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Time- and dose-response of 6-hydroxydopamine on locus coeruleus noradrenegric neurons in c57bl/6 mice
Szot P, Franklin A, White S, Raskind M (2010) Time- and dose-response of 6-hydroxydopamine on locus coeruleus noradrenegric neurons in c57bl/6 mice. Neuroscience 2010 Abstracts 157.20/R1. Society for Neuroscience, San Diego, CA.
Summary: Locus coeruleus (LC) noradrenergic neurons are severely reduced in Alzheimer’s and Parkinson’s disease. However, it is unclear why these neurons are lost and the consequence of this loss on the progression and symptoms of these neurodegenerative disorders. Therefore, establishing an animal model of LC noradrenergic neuronal loss is critical in determining how the LC contributes to these disorders. The purpose of this study was to determine the dose- and time-response of noradrenergic neurotoxicity of 6-hydroydopamine (6OHDA) in adult male C57BL/6 mice. Our laboratory recently demonstrated that DSP4 does not result in a loss of LC noradrenergic neurons. Neurotoxicity of 6OHDA on LC noradrenergic neurons was determined by measuring tyrosine hydroxylase (TH) mRNA expression and TH-immunoreactivity (IR) in LC noradrenergic neurons. TH mRNA was quantitated using MCID (OD), while TH-IR was used to determine if protein levels reflected what was observed with mRNA. 6OHDA (20 µg/µl bilaterally) and dopamine beta-hydroxylase-saporin (DBH-saporin; 1 µg/µl bilaterally) were initially administered into the lateral ventricles (icv) and sacrificed 2 weeks later. 6OHDA reduced TH mRNA and -IR in both the dopaminergic neurons of the substantia nigra (SNpc) and ventral tegmental nucleus (VTA), and LC by -46%, -65% and -63%, respectively. DBH-saporin icv injection did not affect dopaminergic or noradrenergic neurons. Injection of DBH-saporin into the LC (0.1 µg/µl unilaterally) also did not affect LC noradrenergic neurons 2 weeks later. As a time-course 6OHDA (7 µg/µl) was injected unilaterally into the LC (vehicle was administered in the alternate LC) and sacrificed 3 days, 2 and 3 weeks later. A loss of LC noradrenergic neurons was observed only 3 weeks later (-81.4%). 6OHDA was then injected unilaterally into the LC at 7, 10, and 14 ug/ul (vehicle was administered in the alternate LC) and sacrificed 2 weeks later. The 7 µg/µl dose of 6OHDA did not affect TH mRNA in the LC as compared to control side (-19%), 10 ug/ul 6OHDA significantly reduced TH mRNA in the LC by ~55%, and 14 ug/ul 6OHDA dramatically reduced TH mRNA in the LC by ~90%. TH-IR in the LC of the three different 6OHDA doses reflected closely the TH mRNA data. 6OHDA at the dose of 14 µg/µl, which resulted in a near complete loss of LC noradrenergic neurons, did not affect dopaminergic neurons in the SN (-9%) and VTA (+17%). These data indicate that DBH-saporin, at the parameters studied, did not affect mouse LC noradrenergic neurons. 6OHDA demonstrated a time- and dose-response reduction of mouse LC noradrenergic neurons. The consequence of this LC neuronal loss on forebrain noradrenergic markers will also be presented.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Locus ceruleus and anterior cingulate cortex sustain wakefulness in a novel environment.
Gompf HS, Mathai C, Fuller PM, Wood DA, Pedersen NP, Saper CB, Lu J (2010) Locus ceruleus and anterior cingulate cortex sustain wakefulness in a novel environment. J Neurosci 30(43):14543-14551. doi: 10.1523/JNEUROSCI.3037-10.2010
Objective: To examine arousal due to environmental stimuli after lesioning of the Locus ceruleus (LC).
Summary: Lesioned animals did not show sustained neurobehavioral and EEG arousal in response to a novel environment. The data suggest sustained attention requires an interaction between the LC and the anterior cingulate cortex.
