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Sensory and sympathetic nerves are depleted in the knee synovium of vitamin D deficient rats
Abstracts / Autonomic Neuroscience: Basic and Clinical 192 (2015) 56–141
Expression of the hyperpolarization-activated cation current (Ih) and consequences for synaptic integration were examined in sympathetic neurons of the rat superior cervical ganglion (SCG). Whole-cell recordings of membrane potential (Vm) from dissociated SCG neurons revealed prominent ‘sag’ responses to hyperpolarizing current steps. ZD7288, which blocks Ih, antagonized the sag and hyperpolarized Vrest by 3-7 mV. Similar sag responses were observed in whole-cell recordings from the acutely isolated intact SCG. Ih responses were seen in virtually all cells and therefore all sympathetic phenotypes. qPCR detected mRNAs for all four hcn isoforms in SCG homogenates. Voltage-clamp analysis of Ih revealed that SCG neurons express 1-3 nS of h-conductance (gh). The small magnitude of gh explains why it escaped detection in previous microelectrode studies. The consequences of Ih for ganglionic integration were tested using virtual nicotinic synapses in dynamic clamp experiments in cell culture. Blocking native Ih with ZD7288 produced an approximate doubling of thresholdsynaptic conductance (thresh-gsyn). This led to an increase in synaptic gain that varied with the initial settings for synaptic strength. Using the voltage-clamp data we created a biophysical model for gh and used it to produce a virtual gh with the dynamic clamp. Adding back virtual gh to neurons treated with ZD7288 reconstituted the original Vrest, thresh-gsyn and synaptic gain. These results indicate that metabotropic modulation of h-channels will regulate postganglionic sympathetic activity. They also suggest that use of h-channel blockers for cardioprotection may have the beneficial side effect of reducing peripheral sympathetic activity. Supported by AHA grant 13GRNT16850074.
doi:10.1016/j.autneu.2015.07.193
P15.5 Sensory and sympathetic nerves are depleted in the knee synovium of vitamin D deficient rats S.E. Tague, PG Smith Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, USA Rheumatoid arthritis (RA) is a debilitating inflammatory joint disease that can be influenced by environmental factors, including dietary vitamin D deficiency. While the underlying pathology is complex, a prequel to RA is loss of autonomic and sensory synovial innervation. Peripheral nerves express vitamin D receptors and vitamin D can regulate nerve growth and neurotrophin expression, suggesting a link between vitamin D, joint innervation and RA. The aim of the present work was to assess the impact of vitamin D deficiency on nerves and neurotrophin-containing cells in the rat synovium. Sprague Dawley rats were fed either control or vitamin D deficient diets for four weeks. Sections of knee synovium from patella to meniscus were immunostained for the pan-neuronal marker PGP9.5. Axonal subpopulations were identified using selective markers for myelinated fibers (neurofilament H), unmyelinated nerves (peripherin), sympathetic nerves (TH), peptidergic axons (CGRP) and non-peptidergic sensory nerves (GFRα2). In control rats, unmyelinated sensory fibers were denser in intima than in subintima, while sympathetic innervation was confined to the subintima. In vitamin D deficient rats, peptidergic and non-peptidergic sensory nerves in the intima and sympathetic nerves in the subintima were significantly reduced. This was accompanied by a reduction in neurturin expression by synovial mast cells, while NGF expression, present in type B synoviocytes, was unchanged. These findings show that joint innervation is regulated by vitamin D, and deficiency may increase
115
susceptibility to RA by depleting sensory and sympathetic synovial innervation, due in part to reduced synovial neurotrophin content. Supported by HD049615.
