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Locus coeruleus noradrenergic innervation of the amygdala facilitates alerting-induced constriction of the rat tail artery.
Mohammed M, Kulasekara K, Ootsuka Y, Blessing W (2016) Locus coeruleus noradrenergic innervation of the amygdala facilitates alerting-induced constriction of the rat tail artery. Am J Physiol Regul Integr Comp Physiol 310:R1109-1119. doi: 10.1152/ajpregu.00058.2016
Summary: The researchers tested the hypothesis that release of noradrenaline within the amygdala is important for the occurrence of SCVARS (sympathetic cutaneous vasoconstrictor alerting responses). A long-shanked 5-μl glass micropipette calibrated in 100-nl steps, was filled with vehicle or Anti-DBH-SAP (Cat. #IT-03). Anti-DBH-SAP (5 μg in 250 nl) or vehicle was injected into the amygdala during ∼1 min, and the pipette was left in place for an additional The locus coeruleus has been implicated in many aspects of emotional arousal, so that functional inhibition of the extensive locus coeruleus-derived noradrenergic innervation of centers known to be important in emotional arousal, including the amygdala, is likely to contribute to the therapeutic actions of clonidine-like agents. The locus coeruleus also has major reciprocal connections with the orexin-synthesizing neurons in the hypothalamus, and rats with genetically lesioned orexin receptor neurons (alternatively, oen could lesion with Orexin-SAP, Cat. #IT-20) have reduced emotional arousal as reflected in reduced SCVAR responses to alerting stimuli.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Orexin-B-SAP (Cat. #IT-20)
Limiting glucocorticoid secretion increases the anorexigenic property of Exendin-4.
Lee S, Diener K, Kaufman S, Krieger J, Pettersen K, Jejelava N, Arnold M, Watts A, Langhans W (2016) Limiting glucocorticoid secretion increases the anorexigenic property of Exendin-4. Mol Metab 5:552-565. doi: 10.1016/j.molmet.2016.04.008
Summary: Glucagon-like peptide-1 (GLP-1) analogs lower blood surgar levels and cause a loss of appetite. Exendin-4 (Ex-4) is a GLP-1 receptor agonist, and also increases glucocorticoid secretion. Several tests were conducted to determine if the released glucocorticoids interact with Ex-4’s anorexigneic effect. One method involved ablating hindbrain catecholaminergic neurons by stereotaxically injecting 42 ng of Anti-DBH-SAP (Cat. #IT-03) bilaterally into the paraventricular nucleus of the hypothalamus in rats. Animals were injected with equimolar concentrations of unconjugated Saporin (Cat. #PR-01) as a control. Anti-DBH-SAP lesions reduced the efficacy of Ex-4 to increase corticosterone secretion but increased the anorexigenic effect, indicating that Ex-4-dependent corticosterone secretion opposes Ex-4’s actions. Anti-DBH-SAP lesions increased Ex-4’s ability to reduce food intake and body weight.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Saporin (Cat. #PR-01)
Locus coeruleus and tuberomammillary nuclei ablations attenuate hypocretin/orexin antagonist-mediated rem sleep.
Schwartz M, Nguyen A, Warrier D, Palmerston J, Thomas A, Morairty S, Neylan T, Kilduff T (2016) Locus coeruleus and tuberomammillary nuclei ablations attenuate hypocretin/orexin antagonist-mediated rem sleep. eNeuro 3:ENEURO.0018-0016.2016. doi: 10.1523/ENEURO.0018-16.2016
Summary: To examine the mechanism by which the Orexin 1r/Orexin 2r antagonist almorexant decreases wakefulness and increases NREM and REM sleep the authors utilized Anti-DBH-SAP (Cat. #IT-03) and Orexin-B-SAP (Cat. #IT-20). Rats received 3-μg injections of Anti-DBH-SAP into the LC, or bilateral 57-80 ng injections of Orexin-SAP into the TMN. Both conjugates attenuated the increased REM sleep seen upon administration of almorexant without altering almorexant-induced changes in NREM sleep.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Orexin-B-SAP (Cat. #IT-20)
Disruption of spinal noradrenergic activation delays recovery of acute incision-induced hypersensitivity and increases spinal glial activation in the rat.
Arora V, Morado-Urbina C, Aschenbrenner C, Hayashida K, Wang F, Martin T, Eisenach J, Peters C (2016) Disruption of spinal noradrenergic activation delays recovery of acute incision-induced hypersensitivity and increases spinal glial activation in the rat. J Pain 17:190-202. doi: 10.1016/j.jpain.2015.10.009
Summary: A significant percentage of patients who undergo surgery experience prolonged clinically impactful pain, reducing the quality of life and physical function. Disruption of the descending noradrenergic input has been hypothesized to be important to the generation of this type of pain state. Using an acute incision model, the authors administered 5 μg ofAnti-DBH-SAP (Cat. #IT-03) to the L5-L6 interspace of rats. Mouse IgG-SAP (Cat. #IT-18) was used as a control. Lesioned animals demonstrated a significant increase in mechanical hypersensitivity, and a smaller increase in thermal hypersensitivity. This and other results suggest that spinally projecting noradrenergic pathways are necessary for normal recovery from surgical incision, and possibly other types of pain.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Mouse IgG-SAP (Cat. #IT-18)
Catecholaminergic neurons in the comissural region of the nucleus of the solitary tract modulate hyperosmolality-induced responses.
