercise test parameters. No exclusion criteria or statistical analyses were applied. Twenty-one full-text articles, published between 1972 and 2016, were selected, with cohort-ranges of 3-168 patients, mean age-ranges of 5-33 years, and mean follow-up-ranges from immediately to 4 years after surgery. Twelve studies described resting cardiac parameters. Four studies measured cardiac output, where one described 36% immediate increase after surgery, one reported 15% increase after Nuss-bar removal and two found no difference. Three studies demonstrated improvement in mean stroke volume ranges of 22-34% and two studies found no difference. Fifteen studies investigated exercise capacity, with 11 considering peak O 2 pr. kg, where five studies demonstrated improvements with the mean ranging from 8% to 15% after surgery, five studies demonstrated no difference, and one saw a decrease of 19% 3 months after Nuss-bar implantation. A measurable increase in exercise capacity exists following surgery, which may be caused by multiple factors. This may be owed to the relief of compressed cardiac chambers with the increased anterior-posterior thoracic dimensions, which could facilitate an improved filling of the heart. With these results, the positive physiological impact of the surgery is emphasized and the potential gain in cardiac

  9. LRRC10 is required to maintain cardiac function in response to pressure overload.

    Science.gov (United States)

    Brody, Matthew J; Feng, Li; Grimes, Adrian C; Hacker, Timothy A; Olson, Timothy M; Kamp, Timothy J; Balijepalli, Ravi C; Lee, Youngsook

    2016-01-15

    We previously reported that the cardiomyocyte-specific leucine-rich repeat containing protein (LRRC)10 has critical functions in the mammalian heart. In the present study, we tested the role of LRRC10 in the response of the heart to biomechanical stress by performing transverse aortic constriction on Lrrc10-null (Lrrc10(-/-)) mice. Mild pressure overload induced severe cardiac dysfunction and ventricular dilation in Lrrc10(-/-) mice compared with control mice. In addition to dilation and cardiomyopathy, Lrrc10(-/-) mice showed a pronounced increase in heart weight with pressure overload stimulation and a more dramatic loss of cardiac ventricular performance, collectively suggesting that the absence of LRRC10 renders the heart more disease prone with greater hypertrophy and structural remodeling, although rates of cardiac fibrosis and myocyte dropout were not different from control mice. Lrrc10(-/-) cardiomyocytes also exhibited reduced contractility in response to β-adrenergic stimulation, consistent with loss of cardiac ventricular performance after pressure overload. We have previously shown that LRRC10 interacts with actin in the heart. Here, we show that His(150) of LRRC10 was required for an interaction with actin, and this interaction was reduced after pressure overload, suggesting an integral role for LRRC10 in the response of the heart to mechanical stress. Importantly, these experiments demonstrated that LRRC10 is required to maintain cardiac performance in response to pressure overload and suggest that dysregulated expression or mutation of LRRC10 may greatly sensitize human patients to more severe cardiac disease in conditions such as chronic hypertension or aortic stenosis. Copyright © 2016 the American Physiological Society.

  10. Natriuretic peptides in developing medaka embryos: implications in cardiac development by loss-of-function studies.

    Science.gov (United States)

    Miyanishi, Hiroshi; Okubo, Kataaki; Nobata, Shigenori; Takei, Yoshio

    2013-01-01

    Cardiac natriuretic peptides (NPs), atrial NP (ANP) and B-type NP (BNP), and their receptor, guanylyl cyclase (GC)-A have attracted attention of many basic and clinical researchers because of their potent renal and cardiovascular actions. In this study, we used medaka, Oryzias latipes, as a model species to pursue the physiological functions of NPs because it is a suitable model for developmental analyses. Medaka has two ligands, BNP and C-type NP3 (CNP3) (but not ANP), that have greater affinity for the two O. latipes GC-A receptors (OLGC), OLGC7 and OLGC2, respectively. CNP3 is the ancestral molecule of cardiac NPs. Initially, we examined developmental expression of cardiac NP/receptor combinations, BNP/OLGC7 and CNP3/OLGC2, using quantitative real-time PCR and in situ hybridization. BNP and CNP3 mRNA increased at stages 25 (onset of ventricular formation) and 22 (appearance of heart anlage), respectively, whereas both receptor mRNAs increased at as early as stage 12. BNP/OLGC7 transcripts were found in arterial/ventricular tissues and CNP3/OLGC2 transcripts in venous/atrial tissues by in situ hybridization. Thus, BNP and CNP3 can act locally on cardiac myocytes in a paracrine/autocrine fashion. Double knockdown of BNP/OLGC7 genes impaired ventricular development by causing hypoplasia of ventricular myocytes as evidenced by reduced bromodeoxyuridine incorporation. CNP3 knockdown induced hypertrophy of atria and activated the renin-angiotensin system. Collectively, it appears that BNP is important for normal ventricular, whereas CNP3 is important for normal atrial development and performance, a role usually taken by ANP in other vertebrates. The current study provides new insights into the role of cardiac NPs in cardiac development in vertebrates.

  11. Functional modulation of cardiac form through regionally confined cell shape changes.

    Directory of Open Access Journals (Sweden)

    Heidi J Auman

    2007-03-01

    Full Text Available Developing organs acquire a specific three-dimensional form that ensures their normal function. Cardiac function, for example, depends upon properly shaped chambers that emerge from a primitive heart tube. The cellular mechanisms that control chamber shape are not yet understood. Here, we demonstrate that chamber morphology develops via changes in cell morphology, and we determine key regulatory influences on this process. Focusing on the development of the ventricular chamber in zebrafish, we show that cardiomyocyte cell shape changes underlie the formation of characteristic chamber curvatures. In particular, cardiomyocyte elongation occurs within a confined area that forms the ventricular outer curvature. Because cardiac contractility and blood flow begin before chambers emerge, cardiac function has the potential to influence chamber curvature formation. Employing zebrafish mutants with functional deficiencies, we find that blood flow and contractility independently regulate cell shape changes in the emerging ventricle. Reduction of circulation limits the extent of cardiomyocyte elongation; in contrast, disruption of sarcomere formation releases limitations on cardiomyocyte dimensions. Thus, the acquisition of normal cardiomyocyte morphology requires a balance between extrinsic and intrinsic physical forces. Together, these data establish regionally confined cell shape change as a cellular mechanism for chamber emergence and as a link in the relationship between form and function during organ morphogenesis.

  12. An Echocardiographic Study of Left Ventricular Size and Cardiac Function in Adolescent Females with Anorexia Nervosa.

    Science.gov (United States)

    Escudero, Carolina A; Potts, James E; Lam, Pei-Yoong; De Souza, Astrid M; Mugford, Gerald J; Sandor, George G S

    2016-01-01

    This retrospective case-control study investigated cardiac dimensions and ventricular function in female adolescents with anorexia nervosa (AN) compared with controls. Echocardiographic measurements of left ventricular (LV) dimensions, LV mass index, left atrial size and cardiac index were made. Detailed measures of systolic and diastolic ventricular function were made including tissue Doppler imaging. Patients were stratified by body mass index ≤10th percentile (AN ≤ 10th) and >10th percentile (AN > 10th). Ninety-five AN patients and 58 controls were included. AN and AN ≤ 10th groups had reduced LV dimensions, LV mass index, left atrial size and cardiac index compared with controls. There were no differences between groups in measures of systolic function. Measures of diastolic tissue Doppler imaging were decreased in AN and AN ≤ 10th. No differences in echocardiographic measurements existed between controls and AN > 10th. Female adolescents with AN have preserved systolic function and abnormalities of diastolic ventricular function. AN ≤ 10th may be a higher risk group. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.

  13. Gene expression pattern of functional neuronal cells derived from human bone marrow mesenchymal stromal cells

    Directory of Open Access Journals (Sweden)

    Bron Dominique

    2008-04-01

    Full Text Available Abstract Background Neuronal tissue has limited potential to self-renew or repair after neurological diseases. Cellular therapies using stem cells are promising approaches for the treatment of neurological diseases. However, the clinical use of embryonic stem cells or foetal tissues is limited by ethical considerations and other scientific problems. Thus, bone marrow mesenchymal stomal cells (BM-MSC could represent an alternative source of stem cells for cell replacement therapies. Indeed, many studies have demonstrated that MSC can give rise to neuronal cells as well as many tissue-specific cell phenotypes. Methods BM-MSC were differentiated in neuron-like cells under specific induction (NPBM + cAMP + IBMX + NGF + Insulin. By day ten, differentiated cells presented an expression profile of real neurons. Functionality of these differentiated cells was evaluated by calcium influx through glutamate receptor AMPA3. Results Using microarray analysis, we compared gene expression profile of these different samples, before and after neurogenic differentiation. Among the 1943 genes differentially expressed, genes down-regulated are involved in osteogenesis, chondrogenesis, adipogenesis, myogenesis and extracellular matrix component (tuftelin, AGC1, FADS3, tropomyosin, fibronectin, ECM2, HAPLN1, vimentin. Interestingly, genes implicated in neurogenesis are increased. Most of them are involved in the synaptic transmission and long term potentialisation as cortactin, CASK, SYNCRIP, SYNTL4 and STX1. Other genes are involved in neurite outgrowth, early neuronal cell development, neuropeptide signaling/synthesis and neuronal receptor (FK506, ARHGAP6, CDKRAP2, PMCH, GFPT2, GRIA3, MCT6, BDNF, PENK, amphiregulin, neurofilament 3, Epha4, synaptotagmin. Using real time RT-PCR, we confirmed the expression of selected neuronal genes: NEGR1, GRIA3 (AMPA3, NEF3, PENK and Epha4. Functionality of these neuron-like cells was demonstrated by Ca2+ influx through glutamate

  14. Tansig activation function (of MLP network) for cardiac abnormality detection

    Science.gov (United States)

    Adnan, Ja'afar; Daud, Nik Ghazali Nik; Ishak, Mohd Taufiq; Rizman, Zairi Ismael; Rahman, Muhammad Izzuddin Abd

    2018-02-01

    Heart abnormality often occurs regardless of gender, age and races. This problem sometimes does not show any symptoms and it can cause a sudden death to the patient. In general, heart abnormality is the irregular electrical activity of the heart. This paper attempts to develop a program that can detect heart abnormality activity through implementation of Multilayer Perceptron (MLP) network. A certain amount of data of the heartbeat signals from the electrocardiogram (ECG) will be used in this project to train the MLP network by using several training algorithms with Tansig activation function.

  15. Functional 3-D cardiac co-culture model using bioactive chitosan nanofiber scaffolds.

    Science.gov (United States)

    Hussain, Ali; Collins, George; Yip, Derek; Cho, Cheul H

    2013-02-01

    The in vitro generation of a three-dimensional (3-D) myocardial tissue-like construct employing cells, biomaterials, and biomolecules is a promising strategy in cardiac tissue regeneration, drug testing, and tissue engineering applications. Despite significant progress in this field, current cardiac tissue models are not yet able to stably maintain functional characteristics of cardiomyocytes for long-term culture and therapeutic purposes. The objective of this study was to fabricate bioactive 3-D chitosan nanofiber scaffolds using an electrospinning technique and exploring its potential for long-term cardiac function in the 3-D co-culture model. Chitosan is a natural polysaccharide biomaterial that is biocompatible, biodegradable, non-toxic, and cost effective. Electrospun chitosan was utilized to provide structural scaffolding characterized by scale and architectural resemblance to the extracellular matrix (ECM) in vivo. The chitosan fibers were coated with fibronectin via adsorption in order to enhance cellular adhesion to the fibers and migration into the interfibrous milieu. Ventricular cardiomyocytes were harvested from neonatal rats and studied in various culture conditions (i.e., mono- and co-cultures) for their viability and function. Cellular morphology and functionality were examined using immunofluorescent staining for alpha-sarcomeric actin (SM-actin) and gap junction protein, Connexin-43 (Cx43). Scanning electron microscopy (SEM) and light microscopy were used to investigate cellular morphology, spatial organization, and contractions. Calcium indicator was used to monitor calcium ion flux of beating cardiomyocytes. The results demonstrate that the chitosan nanofibers retained their cylindrical morphology in long-term cell cultures and exhibited good cellular attachment and spreading in the presence of adhesion molecule, fibronectin. Cardiomyocyte mono-cultures resulted in loss of cardiomyocyte polarity and islands of non-coherent contractions. However

  16. Thyroid hormone is required for hypothalamic neurons regulating cardiovascular functions

    NARCIS (Netherlands)

    Mittag, J.; Lyons, D.J.; Sällström, J.; Vujoviv, M.; Dudazy-Gralla, S.; Warner, A.; Wallis, K.; Alkemade, A.; Nordström, K.; Monyer, H.; Broberger, C.; Arner, A.; Vennström, B.

    2013-01-01

    Thyroid hormone is well known for its profound direct effects on cardiovascular function and metabolism. Recent evidence, however, suggests that the hormone also regulates these systems indirectly through the central nervous system. While some of the molecular mechanisms underlying the hormone’s

  17. ATF3 expression improves motor function in the ALS mouse model by promoting motor neuron survival and retaining muscle innervation.

    Science.gov (United States)

    Seijffers, Rhona; Zhang, Jiangwen; Matthews, Jonathan C; Chen, Adam; Tamrazian, Eric; Babaniyi, Olusegun; Selig, Martin; Hynynen, Meri; Woolf, Clifford J; Brown, Robert H

    2014-01-28

    ALS is a fatal neurodegenerative disease characterized by a progressive loss of motor neurons and atrophy of distal axon terminals in muscle, resulting in loss of motor function. Motor end plates denervated by axonal retraction of dying motor neurons are partially reinnervated by remaining viable motor neurons; however, this axonal sprouting is insufficient to compensate for motor neuron loss. Activating transcription factor 3 (ATF3) promotes neuronal survival and axonal growth. Here, we reveal that forced expression of ATF3 in motor neurons of transgenic SOD1(G93A) ALS mice delays neuromuscular junction denervation by inducing axonal sprouting and enhancing motor neuron viability. Maintenance of neuromuscular junction innervation during the course of the disease in ATF3/SOD1(G93A) mice is associated with a substantial delay in muscle atrophy and improved motor performance. Although disease onset and mortality are delayed, disease duration is not affected. This study shows that adaptive axonal growth-promoting mechanisms can substantially improve motor function in ALS and importantly, that augmenting viability of the motor neuron soma and maintaining functional neuromuscular junction connections are both essential elements in therapy for motor neuron disease in the SOD1(G93A) mice. Accordingly, effective protection of optimal motor neuron function requires restitution of multiple dysregulated cellular pathways.

  18. Regulated appearance of NMDA receptor subunits and channel functions during in vitro neuronal differentiation

    NARCIS (Netherlands)

    Jelitai, Márta; Schlett, Katalin; Varju, Patrícia; Eisel, Ulrich; Madarász, Emília

    The schedule of NMDA receptor subunit expression and the appearance of functional NMDA-gated ion channels were investigated during the retinoic acid (RA) induced neuronal differentiation of NE-4C, a p53-deficient mouse neuroectodermal progenitor cell line. NR2A. NR2B, and NR2D subunit transcripts

  19. Glutamate mediates the function of melanocortin receptor 4 on sim1 neurons in body weight regulation

    Science.gov (United States)

    The melanocortin receptor 4 (MC4R) is a well-established mediator of body weight homeostasis. However, the neurotransmitter(s) that mediate MC4R function remain largely unknown; as a result, little is known about the second-order neurons of the MC4R neural pathway. Single-minded 1 (Sim1)-expressing ...

  20. [Limits of cardiac functional adaptation in "top level" resistance athletes].

    Science.gov (United States)

    Carù, B; Righetti, G; Bossi, M; Gerosa, C; Gazzotti, G; Maranetto, D

    2001-02-01

    Sports activity, particularly when performed at high level, provokes cardiovascular adjustments depending on the type of sport and on the level of the load. We evaluated 15 athletes from the Italian national team during a non-agonistic period of cross country skiing, with non-invasive tests including exercise test, color Doppler echocardiography, Holter monitoring, physical examination and standard rest electrocardiogram. Physical examination, rest electrocardiogram, exercise testing and echocardiography were all within the range of the expected values for this type of subjects. Holter monitoring recorded during the periods of agonistic activity revealed significant hypokinetic arrhythmias such as severe bradycardia, pauses, I and II degree atrioventricular blocks, and complete atrioventricular block in 2 cases; these features were not observed on Holter monitoring recorded during the non-agonistic period. The perfect health status of subjects and their racing results may bring about physiological functional adjustments, but these observations suggest the need for a follow-up to evaluate possible pathologic outcomes.

