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Phox2b-expressing neurons of the parafacial region regulate breathing rate, inspiration, and expiration in conscious rats.
Abbott SB, Stornetta RL, Coates MB, Guyenet PG (2011) Phox2b-expressing neurons of the parafacial region regulate breathing rate, inspiration, and expiration in conscious rats. J Neurosci 31(45):16410-16422. doi: 10.1523/JNEUROSCI.3280-11.2011
Summary: Neurons in the retrotrapezoid nucleus (RTN) are involved in the CO2-dependent control of breathing in conscious and anesthetized rats. In this work the authors specifically examined Phox2b-expressing glutaminergic neurons in the RTN. Rats received 44 ng of DBH-SAP (Cat. #IT-03) into the lateral horn of the second thoracic segment in order to eliminate C1 neurons that project to the spinal cord. The data demonstrate regulation of lung ventilation by RTN-Phox2b neurons, and also that these neurons are not rhythmogenic in adults.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
The sympathetic nervous system stimulates anti-inflammatory B cells in collagen-type II-induced arthritis.
Pongratz G, Melzer M, Straub R (2012) The sympathetic nervous system stimulates anti-inflammatory B cells in collagen-type II-induced arthritis. Ann Rheum Dis 71(3):432-9. doi: 10.1136/ard.2011.153056
Summary: The sympathetic nervous system exerts anti-inflammatory effects on collagen-induced arthritis. To examine whether these effects are mediated by B-cells producing interleukin-10 (IL-10) the authors treated mice with 5 µg intraperitoneal injections of anti-DBH-SAP (Cat. #IT-03). The sympathectomy efficacy was assessed by analyzing norepinephrine levels in the spleen. The data suggest that increasing the number of IL-10 producing B cells can slow down arthritis progression.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Minireview: The value of looking backward: the essential role of the hindbrain in counterregulatory responses to glucose deficit.
Ritter S, Li AJ, Wang Q, Dinh TT (2011) Minireview: The value of looking backward: the essential role of the hindbrain in counterregulatory responses to glucose deficit. Endocrinology 152(11):4019-4032. doi: 10.1210/en.2010-1458
Summary: This review examines work addressing how particular glucose-sensing cells function in glucoregulation under specific physiological or pathological conditions. There are specific populations of norepinephrine (NE) and epinephrine (E) neurons in the hindbrain that mediate these responses. The use of anti-DBH-SAP (Cat. #IT-03) to eliminate selective NE/E subgroups without disrupting basic functions is discussed.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Patterning of somatosympathetic reflexes reveals nonuniform organization of presympathetic drive from C1 and non-C1 RVLM neurons.
Burke PG, Neale J, Korim WS, McMullan S, Goodchild AK (2011) Patterning of somatosympathetic reflexes reveals nonuniform organization of presympathetic drive from C1 and non-C1 RVLM neurons. Am J Physiol Regul Integr Comp Physiol 301(4):R1112-R1122. doi: 10.1152/ajpregu.00131.2011
Summary: Some neurons in the rostral ventrolateral medulla are part of the circuitry that helps maintain blood pressure. This control is exerted through both feed-forward and reflex adjustment mechanisms. The authors used bilateral injections of anti-DBH-SAP (Cat. #IT-03, 24 ng per side) into the spinal cord of rats between T1 and T2 to better understand the organization of this circuitry. Mouse IgG-SAP (Cat. #IT-18) was used as a control. The results suggest that myelinated neurons may control baseline tone, while stressor response uses unmyelinated neurons.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Mouse IgG-SAP (Cat. #IT-18)
Brain stem catecholamines circuitry: Activation by alcohol and role in the hypothalamic-pituitary-adrenal response to this drug.
Lee S, Craddock Z, Rivier C (2011) Brain stem catecholamines circuitry: Activation by alcohol and role in the hypothalamic-pituitary-adrenal response to this drug. J Neuroendocrinol 23(6):531-541. doi: 10.1111/j.1365-2826.2011.02131.x
Summary: In this work the authors investigated mechanisms underlying the stimulatory effect of alcohol on the hypothalamic-pituitary-adrenal axis (HPA). One method used was 33-ng injections of anti-DBH-SAP (Cat. #IT-03) into the A2/C2/C3 and A1/C1 regions. The data generated show that catecholamines, especially in the brainstem, regulate the HPA response to alcohol. This regulation utilizes α1-adrenergic receptors. Administration of anti-DBH-SAP to the A1-A2/C1-C3 regions disrupted the catecholaminergic input to the paraventricular nucleus.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Participation of hindbrain AMP-activated protein kinase in glucoprivic feeding.