Usage: Anti-DBH-SAP (0.25-1 µg) was injected into the lateral ventricle of rats.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Noradrenergic nuclei that receive sensory input during mating and project to the ventromedial hypothalamus play a role in mating-induced pseudopregnancy in the female rat.
Northrop LE, Polston EK, Erskine MS (2010) Noradrenergic nuclei that receive sensory input during mating and project to the ventromedial hypothalamus play a role in mating-induced pseudopregnancy in the female rat. J Neuroendocrinol 22(10):1061-1071. doi: 10.1111/j.1365-2826.2010.02049.x
Summary: Maintenance of pregnancy or pseudopregnancy in rats is maintained by bicircadian prolactin surges induced by vaginal-cervical stimulation. In order to test the hypothesis that medullary noradrenergic cell groups are involved in this process the authors infused rats with either 2 ng or 60 ng anti-DBH-SAP (Cat. #IT-03) into the ventrolateral division of the ventromedial hypothalamus (VMHv1) and the posterodorsal medial amygdala. Mouse IgG-Sap (Cat. #IT-18) was used as a control. The data confirm that noradrenergic neurons are involved in the maintenance of pregnancy or pseudopregnancy.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Mouse IgG-SAP (Cat. #IT-18)
Contribution of limbic norepinephrine to cannabinoid-induced aversion.
Carvalho AF, Reyes AR, Sterling RC, Unterwald E, Van Bockstaele EJ (2010) Contribution of limbic norepinephrine to cannabinoid-induced aversion. Psychopharmacology (Berl) 211(4):479-491. doi: 10.1007/s00213-010-1923-7
Summary: The authors used bilateral injections of anti-DBH-SAP (Cat. #IT-03) into the nucleus accumbens and the bed nucleus of the stria terminalis to investigate the role of neuroepinephrine in cannabinoid-induced aversion and anxiety. Lesioned animals received bilateral 52.5 ng-injections of anti-DBH-SAP into the nucleus accumbens or 63 ng into the bed nucleus of the stria terminalis. Saporin (Cat. #PR-01) was used as a control. Lesioned animals displayed reversed aversive behavior, but no change in anxiety-like behavior.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Saporin (Cat. #PR-01)
Noradrenergic neurons of the area postrema mediate amylin’s hypophagic action.
Potes CS, Turek VF, Cole RL, Vu C, Roland BL, Roth JD, Riediger T, Lutz TA (2010) Noradrenergic neurons of the area postrema mediate amylin’s hypophagic action. Am J Physiol Regul Integr Comp Physiol 299(2):R623-631. doi: 10.1152/ajpregu.00791.2009
Summary: Amylin decreases food intake in rats and is a satiation signal affecting the area postrema (AP). This work investigated the role of noradrenergic neurons in amylin activity. Rats received a total of 50 ng of anti-DBH-SAP (Cat. #IT-03) into the AP and 25 ng into the lateral parabrachial nucleus. Mouse IgG-SAP (Cat. #IT-18) was used as a control. Rats showing a >50% lesion of noradrenergic neurons were unresponsive to low doses of amylin, suggesting that noradrenergic neurons are part of the amylin pathway.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Mouse IgG-SAP (Cat. #IT-18)
Splanchnic sympathectomy prevents translocation and spreading of E coli but not S aureus in liver cirrhosis.
Worlicek M, Knebel K, Linde HJ, Moleda L, Scholmerich J, Straub RH, Wiest R (2010) Splanchnic sympathectomy prevents translocation and spreading of E coli but not S aureus in liver cirrhosis. Gut 59(8):1127-1134. doi: 10.1136/gut.2009.185413
Summary: Advanced cirrhosis activates the sympathetic nervous system. This work investigates the role of the sympathetic nervous system (SNS) in spontaneous bacterial peritonitis – which is mainly caused by translocation of enteric Gram-negative bacteria. Rats received 15 µg intraperitoneal injections of anti-DBH-SAP (Cat. #IT-03). Lesioned animals displayed increased susceptibility to bacterial translocation and infection with E. coli but not S. aureus. This suggests the SNS plays an important role in the immune response to Gram-negative bacteria.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Hindbrain catecholamine neurons modulate the growth hormone but not the feeding response to ghrelin.