  1. Blood conservation techniques and platelet function in cardiac surgery.

    Science.gov (United States)

    Boldt, J; Zickmann, B; Czeke, A; Herold, C; Dapper, F; Hempelmann, G

    1991-09-01

    Postoperative alterations in platelet function induced by cardiopulmonary bypass (CPB) are of importance. The effect on platelet aggregation of three different techniques for reducing blood consumption was studied in 30 patients undergoing elective aortocoronary bypass grafting from the beginning of anesthesia until the 1st postoperative day. The patients were randomly divided into three groups, in which 1) a cell separator was used during and after CPB; 2) a hemofiltration device was used; and 3) high-dose aprotinin was used in order to reduce the need of homologous blood. A fourth group undergoing neurosurgery procedures served as a control. Platelet aggregation induced by adenosine diphosphate (concentration 0.25, 0.50, 1.0, and 2.0 microM), collagen (4 microliters/ml), and epinephrine (25 microM) was determined by the turbidimetric method. Platelet aggregation was not significantly changed in the control group, indicating that the operation itself did not impair platelet function. At the end of the operation (after retransfusion of the salvaged pump blood), the maximum aggregation and maximum gradient of aggregation induced by all three inductors were most reduced (significantly) in the cell-separator patients. On the 1st postoperative day, platelet aggregation in the hemofiltration patients and the patients treated with aprotinin had normalized. Aggregation of patients pretreated with high-dose aprotinin was not different from that of the hemofiltration patients throughout the investigation. Blood loss was significantly highest in the cell-separator group (770 +/- 400 ml on the 1st postoperative day) but was not different between the hemofiltration (390 +/- 230 ml) and the aprotinin-treated patients (260 +/- 160 ml).(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Preserved cardiac function despite marked impairment of cAMP generation.

    Directory of Open Access Journals (Sweden)

    Mei Hua Gao

    Full Text Available So many clinical trials of positive inotropes have failed, that it is now axiomatic that agents that increase cAMP are deleterious to the failing heart. An alternative strategy is to alter myocardial Ca(2+ handling or myofilament response to Ca(2+ using agents that do not affect cAMP. Although left ventricular (LV function is tightly linked to adenylyl cyclase (AC activity, the beneficial effects of AC may be independent of cAMP and instead stem from effects on Ca(2+ handling. Here we ask whether an AC mutant molecule that reduces LV cAMP production would have favorable effects on LV function through its effects on Ca(2+ handling alone.We generated transgenic mice with cardiac-directed expression of an AC6 mutant (AC6mut. Cardiac myocytes showed impaired cAMP production in response to isoproterenol (74% reduction; p<0.001, but LV size and function were normal. Isolated hearts showed preserved LV function in response to isoproterenol stimulation. AC6mut expression was associated with increased sarcoplasmic reticulum Ca(2+ uptake and the EC50 for SERCA2a activation was reduced. Cardiac myocytes isolated from AC6mut mice showed increased amplitude of Ca(2+ transients in response to isoproterenol (p = 0.0001. AC6mut expression also was associated with increased expression of LV S100A1 (p = 0.03 and reduced expression of phospholamban protein (p = 0.01.LV AC mutant expression is associated with normal cardiac function despite impaired cAMP generation. The mechanism appears to be through effects on Ca(2+ handling - effects that occur despite diminished cAMP.

  3. Anti-tachycardia therapy can improve altered cardiac adrenergic function in tachycardia-induced cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Ohkusu, Yasuo; Takahashi, Nobukazu; Ishikawa, Toshiyuki [Yokohama City Univ. (Japan). School of Medicine] [and others

    2002-11-01

    We investigated whether anti-tachycardia therapy might improve the altered cardiac adrenergic and systolic function in tachycardia-induced cardiomyopathy (TC) in contrast to dilated cardiomyopathy (DCM). The subjects were 23 patients with heart failure, consisting of 8 patients with TC (43.6{+-}10.0 yrs) and 15 with DCM (45.3{+-}8.2 yrs). TC was determined as impairment of left ventricular function secondary to chronic or very frequent arrhythmia during more than 10% of the day. All patients were receiving anti-tachycardia treatment. Cardiac {sup 123}I-MIBG uptake was assessed as the heart/mediastinum activity ratio (H/M) before and after treatment. Left ventricular ejection fraction (LVEF) was also assessed. In the baseline study, H/M and LVEF showed no difference between TC and DCM (2.21{+-}0.44 vs. 2.10{+-}0.42, 35.3{+-}13.1 vs. 36.0{+-}10.9%, respectively). After treatment, the degree of change in H/M and LVEF differed significantly (0.41{+-}0.34 vs. 0.08{+-}0.20, 20.5{+-}14.4 vs. -2.1{+-}9.6%, p<0.01). In TC, heart failure improved after a shorter duration of treatment (p<0.05). In conclusion, anti-tachycardia therapy can improve altered cardiac adrenergic function and systolic function in patients with TC over a shorter period than in those with DCM. (author)

  4. Structural and functional cardiac changes in myotonic dystrophy type 1: a cardiovascular magnetic resonance study

    Directory of Open Access Journals (Sweden)

    Hermans Mieke CE

    2012-07-01

    Full Text Available Abstract Background Myotonic dystrophy type 1 (MD1 is a neuromuscular disorder with potential involvement of the heart and increased risk of sudden death. Considering the importance of cardiomyopathy as a predictor of prognosis, we aimed to systematically evaluate and describe structural and functional cardiac alterations in patients with MD1. Methods Eighty MD1 patients underwent physical examination, electrocardiography (ECG, echocardiography and cardiovascular magnetic resonance (CMR. Blood samples were taken for determination of NT-proBNP plasma levels and CTG repeat length. Results Functional and structural abnormalities were detected in 35 patients (44%. Left ventricular systolic dysfunction was found in 20 cases, left ventricular dilatation in 7 patients, and left ventricular hypertrophy in 6 patients. Myocardial fibrosis was seen in 10 patients (12.5%. In general, patients had low left ventricular mass indexes. Right ventricular involvement was uncommon and only seen together with left ventricular abnormalities. Functional or structural cardiac involvement was associated with age (p = 0.04, male gender (p Conclusions CMR can be useful to detect early structural and functional myocardial abnormalities in patients with MD1. Myocardial involvement is strongly associated with conduction abnormalities, but a normal ECG does not exclude myocardial alterations. These findings lend support to the hypothesis that MD1 patients have a complex cardiac phenotype, including both myocardial and conduction system alteration.

  5. Pulse wave velocity and cardiac autonomic function in type 2 diabetes mellitus.

    Science.gov (United States)

    Chorepsima, Stamatina; Eleftheriadou, Ioanna; Tentolouris, Anastasios; Moyssakis, Ioannis; Protogerou, Athanasios; Kokkinos, Alexandros; Sfikakis, Petros P; Tentolouris, Nikolaos

    2017-05-19

    Increased carotid-femoral pulse wave velocity (PWV) has been associated with incident cardiovascular disease, independently of traditional risk factors. Cardiac autonomic dysfunction is a common complication of diabetes and has been associated with reduced aortic distensibility. However, the association of cardiac autonomic dysfunction with PWV is not known. In this study we examined the association between cardiac autonomic function and PWV in subjects with type 2 diabetes mellitus. A total of 290 patients with type 2 diabetes were examined. PWV was measured at the carotid-femoral segment with applanation tonometry. Central mean arterial blood pressure (MBP) was determined by the same apparatus. Participants were classified as having normal (n = 193) or abnormal (n = 97) PWV values using age-corrected values. Cardiac autonomic nervous system activity was determined by measurement of parameters of heart rate variability (HRV). Subjects with abnormal PWV were older, had higher arterial blood pressure and higher heart rate than those with normal PWV. Most of the values of HRV were significantly lower in subjects with abnormal than in those with normal PWV. Multivariate analysis, after controlling for various confounding factors, demonstrated that abnormal PWV was associated independently only with peripheral MBP [odds ratio (OR) 1.049, 95% confidence intervals (CI) 1.015-1.085, P = 0.005], central MBP (OR 1.052, 95% CI 1.016-1.088, P = 0.004), log total power (OR 0.490, 95% CI 0.258-0.932, P = 0.030) and log high frequency power (OR 0.546, 95% CI 0.301-0.991, P = 0.047). In subjects with type 2 diabetes, arterial blood pressure and impaired cardiac autonomic function is associated independently with abnormal PWV.

  6. A powerful transgenic tool for fate mapping and functional analysis of newly generated neurons

    Directory of Open Access Journals (Sweden)

    Vogt Weisenhorn Daniela M

    2010-12-01

    Full Text Available Abstract Background Lack of appropriate tools and techniques to study fate and functional integration of newly generated neurons has so far hindered understanding of neurogenesis' relevance under physiological and pathological conditions. Current analyses are either dependent on mitotic labeling, for example BrdU-incorporation or retroviral infection, or on the detection of transient immature neuronal markers. Here, we report a transgenic mouse model (DCX-CreERT2 for time-resolved fate analysis of newly generated neurons. This model is based on the expression of a tamoxifen-inducible Cre recombinase under the control of a doublecortin (DCX promoter, which is specific for immature neuronal cells in the CNS. Results In the DCX-CreERT2 transgenic mice, expression of CreERT2 was restricted to DCX+ cells. In the CNS of transgenic embryos and adult DCX-CreERT2 mice, tamoxifen administration caused the transient translocation of CreERT2 to the nucleus, allowing for the recombination of loxP-flanked sequences. In our system, tamoxifen administration at E14.5 resulted in reporter gene activation throughout the developing CNS of transgenic embryos. In the adult CNS, neurogenic regions were the primary sites of tamoxifen-induced reporter gene activation. In addition, reporter expression could also be detected outside of neurogenic regions in cells physiologically expressing DCX (e.g. piriform cortex, corpus callosum, hypothalamus. Four weeks after recombination, the vast majority of reporter-expressing cells were found to co-express NeuN, revealing the neuronal fate of DCX+ cells upon maturation. Conclusions This first validation demonstrates that our new DCX-CreERT2 transgenic mouse model constitutes a powerful tool to investigate neurogenesis, migration and their long-term fate of neuronal precursors. Moreover, it allows for a targeted activation or deletion of specific genes in neuronal precursors and will thereby contribute to unravel the molecular

  7. Evaluation of cardiac motion and function by cine magnetic resonance imaging

    International Nuclear Information System (INIS)

    Kondo, Takeshi; Kurokawa, Hiroshi; Anno, Hirofumi

    1992-01-01

    Cardiac cine magnetic resonance imaging (MRI) was studied to evaluate the cardiac motion and function, and a water-stream phantom study was performed to clarify whether it was possible to quantitatively assess the valvular regurgitation flow by the size of the flow void. In normal subjects, the left ventricular (LV) epicardial apex swung up to the base only a few millimeters, and the mitral annulus ring moved about 14 mm as mean value toward the apex during systole. Those motions of mitral annulus ring may contribute to the left atrial filling. The LV longitudinal shortening and torsions were shown by the tagging method. This tagging method was the best method for estimating cardiac motions. Cardiac cine MRI using software including a modified Simpson's method program and a wall motion analysis program was useful for routine LV volumetry and wall motion analysis because it was a simple and reliable method. Our water-stream phantom studies demonstrated that it might be difficult to perform quantitative evaluation of valvular regurgitation flow by using only the size of the flow void without acquiring information relating to the orifice area. (author)

  8. Pioglitazone improves cardiac function and alters myocardial substrate metabolism without affecting cardiac triglyceride accumulation and high-energy phosphate metabolism in patients with well-controlled type 2 diabetes mellitus

    NARCIS (Netherlands)

    van der Meer, Rutger W.; Rijzewijk, Luuk J.; de Jong, Hugo W. A. M.; Lamb, Hildo J.; Lubberink, Mark; Romijn, Johannes A.; Bax, Jeroen J.; de Roos, Albert; Kamp, Otto; Paulus, Walter J.; Heine, Robert J.; Lammertsma, Adriaan A.; Smit, Johannes W. A.; Diamant, Michaela

    2009-01-01

    Cardiac disease is the leading cause of mortality in type 2 diabetes mellitus (T2DM). Pioglitazone has been associated with improved cardiac outcome but also with an elevated risk of heart failure. We determined the effects of pioglitazone on myocardial function in relation to cardiac high-energy

  9. A high-sugar and high-fat diet impairs cardiac systolic and diastolic function in mice.

    Science.gov (United States)

    Carbone, Salvatore; Mauro, Adolfo G; Mezzaroma, Eleonora; Kraskauskas, Donatas; Marchetti, Carlo; Buzzetti, Raffaella; Van Tassell, Benjamin W; Abbate, Antonio; Toldo, Stefano

    2015-11-01

    Heart failure (HF) is a clinical syndrome characterized by dyspnea, fatigue, exercise intolerance and cardiac dysfunction. Unhealthy diet has been associated with increased risk of obesity and heart disease, but whether it directly affects cardiac function, and promotes the development and progression of HF is unknown. We fed 8-week old male or female CD-1 mice with a standard diet (SD) or a diet rich in saturated fat and sugar, resembling a "Western" diet (WD). Cardiac systolic and diastolic function was measured at baseline and 4 and 8 weeks by Doppler echocardiography, and left ventricular (LV) end-diastolic pressure (EDP) by cardiac catheterization prior to sacrifice. An additional group of mice received WD for 4 weeks followed by SD (wash-out) for 8 weeks. WD-fed mice experienced a significant decreased in LV ejection fraction (LVEF), reflecting impaired systolic function, and a significant increase in isovolumetric relaxation time (IRT), myocardial performance index (MPI), and LVEDP, showing impaired diastolic function, without any sex-related differences. Switching to a SD after 4 weeks of WD partially reversed the cardiac systolic and diastolic dysfunction. A diet rich in saturated fat and sugars (WD) impairs cardiac systolic and diastolic function in the mouse. Further studies are required to define the mechanism through which diet affects cardiac function, and whether dietary interventions can be used in patients with, or at risk for, HF. Published by Elsevier Ireland Ltd.

  10. Natural aminoacyl tRNA synthetase fragment enhances cardiac function after myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Margaret E McCormick

    Full Text Available A naturally-occurring fragment of tyrosyl-tRNA synthetase (TyrRS has been shown in higher eukaryotes to 'moonlight' as a pro-angiogenic cytokine in addition to its primary role in protein translation. Pro-angiogenic cytokines have previously been proposed to be promising therapeutic mechanisms for the treatment of myocardial infarction. Here, we show that systemic delivery of the natural fragment of TyRS, mini-TyrRS, improves heart function in mice after myocardial infarction. This improvement is associated with reduced formation of scar tissue, increased angiogenesis of cardiac capillaries, recruitment of c-kitpos cells and proliferation of myocardial fibroblasts. This work demonstrates that mini-TyrRS has beneficial effects on cardiac repair and regeneration and offers support for the notion that elucidation of the ever expanding repertoire of noncanonical functions of aminoacyl tRNA synthetases offers unique opportunities for development of novel therapeutics.

  11. Cardiodynamicsgram: a novel tool for monitoring cardiac function in exercise training.

    Science.gov (United States)

    Wen, Xu; Guo, Bokai; Gong, Yinglan; Xia, Ling; Yu, Jie

    2018-04-27

    This study evaluated the feasibility of cardiodynamicsgram (CDG) for monitoring the cardiac functions of athletes and exercisers. CDG could provide an effective, simple, and economical tool for exercise training. Seventeen middle-distance race athletes aged 14-28 years old were recruited. CDG tests and blood test including creatine kinase (CK), CK-MB isoenzyme, and high-sensitivity troponin I (hsTnI) were performed before a high-intensity prolonged training, as well as 2 and 14 h after training, respectively. The CDG test result was unsatisfactory when the CK test result was used as standard. However, the accuracy of CDG test was about 80% when CK-MB and hsTnI were used as standards. Thus, CDG offers a noninvasive, simple, and economical approach for monitoring the cardiac function of athletes and exercisers during exercise training. Nonetheless, the applicability of CDG needs further investigation.

