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Alteration of BDNF and noradrenergic markers in locus coeruleus in a mouse model of cancer-induced bone pain
Yuan M, Zhang L, Zhu H, Xie M (2025) Alteration of BDNF and noradrenergic markers in locus coeruleus in a mouse model of cancer-induced bone pain. PLoS One 20(8):e0330207. doi: 10.1371/journal.pone.0330207 PMID: 40811566
Objective: To examine the expression and localization of BDNF and NE neuron-specific proteins in the locus coeruleus (LC) of mice with cancer-induced bone pain (CIBP).
Summary: CIBP mice exhibited enhanced neuronal activity in the LC, upregulation of noradrenergic markers, and BDNF/TrkB-mediated modulation of noradrenergic neurons. Concurrently, inhibitory signalling was attenuated in the spinal dorsal horn (SDH).
Usage: Selective ablation of noradrenergic neurons via intracerebroventricular anti-DBH-SAP (IT-03) administration reduces mechanical and cold allodynia, suggesting that LC-spinal cord pathway activity is critical for pain modulation.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
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Cognitive and histopathological alterations in rat models of early- and late-phase memory dysfunction: Effects of sigma-1 receptor activation
Kostenko A, Prezzavento O, de Leo G, D’Arco D, Gulion R, Caccamo A, Leanza G (2024) Cognitive and histopathological alterations in rat models of early- and late-phase memory dysfunction: Effects of sigma-1 receptor activation. J Alzheimers Dis 101(3) doi: 10.3233/JAD-240618 PMID: 39240642
Objective: This study sought to assess the role of (±)-cyclopropane carboxylate (PPCC) on working memory deficits caused by noradrenergic depletion.
Summary: While (±)-PPCC alone at a dose of 1 mg/kg/day failed to affect working memory in lesioned animals, its association with the α2 adrenergic receptor agonist clonidine, completely blocked noradrenaline release, significantly improving rat performance. This effect, distinct from noradrenaline activity, is likely to result from a direct action of the (±)-PPCC compound onto sigma-1 receptors, as pre-treatment with the selective sigma-1 receptor antagonist BD-1047 reversed the improved working memory performance. Despite such clear functional effects, the treatment did not affect noradrenergic neuron survival or terminal fiber proliferation.
Usage: Bilateral intraventricular injections of anti-DBH-saporin (IT-03). Either 1.25μg or 2.5μg of the immunotoxin was dissolved in 7μl of sterile PBS and administered into each lateral ventricle (resulting in a total of 2.5μg or 5.0μg per rat in a 7 + 7μl volume of vehicle).
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Brainstem Dbh+ neurons control allergen-induced airway hyperreactivity
Su Y, Xu J, Zhu Z, Chin J, Xu L, Yu H, Nudell V, Dash B, Moya EA, Ye L, Nimmerjahn A, Sun X (2024) Brainstem Dbh+ neurons control allergen-induced airway hyperreactivity. Nature 631(8021):601-609. doi: 10.1038/s41586-024-07608-5 PMID: 38987587
Objective: To map a full allergen circuit from the lung to the brainstem and back to the lung. Repeated exposure of mice to inhaled allergen activated the nuclei of solitary tract (nTS) neurons in a mast cell-, interleukin-4 (IL-4)- and vagal nerve-dependent manner.
Summary: Ablation or chemogenetic inactivation of Dbh+nTS neurons blunted hyperreactivity whereas chemogenetic activation promoted it. Viral tracing indicated that Dbh+nTS neurons project to the nucleus ambiguous (NA) and that NA neurons are necessary and sufficient to relay allergen signals to postganglionic neurons that directly drive airway constriction. Delivery of noradrenaline antagonists to the NA blunted hyperreactivity, suggesting noradrenaline as the transmitter between Dbh+nTS and NA.
Usage: To determine whether Dbh+nTS neurons are essential for hyperreactivity chemical ablation, anti-dopamine beta-hydroxylase antibody conjugated to saporin (Anti-DBH-SAP, IT-03), shown to be specific for DBH+neurons, was injected into the nTS.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Cardiorespiratory disturbances in Alzheimer’s disease: A focus on the contribution of sympathetic premotor neurons
Toledo C, Del Rio R (2024) Cardiorespiratory disturbances in Alzheimer’s disease: A focus on the contribution of sympathetic premotor neurons. Am Physiol Summit 39(S1) doi: 10.1152/physiol.2024.39.S1.2540
Objective: To characterize cardiorespiratory function in AD patients and then to determine the role of RVLM-C1 neurons in autonomic and sleep-disordered breathing in APP/PS1 double transgenic mice, and experimental model showing AD-like pathology.
Summary: Results show that RVLM-C1 neurons play a main role in the development/maintenance of cardiorespiratory disorders in experimental AD.
Usage: Bilateral stereotaxic injections of Anti-DBH-SAP (IT-03) into the RVLM were used to selectively destroy C1 neurons.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
An ascending vagal sensory-central noradrenergic pathway modulates retrieval of passive avoidance memory
Edwards CM, Guerrero IE, Thompson D, Dolezel T, Rinaman L (2024) An ascending vagal sensory-central noradrenergic pathway modulates retrieval of passive avoidance memory. bioRxiv 2024.04.09.588717. doi: 10.1101/2024.04.09.588717 PMID: 38645069
Objective: To investigate the role of a gut vagal afferent-to-central noradrenergic pathway in modulating the retrieval of conditioned passive avoidance memory in rats.
Summary: This study explores how visceral sensory feedback via vagal afferents and central noradrenergic neurons influences passive avoidance memory retrieval. By lesioning specific neural pathways in adult male rats, the researchers demonstrate that disruption of these circuits significantly increased conditioned passive avoidance behavior, suggesting a critical role for these pathways in integrating interoceptive signals with contextual cues to modulate learned avoidance behaviors.
