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Brainstem pre-sympathetic neurons contribute to irregular breathing patterns in volume overload heart failure.
Toledo C, Andrade DC, Del Rio R (2019) Brainstem pre-sympathetic neurons contribute to irregular breathing patterns in volume overload heart failure. FASEB J 33(1):lb630. Experimental Biology 2019 Meeting Abstracts doi: 10.1096/fasebj.2019.33.1_supplement.lb630
Objective: To investigate the contribution of RVLM-C1 neurons on breathing disorders in chronic heart failure (CHF).
Summary: RVLM-C1 neurons play a critical role in the maintenance of altered breathing patterns in CHF rats and highlighted their contribution to the worsening of cardiac function during central chemoreflex activation. DBH-SAP treatment decreased active expiration in CHF rats and deleterious effects of central chemoreflex activation on diastolic cardiac function and cardiac autonomic control were blunted.
Usage: Stereotaxic bilateral injections of Anti-DBH-SAP (5 ng/150 nl).
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Spinal α2-adrenoceptors and neuropathic pain modulation; therapeutic target.
Bahari Z, Meftahi GH (2019) Spinal α2-adrenoceptors and neuropathic pain modulation; therapeutic target. Br J Pharmacol 176(14):2366-2381. doi: 10.1111/bph.14580
Objective: To provide an an overview of the cellular mechanisms through which brainstem adrenergic descending inhibitory processing can alter spinal pain transmission to the higher centres, and how these pathways change in neuropathic pain conditions focusing on the role of spinal α2‐adrenoceptors in the spinal dorsal horn.
Summary: The α2‐adrenoceptor agonist may be useful to treat neuropathic pain.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Noradrenergic terminals are the primary source of α2-adrenoceptor mediated dopamine release in the medial prefrontal cortex.
Devoto P, Flore G, Saba P, Scheggi S, Mulas G, Gambarana C, Spiga S, Gessa GL (2019) Noradrenergic terminals are the primary source of α2-adrenoceptor mediated dopamine release in the medial prefrontal cortex. Prog Neuropsychopharmacol Biol Psychiatry 90:97-103. doi: 10.1016/j.pnpbp.2018.11.015
Objective: To clarify the relative contribution of dopamine (DA) release from noradrenergic and dopaminergic terminals to DA output induced by blockade of α2-adrenoreceptors and the norepinephrine transporter.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Ablation of brainstem C1 neurons improves cardiac function in volume overload heart failure.
Andrade DC, Toledo C, Díaz HS, Lucero C, Arce-Álvarez A, Oliveira LM, Takakura AC, Moreira TS, Schultz HD, Marcus NJ, Alcayaga J, Del Rio R (2019) Ablation of brainstem C1 neurons improves cardiac function in volume overload heart failure. Clin Sci (Lond) 133(3):393-405. doi: 10.1042/CS20180589
Objective: To determine the role played by RVLM-C1 neurons in cardiac autonomic imbalance, arrhythmogenesis and cardiac dysfunction in volume overload-induced heart failure.
Summary: RVLM-C1 neurons were selectively ablated using Anti-DBH-SAP and measures of cardiacautonomictone, function, and arrhythmia incidence were evaluated. Cardiac autonomic imbalance, arrhythmogenesis and cardiac dysfunction were present in HF rats and improved after Anti-DBH-SAP treatment.
Usage: 7.5ng/100nl of sterile saline solution was injected bilaterally into the RVLM.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Dissociable effects of noradrenergic and cholinergic lesions of anterior cingulate cortex on distractibility
McGaughy JA, Hutchins DJ, Pimentel AJ, Pimentel CS, Swaine JA (2018) Dissociable effects of noradrenergic and cholinergic lesions of anterior cingulate cortex on distractibility. Neuroscience 2018 Abstracts 238.14 / ZZ15. Society for Neuroscience, San Diego, CA.
Summary: Prior data from our lab and others has shown that that the anterior cingulate cortex (ACC) of the rat is critically involved in many aspects of executive function and cognitive control. Previously, we have shown that excitotoxic lesions of the ACC produced deficits in the ability of male rats to filter salient distractors. Additionally, these same subjects were unable to reverse reinforcement contingencies when tested with complex stimuli (Newman and McGaughy 2011). These deficits in filtering were not attributable to impairments in conditional discrimination learning, impairments in reversal learning with uni-dimensional stimuli or a general distractibility to conspicuous, irrelevant stimuli. In the present study, male, Long-Evans rats were used to determine if lesions to the noradrenergic or cholinergic afferents to ACC could recapitulate the effects of excitotoxic lesions in the same area. Lesions were produced by infusion into rostral ACC of dopamine β hydroxylase saporin or 192 IgG-saporin to deplete norepinephrine or acetylcholine, respectively. After two weeks of recovery from surgery, rats were tested in an intradimensional/extradimensional set-shifting task. This test was selected because of it’s utility in translational neuroscience and it’s sensitivity to several aspects of executive function including susceptibility to salient distractors, the ability to form an attentional set, the ability to shift an attentional set and reversal learning. Preliminary data show that noradrenergic, but not cholinergic lesions recapitulate some, but not all, of the impairments found after excitotoxic lesion of ACC. Specifically noradrenergic lesioned rats were more susceptible to salient distractors than sham-lesioned rats. In contrast to the effects of excitotoxic lesions, noradrenergic lesions did not impair the ability to reverse reinforcement contingencies when using complex stimuli containing salient, irrelevant stimulus dimensions. The extent of the lesions to ACC were assessed using markers for norepinephrine transporters and acetylcholinesterase. Together these data support the hypothesis that norepinephrine in the ACC is critically involved in the ability to filter salient distractors. The significance of these findings will be discussed in terms of the relevance of these data to the treatment of several neuropsychiatric disorders including attention deficit hyperactivity disorder, depression and addiction.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Noradrenergic modulation of the orbitofrontal cortex mediates flexibility of goal-directed behavior
Cerpa J-C, Marchand AR, Wolff M, Parkes SL, Coutureau E (2018) Noradrenergic modulation of the orbitofrontal cortex mediates flexibility of goal-directed behavior. Neuroscience 2018 Abstracts 325.09 / DDD22. Society for Neuroscience, San Diego, CA.