  12. Hypothalamus-pituitary-thyroid axis activity and function of cardiac muscle in energy deficit

    Directory of Open Access Journals (Sweden)

    Katarzyna Lachowicz

    2017-12-01

    Full Text Available Frequently repeated statement that energy restriction is a factor that improves cardiovascular system function seems to be not fully truth. Low energy intake modifies the hypothalamus-pituitary-thyroid axis activity and thyroid hormone peripheral metabolism. Thyroid hormones, as modulators of the expression and activity of many cardiomyocyte proteins, control heart function. Decreased thyroid hormone levels and their disturbanced conversion and action result in alternation of cardiac remodeling, disorder of calcium homeostasis and diminish myocardial contractility. This review provides a summary of the current state of knowledge about the mechanisms of energy restriction effects on thyroidal axis activity, thyroid hormone peripheral metabolism and action in target tissues, especially in cardiac myocytes. We also showed the existence of energy restriction-thyroid-heart pathway.

  13. Cardiac function and tadalafil used for treating fetal growth restriction in pregnant women without cardiovascular disease.

    Science.gov (United States)

    Tanaka, Kayo; Tanaka, Hiroaki; Maki, Shintaro; Kubo, Michiko; Nii, Masafumi; Magawa, Shoichi; Hatano, Fumi; Tsuji, Makoto; Osato, Kazuhiro; Kamimoto, Yuki; Umekawa, Takashi; Ikeda, Tomoaki

    2018-02-20

    The aim of the present study was to evaluate tadalafil for the treatment of fetal growth restriction (FGR) and the cardiac function in pregnant women without cardiovascular disease who used tadalafil for this reason. We examined nine pregnant women without cardiovascular disease who were using tadalafil to treat FGR. Maternal heart rate, systolic blood pressure (BP), and echocardiographic findings were assessed before and after tadalafil use. Diastolic BP was lower after compared to that before using tadalafil, but the difference was not significant. Echocardiographic findings were not significantly different before and after tadalafil use. Tadalafil did not adversely affect pregnant women without cardiovascular disease and was considered acceptable for use since it did not affect the mother's cardiac function.

  14. Exposure to occupational air pollution and cardiac function in workers of the Esfahan Steel Industry, Iran.

    Science.gov (United States)

    Golshahi, Jafar; Sadeghi, Masoumeh; Saqira, Mohammad; Zavar, Reihaneh; Sadeghifar, Mostafa; Roohafza, Hamidreza

    2016-06-01

    Air pollution is recognized as an important risk factor for cardiovascular disease. We investigated association of exposure to occupational air pollution and cardiac function in the workers of the steel industry. Fifty male workers of the agglomeration and coke-making parts of the Esfahan Steel Company were randomly selected (n = 50). Workers in the administrative parts were studied as controls (n = 50). Those with known history of hypertension, dyslipidemia, or diabetes, and active smokers were not included. Data of age, body mass index, employment duration, blood pressure, fasting blood sugar, and lipid profile were gathered. Echocardiography was performed to evaluate cardiac function. Left ventricular ejection fraction was lower in workers of the agglomeration/coke-making parts than in controls (mean difference = 5 to 5.5 %, P steel industry is associated with left heart systolic dysfunction. Possible right heart insults due to air pollution exposure warrant further investigations.

  15. Cell Death, Neuronal Plasticity and Functional Loading in the Development of the Central Nervous System

    Science.gov (United States)

    Keefe, J. R.

    1985-01-01

    Research on the precise timing and regulation of neuron production and maturation in the vestibular and visual systems of Wistar rats and several inbred strains of mice (C57B16 and Pallid mutant) concentrated upon establishing a timing baseline for mitotic development of the neurons of the vestibular nuclei and the peripheral vestibular sensory structures (maculae, cristae). This involved studies of the timing and site of neuronal cell birth and preliminary studies of neuronal cell death in both central and peripheral elements of the mammalian vestibular system. Studies on neuronal generation and maturation in the retina were recently added to provide a mechanism for more properly defining the in utero' developmental age of the individual fetal subject and to closely monitor potential transplacental effects of environmentally stressed maternal systems. Information is given on current efforts concentrating upon the (1) perinatal period of development (E18 thru P14) and (2) the role of cell death in response to variation in the functional loading of the vestibular and proprioreceptive systems in developing mammalian organisms.

  16. New Pharmacotherapy Targeting Cognitive Dysfunction of Schizophrenia via Modulation of GABA Neuronal Function.

    Science.gov (United States)

    Uehara, Takashi; Sumiyoshi, Tomiki; Kurachi, Masayoshi

    2015-01-01

    Schizophrenia is considered a neurodevelopmental and neurodegenerative disorder. Cognitive impairment is a core symptom in patients with the illness, and has been suggested a major predictor of functional outcomes. Reduction of parvalbumin (PV)-positive γ-aminobutyric acid (GABA) interneurons has been associated with the pathophysiology of schizophrenia, in view of the link between the abnormality of GABA neurons and cognitive impairments of the disease. It is assumed that an imbalance of excitatory and inhibitory (E-I) activity induced by low activity of glutamatergic projections and PV-positive GABA interneurons in the prefrontal cortex resulted in sustained neural firing and gamma oscillation, leading to impaired cognitive function. Therefore, it is important to develop novel pharmacotherapy targeting GABA neurons and their activities. Clinical evidence suggests serotonin (5-HT) 1A receptor agonist improves cognitive disturbances of schizophrenia, consistent with results from preclinical studies, through mechanism that corrects E-I imbalance via the suppression of GABA neural function. On the other hand, T-817MA, a novel neurotrophic agent, ameliorated loss of PV-positive GABA neurons in the medial prefrontal cortex and reduction of gamma-band activity, as well as cognitive dysfunction in animal model of schizophrenia. In conclusion, a pharmacotherapy to alleviate abnormalities in GABA neurons through 5-HT1A agonists and T-817MA is expected to prevent the onset and/or progression of schizophrenia.

  17. Studies on functional roles of the histaminergic neuron system by using pharmacological agents, knockout mice and positron emission tomography

    International Nuclear Information System (INIS)

    Watanabe, Takehiko; Yanai, Kazuhiko

    2001-01-01

    Since one of us, Takehiko Watanabe (TW), elucidated the location and distribution of the histaminergic neuron system in the brain with antibody raised against L-histidine decarboxylase (a histamine-forming enzyme, HDC) as a marker in 1984 and came to Tohoku University School of Medicine in Sendai, we have been collaborating on the functions of this neuron system by using pharmacological agents, knockout mice of the histamine-related genes, and, in some cases, positron emission tomography (PET). Many of our graduate students and colleagues have been actively involved in histamine research since 1985. Our extensive studies have clarified some of the functions of histamine neurons using methods from molecular techniques to non-invasive human PET imaging. Histamine neurons are involved in many brain functions, such as spontaneous locomotion, arousal in wake-sleep cycle, appetite control, seizures, learning and memory, aggressive behavior and emotion. Particularly, the histaminergic neuron system is one of the most important neuron systems to maintain and stimulate wakefulness. Histamine also functions as a biprotection system against various noxious and unfavorable stimuli (for examples, convulsion, nociception, drug sensitization, ischemic lesions, and stress). Although activators of histamine neurons have not been clinically available until now, we would like to point out that the activation of the histaminergic neuron system is important to maintain mental health. Here, we summarize the newly-discovered functions of histamine neurons mainly on the basis of results from our research groups. (author)

  18. Studies on functional roles of the histaminergic neuron system by using pharmacological agents, knockout mice and positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Takehiko; Yanai, Kazuhiko [Tohoku Univ., Sendai (Japan). Graduate School of Medicine

    2001-12-01

    Since one of us, Takehiko Watanabe (TW), elucidated the location and distribution of the histaminergic neuron system in the brain with antibody raised against L-histidine decarboxylase (a histamine-forming enzyme, HDC) as a marker in 1984 and came to Tohoku University School of Medicine in Sendai, we have been collaborating on the functions of this neuron system by using pharmacological agents, knockout mice of the histamine-related genes, and, in some cases, positron emission tomography (PET). Many of our graduate students and colleagues have been actively involved in histamine research since 1985. Our extensive studies have clarified some of the functions of histamine neurons using methods from molecular techniques to non-invasive human PET imaging. Histamine neurons are involved in many brain functions, such as spontaneous locomotion, arousal in wake-sleep cycle, appetite control, seizures, learning and memory, aggressive behavior and emotion. Particularly, the histaminergic neuron system is one of the most important neuron systems to maintain and stimulate wakefulness. Histamine also functions as a biprotection system against various noxious and unfavorable stimuli (for examples, convulsion, nociception, drug sensitization, ischemic lesions, and stress). Although activators of histamine neurons have not been clinically available until now, we would like to point out that the activation of the histaminergic neuron system is important to maintain mental health. Here, we summarize the newly-discovered functions of histamine neurons mainly on the basis of results from our research groups. (author)

  19. CARDIAC TRANSPLANT REJECTION AND NON-INVASIVE COMON CAROTID ARTERY WALL FUNCTIONAL INDICES

    Directory of Open Access Journals (Sweden)

    A. O. Shevchenko

    2015-01-01

    Full Text Available Allograft rejection would entail an increase in certain blood biomarkers and active substances derived from activated inflammatory cells which could influence entire vascular endothelial function and deteriorate arterial wall stiffness. We propose that carotid wall functional indices measured with non-invasive ultrasound could we valuable markers of the subclinical cardiac allograft rejection. Aim. Our goal was to analyze the clinical utility of functional common carotid wall (CCW variables measured with high-resolution Doppler ultrasound as a non-invasive screening tool for allograft rejection in cardiac transplant patients (pts. Methods. One hundred and seventy one pts included 93 cardiac recipients, 30 dilated cardiomyopathy waiting list pts, and 48 stable coronary artery disease (SCAD pts without decompensated heart failure were included. Along with resistive index (Ri, pulsative index (Pi, and CCW intima-media thickness (IMT, CCW rigidity index (iRIG was estimated using empirical equation. Non-invasive evaluation was performed in cardiac transplant recipients prior the endomyo- cardial biopsy. Results. Neither of Ri, Pi, or CCW IMT were different in studied subgroups. iRIG was signifi- cantly lower in SCAD pts when compared to the dilated cardiomyopathy subgroup. The later had similar values with cardiac transplant recipients without rejection. Antibody-mediated and cellular rejection were found in 22 (23.7% and 17 (18.3% cardiac recipients, respectively. Mean iRIG in pts without rejection was significantly lower in comparison to antibody-mediated rejection and cell-mediated (5514.7 ± 2404.0 vs 11856.1 ± 6643.5 and 16071.9 ± 10029.1 cm/sec2, respectively, p = 0.001. Area under ROC for iRIG was 0.90 ± 0.03 units2. Analysis showed that iRIG values above estimated treshold 7172 cm/sec2 suggested relative risk of any type of rejection 17.7 (95%CI = 6.3–49.9 sensitivity 80.5%, specificity – 81.1%, negative predictive value – 84

  20. Renal and cardiac function during alpha1-beta-blockade in congestive heart failure

    DEFF Research Database (Denmark)

    Heitmann, M; Davidsen, U; Stokholm, K H

    2002-01-01

    The kidney and the neurohormonal systems are essential in the pathogenesis of congestive heart failure (CHF) and the physiologic response. Routine treatment of moderate to severe CHF consists of diuretics, angiotensin-converting enzyme (ACE) inhibition and beta-blockade. The need for control...... of renal function during initiation of ACE-inhibition in patients with CHF is well known. The aim of this study was to investigate whether supplementation by a combined alpha1-beta-blockade to diuretics and ACE-inhibition might improve cardiac function without reducing renal function....

  1. Resistance Training After Myocardial Infarction in Rats: Its Role on Cardiac and Autonomic Function

    International Nuclear Information System (INIS)

    Grans, Camilla Figueiredo; Feriani, Daniele Jardim; Abssamra, Marcos Elias Vergilino; Rocha, Leandro Yanase; Carrozzi, Nicolle Martins; Mostarda, Cristiano; Figueroa, Diego Mendrot; Angelis, Kátia De; Irigoyen, Maria Cláudia; Rodrigues, Bruno

    2014-01-01

    Although resistance exercise training is part of cardiovascular rehabilitation programs, little is known about its role on the cardiac and autonomic function after myocardial infarction. To evaluate the effects of resistance exercise training, started early after myocardial infarction, on cardiac function, hemodynamic profile, and autonomic modulation in rats. Male Wistar rats were divided into four groups: sedentary control, trained control, sedentary infarcted and trained infarcted rats. Each group with n = 9 rats. The animals underwent maximum load test and echocardiography at the beginning and at the end of the resistance exercise training (in an adapted ladder, 40% to 60% of the maximum load test, 3 months, 5 days/week). At the end, hemodynamic, baroreflex sensitivity and autonomic modulation assessments were made. The maximum load test increased in groups trained control (+32%) and trained infarcted (+46%) in relation to groups sedentary control and sedentary infarcted. Although no change occurred regarding the myocardial infarction size and systolic function, the E/A ratio (-23%), myocardial performance index (-39%) and systolic blood pressure (+6%) improved with resistance exercise training in group trained infarcted. Concomitantly, the training provided additional benefits in the high frequency bands of the pulse interval (+45%), as well as in the low frequency band of systolic blood pressure (-46%) in rats from group trained infarcted in relation to group sedentary infarcted. Resistance exercise training alone may be an important and safe tool in the management of patients after myocardial infarction, considering that it does not lead to significant changes in the ventricular function, reduces the global cardiac stress, and significantly improves the vascular and cardiac autonomic modulation in infarcted rats

  2. Resistance Training After Myocardial Infarction in Rats: Its Role on Cardiac and Autonomic Function

    Directory of Open Access Journals (Sweden)

    Camilla Figueiredo Grans

    2014-07-01

    Full Text Available Background: Although resistance exercise training is part of cardiovascular rehabilitation programs, little is known about its role on the cardiac and autonomic function after myocardial infarction. Objective: To evaluate the effects of resistance exercise training, started early after myocardial infarction, on cardiac function, hemodynamic profile, and autonomic modulation in rats. Methods: Male Wistar rats were divided into four groups: sedentary control, trained control, sedentary infarcted and trained infarcted rats. Each group with n = 9 rats. The animals underwent maximum load test and echocardiography at the beginning and at the end of the resistance exercise training (in an adapted ladder, 40% to 60% of the maximum load test, 3 months, 5 days/week. At the end, hemodynamic, baroreflex sensitivity and autonomic modulation assessments were made. Results: The maximum load test increased in groups trained control (+32% and trained infarcted (+46% in relation to groups sedentary control and sedentary infarcted. Although no change occurred regarding the myocardial infarction size and systolic function, the E/A ratio (-23%, myocardial performance index (-39% and systolic blood pressure (+6% improved with resistance exercise training in group trained infarcted. Concomitantly, the training provided additional benefits in the high frequency bands of the pulse interval (+45%, as well as in the low frequency band of systolic blood pressure (-46% in rats from group trained infarcted in relation to group sedentary infarcted. Conclusion: Resistance exercise training alone may be an important and safe tool in the management of patients after myocardial infarction, considering that it does not lead to significant changes in the ventricular function, reduces the global cardiac stress, and significantly improves the vascular and cardiac autonomic modulation in infarcted rats.