Freiria-Oliveira A, Blanch G, Pedrino G, Cravo S, Murphy D, Menani J, Colombari D (2015) Catecholaminergic neurons in the comissural region of the nucleus of the solitary tract modulate hyperosmolality-induced responses. Am J Physiol Regul Integr Comp Physiol 309:R1082-1091. doi: 10.1152/ajpregu.00432.2014
Summary: Body fluid homeostasis and cardiovascular regulation are thought to be at least in part controlled by noradrenergic A2 neurons found in the nucleus of the solitary tract (NTS). In this work the authors investigated the involvement of A2 neurons of the commissural NTS in arterial pressure, as well as several body fluid homeostasis parameters. Rats received 12.6-ng injections of Anti-DBH-SAP (Cat. #IT-03) into the commissural NTS. Mouse IgG-SAP (Cat. #IT-18) was used as a control. Lesioned animals displayed increased c-Fos expression in the hypothalamic paraventricular nucleus when treated with hypertonic NaCl, and increased arterial pressure. The data indicate that commissural NTS A2 neurons are essential for inhibitory mechanisms that reduce water intake and pressor response to an acute increase in plasma osmolality.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Mouse IgG-SAP (Cat. #IT-18)
A2 noradrenergic neurons regulate forced swim test immobility
Nam H, Kerman I (2015) A2 noradrenergic neurons regulate forced swim test immobility. Neuroscience 2015 Abstracts 718.10/Y20. Society for Neuroscience, Chicago IL.
Summary: The Wistar-Kyoto rat (WKY) is a well-established animal model of depression- and anxiety-like behavior, characterized by high immobility during the forced swim test (FST) along with a generally inhibited phenotype on related tests of emotional behaviors. Extensive literature indicates that deficits in noradrenergic neurotransmission may contribute to these behavioral traits. Previously, we have reported that the WKY rats are more immobile compared to other rat strains from the beginning of their training phase of the FST, and that they become even more immobile during the testing phase on the next day. We hypothesized that higher immobility during the FST and the greater increase in immobility throughout different phases of the FST are two separate components of rats’ behavior likely mediated by different central mechanisms. We sought to identify the central circuits responsible for these behavioral components by studying activation of neurons within central noradrenergic cell groups during different phases of the FST. The WKY rats along with its parent strain, Wistar rats that experienced either the: 1) 5 minutes training phase (D1), or 2) entire FST (D1 and D2) were compared. Using double-immunocytochemistry for tyrosine hydroxylase and for c-Fos, we determined that within the A2 cell group significantly more noradrenergic neurons were activated in the Wistar than in WKY rats at D1. At D2 WKYs increased their activation of the A2 noradrenergic neurons, and this activation was equivalent to that of the Wistar group. Based on these results, we further investigated the role of A2 cell group during the FST using anti-DBH conjugated saporin (DSAP) to selectively destroy noradrenergic neurons within the area. The Wistar rats treated with DSAP were more immobile during both D1 and D2 of the FST as compared to the rats treated with the vehicle only. Together these data indicate that the A2 noradrenergic cell group regulates FST immobility in rats, and that its activation may contribute to the unique behavioral phenotype of WKY rats. Future experiments aimed at selective activation of A2 noradrenergic neurons will be required to fully elucidate the role of these neurons in mediating behavioral despair and learned helplessness.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Astrocytic lesions that spare neurons in the nucleus tractus solitarii interfere with cardiorespiratory control
Richerson GB, Dragon DN, Jones S, Wu Y, Talman WT (2015) Astrocytic lesions that spare neurons in the nucleus tractus solitarii interfere with cardiorespiratory control. Neuroscience 2015 Abstracts 297.15/B100. Society for Neuroscience, Chicago IL.