Li AJ, Wang Q, Ritter S (2011) Participation of hindbrain AMP-activated protein kinase in glucoprivic feeding. Diabetes 60(2):436-442. doi: 10.2337/db10-0352
Summary: Catecholamine neurons innervating the medial hypothalamus are involved in the control of glucoprivic feeding as well as other responses to glucose deficit. Rats received bilateral 82-ng injections of anti-DBH-SAP (Cat. #IT-03) into the paraventricular hypothalamic nucleus. Saporin (Cat. #PR-01) was used as a control. Lesioned animals did not respond to the administration of a competitive glucose inhibitor, nor did they display phosphorylation of pAMPKα, suggesting that AMPK may be part of a glucose- sensing mechanism.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Saporin (Cat. #PR-01)
Featured Article: Targeted lesion of caudal brainstem catecholamine neurons reveals their role in symptoms of fatigue
Goehler LE, Gaykema RPA (2011) Featured Article: Targeted lesion of caudal brainstem catecholamine neurons reveals their role in symptoms of fatigue. Targeting Trends 12(1)
Related Products: Anti-DBH-SAP (Cat. #IT-03), Mouse IgG-SAP (Cat. #IT-18)
Defining the role of norepinephrine in cannabinoid-induced aversion and anxiety
Carvalho AF, Van Bockstaele E (2010) Defining the role of norepinephrine in cannabinoid-induced aversion and anxiety. Neuroscience 2010 Abstracts 833.3. Society for Neuroscience, San Diego, CA.
Summary: In the central nervous system, cannabinoids have been shown to regulate neurotransmitter release, control the hypothalamic-pituitary-adrenal axis and impact several physiological systems, such as food intake, pain and emotion perception. Manipulation of the cannabinoid system using exogenous compounds has been explored as a potential therapeutic for several disorders; however some severe side effects have been reported. Understanding the neural circuits and neurochemical substrates impacted by cannabinoids will provide a better means of gauging their actions within the central nervous system that may contribute to the expression of unwanted side effects. Previous work from our lab had shown that the cannabinoid receptor (CBr) agonist WIN 55,212-2 is able to induce changes in noradrenergic transmission in limbic structures such as prefrontal cortex (PFC) and the nucleus accumbens (Acb). Moreover, we have previously reported that norepinephrine in the nucleus accumbens (Acb) is critical for WIN 55,212-2-induced aversion, as measured by the place conditioning paradigm. In the present study, we further explore the role of norepinephrine in cannabinoid-induced behaviors. More specifically, we investigate whether norepinephrine in the limbic forebrain of rats is important for the anxiety induced by WIN 55,212-2 (3.0 mg/kg, i.p.). Lesion of noradrenergic neurons in the Acb and bed nucleus of the stria terminalis (BNST) was achieved by the intracerebral injection of the toxin saporin conjugated with an antibody that recognizes the enzyme dopamine-beta-hydroxylase (DBH). This toxin yields a specific lesion of noradrenergic neurons. The anxiogenic effects of WIN 55,212-2 were then measured in the elevated zero maze. The results show that depletion of noradrenergic innervation of the Acb and BNST did not reduce the anxiogenic properties of WIN 55,212-2. These results, together with our previous findings, suggest that the anxiogenic and aversive properties of the CBr agonist WIN 55,212-2 are differentially regulated, with the aversive effects being dependent on noradrenergic transmission within the Acb and the anxiogenic effects being regulated by a, yet to be determined, alternative mechanism/circuit.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Patterning of somatosympathetic reflexes: Identification of distinct bulbospinal sympathoexcitatory RVLM projections by conduction velocity and catecholamine phenotype
Burke PG, Neale J, Korim WS, Mcmullan S, Pilowsky PM, Goodchild AK (2010) Patterning of somatosympathetic reflexes: Identification of distinct bulbospinal sympathoexcitatory RVLM projections by conduction velocity and catecholamine phenotype. Neuroscience 2010 Abstracts 694.11/HHH34. Society for Neuroscience, San Diego, CA.