  3. Image processing of x-ray left ventricular cineangiocardiograms and displays of cardiac functions

    International Nuclear Information System (INIS)

    Eiho, Shigeru; Yamada, Shigeru; Kuwahara, Michiyoshi

    1980-01-01

    Cineangiocardiography has been often used as one of the highly helpful techniques to examine the cardiac function. This paper deals with the method of tracing automatically the boundaries of the left ventricle on cineangiocardiograms, the method to evaluate and display various cardiac functions, the method to reconstruct the left ventricular cavity from biplane cineangiocardiograms and the method to display a 3-dimensional shape of the left ventricle reconstructed. Our algorithm of boundary tracing is based on a heuristic search for a local maximum of the changing rate in the gray level of cineangiocardiogram. The boundaries of endocardial margins of the left ventricle on 80 to 120 consecutive frames are automatically traced by our method. By using the detected boundaries of the left ventricle, a lot of quantitative information may be established on the cardiac function. The volume change, the wall motions and the %-shortening are displayed graphically. The motion of the boundary of the left ventricle is displayed on a CRT as a moving picture. The left ventricular cavity is reconstructed from the detected boundaries of the left ventricle on biplane cineangiocardiograms. A reconstructed image can be shown as superimposed lines or halftone planes to produce a 3-dimensional perspective. The %-shortening which shows the contractility of the regional myocardium is displayed on a silhouette of the left ventricle. We can easily recognize the abnormal area of contraction and the level and spread of abnormality from this displayed image. With the use of the system described in this paper, we can grasp the movement of the left ventricle exactly and evaluate the cardiac function quantitatively. (author)

  4. Resistance Training After Myocardial Infarction in Rats: Its Role on Cardiac and Autonomic Function

    Energy Technology Data Exchange (ETDEWEB)

    Grans, Camilla Figueiredo; Feriani, Daniele Jardim; Abssamra, Marcos Elias Vergilino; Rocha, Leandro Yanase; Carrozzi, Nicolle Martins [Laboratório do Movimento Humano, Universidade São Judas Tadeu (USJT), São Paulo, SP (Brazil); Mostarda, Cristiano [Departamento de Educação Física, Universidade Federal do Maranhão (UFMA), São Luís, MA (Brazil); Figueroa, Diego Mendrot [Laboratório de Hipertensão Experimental, Instituto do Coração (InCor), Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, SP (Brazil); Angelis, Kátia De [Laboratório de Fisiologia Translacional, Universidade Nove de Julho (Uninove), São Paulo, SP (Brazil); Irigoyen, Maria Cláudia [Laboratório de Hipertensão Experimental, Instituto do Coração (InCor), Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, SP (Brazil); Rodrigues, Bruno, E-mail: bruno.rodrigues@incor.usp.br [Laboratório do Movimento Humano, Universidade São Judas Tadeu (USJT), São Paulo, SP (Brazil)

    2014-07-15

    Although resistance exercise training is part of cardiovascular rehabilitation programs, little is known about its role on the cardiac and autonomic function after myocardial infarction. To evaluate the effects of resistance exercise training, started early after myocardial infarction, on cardiac function, hemodynamic profile, and autonomic modulation in rats. Male Wistar rats were divided into four groups: sedentary control, trained control, sedentary infarcted and trained infarcted rats. Each group with n = 9 rats. The animals underwent maximum load test and echocardiography at the beginning and at the end of the resistance exercise training (in an adapted ladder, 40% to 60% of the maximum load test, 3 months, 5 days/week). At the end, hemodynamic, baroreflex sensitivity and autonomic modulation assessments were made. The maximum load test increased in groups trained control (+32%) and trained infarcted (+46%) in relation to groups sedentary control and sedentary infarcted. Although no change occurred regarding the myocardial infarction size and systolic function, the E/A ratio (-23%), myocardial performance index (-39%) and systolic blood pressure (+6%) improved with resistance exercise training in group trained infarcted. Concomitantly, the training provided additional benefits in the high frequency bands of the pulse interval (+45%), as well as in the low frequency band of systolic blood pressure (-46%) in rats from group trained infarcted in relation to group sedentary infarcted. Resistance exercise training alone may be an important and safe tool in the management of patients after myocardial infarction, considering that it does not lead to significant changes in the ventricular function, reduces the global cardiac stress, and significantly improves the vascular and cardiac autonomic modulation in infarcted rats.

  5. Resistance Training After Myocardial Infarction in Rats: Its Role on Cardiac and Autonomic Function

    Science.gov (United States)

    Grans, Camilla Figueiredo; Feriani, Daniele Jardim; Abssamra, Marcos Elias Vergilino; Rocha, Leandro Yanase; Carrozzi, Nicolle Martins; Mostarda, Cristiano; Figueroa, Diego Mendrot; Angelis, Kátia De; Irigoyen, Maria Cláudia; Rodrigues, Bruno

    2014-01-01

    Background Although resistance exercise training is part of cardiovascular rehabilitation programs, little is known about its role on the cardiac and autonomic function after myocardial infarction. Objective To evaluate the effects of resistance exercise training, started early after myocardial infarction, on cardiac function, hemodynamic profile, and autonomic modulation in rats. Methods Male Wistar rats were divided into four groups: sedentary control, trained control, sedentary infarcted and trained infarcted rats. Each group with n = 9 rats. The animals underwent maximum load test and echocardiography at the beginning and at the end of the resistance exercise training (in an adapted ladder, 40% to 60% of the maximum load test, 3 months, 5 days/week). At the end, hemodynamic, baroreflex sensitivity and autonomic modulation assessments were made. Results The maximum load test increased in groups trained control (+32%) and trained infarcted (+46%) in relation to groups sedentary control and sedentary infarcted. Although no change occurred regarding the myocardial infarction size and systolic function, the E/A ratio (-23%), myocardial performance index (-39%) and systolic blood pressure (+6%) improved with resistance exercise training in group trained infarcted. Concomitantly, the training provided additional benefits in the high frequency bands of the pulse interval (+45%), as well as in the low frequency band of systolic blood pressure (-46%) in rats from group trained infarcted in relation to group sedentary infarcted. Conclusion Resistance exercise training alone may be an important and safe tool in the management of patients after myocardial infarction, considering that it does not lead to significant changes in the ventricular function, reduces the global cardiac stress, and significantly improves the vascular and cardiac autonomic modulation in infarcted rats. PMID:25014059

  6. Characterization of upper thoracic spinal neurons receiving noxious cardiac and/or somatic inputs in diabetic rats

    DEFF Research Database (Denmark)

    Ghorbani, Marie Louise M; Qin, Chao; Wu, Mingyuan

    2011-01-01

    The aim of the present study was to examine spinal processing of cardiac and somatic nociceptive input in rats with STZ-induced diabetes. Type 1 diabetes was induced with streptozotocin (50mg/kg) in 14 male Sprague-Dawley rats and citrate buffer was injected in 14 control rats. After 4-11weeks...

  7. Long-term modulation of the intrinsic cardiac nervous system by spinal cord neurons in normal and ischaemic hearts

    NARCIS (Netherlands)

    Armour, JA; Linderoth, B; Arora, RC; DeJongste, MJL; Ardell, JL; Kingma, JG; Hill, M; Foreman, RD

    2002-01-01

    Electrical excitation of the dorsal aspect of the rostral thoracic spinal cord imparts long-term therapeutic benefits to patients with angina pectoris. Such spinal cord stimulation also induces short-term suppressor effects on the intrinsic cardiac nervous system. The purpose of this study was to

  8. Cardiovascular measurement and cardiac function analysis with electron beam computed tomography in health Chinese people (50 cases report)

    International Nuclear Information System (INIS)

    Lu Bin; Dai Ruping; Zhang Shaoxiong; Bai Hua; Jing Baolian; Cao Cheng; He Sha; Ren Li

    1998-01-01

    Purpose: To quantitatively measure cardiovascular diameters and function parameters by using electron beam computed tomography, EBCT. Methods: Men 50 health Chinese people accepted EBCT common transverse and short-axis enhanced movie scan (27 men, 23 women, average age 47.7 years.). The transverse scan was used to measure the diameters of the ascending aorta, descending aorta, pulmonary artery and left atrium. The movie study was used to measure the left ventricular myocardium thickness and analysis global, sectional and segmental function of the right and left ventricles. Results: The cardiovascular diameters and cardiac functional parameters were calculated. The diameters and most functional parameters (end syspoble volume, syspole volume, ejection fraction, cardiac-output, cardiac index) of normal Chinese men were greater than those of women (P>0.05). However, the EDV and MyM(myocardium mass) of both ventricles were significant (p<0.01). Conclusion: EBCT is a minimally invasive method for cardiovascular measurement and cardiac function evaluation

  9. Combining computer modelling and cardiac imaging to understand right ventricular pump function.

    Science.gov (United States)

    Walmsley, John; van Everdingen, Wouter; Cramer, Maarten J; Prinzen, Frits W; Delhaas, Tammo; Lumens, Joost

    2017-10-01

    Right ventricular (RV) dysfunction is a strong predictor of outcome in heart failure and is a key determinant of exercise capacity. Despite these crucial findings, the RV remains understudied in the clinical, experimental, and computer modelling literature. This review outlines how recent advances in using computer modelling and cardiac imaging synergistically help to understand RV function in health and disease. We begin by highlighting the complexity of interactions that make modelling the RV both challenging and necessary, and then summarize the multiscale modelling approaches used to date to simulate RV pump function in the context of these interactions. We go on to demonstrate how these modelling approaches in combination with cardiac imaging have improved understanding of RV pump function in pulmonary arterial hypertension, arrhythmogenic right ventricular cardiomyopathy, dyssynchronous heart failure and cardiac resynchronization therapy, hypoplastic left heart syndrome, and repaired tetralogy of Fallot. We conclude with a perspective on key issues to be addressed by computational models of the RV in the near future. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

  10. Usefulness of true FISP cine MR imaging in patients with poor cardiac function

    Energy Technology Data Exchange (ETDEWEB)

    Sakuma, Toshiharu; Yamada, Naoaki; Motooka, Makoto; Enomoto, Naoyuki; Maeshima, Isamu; Matsuda, Kazuhide; Urayama, Shinichi; Ikeo, Miki [National Cardiovascular Center, Suita, Osaka (Japan)

    2002-01-01

    This study was done to assess the value of True FISP cine in patients with poor cardiac function. True FISP cine and FLASH cine imaging were performed on a 1.5 T machine. Both short axis and horizontal long axis imaging sections were used. The imaging sections used a Matrix (120 x 128), FOV (24 x 32 cm), and had a slice thickness of 8 mm. The imaging time for True FISP cine was 8 heart beats and 17 heart beats for FLASH cine. The contrast-to-noise ratio between the blood and myocardium (CNR) was measured at enddiastole and endsystole. The subjects in the study were 10 healty volunteers (average age 26.5{+-}3.2 years) and 12 patients with hypofunction (average age 53.9{+-}13.2 years). In the volunteers, the CNR of the short axis imaging was similar in both True FISP (24.6{+-}3.7) and FLASH (23.4{+-}5.9). In the patients with poor cardiac function however, the CNR of True FISP was larger than FLASH in both the short and long axis. In the short axis (22.7{+-}6.1 vs. 17.9{+-}5.3, P<0.01) and in the long axis (17.4{+-}4.3 vs. 9.3{+-}4.0, P<0.01). We conclude that True FISP cine has a higher contrast in a shorter imaging time than FLASH cine. True FISP cine is especially useful in patients with poor cardiac function. (author)

  11. Anti-Tribbles Pseudokinase 2 (TRIB2)-Immunization Modulates Hypocretin/Orexin Neuronal Functions.

    Science.gov (United States)

    Tanaka, Susumu; Honda, Yoshiko; Honda, Makoto; Yamada, Hisao; Honda, Kazuki; Kodama, Tohru

    2017-01-01

    Recent findings showed that 16%-26% of narcolepsy patients were positive for anti-tribbles pseudokinase 2 (TRIB2) antibody, and the intracerebroventricular administration of immunoglobulin-G purified from anti-TRIB2 positive narcolepsy patients caused hypocretin/orexin neuron loss. We investigated the pathophysiological role of TRIB2 antibody using TRIB2-immunized rats and hypocretin/ataxin-3 transgenic (ataxin-3) mice. Plasma, cerebrospinal fluid (CSF), and hypothalamic tissues from TRIB2-immunized rats were collected. Anti-TRIB2 titers, hypocretin contents, mRNA expressions, the cell count of hypocretin neurons, and immunoreactivity of anti-TRIB2 antibodies on hypocretin neurons were investigated. The plasma from ataxin-3 mice was also used to determine the anti-TRIB2 antibody titer changes following the loss of hypocretin neurons. TRIB2 antibody titers increased in the plasma and CSF of TRIB2-immunized rats. The hypothalamic tissue immunostained with the sera from TRIB2-immunized rats revealed positive signals in the cytoplasm of hypcretin neurons. While no changes were found regarding hypothalamic hypocretin contents or cell counts, but there were significant decreases of the hypocretin mRNA level and release into the CSF. The plasma from over 26-week-old ataxin-3 mice, at the advanced stage of hypocretin cell destruction, showed positive reactions against TRIB2 antigen, and positive plasma also reacted with murine hypothalamic hypocretin neurons. Our results suggest that the general activation of the immune system modulates the functions of hypocretin neurons. The absence of a change in hypocretin cell populations suggested that factors other than anti-TRIB2 antibody play a part in the loss of hypocretin neurons in narcolepsy. The increased anti-TRIB2 antibody after the destruction of hypocretin neurons suggest that anti-TRIB2 antibody in narcolepsy patients is the consequence rather than the inciting cause of hypocretin cell destruction. © Sleep Research

  12. Midbrain and forebrain patterning delivers immunocytochemically and functionally similar populations of neuropeptide Y containing GABAergic neurons.

    Science.gov (United States)

    Khaira, S K; Nefzger, C M; Beh, S J; Pouton, C W; Haynes, J M

    2011-09-01

    Neurons differentiated in vitro from embryonic stem cells (ESCs) have the potential to serve both as models of disease states and in drug discovery programs. In this study, we use sonic hedgehog (SHH) and fibroblast growth factor 8 (FGF-8) to enrich for forebrain and midbrain phenotypes from mouse ESCs. We then investigate, using Ca(2+) imaging and [(3)H]-GABA release studies, whether the GABAergic neurons produced exhibit distinct functional phenotypes. At day 24 of differentiation, reverse transcriptase-PCR showed the presence of both forebrain (Bf-1, Hesx1, Pgc-1α, Six3) and midbrain (GATA2, GATA3) selective mRNA markers in developing forebrain-enriched cultures. All markers were present in midbrain cultures except for Bf-1 and Pgc-1α. Irrespective of culture conditions all GABA immunoreactive neurons were also immunoreactive to neuropeptide Y (NPY) antibodies. Forebrain and midbrain GABAergic neurons responded to ATP (1 mM), L-glutamate (30 μM), noradrenaline (30 μM), acetylcholine (30 μM) and dopamine (30 μM), with similar elevations of intracellular Ca(2+)([Ca(2+)](i)). The presence of GABA(A) and GABA(B) antagonists, bicuculline (30 μM) and CGP55845 (1 μM), increased the elevation of [Ca(2+)](i) in response to dopamine (30 μM) in midbrain, but not forebrain GABAergic neurons. All agonists, except dopamine, elicited similar [(3)H]-GABA release from forebrain and midbrain cultures. Dopamine (30 μM) did not stimulate significant [(3)H]-GABA release in midbrain cultures, although it was effective in forebrain cultures. This study shows that differentiating neurons toward a midbrain fate restricts the expression of forebrain markers. Forebrain differentiation results in the expression of forebrain and midbrain markers. All GABA(+) neurons contain NPY, and show similar agonist-induced elevations of [Ca(2+)](i) and [(3)H]-GABA release. This study indicates that the pharmacological phenotype of these particular neurons may be independent of the addition of

  13. Evaluation of mRNA expression levels and electrophysiological function of neuron-like cells derived from canine bone marrow stromal cells.

    Science.gov (United States)

    Nakano, Rei; Edamura, Kazuya; Sugiya, Hiroshi; Narita, Takanori; Okabayashi, Ken; Moritomo, Tadaaki; Teshima, Kenji; Asano, Kazushi; Nakayama, Tomohiro

    2013-10-01

    To investigate the in vitro differentiation of canine bone marrow stromal cells (BMSCs) into functional, mature neurons. Bone marrow from 6 adult dogs. BMSCs were isolated from bone marrow and chemically induced to develop into neurons. The morphology of the BMSCs during neuronal induction was monitored, and immunocytochemical analyses for neuron markers were performed after the induction. Real-time PCR methods were used to evaluate the mRNA expression levels of markers for neural stem or progenitor cells, neurons, and ion channels, and western blotting was used to assess the expression of neuronal proteins before and after neuronal induction. The electrophysiological properties of the neuron-like cells induced from canine BMSCs were evaluated with fluorescent dye to monitor Ca(2)+ influx. Canine BMSCs developed a neuron-like morphology after neuronal induction. Immunocytochemical analysis revealed that these neuron-like cells were positive for neuron markers. After induction, the cells' mRNA expression levels of almost all neuron and ion channel markers increased, and the protein expression levels of nestin and neurofilament-L increased significantly. However, the neuron-like cells derived from canine BMSCs did not have the Ca(2)+ influx characteristic of spiking neurons. Although canine BMSCs had neuron-like morphological and biochemical properties after induction, they did not develop the electrophysiological characteristics of neurons. Thus, these results have suggested that canine BMSCs could have the capacity to differentiate into a neuronal lineage, but the differentiation protocol used may have been insufficient to induce development into functional neurons.

  14. Neurogenic Radial Glia-like Cells in Meninges Migrate and Differentiate into Functionally Integrated Neurons in the Neonatal Cortex.