Summary: For an organism, knowledge of the consequences of its actions and the ability to assign a value to these consequences are both crucial processes allowing an appropriate goal-directed response. The major role of prefrontal regions, e.g. insular and medial prefrontal cortices, for these processes has been very well described. However, the mechanism by which the organism quickly adapt this goal-directed response to unexpected environmental changes remains unknown. It is possible to study this ability using instrumental learning. Typically, during an initial phase, an animal must associate voluntary actions with the delivery of rewarding outcomes. Then, during a reversal phase, the animal must respond flexibly to a modification of these associations. Using this task and chemogenetic tools allowing specific inhibition of cerebral regions, we have recently demonstrated a crucial role of the ventrolateral orbitofrontal cortex (vlOFC) for flexible response adaptation during the reversal phase (Parkes et al., 2017). In the present study, we focused on the noradrenaline (NA) input to the vlOFC which has been commonly implicated in flexibility-requiring tasks. In a first experiment, using a toxin (anti-DβH saporin) we selectively depleted noradrenergic fibers in the vlOFC and showed a deficit of behavioral flexibility. Notably, this effect was not only specific to the reversal phase but also to vlOFC input since a similar depletion restricted to the medial portion of the prefrontal cortex had no effect. Using an intersectional chemogenetic approach aiming at selectively targeting the locus cœruleus (LC) input to the vlOFC, we are deciphering the time course of the involvement of this pathway during behavioural flexibility. Taken together, these results demonstrate a central role for noradrenaline input to the vlOFC in behavioural flexibility and reinforce the idea that the LC exerts a strong modulation of OFC functions.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Noradrenergic hypothesis linking neurodegeneration-based cognitive decline and astroglia.
Leanza G, Gulino R, Zorec R (2018) Noradrenergic hypothesis linking neurodegeneration-based cognitive decline and astroglia. Front Mol Neurosci 11:254. doi: 10.3389/fnmol.2018.00254
Objective: To examine noradrenergic dysfunction in AD-related cognitive decline in humans and its potential involvement in AD pathology and disease progression.
Summary: The authors discuss noradrenergic dysfunction in AD-related cognitive decline. The research focuses on animal models to allow the validation of the noradrenergic hypothesis of AD, including those based upon the Anti-DBH-SAP-mediated ablation of LC. The article also addresses how astrocytes may participate in the regulation of neurogenesis, a new strategy for preventing LC neuron loss.
Usage: DBH (–/–) knockout mice do not seem to offer the possibility to obtain partial or graded neurotransmitter depletions. In light of these limitations, the authors used Anti-DBH-SAP which is able to target noradrenergic neurons in the LC with unprecedented selectivity and efficiency. Anti-DBH-SAP was injected bilaterally into the LC.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Involvement of median preoptic nucleus and medullary noradrenergic neurons in cardiovascular and sympathetic responses of hemorrhagic rats
Naves LM, Marques SM, Mourão AA, Fajemiroye JO, Xavier CH, de Castro CH, Rebelo ACS, Rosa DA, Gomes RM, Colombari E, Pedrino GR (2018) Involvement of median preoptic nucleus and medullary noradrenergic neurons in cardiovascular and sympathetic responses of hemorrhagic rats. Sci Rep 8:11276. doi: 10.1038/s41598-018-29310-z
Objective: To evaluate the involvement of median preoptic nucleus (MnPO) and medullary noradrenergic neurons (A1 and A2) in HSS-induced cardiovascular and sympathetic responses in hemorrhagic rats.
Summary: The recovery of MAP and HSS-induced sympathoinhibition in hemorrhaged rats depend on intact neural projections from A1 and A2 to MnPO.
Usage: In order to achieve A1 and/or A2 neuronal lesions, Anti-DBH-SAP (100 nL, 0.105 ng·nL−1 ) was nanoinjected into the CVLM and NTS region, respectively. In sham groups, the equimolar of Saporin (100 nL, 0.022 ng·nL−1 ) was nanoinjected into the same site.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Saporin (Cat. #PR-01)
Why I can’t say “no” to hindbrain catecholamine neurons
Ritter S (2018) Why I can’t say “no” to hindbrain catecholamine neurons. Appetite 126:210. doi: 10.1016/j.appet.2018.02.035
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Essential role of hippocampal noradrenaline in the regulation of spatial working memory and TDP‐43 tissue pathology
Pintus R, Riggi M, Cannarozzo C, Valeri A, de Leo G, Romano M, Gulino R, Leanza G (2018) Essential role of hippocampal noradrenaline in the regulation of spatial working memory and TDP‐43 tissue pathology. J Comp Neurol 526:1131-1147. doi: 10.1002/cne.24397
Objective: To determine the noradrenergic contribution to cognitive and histopathological changes in Alzheimer’s Disease.
Summary: Integrity of ascending noradrenergic inputs to the hippocampus may be required for the regulation of specific aspects of learning and memory and to prevent TDP-43 tissue pathology.
Usage: Anti-DBH-SAP was used at a dose of 0.50 µg dissolved in sterile PBS.
Related Products: Anti-DBH-SAP (Cat. #IT-03)