Summary: The aim of this study was to examine the somatosympathetic reflex (SSR) response of different sympathetic nerves to identify distinct projections of presympathetic vasomotor RVLM neurons by axonal conduction and catecholamine phenotype. All experiments were conducted in urethane-anaesthetised (1.3 g/kg ip), paralysed, vagotomised and artificially ventilated Sprague Dawley rats (n = 44). First, we determined the simultaneous activity of dorsal root potentials and the splanchnic SSR to single shock sciatic nerve (SN) stimulation (single 0.2 ms pulse, 50 sweeps at 0.5-1 Hz, 1-80 V, n=4). Second, we simultaneously recorded the sympathoexcitatory response of multiple, sympathetic nerves (cervical, renal, splanchnic and lumbar) to low (A-fibre afferent; 4-10 V) and high (A- and C-fibre afferents; +40 V) SN stimulation (n=19). Third, we examined the cervical or splanchnic SSR to low intensity SN stimulation in rats following RVLM microinjection of somatostatin (SST) or muscimol (n=8). Fourth, we examined the splanchnic SSR in rats pretreated with intraspinal anti-dopamine-beta-hydroxylase-saporin (anti-DβH-SAP; 24 ng/side, n=8), a neurotoxin that depleted ~70% of catecholamine (C1) neurons in the RVLM compared to IgG-saporin control (n=5). Low intensity SN stimulation evoked biphasic responses in the renal, splanchnic and lumbar nerves but a single peak in the cervical nerve. High intensity SN stimulation evoked triphasic responses in the renal, splanchnic and lumbar nerves and a biphasic cervical response. RVLM injections of SST abolished the early peak of the cervical and splanchnic SSR. Intraspinal pretreatment with anti-DβH-SAP eliminated the late peak of the splanchnic SSR and attenuated the first peak. It is concluded that the mono- or bi-phasic SSR responses are generated by A-fibre afferent inputs driving two classes of bulbospinal sympathoexcitatory RVLM neurons with myelinated or unmyelinated axonal conduction. Secondly, unmyelinated RVLM presympathetic neurons, presumed to be all C1, innervate splanchnic, renal and lumbar SPN, whereas myelinated C1 and non-C1 neurons innervate all sympathetic outflow examined. These findings extend prior evidence that the RVLM expresses several types of phenotypically distinct descending sympathoexcitatory pathways.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Mouse IgG-SAP (Cat. #IT-18)
Hindbrain catecholamine neurons are required for rapid switching of metabolic substrate utilization during glucoprivation
Li A-J, Wang Q, Dinh TT, Ritter S (2010) Hindbrain catecholamine neurons are required for rapid switching of metabolic substrate utilization during glucoprivation. Neuroscience 2010 Abstracts 392.14/III1. Society for Neuroscience, San Diego, CA.
Summary: Glucoprivation is a metabolic emergency in which a rapid and effective system-wide switch to fat metabolism must occur to conserve any available glucose for use by the brain. Glucoprivation stimulates secretion of corticosterone, which is known to play an important role in promoting fat utilization. In previously published work, we showed that injections of the retrogradely transported catecholamine neuron immunotoxin, anti-dopamine beta-hydroxylase conjugated to saporin (DSAP) into the paraventricular nucleus of the hypothalamus (PVH) eliminate the corticosterone response to glucoprivation without impairing the response to a nonmetabolic stressor (swim stress), without altering the circadian rhythm of corticosterone secretion and without damaging the PVH CRF-secreting neurons. Here we microinjected DSAP into the PVH to selectively lesion hindbrain catecholamine neurons innervating this site, thus impairing the glucoprivation-induced corticosterone response. Using indirect calorimetry, we examined metabolic fuel utilization and other metabolic parameters in these lesioned rats under basal and glucoprivic conditions. Under basal conditions, energy expenditure and locomotor activity did not differ between DSAP rats and controls injected with unconjugated saporin (SAP). However, DSAP rats had a higher respiratory exchange ratio (RER) than SAPs, indicating their greater dependence on carbohydrate utilization. Glucoprivation induced by 2-deoxy-D-glucose (2DG, 250 mg/kg) reduced energy expenditure equally in SAP and DSAP rats. However, 2DG rapidly decreased RER to 0.8 (a value indicating ongoing fat metabolism) in the SAP group, but not in the DSAP group. Responses to 2DG persisted for about 6 hours. Adrenal dennervation, which eliminates the adrenal medullary response to glucoprivation, did not alter these responses to 2DG in either SAP or DSAP rats. Results indicate that in the absence of hypothalamically-projecting hindbrain catecholamine neurons, rats cannot efficiently switch their fuel utilization from carbohydrate to fat during glucoprivation, presumably due to a deficient corticosterone response. Results also suggest a previously unrecognized role for these catecholamine neurons in control of basal substrate utilization.
Related Products: Anti-DBH-SAP (Cat. #IT-03)