    Science.gov (United States)

    Bifari, Francesco; Decimo, Ilaria; Pino, Annachiara; Llorens-Bobadilla, Enric; Zhao, Sheng; Lange, Christian; Panuccio, Gabriella; Boeckx, Bram; Thienpont, Bernard; Vinckier, Stefan; Wyns, Sabine; Bouché, Ann; Lambrechts, Diether; Giugliano, Michele; Dewerchin, Mieke; Martin-Villalba, Ana; Carmeliet, Peter

    2017-03-02

    Whether new neurons are added in the postnatal cerebral cortex is still debated. Here, we report that the meninges of perinatal mice contain a population of neurogenic progenitors formed during embryonic development that migrate to the caudal cortex and differentiate into Satb2 + neurons in cortical layers II-IV. The resulting neurons are electrically functional and integrated into local microcircuits. Single-cell RNA sequencing identified meningeal cells with distinct transcriptome signatures characteristic of (1) neurogenic radial glia-like cells (resembling neural stem cells in the SVZ), (2) neuronal cells, and (3) a cell type with an intermediate phenotype, possibly representing radial glia-like meningeal cells differentiating to neuronal cells. Thus, we have identified a pool of embryonically derived radial glia-like cells present in the meninges that migrate and differentiate into functional neurons in the neonatal cerebral cortex. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. The specific case: cardiac amyloidosis as differential diagnosis in case of restricted cardiac pump function; Der besondere Fall. Amyloidose des Herzens als Differenzialdiagnose bei eingeschraenkter kardialer Pumpfunktion

    Energy Technology Data Exchange (ETDEWEB)

    D' Errico, L. [Universitaetsspital Basel (Switzerland). Klinik fuer Radiologie und Nuklearmedizin; Zellweger, M.; Niemann, T.

    2014-03-15

    The NMR imaging data in combination with clinical characterization and echocardiography are consistent with the diagnosis of a cardiac amyloidosis. The article describes disease pattern and diagnosis based on contrast agent accumulation and diastolic functional disturbances. CT was performed to exclude pulmonary embolism.

  16. Effects of milrinone on left ventricular cardiac function during cooling in an intact animal model.

    Science.gov (United States)

    Tveita, Torkjel; Sieck, Gary C

    2012-08-01

    Due to adverse effects of β-receptor agonists reported when applied during hypothermia, left ventricular (LV) cardiac effects of milrinone, a PDE3 inhibitor which mode of action is deprived the sarcolemmal β-receptor-G protein-PKA system, was tested during cooling to 15 °C. Sprague Dawley rats were instrumented to measure left ventricular (LV) pressure-volume changes using a Millar pressure-volume conductance catheter. Core temperature was reduced from 37 to 15 °C (60 min) using internal and external heat exchangers. Milrinone, or saline placebo, was given as continuous i.v. infusions for 30 min at 37 °C and during cooling. In normothermic controls continuous milrinone infusion for 90 min elevated cardiac output (CO) and stroke volume (SV) significantly. Significant differences in cardiac functional variables between the milrinone group and the saline control group during cooling to 15 °C were found: Compared to saline treated animals throughout cooling from 33 to 15 °CSV was significantly elevated in milrinone animals, the index of LV isovolumic relaxation, Tau, was significantly better preserved, and both HR and CO were significantly higher from 33 to 24 °C. Likewise, during cooling between 33 and 28 °C also LVdP/dt(max) was significantly higher in the milrinone group. Milrinone preserved LV systolic and diastolic function at a significantly higher level than in saline controls during cooling to 15 °C. In essential contrast to our previous results when using β-receptor agonists during hypothermia, the present experiment demonstrates the positive inotropic effects of milrinone on LV cardiac function during cooling to 15 °C. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Differential subcellular distribution of ion channels and the diversity of neuronal function.

    Science.gov (United States)

    Nusser, Zoltan

    2012-06-01

    Following the astonishing molecular diversity of voltage-gated ion channels that was revealed in the past few decades, the ion channel repertoire expressed by neurons has been implicated as the major factor governing their functional heterogeneity. Although the molecular structure of ion channels is a key determinant of their biophysical properties, their subcellular distribution and densities on the surface of nerve cells are just as important for fulfilling functional requirements. Recent results obtained with high resolution quantitative localization techniques revealed complex, subcellular compartment-specific distribution patterns of distinct ion channels. Here I suggest that within a given neuron type every ion channel has a unique cell surface distribution pattern, with the functional consequence that this dramatically increases the computational power of nerve cells. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. Analyzing topological characteristics of neuronal functional networks in the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Hu [School of Computer Science and Communication Engineering, Jiangsu University, Jiangsu 212003 (China); School of Computer Science, Fudan University, Shanghai 200433 (China); Yang, Shengtao [Institutes of Brain Science, Fudan University, Shanghai 200433 (China); Song, Yuqing [School of Computer Science and Communication Engineering, Jiangsu University, Jiangsu 212003 (China); Wei, Hui [School of Computer Science, Fudan University, Shanghai 200433 (China)

    2014-08-28

    In this study, we recorded spike trains from brain cortical neurons of several behavioral rats in vivo by using multi-electrode recordings. An NFN was constructed in each trial, obtaining a total of 150 NFNs in this study. The topological characteristics of NFNs were analyzed by using the two most important characteristics of complex networks, namely, small-world structure and community structure. We found that the small-world properties exist in different NFNs constructed in this study. Modular function Q was used to determine the existence of community structure in NFNs, through which we found that community-structure characteristics, which are related to recorded spike train data sets, are more evident in the Y-maze task than in the DM-GM task. Our results can also be used to analyze further the relationship between small-world characteristics and the cognitive behavioral responses of rats. - Highlights: • We constructed the neuronal function networks based on the recorded neurons. • We analyzed the two main complex network characteristics, namely, small-world structure and community structure. • NFNs which were constructed based on the recorded neurons in this study exhibit small-world properties. • Some NFNs have community structure characteristics.

  19. Analyzing topological characteristics of neuronal functional networks in the rat brain

    International Nuclear Information System (INIS)

    Lu, Hu; Yang, Shengtao; Song, Yuqing; Wei, Hui

    2014-01-01

    In this study, we recorded spike trains from brain cortical neurons of several behavioral rats in vivo by using multi-electrode recordings. An NFN was constructed in each trial, obtaining a total of 150 NFNs in this study. The topological characteristics of NFNs were analyzed by using the two most important characteristics of complex networks, namely, small-world structure and community structure. We found that the small-world properties exist in different NFNs constructed in this study. Modular function Q was used to determine the existence of community structure in NFNs, through which we found that community-structure characteristics, which are related to recorded spike train data sets, are more evident in the Y-maze task than in the DM-GM task. Our results can also be used to analyze further the relationship between small-world characteristics and the cognitive behavioral responses of rats. - Highlights: • We constructed the neuronal function networks based on the recorded neurons. • We analyzed the two main complex network characteristics, namely, small-world structure and community structure. • NFNs which were constructed based on the recorded neurons in this study exhibit small-world properties. • Some NFNs have community structure characteristics

  20. Preemptive, but not reactive, spinal cord stimulation mitigates transient ischemia-induced myocardial infarction via cardiac adrenergic neurons

    NARCIS (Netherlands)

    Southerland, E. M.; Milhorn, D. M.; Foreman, R. D.; Linderoth, B.; DeJongste, M. J. L.; Armour, J. A.; Subramanian, V.; Singh, M.; Singh, K.; Ardell, J. L.

    2007-01-01

    Our objective was to determine whether electrical neuromodulation using spinal cord stimulation ( SCS) mitigates transient ischemia-induced ventricular infarction and, if so, whether adrenergic neurons are involved in such cardioprotection. The hearts of anesthetized rabbits, subjected to 30 min of

  1. Prions, From Structure to Epigenetics and Neuronal Functions

    Science.gov (United States)

    Lindquist, Susan

    2012-02-01

    Prions are a unique type of protein that can misfold and convert other proteins to the same shape. The well-characterized yeast prion [PSI+] is formed from an inactive amyloid fiber conformation of the translation-termination factor, Sup35. This altered conformation is passed from mother cells to daughters, acting as a template to perpetuate the prion state and providing a mechanism of protein-based inheritance. We employed a variety of methods to determine the structure of Sup35 amyloid fibrils. First, using fluorescent tags and cross-linking we identified specific segments of the protein monomer that form intermolecular contacts in a ``Head-to-Head,'' ``Tail-to-Tail'' fashion while a central region forms intramolecular contacts. Then, using peptide arrays we mapped the region responsible for the prion transmission barrier between two different yeast species. We have also used optical tweezers to reveal that the non-covalent intermolecular contacts between monomers are unusually strong, and maintain fibril integrity even under forces that partially unfold individual monomers and extend fibril length. Based on the handful of known yeast prion proteins we predicted sequences that could be responsible for prion-like amyloid folding. Our screen identified 19 new candidate prions, whose protein-folding properties and diverse cellular functions we have characterized using a combination of genetic and biochemical techniques. Prion-driven phenotypic diversity increases under stress, and can be amplified by the dynamic maturation of prion-initiating states. These qualities allow prions to act as ``bet-hedging'' devices that facilitate the adaptation of yeast to stressful environments, and might speed the evolution of new traits. Together with Kandel and Si, we have also found that a regulatory protein that plays an important role in synaptic plasticity behaves as a prion in yeast. Cytoplasmic polyAdenylation element binding protein, CPEB, maintains synapses by promoting

  2. Roles of Fukutin, the Gene Responsible for Fukuyama-Type Congenital Muscular Dystrophy, in Neurons: Possible Involvement in Synaptic Function and Neuronal Migration

    International Nuclear Information System (INIS)

    Hiroi, Atsuko; Yamamoto, Tomoko; Shibata, Noriyuki; Osawa, Makiko; Kobayashi, Makio

    2011-01-01

    Fukutin is a gene responsible for Fukuyama-type congenital muscular dystrophy (FCMD), accompanying ocular and brain malformations represented by cobblestone lissencephaly. Fukutin is related to basement membrane formation via the glycosylation of α-dystoglycan (α-DG), and astrocytes play a crucial role in the pathogenesis of the brain lesion. On the other hand, its precise function in neurons is unknown. In this experiment, the roles of fukutin in mature and immature neurons were examined using brains from control subjects and FCMD patients and cultured neuronal cell lines. In quantitative PCR, the expression level of fukutin looked different depending on the region of the brain examined. A similar tendency in DG expression appears to indicate a relation between fukutin and α-DG in mature neurons. An increase of DG mRNA and core α-DG in the FCMD cerebrum also supports the relation. In immunohistochemistry, dot-like positive reactions for VIA4-1, one of the antibodies detecting the glycosylated α-DG, in Purkinje cells suggest that fukutin is related to at least a post-synaptic function via the glycosylation of α-DG. As for immature neurons, VIA4-1 was predominantly positive in cells before and during migration with expression of fukutin, which suggest a participation of fukutin in neuronal migration via the glycosylation of α-DG. Moreover, fukutin may prevent neuronal differentiation, because its expression was significantly lower in the adult cerebrum and in differentiated cultured cells. A knockdown of fukutin was considered to induce differentiation in cultured cells. Fukutin seems to be necessary to keep migrating neurons immature during migration, and also to support migration via α-DG

  3. Nuclear organization in the spinal cord depends on motor neuron lamination orchestrated by catenin and afadin function

    OpenAIRE

    Dewitz, C.; Pimpinella, S.; Hackel, P.; Akalin, A.; Jessell, T.M.; Zampieri, N.

    2018-01-01

    Motor neurons in the spinal cord are found grouped in nuclear structures termed pools, whose position is precisely orchestrated during development. Despite the emerging role of pool organization in the assembly of spinal circuits, little is known about the morphogenetic programs underlying the patterning of motor neuron subtypes. We applied three-dimensional analysis of motor neuron position to reveal the roles and contributions of cell adhesive function by inactivating N-cadherin, catenin, a...

  4. Extrasynaptic neurotransmission in the modulation of brain function. Focus on the striatal neuronal-glial networks

    Directory of Open Access Journals (Sweden)

    Kjell eFuxe

    2012-06-01

    Full Text Available Extrasynaptic neurotransmission is an important short distance form of volume transmission (VT and describes the extracellular diffusion of transmitters and modulators after synaptic spillover or extrasynaptic release in the local circuit regions binding to and activating mainly extrasynaptic neuronal and glial receptors in the neuroglial networks of the brain. Receptor-receptor interactions in G protein-coupled receptor (GPCR heteromers play a major role, on dendritic spines and nerve terminals including glutamate synapses, in the integrative processes of the extrasynaptic signaling. Heteromeric complexes between GPCR and ion-channel receptors play a special role in the integration of the synaptic and extrasynaptic signals. Changes in extracellular concentrations of the classical synaptic neurotransmitters glutamate and GABA found with microdialysis is likely an expression of the activity of the neuron-astrocyte unit of the brain and can be used as an index of VT-mediated actions of these two neurotransmitters in the brain. Thus, the activity of neurons may be functionally linked to the activity of astrocytes, which may release glutamate and GABA to the extracellular space where extrasynaptic glutamate and GABA receptors do exist. Wiring transmission (WT and VT are fundamental properties of all neurons of the CNS but the balance between WT and VT varies from one nerve cell population to the other. The focus is on the striatal cellular networks, and the WT and VT and their integration via receptor heteromers are described in the GABA projection neurons, the glutamate, dopamine, 5-hydroxytryptamine (5-HT and histamine striatal afferents, the cholinergic interneurons and different types of GABA interneurons. In addition, the role in these networks of VT signaling of the energy-dependent modulator adenosine and of endocannabinoids mainly formed in the striatal projection neurons will be underlined to understand the communication in the striatal

  5. Are Cardiac Autonomic Nervous System Activity and Perceived Stress Related to Functional Somatic Symptoms in Adolescents? The TRAILS Study

    NARCIS (Netherlands)

    Janssens, Karin A. M.; Riese, Harriette; Van Roon, Arie M.; Hunfeld, Joke A. M.; Groot, Paul F. C.; Oldehinkel, Albertine J.; Rosmalen, Judith G. M.

    2016-01-01

    Objective Stressors have been related to medically insufficiently explained or functional somatic symptoms (FSS). However, the underlying mechanism of this association is largely unclear. In the current study, we examined whether FSS are associated with different perceived stress and cardiac

  6. Effects of protein-calorie restriction on mechanical function of hypertrophied cardiac muscle

    Directory of Open Access Journals (Sweden)

    Antônio Carlos Cicogna

    1999-04-01

    Full Text Available OBJECTIVE: To assess the effect of food restriction (FR on hypertrophied cardiac muscle in spontaneously hypertensive rats (SHR. METHODS: Isolated papillary muscle preparations of the left ventricle (LV of 60-day-old SHR and of normotensive Wistar-Kyoto (WKY rats were studied. The rats were fed either an unrestricted diet or FR diet (50% of the intake of the control diet for 30 days. The mechanical function of the muscles was evaluated through monitoring isometric and isotonic contractions. RESULTS: FR caused: 1 reduction in the body weight and LV weight of SHR and WKY rats; 2 increase in the time to peak shortening and the time to peak developed tension (DT in the hypertrophied myocardium of the SHR; 3 diverging changes in the mechanical function of the normal cardiac muscles of WKY rats with reduction in maximum velocity of isotonic shortening and of the time for DT to decrease 50% of its maximum value, and increase of the resting tension and of the rate of tension decline. CONCLUSION: Short-term FR causes prolongation of the contraction time of hypertrophied muscles and paradoxal changes in mechanical performance of normal cardiac fibers, with worsening of the shortening indices and of the resting tension, and improvement of the isometric relaxation.

  7. Pulmonary function and health-related quality of life 1-year follow up after cardiac surgery.

    Science.gov (United States)

    Westerdahl, Elisabeth; Jonsson, Marcus; Emtner, Margareta

    2016-07-08

    Pulmonary function is severely reduced in the early period after cardiac surgery, and impairments have been described up to 4-6 months after surgery. Evaluation of pulmonary function in a longer perspective is lacking. In this prospective study pulmonary function and health-related quality of life were investigated 1 year after cardiac surgery. Pulmonary function measurements, health-related quality of life (SF-36), dyspnoea, subjective breathing and coughing ability and pain were evaluated before and 1 year after surgery in 150 patients undergoing coronary artery bypass grafting, valve surgery or combined surgery. One year after surgery the forced vital capacity and forced expiratory volume in 1 s were significantly decreased (by 4-5 %) compared to preoperative values (p < 0.05). Saturation of peripheral oxygen was unchanged 1 year postoperatively compared to baseline. A significantly improved health-related quality of life was found 1 year after surgery, with improvements in all eight aspects of SF-36 (p < 0.001). Sternotomy-related pain was low 1 year postoperatively at rest (median 0 [min-max; 0-7]), while taking a deep breath (0 [0-4]) and while coughing (0 [0-8]). A more pronounced decrease in pulmonary function was associated with dyspnoea limitations and impaired subjective breathing and coughing ability. One year after cardiac surgery static and dynamic lung function measurements were slightly decreased, while health-related quality of life was improved in comparison to preoperative values. Measured levels of pain were low and saturation of peripheral oxygen was same as preoperatively.

