Tapa S, Wang L, Francis Stuart SD, Wang Z, Jiang Y, Habecker BA, Ripplinger CM (2020) Adrenergic supersensitivity and impaired neural control of cardiac electrophysiology following regional cardiac sympathetic nerve loss. Sci Rep 10:18801. doi: 10.1038/s41598-020-75903-y
Summary: The authors present a novel mouse model of regional cardiac sympathetic hypo-innervation utilizing Anti-DBH-SAP.
Usage: Either 5μL of 40 ng/μL Anti-DBH-SAP or Mouse IgG-SAP (control) was applied three times directly to the exposed apical/anterior surface of the heart.
Liu X, Wang D, Wen Y, Zeng L, Li Y, Tao T, Zhao Z, Tao A (2020) Spinal GRPR and NPRA contribute to chronic itch in a murine model of allergic contact dermatitis. J Invest Dermatol 140(9):1856-1866.e7. doi: 10.1016/j.jid.2020.01.016
Objective: The authors investigated the peripheral and spinal mechanisms responsible for prolonged itch in a mouse model of allergic contact dermatitis (ACD) induced by squaric acid dibutylester (SADBE).
Summary: Targeting gastrin-releasing peptide receptor (GRPR) and natriuretic peptide receptor A (NPRA) may provide effective treatments for ACD associated chronic pruritus.
Usage: A single dose of Bombesin-SAP (400 ng) and Blank-SAP (400 ng) or two doses of Nppb-SAP (BNP-SAP; 650 ng) and Blank-SAP (650 ng) were administered via intrathecal injection.
Kiguchi N, Uta D, Ding H, Uchida H, Saika F, Matsuzaki S, Fukazawa Y, Abe M, Sakimura K, Ko MC, Kishioka S (2020) GRP receptor and AMPA receptor cooperatively regulate itch-responsive neurons in the spinal dorsal horn. Neuropharmacology 170:108025. doi: 10.1016/j.neuropharm.2020.108025
Objective: To investigate the mechanisms for the activation of itch-responsive GRPR+ neurons in the spinal dorsal horn (SDH).
Summary: These findings demonstrate that GRP and glutamate cooperatively regulate GRPR+ AMPAR+ neurons in SDH, mediating itch sensation. GRP–GRPR and the glutamate–AMPAR system may play pivotal roles in the spinal transmission of itch in rodents and nonhuman primates.
Usage: Bombesin-SAP and Blank-SAP were administered i.t. (5 μg/5 μl).
Harris RBS (2020) Loss of leptin receptor-expressing cells in the hindbrain decreases forebrain leptin sensitivity. Am J Physiol Endocrinol Metab 318(5):E806-E816. doi: 10.1152/ajpendo.00020.2020
Objective: This study tested whether loss of hindbrain leptin receptor signaling changed sensitivity to forebrain leptin.
Summary: Loss of VMH (ventromedial nucleus of hippocampus) leptin receptor-expressing cells prevents weight loss. The integrated response between the hindbrain and forebrain is heavily dependent upon leptin activity in the VMH.
Usage: To test forebrain leptin sensitivity Leptin-SAP and Blank-SAP rats received third ventricle injections of 0, 0.05, 0.1, 0.25 or 0.5 μg leptin.
Qian L, Kasas L, Milne MR, Rawashdeh O, Marks N, Sharma A, Bellingham MC, Coulson EJ (2020) Cholinergic basal forebrain degeneration due to obstructive sleep apnoea increases Alzheimer’s pathology in mice. bioRxiv 2020.03.12.989848. doi: 10.1101/2020.03.12.989848
Usage: bilateral injections of urotensin II-saporin (UII-SAP; 0.07 μg/μL per site – unless stated otherwise; generous gift from Advanced Targeting Systems)
Bernabe CS, Caliman IF, Truitt WA, Molosh AI, Lowry CA, Hay-Schmidt A, Shekhar A, Johnson PL (2020) Using loss- and gain-of-function approaches to target amygdala-projecting serotonergic neurons in the dorsal raphe nucleus that enhance anxiety-related and conditioned fear behaviors. J Psychopharmacol 34(4):400-411. doi: 10.1177/0269881119900981
Objective: To investigate the role of amygdala-projecting 5-HT neurons in the DR in innate anxiety and conditioned fear behaviors.
Summary: The studies support the hypothesis that amygdala-projecting 5-HT neurons in the DR represent an anxiety and fear-on network.
Usage: Each rat received two bilateral microinjections per site (100 nL each, 1 μM in artificial cerebrospinal fluid) of either Anti-SERT-SAP or the control Mouse IgG-SAP.
Zhang F, Huan L, Xu T, Li G, Zheng B, Zhao H, Guo Y, Shi J, Sun J, Chen A (2020) Inflammatory macrophages facilitate mechanical stress-induced osteogenesis. Aging (Albany NY) 12(4):3617-3625. doi: 10.18632/aging.102833
Summary: In a mouse model of distraction osteogenesis (DO), there was significant increase in macrophages in the regeneration area. This suggests that targeting inflammatory macrophages may help to improve clinical bone repair.
Usage: For saporin-mediated depletion of macrophages, DO-surgery-treated mice received an intraventricular (iv) injection of either Mac-1-SAP or Rat IgG-SAP (20µg) once every 3 days.
Crevier-Sorbo G, Rymar, VV,Crevier-Sorbo R, Sadikot AF (2020) Thalamostriatal degeneration contributes to dystonia and cholinergic interneuron dysfuntion in a mouse model of huntington’s disease. Acta Neruopatho Commun 8(1):14. doi: 10.1186/s40478-020-0878-0 PMID: 32033588
Objective: To ablate the neurons of the Thalamostrial system (TS) to elucidate their role in the motor symptoms of Huntington’s Disease.
Summary: Huntington’s disease is an autosomal disorder characterized by involuntary movement and striatal neuronal loss. Glutaminergic input from the TS is implicated in disease progression and motor deficits. Anti-ChAT-SAP is used to ablate neurons in the Thalamostrial system to understand the role these neurons played in Huntington’s.
Usage: Mice underwent unilateral, striatal injections with either Anti-ChAT-SAP (IT-42) or Rabbit IgG-SAP (IT-35). The total volume and concentration of either saporin construct was the same (0.7 μL of 0.6 μg/μL solution).
Kelly SC, McKay EC, Beck JS, Collier TJ, Dorrance AM, Counts SE (2019) Locus coeruleus degeneration induces forebrain vascular pathology in a transgenic rat model of alzheimer’s disease. J Alzheimers Dis 70(2):371-388. doi: 10.3233/JAD-190090 PMID: 31177220
Objective: To understand the extent to which locus coeruleus projection system degeneration influences vascular pathology.
Summary: Noradrenergic locus coeruleus (LC) neuron loss is a significant feature of mild cognitive impairment and Alzheimer’s disease (AD). The authors stereotactically lesioned LC projection neurons innervating the prefrontal cortex of six-month-old Tg344–19 AD rats using DBH-SAP, or an untargeted control IgG-SAP. DBH-sap-lesioned animals performed significantly worse than IgG-sap animals on the Barnes maze task in measures of both spatial and working memory. DBH-sap-lesioned rats also displayed increased amyloid and inflammation pathology compared to IgG-sap controls. Results indicate that LC projection system degeneration is a nexus lesion that compromises both vascular and neuronal function in cognitive brain areas during the prodromal stages of AD.
Usage: Anti-DBH-SAP (IT-03) or control Mouse IgG-sap (IT-18) were administered to the PFC bilaterally ( 2.5 μg/injection).