doi:10.1016/j.autneu.2015.07.194
P15.6 Thyroid deficiency during antenatal and early postnatal development affects cardiovascular control in adult rat offspring O.S. Tarasovaa,b, S.I. Sofronovaa, E.K. Selivanovab, A.A. Martyanova,b, E.V. Lukoshkovaa a Laboratory of Exercise Physiology, SRC RF Institute for Biomedical Problems RAS b Faculty of Biology, M.V.Lomonosov Moscow State University, Moscow, Russian Federation Backgroud and Aim. Thyroid hormones are important for proper development of cardiovascular system, but delayed consequences of early thyroid deficiency are purely investigated. In this study we aimed the effects of antenatal and early postnatal hypothyroidism on cardiovascular system regulation in adult rats. Methods. Dams were treated with propylthiouracil in drinking water (PTU, 5 ppm) throughout pregnancy and 2 weeks after delivery. Hemodynamic measurements were performed in male offspring aged 10-12 weeks. Blood pressure was recorded through a catheter in conscious unrestrained rats and processed beat-to-beat to estimate mean arterial pressure (MAP) and heart rate (HR) values. MAP power spectra were computed using a fast Fourier transform. Results. Total T4 and free T3 blood levels in offspring of PTU-treated dams compared to respective controls were prominently lower in 2-week age but higher in 10-week age. PTU group had lower HR level after cardiac autonomic blockade, developed smaller tachycardic response to tyramine and smaller pressor response to NO-synthase inhibitor. Along with that PTU group demonstrated the signs of increased sympathetic activity, such as moderate increase of MAP, increase of MAP spectral power in 0.25-0.6 Hz frequency band and enhanced depressor response to ganglionic blockade. Conclusions. Cardiovascular consequences of thyroid deficiency in early development may persist in adult age even if the levels of thyroid hormones are restored. Such hemodynamic changes may be co-directional with the changes during acute hypothyroidism or compensatory transformed into opposite changes. Supported by the Russian Science Foundation (Grant N 14-15-00704).
doi:10.1016/j.autneu.2015.07.195
P15.7 Sympathetic nerve to the ovary regulates ovarian testosterone secretion in female rats S. Uchida, F. Kagitani Department of Autonomic Neuroscience, Tokyo Metropolitan Institute of Gerontology, Japan Previously, we demonstrated that electrical stimulation of the superior ovarian nerve (SON), but not the ovarian nerve plexus (ONP), reduces the secretion rate of estradiol from the ovary via activation of alpha 2-adrenoceptors in rats. The inhibitory effect of SON on estradiol secretion may be due to reduced production of testosterone, a direct
Expression of the hyperpolarization-activated cation current (Ih) and consequences for synaptic integration were examined in sympathetic neurons of the rat superior cervical ganglion (SCG). Whole-cell recordings of membrane potential (Vm) from dissociated SCG neurons revealed prominent ‘sag’ responses to hyperpolarizing current steps. ZD7288, which blocks Ih, antagonized the sag and hyperpolarized Vrest by 3-7 mV. Similar sag responses were observed in whole-cell recordings from the acutely isolated intact SCG. Ih responses were seen in virtually all cells and therefore all sympathetic phenotypes. qPCR detected mRNAs for all four hcn isoforms in SCG homogenates. Voltage-clamp analysis of Ih revealed that SCG neurons express 1-3 nS of h-conductance (gh). The small magnitude of gh explains why it escaped detection in previous microelectrode studies. The consequences of Ih for ganglionic integration were tested using virtual nicotinic synapses in dynamic clamp experiments in cell culture. Blocking native Ih with ZD7288 produced an approximate doubling of thresholdsynaptic conductance (thresh-gsyn). This led to an increase in synaptic gain that varied with the initial settings for synaptic strength. Using the voltage-clamp data we created a biophysical model for gh and used it to produce a virtual gh with the dynamic clamp. Adding back virtual gh to neurons treated with ZD7288 reconstituted the original Vrest, thresh-gsyn and synaptic gain. These results indicate that metabotropic modulation of h-channels will regulate postganglionic sympathetic activity. They also suggest that use of h-channel blockers for cardioprotection may have the beneficial side effect of reducing peripheral sympathetic activity. Supported by AHA grant 13GRNT16850074.