  8. Testosterone receptor blockade after trauma-hemorrhage improves cardiac and hepatic functions in males.

    Science.gov (United States)

    Remmers, D E; Wang, P; Cioffi, W G; Bland, K I; Chaudry, I H

    1997-12-01

    Although studies have shown that testosterone receptor blockade with flutamide after hemorrhage restores the depressed immune function, it remains unknown whether administration of flutamide following trauma and hemorrhage and resuscitation has any salutary effects on the depressed cardiovascular and hepatocellular functions. To study this, male rats underwent a laparotomy (representing trauma) and were then bled and maintained at a mean arterial pressure (MAP) of 40 mmHg until the animals could not maintain this pressure. Ringer lactate was given to maintain a MAP of 40 mmHg until 40% of the maximal shed blood volume was returned in the form of Ringer lactate. The rats were then resuscitated with four times the shed blood volume in the form of Ringer lactate over 60 min. Flutamide (25 mg/kg) or an equal volume of the vehicle propanediol was injected subcutaneously 15 min before the end of resuscitation. Various in vivo heart performance parameters (e.g., maximal rate of the pressure increase or decrease), cardiac output, and hepatocellular function (i.e., the maximum velocity and the overall efficiency of indocyanine green clearance) were determined at 20 h after resuscitation. Additionally, hepatic microvascular blood flow (HMBF) was determined using a laser Doppler flowmeter. The results indicate that left ventricular performance, cardiac output, HMBF, and hepatocellular function decreased significantly at 20 h after the completion of trauma, hemorrhage, and resuscitation. Administration of the testosterone receptor blocker flutamide, however, significantly improved cardiac performance, HMBF, and hepatocellular function. Thus flutamide appears to be a novel and useful adjunct for improving cardiovascular and hepatocellular functions in males following trauma and hemorrhagic shock.

  9. Relationship between myocardial T2* values and cardiac volumetric and functional parameters in β-thalassemia patients evaluated by cardiac magnetic resonance in association with serum ferritin levels

    Energy Technology Data Exchange (ETDEWEB)

    Liguori, Carlo, E-mail: c.liguori@unicampus.it [Department of Diagnostic Imaging, Campus Bio Medico University, via Alvaro del Portillo 200, 00128 Rome (Italy); Pitocco, Francesca, E-mail: f.pitocco@unicampus.it [Department of Diagnostic Imaging, Campus Bio Medico University, via Alvaro del Portillo 200, 00128 Rome (Italy); Di Giampietro, Ilenia, E-mail: i.digiampietro@unicampus.it [Department of Diagnostic Imaging, Campus Bio Medico University, via Alvaro del Portillo 200, 00128 Rome (Italy); Vivo, Aldo Eros de, E-mail: devivoeros@gmail.com [Department of Diagnostic Imaging, Campus Bio Medico University, via Alvaro del Portillo 200, 00128 Rome (Italy); Schena, Emiliano, E-mail: e.schena@unicampus.it [Unit of Measurements and Biomedical Instrumentation, Campus Bio Medico University, via Alvaro del Portillo 200, 00128 Rome (Italy); Cianciulli, Paolo, E-mail: CIANCIULLI.PAOLO@aslrmc.it [Thalassemia Unit, Ospedale Sant Eugenio, Piazzale dell’Umanesimo 10, 00143 Rome (Italy); Zobel, Bruno Beomonte, E-mail: b.zobel@unicampus.it [Department of Diagnostic Imaging, Campus Bio Medico University, via Alvaro del Portillo 200, 00128 Rome (Italy)

    2013-09-15

    Purpose: Myocardial T2* cardiovascular magnetic resonance provides a rapid and reproducible assessment of cardiac iron load in thalassemia patients. Although cardiac involvement is mainly characterized by left ventricular dysfunction caused by iron overload, little is known about right ventricular function. The aim of this study was to assess the relationship between T2* value in myocardium and left–right ventricular volumetric and functional parameters and to evaluate the existing associations between left–right ventricles volumetric and functional parameter, myocardial T2* values and blood ferritin levels. Materials and methods: A retrospective analysis of 208 patients with β-thalassemia major and thalassemia intermedia was performed (109 males and 99 females; mean age 37.7 ± 13 years; 143 thalassemia major, 65 thalassemia intermedia). Myocardial iron load was assessed by T2* measurements, and volumetric functions were analyzed using the steady state free precession sequence. Results: A significant correlation was observed between EFLV and T2* (p = 0.0001), EFRV and T2* (p = 0.0279). An inverse correlation was present between DVLV and T2* (p = 0.0468), SVLV and T2* (p = 0.0003), SVRV and T2* (p = 0.0001). There was no significant correlation between cardiac T2* and LV–RV mass indices. A significant correlation was observed between T2* and serum ferritin levels (p < 0.001) and between EFLV and serum ferritin (p < 0.05). Conclusion: Myocardial iron load assessed by T2* cardiac magnetic resonance is associated with deterioration in left–right ventricular function; this is more evident when T2* values fall below 14 ms. CMR appears to be a promising approach for cardiac risk evaluation in TM patients.

  10. Relationship between myocardial T2* values and cardiac volumetric and functional parameters in β-thalassemia patients evaluated by cardiac magnetic resonance in association with serum ferritin levels

    International Nuclear Information System (INIS)

    Liguori, Carlo; Pitocco, Francesca; Di Giampietro, Ilenia; Vivo, Aldo Eros de; Schena, Emiliano; Cianciulli, Paolo; Zobel, Bruno Beomonte

    2013-01-01

    Purpose: Myocardial T2* cardiovascular magnetic resonance provides a rapid and reproducible assessment of cardiac iron load in thalassemia patients. Although cardiac involvement is mainly characterized by left ventricular dysfunction caused by iron overload, little is known about right ventricular function. The aim of this study was to assess the relationship between T2* value in myocardium and left–right ventricular volumetric and functional parameters and to evaluate the existing associations between left–right ventricles volumetric and functional parameter, myocardial T2* values and blood ferritin levels. Materials and methods: A retrospective analysis of 208 patients with β-thalassemia major and thalassemia intermedia was performed (109 males and 99 females; mean age 37.7 ± 13 years; 143 thalassemia major, 65 thalassemia intermedia). Myocardial iron load was assessed by T2* measurements, and volumetric functions were analyzed using the steady state free precession sequence. Results: A significant correlation was observed between EFLV and T2* (p = 0.0001), EFRV and T2* (p = 0.0279). An inverse correlation was present between DVLV and T2* (p = 0.0468), SVLV and T2* (p = 0.0003), SVRV and T2* (p = 0.0001). There was no significant correlation between cardiac T2* and LV–RV mass indices. A significant correlation was observed between T2* and serum ferritin levels (p < 0.001) and between EFLV and serum ferritin (p < 0.05). Conclusion: Myocardial iron load assessed by T2* cardiac magnetic resonance is associated with deterioration in left–right ventricular function; this is more evident when T2* values fall below 14 ms. CMR appears to be a promising approach for cardiac risk evaluation in TM patients

  11. Can Functional Cardiac Age be Predicted from ECG in a Normal Healthy Population

    Science.gov (United States)

    Schlegel, Todd; Starc, Vito; Leban, Manja; Sinigoj, Petra; Vrhovec, Milos

    2011-01-01

    In a normal healthy population, we desired to determine the most age-dependent conventional and advanced ECG parameters. We hypothesized that changes in several ECG parameters might correlate with age and together reliably characterize the functional age of the heart. Methods: An initial study population of 313 apparently healthy subjects was ultimately reduced to 148 subjects (74 men, 84 women, in the range from 10 to 75 years of age) after exclusion criteria. In all subjects, ECG recordings (resting 5-minute 12-lead high frequency ECG) were evaluated via custom software programs to calculate up to 85 different conventional and advanced ECG parameters including beat-to-beat QT and RR variability, waveform complexity, and signal-averaged, high-frequency and spatial/spatiotemporal ECG parameters. The prediction of functional age was evaluated by multiple linear regression analysis using the best 5 univariate predictors. Results: Ignoring what were ultimately small differences between males and females, the functional age was found to be predicted (R2= 0.69, P ECGs, functional cardiac age can be estimated by multiple linear regression analysis of mostly advanced ECG results. Because some parameters in the regression formula, such as QTcorr, high frequency QRS amplitude and P-wave width also change with disease in the same direction as with increased age, increased functional age of the heart may reflect subtle age-related pathologies in cardiac electrical function that are usually hidden on conventional ECG.

  12. Intravital imaging of cardiac function at the single-cell level.

    Science.gov (United States)

    Aguirre, Aaron D; Vinegoni, Claudio; Sebas, Matt; Weissleder, Ralph

    2014-08-05

    Knowledge of cardiomyocyte biology is limited by the lack of methods to interrogate single-cell physiology in vivo. Here we show that contracting myocytes can indeed be imaged with optical microscopy at high temporal and spatial resolution in the beating murine heart, allowing visualization of individual sarcomeres and measurement of the single cardiomyocyte contractile cycle. Collectively, this has been enabled by efficient tissue stabilization, a prospective real-time cardiac gating approach, an image processing algorithm for motion-artifact-free imaging throughout the cardiac cycle, and a fluorescent membrane staining protocol. Quantification of cardiomyocyte contractile function in vivo opens many possibilities for investigating myocardial disease and therapeutic intervention at the cellular level.

  13. Effects of cigarette smoking on cardiac autonomic function during dynamic exercise.

    Science.gov (United States)

    Mendonca, Goncalo V; Pereira, Fernando D; Fernhall, Bo

    2011-06-01

    The purpose of this study was to investigate the acute effect of cigarette smoking on cardiac autonomic function in young adult smokers during dynamic exercise. Fourteen healthy young smokers (21.4 ± 3.4 years) performed peak and submaximal exercise protocols under control and smoking conditions. Resting and submaximal beat-to-beat R-R series were recorded and spectrally decomposed using the fast Fourier transformation. Smoking resulted in a significant decrease in work time, VO(2peak) and peak O(2) pulse (P exercise after smoking (P smoking, both at rest and during exercise (P smoking (P smoking, but only at rest (P smoking is accompanied by acute changes in heart rate spectral components both at rest and during exercise. Therefore, the cardiac autonomic control is altered by smoking not only at rest, but also during exercise, resulting in reduced vagal modulation and increased sympathetic dominance.

  14. Functional Near-Infrared Fluorescence Imaging for Cardiac Surgery and Targeted Gene Therapy

    Directory of Open Access Journals (Sweden)

    Akira Nakayama

    2002-10-01

    Full Text Available Cardiac revascularization is presently performed without realtime visual assessment of myocardial blood flow or perfusion. Moreover, gene therapy of the heart cannot, at present, be directed to specific territories at risk for myocardial infarction. We have developed a surgical imaging system that exploits the low autofluorescence, deep tissue penetration, low tissue scatter, and invisibility of near-infrared (NIR fluorescent light. By completely isolating visible and NIR light paths, one is able to visualize, simultaneously, the anatomy and/or function of the heart, or any desired tissue. In rat model systems, we demonstrate that the heptamethine indocyanine-type NIR fluorophores IR-786 and the carboxylic acid form of IRDye78 can be injected intravenously in the living animal to provide real-time visual assessment of myocardial blood flow or perfusion intraoperatively. This imaging system may prove useful for the refinement of revascularization techniques, and for the administration of cardiac gene therapy.

  15. Hyperpolarized metabolic MR in the study of cardiac function and disease

    DEFF Research Database (Denmark)

    Lauritzen, M. H.; Søgaard, L. V.; Madsen, Pia Lisbeth

    2014-01-01

    Several diseases of the heart have been linked to an insufficient ability to generate enough energy (ATP) to sustain proper heart function. Hyperpolarized magnetic resonance (MR) is a novel technique that can visualize and quantify myocardial energy metabolism. Hyperpolarization enhances the MR...... signal from a biological molecule of interest by more than 10,000 times, making it possible to measure its cellular uptake and conversion in specific enzymatic pathways in real time. We review the role of hyperpolarized MR in identifying changes in cardiac metabolism in vivo, and present the extensive...... literature on hyperpolarized pyruvate that has been used to characterize cardiac disease in various in vivo models, such as myocardial ischemia, hypertension, diabetes, hyperthyroidism and heart failure. The technical aspects of the technique are presented as well as the challenges of translating...

  16. Efficacy of cardiac resynchronization with defibrillator insertion in patients undergone coronary artery bypass graft: A cohort study of cardiac function

    Directory of Open Access Journals (Sweden)

    Reza Karbasi Afshar

    2015-01-01

    Full Text Available Introduction: Cardiac resynchronization therapy (CRT is a proven therapeutic method in selected patients with heart failure and systolic dysfunction which increases left ventricular function and patient survival. We designed a study that included patients undergoing coronary artery bypass graft (CABG, with and without CRT-defibrillator (CRT-D inserting and then measured its effects on these two groups. Patients and Methods: Between 2010 and 2013, we conducted a prospective cohort study on 100 coronary artery disease patients where candidate for CABG. Then based on the receiving CRT-D, the patients were categorized in two groups; Group 1 ( n = 48, with CRT-D insertion before CABG and Group 2 ( n = 52 without receiving CRT-D. Thereafter both of these groups were followed-up at 1-3 months after CABG for mortality, hospitalization, atrial fibrillation (AF, echocardiographic assessment, and New York Heart Association (NYHA class level. Results: The mean age of participants in Group 1 (48 male and in Group 2 (52 male was 58 ± 13 and 57 ± 12 respectively. Difference between Groups 1 and 2 in cases of mean left ventricular ejection fraction (LVEF changes and NYHA class level was significant ( P > 0.05. Hospitalization ( P = 0.008, mortality rate ( P = 0.007, and AF were significantly different between these two groups. Conclusions: The results showed that the increase in LVEF and patient′s improvement according to NYHA-class was significant in the first group, and readmission, mortality rate and AF was increased significantly in the second group.

  17. EEG study of the mirror neuron system in children with high functioning autism.

    Science.gov (United States)

    Raymaekers, Ruth; Wiersema, Jan Roelf; Roeyers, Herbert

    2009-12-22

    Individuals with Autism Spectrum Disorder (ASD) are characterised by an impaired imitation, thought to be critical for early affective, social and communicative development. One neurological system proposed to underlie this function is the mirror neuron system (MNS) and previous research has suggested a dysfunctional MNS in ASD. The EEG mu frequency, more precisely the reduction of the mu power, is considered to be an index for mirror neuron functioning. In this work, EEG registrations are used to evaluate the mirror neuron functioning of twenty children with high functioning autism (HFA) between 8 and 13 years. Their mu suppression to self-executed and observed movement is compared to typically developing peers and related to age, intelligence and symptom severity. Both groups show significant mu suppression to both self and observed hand movements. No group differences are found in either condition. These results do not support the hypothesis that HFA is associated with a dysfunctional MNS. The discrepancy with previous research is discussed in light of the heterogeneity of the ASD population.

  18. Evaluation of cardiac morphology and function in mitral stenosis using CT

    Energy Technology Data Exchange (ETDEWEB)

    Ohnishi, Masaki [Chiba Univ. (Japan). School of Medicine

    1992-11-01

    The purpose of this study was to evaluate cardiac morphology and function in patients with mitral stenosis (MS). The subjects consisted of 96 patients (23 males and 73 females) with MS who underwent plain and contrast-enhanced CT. Follow-up examinations were performed at least twice in 42 patients, including 18 who were examined before and after surgery. The volume of each cardiac chamber was calculated by Simpson's rule and was divided by body surface area (BSA). The average left atrial (LA) volume was 171[+-]80 cm[sup 3]/m[sup 2] BSA in the 96 MS patients, and 46[+-]10 cm[sup 3]/m[sup 2] BSA in normal control subjects. Atrial fibrillation (Af) was present in 61 patients (64%), and left atrial thrombi were detected in 15 (25%) of them. LA volume increased by 16% in 24 patients without surgery during a mean follow-up period of 4.1 years. The LA tended to enlarge more in the patients with a smaller mitral valve area, a larger LA volume at the first examination, or Af. In 18 patients, after open surgery or percutaneous transvenous mitral commissurotomy, pulmonary CT values decreased significantly as a result of the improvement of pulmonary congestion. LA and RA volume decreased significantly and LV volume increased after surgery. It was concluded that CT was useful for evaluating cardiac function and morphological changes, not only by detecting mitral valve calcification and LA thrombi but also by measuring cardiac volume and pulmonary CT values. (author).