Usage: 250 ng of CCK-SAP (IT-31) was bilaterally injected into the nodose ganglion to selectively lesion gastrointestinal vagal afferents. 80 ng of Anti-DBH-SAP (IT-03) was injected bilaterally into the ventrolateral bed nucleus of the stria terminalis (vlBNST) to selectively lesion noradrenergic inputs to the anterior vlBNST.
Related Products: CCK-SAP (Cat. #IT-31), Anti-DBH-SAP (Cat. #IT-03)
Reduction of body weight by increased loading is associated with activation of norepinephrine neurones in the medial nucleus of the solitary tract
Zlatkovic J, Dalmau Gasull A, Hägg D, Font-Gironès F, Bellman J, Meister B, Palsdottir V, Ruud J, Ohlsson C, Dickson SL, Anesten F, Jansson JO (2023) Reduction of body weight by increased loading is associated with activation of norepinephrine neurones in the medial nucleus of the solitary tract. J Neuroendocrinol 35(12):e13352. doi: 10.1111/jne.13352 PMID: 37885347
Objective: To show that the feed-back regulation of body weight, initiated by a novel leptin-independent body weight homeostat, involves a CNS mechanism
Summary: In conclusion, increased load appears to reduce body weight and food intake via activation of norepinephrine neurones in the medial nucleus of the solitary tract.
Usage: 5 ng of Anti-DBH-SAP (IT-03) was bilaterally injected into the NTS in Male C57/B6J mice and Sprague–Dawley rats.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Regulation of nociception threshold by norepinephrine through adrenergic α2 receptor in rat models of Parkinson’s disease
Gao Q, Zhang Y, Wang X, Wang R, Zhang L (2024) Regulation of nociception threshold by norepinephrine through adrenergic α2 receptor in rat models of Parkinson’s disease. CNS Neurosci Ther 30(3):e14446. doi: 10.1111/cns.14446 PMID: 37721421
Objective: To investigate the effect of norepinephrine on the activation of brain cells through adrenergic α2 receptor, to regulate the nociception threshold in a 6-OHDA-induced animal model of Parkinson’s disease (PD).
Summary: The change of norepinephrine content can affect the activation of prefrontal and cingulate gyrus glial cells and participate in the regulation of nociception threshold in PD rats. Adrenergic α2 receptor agonist and central presynaptic membrane α2 receptor blocker both affect cell activation and improve hyperalgesia.
Usage: 4 μL of Anti-DBH-saporin was injected into the right lateral ventricle (1.25 μg/μL, 0.9% NaCl dilution), and injected at the rate of 1 μL/min.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Locus coeruleus-noradrenergic modulation of trigeminal pain: Implications for trigeminal neuralgia and psychiatric comorbidities
Donertas-Ayaz B, Caudle RM (2023) Locus coeruleus-noradrenergic modulation of trigeminal pain: Implications for trigeminal neuralgia and psychiatric comorbidities. Neurobiol Pain 13:100124. doi: 10.1016/j.ynpai.2023.100124 PMID: 36974102
Objective: To summarize the knowledge about the involvement of noradrenaline in acute and chronic trigeminal pain conditions and how the activity of the locus coeruleus (LC) noradrenergic neurons changes in response to acute and chronic pain conditions and how these changes might be involved in pain-related comorbidities including anxiety, depression, and sleep disturbance.
Summary: LC inhibition of nociceptive transmission in acute pain and in longterm neuropathic pain increases the tonic activity of LC-NA neurons. These changes may contribute to impaired descending pain modulation and pain-related comorbidities such as depression, anxiety, and sleep disorders.
Usage: Elimination of NA neurons via injection of anti-dopamine β-hydroxylase-saporin (Anti-DBH-SAP) into the lateral ventricle and trigeminal brainstem nuclei three weeks after infraorbital nerve injury attenuated mechanical allodynia
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Adrenergic signalling to astrocytes in anterior cingulate cortex contributes to pain-related aversive memory in rats
Iqbal Z, Lei Z, Ramkrishnan AS, Liu S, Hasan M, Akter M, Lam YY, Li Y (2023) Adrenergic signalling to astrocytes in anterior cingulate cortex contributes to pain-related aversive memory in rats. Commun Biol 6:10. doi: 10.1038/s42003-022-04405-6 PMID: 36604595
Objective: To identify the role of norepinephrine in colorectal distention (sub-threshold for acute pain) induced conditioned place avoidance and plasticity gene expression in the anterior cingulate cortex (ACC).
Summary: The findings suggest that projection-specific adrenergic astrocytic signaling in ACC is integral to system-wide neuromodulation in response to visceral stimuli and plays a key role in mediating pain-related aversion consolidation and memory formation.
Usage: 0.25 ug of Anti-DBH-SAP (1 μg/μl) was injected into each hemisphere of locus coeruleus (LC).
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Towards astroglia-based noradrenergic hypothesis of Alzheimer’s disease
Leanza G, Zorec R (2023) Towards astroglia-based noradrenergic hypothesis of Alzheimer’s disease. Function (Oxf) 4(1):zqac060., IT. doi: 10.1093/function/zqac060 PMID: 36590326
Summary: These results indicate a prominent role of NA-neurons vs. ACh neurons in impairments of working memory, relevant for AD, and are consistent with an astrocyte-specific metabolic impairment in a mouse model of intellectual disability.
Usage: Bilateral icv injection of 192-IgG-SAP and/or Anti-DBH-SAP
Related Products: 192-IgG-SAP (Cat. #IT-01), Anti-DBH-SAP (Cat. #IT-03)