Emanuel AJ, Ritter S (2010) Hindbrain catecholamine neurons modulate the growth hormone but not the feeding response to ghrelin. Endocrinology 151(7):3237-3246. doi: 10.1210/en.2010-0219
Summary: In this work the authors investigated the role of hindbrain catecholamine neurons in the response to a gastrointestinal peptide, ghrelin. Rats received 42 ng injections of anti-DBH-SAP (Cat. #IT-03) into the paraventricular nucleus of the hypothalamus. Saporin (Cat. #PR-01) was used as a control. Lesioned animals had a prolonged growth hormone (GH) response to ghrelin administration as compared to controls, but the feeding response was unchanged. The results indicate that ghrelin or GH may be involved with a negative feedback response controlling GH levels.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Saporin (Cat. #PR-01)
Selective lesion of the developing central noradrenergic system: Short- and long-term effects and reinnervation by noradrenergic-rich tissue grafts.
Coradazzi M, Gulino R, Garozzo S, Leanza G (2010) Selective lesion of the developing central noradrenergic system: Short- and long-term effects and reinnervation by noradrenergic-rich tissue grafts. J Neurochem 114(3):761-771. doi: 10.1111/j.1471-4159.2010.06800.x
Summary: The authors removed noradrenergic neurons in the locus coeruleus/subcoeruleus complex of neonatal rats with 0.25-1.0 µg bilateral injections of anti-DBH-SAP (Cat. #IT-03). No damage was seen in dopaminergic, adrenergic, serotonergic, or cholinergic neurons after this treatment. Rats receiving fetal locus coeruleus tissue implants showed significant post-lesion recovery suggesting that this model can be used to investigate compensatory reinnervation and functional recovery in the central nervous system.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Cardiovascular and behavioural responses to conditioned fear and restraint are not affected by retrograde lesions of A5 and C1 bulbospinal neurons.
Vianna DM, Carrive P (2010) Cardiovascular and behavioural responses to conditioned fear and restraint are not affected by retrograde lesions of A5 and C1 bulbospinal neurons. Neuroscience 166:1210-1218. doi: 10.1016/j.neuroscience.2010.01.039
Summary: To investigate the role of A5 neurons in some forms of psychological stress the authors injected 22 or 44 ng of anti-DBH-SAP (Cat. #IT-03) into the spinal cord of rats. Mouse IgG-SAP (Cat. #IT-18) was used as a control. The data shows that A5 presympathetic neurons are not essential for the expression of the tachycardic and pressor responses to conditioned fear and restraint.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Mouse IgG-SAP (Cat. #IT-18)
The hyperalgesic effects induced by the injection of angiotensin II into the caudal ventrolateral medulla are mediated by the pontine A(5) noradrenergic cell group.
Marques-Lopes J, Pinho D, Albino-Teixeira A, Tavares I (2010) The hyperalgesic effects induced by the injection of angiotensin II into the caudal ventrolateral medulla are mediated by the pontine A(5) noradrenergic cell group. Brain Res 1325:41-52. doi: 10.1016/j.brainres.2010.02.043
Summary: Injection of angiotensin II into the caudal ventrolateral medulla (CVLM) has been shown to induce angiotensin type 1 receptor-mediated hyperalgesia. Here the authors lesioned the pontine A5 cell group with anti-DBH-SAP (Cat. #IT-03) to evaluate the role of these neurons in this model. Rats received a 1.1 µg injection of anti-DBH-SAP into the CVLM. Behavioral responses indicate that loss of noradrenergic neurons in the CVLM partially prevented angiotensin II-induced hyperalgesia.
Related Products: Anti-DBH-SAP (Cat. #IT-03)