  19. Immune function surveillance: association with rejection, infection and cardiac allograft vasculopathy.

    Science.gov (United States)

    Heikal, N M; Bader, F M; Martins, T B; Pavlov, I Y; Wilson, A R; Barakat, M; Stehlik, J; Kfoury, A G; Gilbert, E M; Delgado, J C; Hill, H R

    2013-01-01

    Rejection, cardiac allograft vasculopathy (CAV), and infection are significant causes of mortality in heart transplantation recipients. Assessing the immune status of a particular patient remains challenging. Although endomyocardial biopsy (EMB) and angiography are effective for the identification of rejection and CAV, respectively, these are expensive, invasive, and may have numerous complications. The aim of this study was to evaluate the immune function and assess its utility in predicting rejection, CAV, and infection in heart transplantation recipients. We prospectively obtained samples at the time of routine EMB and when clinically indicated for measurement of the ImmuKnow assay (IM), 12 cytokines and soluble CD30 (sCD30). EMB specimens were evaluated for acute cellular rejection, and antibody-mediated rejection (AMR). CAV was diagnosed by the development of angiographic coronary artery disease. Infectious episodes occurring during the next 30 days after testing were identified by the presence of positive bacterial or fungal cultures and/or viremia that prompted treatment with antimicrobials. We collected 162 samples from 56 cardiac transplant recipients. There were 31 infection episodes, 7 AMR, and 4 CAV cases. The average IM value was significantly lower during infection, (P = .04). Soluble CD30 concentrations showed significantly positive correlation with infection episodes, (P = .001). Significant positive correlation was observed between interleukin-5(IL-5) and AMR episodes (P = .008). Tumor necrosis factor-α and IL-8 showed significant positive correlation with CAV (P = .001). Immune function monitoring appears promising in predicting rejection, CAV, and infection in cardiac transplantation recipients. This approach may help in more individualized immunosuppression and it may also minimize unnecessary EMBs and cardiac angiographies. Published by Elsevier Inc.

  20. Neuraminidases 3 and 4 regulate neuronal function by catabolizing brain gangliosides.

    Science.gov (United States)

    Pan, Xuefang; De Aragão, Camila De Britto Pará; Velasco-Martin, Juan P; Priestman, David A; Wu, Harry Y; Takahashi, Kohta; Yamaguchi, Kazunori; Sturiale, Luisella; Garozzo, Domenico; Platt, Frances M; Lamarche-Vane, Nathalie; Morales, Carlos R; Miyagi, Taeko; Pshezhetsky, Alexey V

    2017-08-01

    Gangliosides (sialylated glycolipids) play an essential role in the CNS by regulating recognition and signaling in neurons. Metabolic blocks in processing and catabolism of gangliosides result in the development of severe neurologic disorders, including gangliosidoses manifesting with neurodegeneration and neuroinflammation. We demonstrate that 2 mammalian enzymes, neuraminidases 3 and 4, play important roles in catabolic processing of brain gangliosides by cleaving terminal sialic acid residues in their glycan chains. In neuraminidase 3 and 4 double-knockout mice, G M3 ganglioside is stored in microglia, vascular pericytes, and neurons, causing micro- and astrogliosis, neuroinflammation, accumulation of lipofuscin bodies, and memory loss, whereas their cortical and hippocampal neurons have lower rate of neuritogenesis in vitro Double-knockout mice also have reduced levels of G M1 ganglioside and myelin in neuronal axons. Furthermore, neuraminidase 3 deficiency drastically increased storage of G M2 in the brain tissues of an asymptomatic mouse model of Tay-Sachs disease, a severe human gangliosidosis, indicating that this enzyme is responsible for the metabolic bypass of β-hexosaminidase A deficiency. Together, our results provide the first in vivo evidence that neuraminidases 3 and 4 have important roles in CNS function by catabolizing gangliosides and preventing their storage in lipofuscin bodies.-Pan, X., De Britto Pará De Aragão, C., Velasco-Martin, J. P., Priestman, D. A., Wu, H. Y., Takahashi, K., Yamaguchi, K., Sturiale, L., Garozzo, D., Platt, F. M., Lamarche-Vane, N., Morales, C. R., Miyagi, T., Pshezhetsky, A. V. Neuraminidases 3 and 4 regulate neuronal function by catabolizing brain gangliosides. © FASEB.

  1. Sim1 Neurons Are Sufficient for MC4R-Mediated Sexual Function in Male Mice.

    Science.gov (United States)

    Semple, Erin; Hill, Jennifer W

    2018-01-01

    Sexual dysfunction is a poorly understood condition that affects up to one-third of men around the world. Existing treatments that target the periphery do not work for all men. Previous studies have shown that central melanocortins, which are released by pro-opiomelanocortin neurons in the arcuate nucleus of the hypothalamus, can lead to male erection and increased libido. Several studies specifically implicate the melanocortin 4 receptor (MC4R) in the central control of sexual function, but the specific neural circuitry involved is unknown. We hypothesized that single-minded homolog 1 (Sim1) neurons play an important role in the melanocortin-mediated regulation of male sexual behavior. To test this hypothesis, we examined the sexual behavior of mice expressing MC4R only on Sim1-positive neurons (tbMC4Rsim1 mice) in comparison with tbMC4R null mice and wild-type controls. In tbMC4Rsim1 mice, MC4R reexpression was found in the medial amygdala and paraventricular nucleus of the hypothalamus. These mice were paired with sexually experienced females, and their sexual function and behavior was scored based on mounting, intromission, and ejaculation. tbMC4R null mice showed a longer latency to mount, a reduced intromission efficiency, and an inability to reach ejaculation. Expression of MC4R only on Sim1 neurons reversed the sexual deficits seen in tbMC4R null mice. This study implicates melanocortin signaling via the MC4R on Sim1 neurons in the central control of male sexual behavior. Copyright © 2018 Endocrine Society.

  2. Chronic resuscitation after trauma-hemorrhage and acute fluid replacement improves hepatocellular function and cardiac output.

    Science.gov (United States)

    Remmers, D E; Wang, P; Cioffi, W G; Bland, K I; Chaudry, I H

    1998-01-01

    To determine whether prolonged (chronic) resuscitation has any beneficial effects on cardiac output and hepatocellular function after trauma-hemorrhage and acute fluid replacement. Acute fluid resuscitation after trauma-hemorrhage restores but does not maintain the depressed hepatocellular function and cardiac output. Male Sprague-Dawley rats underwent a 5-cm laparotomy (i.e., trauma was induced) and were bled to and maintained at a mean arterial pressure of 40 mmHg until 40% of maximal bleed-out volume was returned in the form of Ringer's lactate (RL). The animals were acutely resuscitated with RL using 4 times the volume of maximum bleed-out over 60 minutes, followed by chronic resuscitation of 0, 5, or 10 mL/kg/hr RL for 20 hours. Hepatocellular function was determined by an in vivo indocyanine green clearance technique. Hepatic microvascular blood flow was assessed by laser Doppler flowmetry. Plasma levels of interleukin-6 (IL-6) were determined by bioassay. Chronic resuscitation with 5 mL/kg/hr RL, but not with 0 or 10 mL/kg/hr RL, restored cardiac output, hepatocellular function, and hepatic microvascular blood flow at 20 hours after hemorrhage. The regimen above also reduced plasma IL-6 levels. Because chronic resuscitation with 5 mL/kg/hr RL after trauma-hemorrhage and acute fluid replacement restored hepatocellular function and hepatic microvascular blood flow and decreased plasma levels of IL-6, we propose that chronic fluid resuscitation in addition to acute fluid replacement should be routinely used in experimental studies of trauma-hemorrhage.

  3. Chronic mitral regurgitation detected on cardiac MDCT: differentiation between functional and valvular aetiologies.

    LENUS (Irish Health Repository)

    Killeen, Ronan P

    2012-02-01

    OBJECTIVE: To determine whether cardiac computed tomography (MDCT) can differentiate between functional and valvular aetiologies of chronic mitral regurgitation (MR) compared with echocardiography (TTE). METHODS: Twenty-seven patients with functional or valvular MR diagnosed by TTE and 19 controls prospectively underwent cardiac MDCT. The morphological appearance of the mitral valve (MV) leaflets, MV geometry, MV leaflet angle, left ventricular (LV) sphericity and global\\/regional wall motion were analysed. The coronary arteries were evaluated for obstructive atherosclerosis. RESULTS: All control and MR cases were correctly identified by MDCT. Significant differences were detected between valvular and control groups for anterior leaflet length (30 +\\/- 7 mm vs. 22 +\\/- 4 mm, P < 0.02) and thickness (3.0 +\\/- 1 mm vs. 2.2 +\\/- 1 mm, P < 0.01). High-grade coronary stenosis was detected in all patients with functional MR compared with no controls (P < 0.001). Significant differences in those with\\/without MV prolapse were detected in MV tent area (-1.0 +\\/- 0.6 mm vs. 1.3 +\\/- 0.9 mm, P < 0.0001) and MV tent height (-0.7 +\\/- 0.3 mm vs. 0.8 +\\/- 0.8 mm, P < 0.0001). Posterior leaflet angle was significantly greater for functional MR (37.9 +\\/- 19.1 degrees vs. 22.9 +\\/- 14 degrees , P < 0.018) and less for valvular MR (0.6 +\\/- 35.5 degrees vs. 22.9 +\\/- 14 degrees, P < 0.017). Sensitivity, specificity, and positive and negative predictive values of MDCT were 100%, 95%, 96% and 100%. CONCLUSION: Cardiac MDCT allows the differentiation between functional and valvular causes of MR.

  4. Prediction of cardiac sympathetic nerve activity and cardiac functional outcome after treatment in patients with dilated cardiomyopathy. Examination using dobutamine gated blood pool scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Kasama, Shu; Toyama, Takuji; Iwasaki, Tsutomu; Suzuki, Tadashi [Gunma Univ., Maebashi (Japan). School of Medicine; Hoshizaki, Hiroshi; Oshima, Shigeru; Taniguchi, Koichi; Nagai, Ryozo

    2000-07-01

    This study evaluated whether dobutamine gated blood pool scintigraphy can predict improvement of cardiac sympathetic nerve activity and cardiac function. Sixteen patients (10 men and 6 women, mean age 59{+-}13 years) with dilated cardiomyopathy underwent dobutamine gated blood pool scintigraphy to measure left ventricular ejection fraction (LVEF) using tracer at 0, 5, 10 and 15 {mu}g/kg/min before treatment. Patients were divided into good responders (LVEF increase {>=}15%) 8 patients (GR Group) and poor responders (LVEF increase <15%) 8 patients (PR Group) after treatment with {beta}-blocker or amiodarone with a background treatment of digitalis, diuretics and angiotensin converting enzyme inhibitor. I-123 metaiodobenzylguanidine (MIBG) imaging to evaluate cardiac sympathetic nerve activity and echocardiography were performed before and at one year after treatment. MIBG imaging was obtained 4 hours after tracer injection, and the heart/mediastinum count ratio (H/M ratio) calculated from the anterior planar image and the total defect score (TDS) from the single photon emission computed tomography image. LVEF and left ventricular endo-diastolic dimension (LVDd) were measured by echocardiography and New York Heart Association (NYHA) functional class was evaluated. The GR Group showed TDS decreased from 28{+-}6 to 17{+-}12 (p<0.05), H/M ratio increased from 1.79{+-}0.26 to 2.07{+-}0.32 (p<0.05), LVEF increased from 29{+-}8% to 48{+-}10% (p<0.01), and LVDd decreased from 65{+-}4 mm to 58{+-}5 mm (p<0.05). In contrast, the PR group showed no significant changes in TDS. H/M ratio, LVEF and LVDd. NYHA functional class improved in both groups. The improvement was better in the GR Group than in the PR group. Dobutamine gated blood pool scintigraphy is useful to predict the improvement of the cardiac sympathetic nerve activity and cardiac function, and symptoms after treatment in patients with dilated cardiomyopathy. (author)

  5. Intrinsic electrical properties of mammalian neurons and CNS function: a historical perspective

    Science.gov (United States)

    Llinás, Rodolfo R.

    2014-01-01

    This brief review summarizes work done in mammalian neuroscience concerning the intrinsic electrophysiological properties of four neuronal types; Cerebellar Purkinje cells, inferior olivary cells, thalamic cells, and some cortical interneurons. It is a personal perspective addressing an interesting time in neuroscience when the reflex view of brain function, as the paradigm to understand global neuroscience, began to be modified toward one in which sensory input modulates rather than dictates brain function. The perspective of the paper is not a comprehensive description of the intrinsic electrical properties of all nerve cells but rather addresses a set of cell types that provide indicative examples of mechanisms that modulate brain function. PMID:25408634

  6. INTRINSIC ELECTRICAL PROPERTIES OF MAMMALIAN NEURONS AND CNS FUNCTION: A HISTORICAL PERSPECTIVE

    Directory of Open Access Journals (Sweden)

    Rodolfo R Llinas

    2014-11-01

    Full Text Available This brief review summarizes work done in mammalian neuroscience concerning the intrinsic electrophysiological properties of four neuronal types; Cerebellar Purkinje cells, inferior olivary cells, thalamic cells, and some cortical interneurons. It is a personal perspective addressing an interesting time in neuroscience when the reflex view of brain function, as the paradigm to understand global neuroscience, began to be modified towards one in which sensory input modulates rather than dictates brain function. The perspective of the paper is not a comprehensive description of the intrinsic electrical properties of all nerve cells but rather addresses a set of cell types that provide indicative examples of mechanisms that modulate brain function.

  7. Von Economo Neurons and Fork Cells: A Neurochemical Signature Linked to Monoaminergic Function.

    Science.gov (United States)

    Dijkstra, Anke A; Lin, Li-Chun; Nana, Alissa L; Gaus, Stephanie E; Seeley, William W

    2018-01-01

    The human anterior cingulate and frontoinsular cortices are distinguished by 2 unique Layer 5 neuronal morphotypes, the von Economo neurons (VENs) and fork cells, whose biological identity remains mysterious. Insights could impact research on diverse neuropsychiatric diseases to which these cells have been linked. Here, we leveraged the Allen Brain Atlas to evaluate mRNA expression of 176 neurotransmitter-related genes and identified vesicular monoamine transporter 2 (VMAT2), gamma-aminobutyric acid (GABA) receptor subunit θ (GABRQ), and adrenoreceptor α-1A (ADRA1A) expression in human VENs, fork cells, and a minority of neighboring Layer 5 neurons. We confirmed these results using immunohistochemistry or in situ hybridization. VMAT2 and GABRQ expression was absent in mouse cerebral cortex. Although VMAT2 is known to package monoamines into synaptic vesicles, in VENs and fork cells its expression occurs in the absence of monoamine-synthesizing enzymes or reuptake transporters. Thus, VENs and fork cells may possess a novel, uncharacterized mode of cortical monoaminergic function that distinguishes them from most other mammalian Layer 5 neurons. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  8. Function of a fly motion-sensitive neuron matches eye movements during free flight.

    Directory of Open Access Journals (Sweden)

    Roland Kern

    2005-06-01

    Full Text Available Sensing is often implicitly assumed to be the passive acquisition of information. However, part of the sensory information is generated actively when animals move. For instance, humans shift their gaze actively in a sequence of saccades towards interesting locations in a scene. Likewise, many insects shift their gaze by saccadic turns of body and head, keeping their gaze fixed between saccades. Here we employ a novel panoramic virtual reality stimulator and show that motion computation in a blowfly visual interneuron is tuned to make efficient use of the characteristic dynamics of retinal image flow. The neuron is able to extract information about the spatial layout of the environment by utilizing intervals of stable vision resulting from the saccadic viewing strategy. The extraction is possible because the retinal image flow evoked by translation, containing information about object distances, is confined to low frequencies. This flow component can be derived from the total optic flow between saccades because the residual intersaccadic head rotations are small and encoded at higher frequencies. Information about the spatial layout of the environment can thus be extracted by the neuron in a computationally parsimonious way. These results on neuronal function based on naturalistic, behaviourally generated optic flow are in stark contrast to conclusions based on conventional visual stimuli that the neuron primarily represents a detector for yaw rotations of the animal.