doi:10.1016/j.autneu.2015.07.193
P15.5 Sensory and sympathetic nerves are depleted in the knee synovium of vitamin D deficient rats S.E. Tague, PG Smith Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, USA Rheumatoid arthritis (RA) is a debilitating inflammatory joint disease that can be influenced by environmental factors, including dietary vitamin D deficiency. While the underlying pathology is complex, a prequel to RA is loss of autonomic and sensory synovial innervation. Peripheral nerves express vitamin D receptors and vitamin D can regulate nerve growth and neurotrophin expression, suggesting a link between vitamin D, joint innervation and RA. The aim of the present work was to assess the impact of vitamin D deficiency on nerves and neurotrophin-containing cells in the rat synovium. Sprague Dawley rats were fed either control or vitamin D deficient diets for four weeks. Sections of knee synovium from patella to meniscus were immunostained for the pan-neuronal marker PGP9.5. Axonal subpopulations were identified using selective markers for myelinated fibers (neurofilament H), unmyelinated nerves (peripherin), sympathetic nerves (TH), peptidergic axons (CGRP) and non-peptidergic sensory nerves (GFRα2). In control rats, unmyelinated sensory fibers were denser in intima than in subintima, while sympathetic innervation was confined to the subintima. In vitamin D deficient rats, peptidergic and non-peptidergic sensory nerves in the intima and sympathetic nerves in the subintima were significantly reduced. This was accompanied by a reduction in neurturin expression by synovial mast cells, while NGF expression, present in type B synoviocytes, was unchanged. These findings show that joint innervation is regulated by vitamin D, and deficiency may increase
115
susceptibility to RA by depleting sensory and sympathetic synovial innervation, due in part to reduced synovial neurotrophin content. Supported by HD049615.
doi:10.1016/j.autneu.2015.07.194
P15.6 Thyroid deficiency during antenatal and early postnatal development affects cardiovascular control in adult rat offspring O.S. Tarasovaa,b, S.I. Sofronovaa, E.K. Selivanovab, A.A. Martyanova,b, E.V. Lukoshkovaa a Laboratory of Exercise Physiology, SRC RF Institute for Biomedical Problems RAS b Faculty of Biology, M.V.Lomonosov Moscow State University, Moscow, Russian Federation Backgroud and Aim. Thyroid hormones are important for proper development of cardiovascular system, but delayed consequences of early thyroid deficiency are purely investigated. In this study we aimed the effects of antenatal and early postnatal hypothyroidism on cardiovascular system regulation in adult rats. Methods. Dams were treated with propylthiouracil in drinking water (PTU, 5 ppm) throughout pregnancy and 2 weeks after delivery. Hemodynamic measurements were performed in male offspring aged 10-12 weeks. Blood pressure was recorded through a catheter in conscious unrestrained rats and processed beat-to-beat to estimate mean arterial pressure (MAP) and heart rate (HR) values. MAP power spectra were computed using a fast Fourier transform. Results. Total T4 and free T3 blood levels in offspring of PTU-treated dams compared to respective controls were prominently lower in 2-week age but higher in 10-week age. PTU group had lower HR level after cardiac autonomic blockade, developed smaller tachycardic response to tyramine and smaller pressor response to NO-synthase inhibitor. Along with that PTU group demonstrated the signs of increased sympathetic activity, such as moderate increase of MAP, increase of MAP spectral power in 0.25-0.6 Hz frequency band and enhanced depressor response to ganglionic blockade. Conclusions. Cardiovascular consequences of thyroid deficiency in early development may persist in adult age even if the levels of thyroid hormones are restored. Such hemodynamic changes may be co-directional with the changes during acute hypothyroidism or compensatory transformed into opposite changes. Supported by the Russian Science Foundation (Grant N 14-15-00704).
doi:10.1016/j.autneu.2015.07.195
P15.7 Sympathetic nerve to the ovary regulates ovarian testosterone secretion in female rats S. Uchida, F. Kagitani Department of Autonomic Neuroscience, Tokyo Metropolitan Institute of Gerontology, Japan Previously, we demonstrated that electrical stimulation of the superior ovarian nerve (SON), but not the ovarian nerve plexus (ONP), reduces the secretion rate of estradiol from the ovary via activation of alpha 2-adrenoceptors in rats. The inhibitory effect of SON on estradiol secretion may be due to reduced production of testosterone, a direct