Summary: Conjugates of saporin (SAP) have been widely used to target specific neurons while leaving other neurons undisturbed. We found that killing catecholamine neurons bilaterally in the nucleus tractus solitarii (NTS) by injection of the SAP conjugate containing an antibody to dopamine-_-hydroxylase (anti-DBH-SAP) spared non-catecholamine neurons but led to attenuation of baroreceptor reflexes, lability of arterial pressure, and, in some animals, sudden death. In contrast, selective targeting of catecholamine neurons with 6-hydroxydopamine produced no such cardiovascular events. We hypothesized that SAP conjugates may target non-neuronal cells in the NTS. Indeed, we found that local astrocytes were killed by the conjugates as well as by unconjugated SAP itself. SAP injections into the NTS led to death of astrocytes that expressed glial fibrillary acidic protein (GFAP) but did not affect neuronal structural markers and neuronal biosynthetic enzymes. Our recent studies further suggest that local neurons are physiologically intact. Nonetheless, SAP injections into the NTS significantly reduced cardiovascular responses elicited by glutamate agonists injected into the NTS, and bilateral injections of SAP into the NTS led to attenuation of cardiovascular reflexes whose pathways pass through the NTS, lability of arterial pressure, damage to cardiac myocytes and sudden death resulting from asystole. When asystole and death followed SAP treatment the fatal arrhythmia followed progressive bradycardia. In that treated animals demonstrate altered ventilatory function, we conjecture that it is altered ventilation that leads to cardiac compromise and death.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Direct impact of dopaminergic and noradrenergic systems on adult-hippocampal neurogenesis in adult rats and the relevance to dementia in Parkinson’s disease
Ermine C, Wright JL, Parish CL, Thompson LH (2015) Direct impact of dopaminergic and noradrenergic systems on adult-hippocampal neurogenesis in adult rats and the relevance to dementia in Parkinson’s disease. Neuroscience 2015 Abstracts 217.06/C66. Society for Neuroscience, Chicago IL.
Summary: A key pathological feature of Parkinson’s disease (PD) is the progressive degeneration of midbrain dopaminergic neurons, causing motor dysfunction. However there are a range of ‘non-movement’ related features (including cognitive dysfunction, dementia and sleep disorder), which are not alleviated by dopamine replacement therapy. We are currently investigating the hypothesis that reduced hippocampal neurogenesis contributes to cognitive dysfunction in PD. We aim to characterise the effect of the dopaminergic and noradrenergic system on the adult-hippocampal neurogenesis in order to identify potential targets for the treatment cognitive impairments related to neurogenesis. We induced lesions of the different systems in adult rats using stereotaxic injections of toxins: 6-hydroxydopamine (dopaminergic system) and anti-dopa-β-hydroxylase-saporin (noradrenergic system). Four weeks later, the new cells were marked by pulses of bromodeoxyuridine (Brd-U) twice daily for 1 week. The animals were then sacrificed 4 weeks later for tissue collection. A high-performance liquid chromatography has confirmed that both lesions were successful: dopamine level in the striatum dropped to 20% and noradrenaline level in the hippocampus dropped to 8.3%. Surprisingly there was no difference in the number of Brd-U positive cells or in the number of double positive Brd-U/NeuN cells between our groups. The results show that while both noradrenergic and dopaminergic systems are implicated in the onsets of non-motor symptoms, they may not act through the regulation of adult-hippocampal neurogenesis like it was previously thought. Importantly our project has allowed reconsideration of how neurogenesis is involved in PD and redirected the therapies to better potential targets for treatment.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Selective inhibition of dopamine-beta-hydroxylase enhances dopamine release from noradrenergic terminals in the medial prefrontal cortex.
Devoto P, Flore G, Saba P, Frau R, Gessa G (2015) Selective inhibition of dopamine-beta-hydroxylase enhances dopamine release from noradrenergic terminals in the medial prefrontal cortex. Brain Behav 5:e00393. doi: 10.1002/brb3.393
Summary: Dopamine-beta-hydroxylase (DBH) is a neuronal enzyme that is a potential target for the treatment of cocaine abuse, alcohol dependence, and eating disorders. Here the authors administered 5 μg of icv Anti-DBH-SAP (Cat. #IT-03) to rats, and assessed the effect of the dopaminergic lesion on levels of extracellular dopamine. Mouse IgG-SAP (Cat. #IT-18) and saporin (Cat. #PR-01) were used as controls. Extracellular levels of dopamine were significantly increased in both lesioned animals and those treated with the DBH inhibitor nepicastat. Clonadine could reverse the nepicastat effect, but not the effect of Anti-DBH-SAP treatement. The data demonstrate a mechanism for the synergistic effect of cocaine on nepicastat-induced dopamine release.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Mouse IgG-SAP (Cat. #IT-18), Saporin (Cat. #PR-01)
Orexin-A enhances feeding in male rats by activating hindbrain catecholamine neurons.
Li A, Wang Q, Davis H, Wang R, Ritter S (2015) Orexin-A enhances feeding in male rats by activating hindbrain catecholamine neurons. Am J Physiol Regul Integr Comp Physiol 309:R358-367. doi: 10.1152/ajpregu.00065.2015
Summary: Although administration of orexin, norepinephrine, and epinephrine all induce significantly increased food intake, the potential interaction between the networks affected by these molecules has not been studied. In this work, the authors investigate the hypothesis that orexin neurons may stimulate feeding through the activation of catecholamine neurons. Rats received 82-ng injections of Anti-DBH-SAP (Cat. #IT-03) into the hypothalamus in order to lesion hypothalamically-projecting catecholamine neurons. Saporin (Cat. #PR-01) was used as a control. While the normal response to orexin A is increased food intake, lesioned animals did not display this response, indicating that catecholamine neurons are necessary for orexin modulation of food intake.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Saporin (Cat. #PR-01)