  9. Right and left ventricular cardiac function in a developed world population with human immunodeficiency virus studied with radionuclide ventriculography

    DEFF Research Database (Denmark)

    Lebech, Anne-Mette; Gerstoft, Jan; Hesse, Birger

    2004-01-01

    . No correlations were found between reduced cardiac function and levels of the 3 peptides measured. CONCLUSIONS: No major dysfunction of the left ventricle is present in a developed world HIV population. However, a small but significant part of this population has modestly reduced right-sided systolic function.......-associated morbidity and mortality rates. Accordingly, the prevalence of HIV-associated cardiac dysfunction may also have changed. The aim of the study was to establish the prevalence of right- and left-sided cardiac dysfunction in a Danish HIV population, most of whom were undergoing HAART, with radionuclide...... ventricular ejection fraction and 6 (7%) had a reduced right ventricle ejection fraction (0.35-0.42) compared with reference values from the age- and sex-matched reference population. Patients with HIV and reduced cardiac function did not differ in the duration of HIV, CD4 count, CD4 nadir, or HIV RNA load...

  10. Muscle-Derived GDNF: A Gene Therapeutic Approach for Preserving Motor Neuron Function in ALS

    Science.gov (United States)

    2015-08-01

    other disease monitoring strategies ( Beam walking , Electrical impedance myography (EIM) and MRI) were not performed. We considered that the multiple...core: Beam walking and data analysis performed by Svendsen lab staff • Reagents and supplies were not all purchased • Reduced experimental load...function has been shown in acute models of motor neuron injury and in transgenic mouse models of ALS using various delivery strategies by a number

  11. Arrested neuronal proliferation and impaired hippocampal function following fractionated brain irradiation in the adult rat

    DEFF Research Database (Denmark)

    Madsen, Torsten Meldgaard; Kristjansen, P.E.G.; Bolwig, Tom Gert

    2003-01-01

    irradiation blocked the formation of new neurons in the dentate gyrus of the hippocampus. At different time points after the termination of the irradiation procedure, the animals were tested in two tests of short-term memory that differ with respect to their dependence on hippocampal function. Eight and 21...... that blocked neurogenesis contributes to the reported deleterious side effects of this treatment, consisting of memory impairment, dysphoria and lethargy....

  12. Intrinsic electrical properties of mammalian neurons and CNS function: a historical perspective

    OpenAIRE

    Llinás, Rodolfo R.

    2014-01-01

    This brief review summarizes work done in mammalian neuroscience concerning the intrinsic electrophysiological properties of four neuronal types; Cerebellar Purkinje cells, inferior olivary cells, thalamic cells, and some cortical interneurons. It is a personal perspective addressing an interesting time in neuroscience when the reflex view of brain function, as the paradigm to understand global neuroscience, began to be modified towards one in which sensory input modulates rather than dictate...

  13. Absence of alsin function leads to corticospinal motor neuron vulnerability via novel disease mechanisms.

    Science.gov (United States)

    Gautam, Mukesh; Jara, Javier H; Sekerkova, Gabriella; Yasvoina, Marina V; Martina, Marco; Özdinler, P Hande

    2016-03-15

    Mutations in the ALS2 gene result in early-onset amyotrophic lateral sclerosis, infantile-onset ascending hereditary spastic paraplegia and juvenile primary lateral sclerosis, suggesting prominent upper motor neuron involvement. However, the importance of alsin function for corticospinal motor neuron (CSMN) health and stability remains unknown. To date, four separate alsin knockout (Alsin(KO)) mouse models have been generated, and despite hopes of mimicking human pathology, none displayed profound motor function defects. This, however, does not rule out the possibility of neuronal defects within CSMN, which is not easy to detect in these mice. Detailed cellular analysis of CSMN has been hampered due to their limited numbers and the complex and heterogeneous structure of the cerebral cortex. In an effort to visualize CSMN in vivo and to investigate precise aspects of neuronal abnormalities in the absence of alsin function, we generated Alsin(KO)-UeGFP mice, by crossing Alsin(KO) and UCHL1-eGFP mice, a CSMN reporter line. We find that CSMN display vacuolated apical dendrites with increased autophagy, shrinkage of soma size and axonal pathology even in the pons region. Immunocytochemistry coupled with electron microscopy reveal that alsin is important for maintaining cellular cytoarchitecture and integrity of cellular organelles. In its absence, CSMN displays selective defects both in mitochondria and Golgi apparatus. UCHL1-eGFP mice help understand the underlying cellular factors that lead to CSMN vulnerability in diseases, and our findings reveal unique importance of alsin function for CSMN health and stability. © The Author 2016. Published by Oxford University Press.

  14. Differential activation of an identified motor neuron and neuromodulation provide Aplysia's retractor muscle an additional function.

    Science.gov (United States)

    McManus, Jeffrey M; Lu, Hui; Cullins, Miranda J; Chiel, Hillel J

    2014-08-15

    To survive, animals must use the same peripheral structures to perform a variety of tasks. How does a nervous system employ one muscle to perform multiple functions? We addressed this question through work on the I3 jaw muscle of the marine mollusk Aplysia californica's feeding system. This muscle mediates retraction of Aplysia's food grasper in multiple feeding responses and is innervated by a pool of identified neurons that activate different muscle regions. One I3 motor neuron, B38, is active in the protraction phase, rather than the retraction phase, suggesting the muscle has an additional function. We used intracellular, extracellular, and muscle force recordings in several in vitro preparations as well as recordings of nerve and muscle activity from intact, behaving animals to characterize B38's activation of the muscle and its activity in different behavior types. We show that B38 specifically activates the anterior region of I3 and is specifically recruited during one behavior, swallowing. The function of this protraction-phase jaw muscle contraction is to hold food; thus the I3 muscle has an additional function beyond mediating retraction. We additionally show that B38's typical activity during in vivo swallowing is insufficient to generate force in an unmodulated muscle and that intrinsic and extrinsic modulation shift the force-frequency relationship to allow contraction. Using methods that traverse levels from individual neuron to muscle to intact animal, we show how regional muscle activation, differential motor neuron recruitment, and neuromodulation are key components in Aplysia's generation of multifunctionality. Copyright © 2014 the American Physiological Society.

  15. New Pharmacotherapy Targeting Cognitive Dysfunction of Schizophrenia via Modulation of GABA Neuronal Function

    OpenAIRE

    Jeon, Won Je; Sumiyoshi, Tomiki; Kurachi, Masayoshi

    2015-01-01

    Schizophrenia is considered a neurodevelopmental and neurodegenerative disorder. Cognitive impairment is a core symptom in patients with the illness, and has been suggested a major predictor of functional outcomes. Reduction of parvalbumin (PV)-positive ?-aminobutyric acid (GABA) interneurons has been associated with the pathophysiology of schizophrenia, in view of the link between the abnormality of GABA neurons and cognitive impairments of the disease. It is assumed that an imbalance of exc...

  16. Neuroserpin and brain-derived neurotrophic factor in neuroendocrine and neuronal plasticity. Functional studies in (transgenic) Xenopus intermediate pituitary cells

    NARCIS (Netherlands)

    Rotteveel-de Groot, D.M. de

    2007-01-01

    The molecular mechanisms underlying neuronal plasticity, i.e. the capacity of the brain to continuously adapt its structural organization to new situations, remain largely unknown. In this thesis, we explored functional aspects of two proteins that presumably play a role in neuronal plasticity,

  17. Developmental profiles of the intrinsic properties and synaptic function of auditory neurons in preterm and term baboon neonates.

    Science.gov (United States)

    Kim, Sei Eun; Lee, Seul Yi; Blanco, Cynthia L; Kim, Jun Hee

    2014-08-20

    The human fetus starts to hear and undergoes major developmental changes in the auditory system during the third trimester of pregnancy. Although there are significant data regarding development of the auditory system in rodents, changes in intrinsic properties and synaptic function of auditory neurons in developing primate brain at hearing onset are poorly understood. We performed whole-cell patch-clamp recordings of principal neurons in the medial nucleus of trapezoid body (MNTB) in preterm and term baboon brainstem slices to study the structural and functional maturation of auditory synapses. Each MNTB principal neuron received an excitatory input from a single calyx of Held terminal, and this one-to-one pattern of innervation was already formed in preterm baboons delivered at 67% of normal gestation. There was no difference in frequency or amplitude of spontaneous excitatory postsynaptic synaptic currents between preterm and term MNTB neurons. In contrast, the frequency of spontaneous GABA(A)/glycine receptor-mediated inhibitory postsynaptic synaptic currents, which were prevalent in preterm MNTB neurons, was significantly reduced in term MNTB neurons. Preterm MNTB neurons had a higher input resistance than term neurons and fired in bursts, whereas term MNTB neurons fired a single action potential in response to suprathreshold current injection. The maturation of intrinsic properties and dominance of excitatory inputs in the primate MNTB allow it to take on its mature role as a fast and reliable relay synapse. Copyright © 2014 the authors 0270-6474/14/3411399-06$15.00/0.

  18. A single hidden layer feedforward network with only one neuron in the hidden layer can approximate any univariate function

    OpenAIRE

    Guliyev , Namig; Ismailov , Vugar

    2016-01-01

    The possibility of approximating a continuous function on a compact subset of the real line by a feedforward single hidden layer neural network with a sigmoidal activation function has been studied in many papers. Such networks can approximate an arbitrary continuous function provided that an unlimited number of neurons in a hidden layer is permitted. In this paper, we consider constructive approximation on any finite interval of $\\mathbb{R}$ by neural networks with only one neuron in the hid...

  19. Long-lasting functional disabilities in patients who recover from coma after cardiac operations.

    Science.gov (United States)

    Rodriguez, Rosendo A; Nair, Shona; Bussière, Miguel; Nathan, Howard J

    2013-03-01

    Uncertainty regarding the long-term functional outcome of patients who awaken from coma after cardiac operations is difficult for families and physicians and may delay rehabilitation. We studied the long-term functional status of these patients to determine if duration of coma predicted outcome. We followed 71 patients who underwent cardiac operations; recovered their ability to respond to verbal commands after coma associated with postoperative stroke, encephalopathy, and/or seizures; and were discharged from the hospital. The Glasgow Outcome Scale Extended (GOSE) was used to assess functional disability 2 to 4 years after discharge. Outcomes were classified as favorable (GOSE scores 7 and 8) and unfavorable (GOSE scores 1-6). Of 71 patients identified, 39 were interviewed, 15 died, 1 refused to be interviewed, and 16 were lost to follow-up. Of the 54 patients with completed GOSE evaluations, only 15 (28%) had favorable outcomes. Among patients with unfavorable outcomes, 15 (28%) died, 14 (26%) survived with moderate disabilities, and 10 (18%) had severe disabilities. Factors associated with unfavorable outcomes were increases in duration of coma (p = 0.007), time in intensive care (p = 0.006), length of hospitalization (p = 0.004), and postoperative serum creatine kinase levels (p = 0.006). Only duration of coma was an independent predictor of unfavorable outcome (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.008-1.537; p = 0.042). Patients with durations of coma greater than 4 days were more likely to have unfavorable outcomes (OR, 5.1; 95% CI, 1.3-21.3; p = 0.02). Two thirds of comatose patients who survived to discharge after cardiac operations had unfavorable long-term functional outcomes. A longer duration of unconsciousness is a predictor of unfavorable outcome. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  20. Functional analysis of neuronal microRNAs in Caenorhabditis elegans dauer formation by combinational genetics and Neuronal miRISC immunoprecipitation.

    Directory of Open Access Journals (Sweden)

    Minh T Than

    2013-06-01

    Full Text Available Identifying the physiological functions of microRNAs (miRNAs is often challenging because miRNAs commonly impact gene expression under specific physiological conditions through complex miRNA::mRNA interaction networks and in coordination with other means of gene regulation, such as transcriptional regulation and protein degradation. Such complexity creates difficulties in dissecting miRNA functions through traditional genetic methods using individual miRNA mutations. To investigate the physiological functions of miRNAs in neurons, we combined a genetic "enhancer" approach complemented by biochemical analysis of neuronal miRNA-induced silencing complexes (miRISCs in C. elegans. Total miRNA function can be compromised by mutating one of the two GW182 proteins (AIN-1, an important component of miRISC. We found that combining an ain-1 mutation with a mutation in unc-3, a neuronal transcription factor, resulted in an inappropriate entrance into the stress-induced, alternative larval stage known as dauer, indicating a role of miRNAs in preventing aberrant dauer formation. Analysis of this genetic interaction suggests that neuronal miRNAs perform such a role partly by regulating endogenous cyclic guanosine monophosphate (cGMP signaling, potentially influencing two other dauer-regulating pathways. Through tissue-specific immunoprecipitations of miRISC, we identified miRNAs and their likely target mRNAs within neuronal tissue. We verified the biological relevance of several of these miRNAs and found that many miRNAs likely regulate dauer formation through multiple dauer-related targets. Further analysis of target mRNAs suggests potential miRNA involvement in various neuronal processes, but the importance of these miRNA::mRNA interactions remains unclear. Finally, we found that neuronal genes may be more highly regulated by miRNAs than intestinal genes. Overall, our study identifies miRNAs and their targets, and a physiological function of these miRNAs in

  1. Cardiac MRI in pulmonary artery hypertension: correlations between morphological and functional parameters and invasive measurements

    Energy Technology Data Exchange (ETDEWEB)

    Alunni, Jean-Philippe; Otal, Philippe; Rousseau, Herve; Chabbert, Valerie [CHU Rangueil, Department of Radiology, Toulouse (France); Degano, Bruno; Tetu, Laurent; Didier, Alain [CHU Larrey, Department of Pneumology, Toulouse (France); Arnaud, Catherine [CHU Rangueil, Department of Methods in Clinical Research, Toulouse (France); Blot-Souletie, Nathalie [CHU Rangueil, Department of Cardiology, Toulouse (France)

    2010-05-15

    To compare cardiac MRI with right heart catheterisation in patients with pulmonary hypertension (PH) and to evaluate its ability to assess PH severity. Forty patients were included. MRI included cine and phase-contrast sequences, study of ventricular function, cardiac cavity areas and ratios, position of the interventricular septum (IVS) in systole and diastole, and flow measurements. We defined four groups according to the severity of PH and three groups according to IVS position: A, normal position; B, abnormal in diastole; C, abnormal in diastole and systole. IVS position was correlated with pulmonary artery pressures and PVR (pulmonary vascular resistance). Median pulmonary artery pressures and resistance were significantly higher in patients with an abnormal septal position compared with those with a normal position. Correlations were good between the right ventricular ejection fraction and PVR, right ventricular end-systolic volume and PAP, percentage of right ventricular area change and PVR, and diastolic and systolic ventricular area ratio and PVR. These parameters were significantly associated with PH severity. Cardiac MRI can help to assess the severity of PH. (orig.)

  2. Cardiac magnetic resonance imaging in evaluation of anatomical structure and function of the ventricles

    International Nuclear Information System (INIS)

    Suzuki, Jun-ichi; Usui, Masahiro; Takenaka, Katsu

    1990-01-01

    Cardiac magnetic resonance imaging (MRI) is being widely employed for evaluation of cardiovascular anatomies and functions. However, the indications for cardiac MRI to obtain information which cannot be obtained using other conventional methods have not yet been determined. To demonstrate the usefulness of MRI in delineating the apex of the left ventricle and free wall of the right ventricle, end-diastolic short axis MRI images were obtained in 20 patients with apical hypertrophy and in 9 normal volunteers. To compare the accuracy of estimations of left ventricular volumes obtained using the modified Simpson's method of MRI with that using the MRI area length method, 19 patients, in whom left ventriculography had been performed, were studied. The apex of the left ventricle was evaluated circumferentially and distribution of hypertrophied muscles was defined. Sixty-five percent of the length of the right ventricular free wall was clearly delineated. Correlation coefficients of the ejection fraction between MRI and angiography were 0.85 with the modified Simpson's method of MRI, and 0.62 with the area length method of MRI. Three themes were chosen to demonstrate good clinical indications for cardiac MRI. (author)

  3. Cardiac function and myocardial perfusion immediately following maximal treadmill exercise inside the MRI room

    Directory of Open Access Journals (Sweden)

    Ballinger Michelle R

    2008-01-01

    Full Text Available Abstract Treadmill exercise stress testing is an essential tool in the prevention, dete