Borkowski LF, & Nichols NL. A2A and 5-HT Receptors are Differentially Required for Respiratory Plasticity Over the Course of Motor Neuron Loss in Intrapleurally CTB-SAP Treated Rats. (2019). FASEB J, 33 (1_supplement):843.843-843.843.
IT-14: CTB-SAP Dose: Bilateral, intrapleural injections of: 1) CTB-SAP (25 μg), or 2) un-conjugated CTB and SAP (control) in rats.
Toledo C, Andrade DC, & Del Rio R. Brainstem pre-sympathetic neurons contribute to irregular breathing patterns in volume overload heart failure. (2019). The FASEB Journal, 33 (1_supplement):lb630-lb630.
Sajjadi E, Seven YB, Simon AK, Zwick A, Satriotomo I, & Mitchell GS. Adenosine 2A Receptor Inhibition Promotes Neuroprotection Following Toxic Insult to Phrenic Motor Neurons. (2019). FASEB J, 33 (1_supplement):844.843-844.843.
IT-14: CTB-SAP Dose: CTB-SAP selectively killed nearly all phrenic motor neurons within a week and caused diaphragm paralysis (p<0.01).
Souza G, Stornetta R, Stornetta D, Abbott S, & Guyenet P. Contribution of retrotrapezoid nucleus and carotid bodies to asphyxia-induced arousal in rats. (2019). FASEB J, 33 (1_supplement):733.736-733.736.
IT-11: SSP-SAP Dose: RTN was nearly completely destroyed with microinjections of SSP-SAP (2.4 ng).
A review of the tools for studying Parkinson’s Disease
These results show that an antibody to the extracellular domain of the dopamine transporter (DAT) can be used to target midbrain dopaminergic neurons and that Anti-DAT-Saporin may be useful for producing a lesion very similar to the naturally-occurring neural degeneration seen in Parkinson’s Disease (Wiley et al., 2003).
Murillo-Rodriguez E, Millan-Aldaco D, Palomero-Rivero M, Morales-Lara D, Mechoulam R, & Drucker-Colin R. Cannabidiol partially blocks the sleepiness in hypocretin-deficient rats. Preliminary data. (2019). CNS NeurolDisord Drug Targets2019/10/24. IT-20: Orexin-SAP
Dobryakova YV, Volobueva MN, Manolova AO, Medvedeva TM, Kvichansky AA, Gulyaeva NV, Markevich VA, Stepanichev MY, & Bolshakov AP. Cholinergic Deficit Induced by Central Administration of 192IgG-Saporin Is Associated with Activation of Microglia and Cell Loss in the Dorsal Hippocampus of Rats. (2019). Front Neurosci, 13 146. 2019/04/02. PMC6424051. IT-01: 192-IgG-SAP
A review of the tools for creating animal models of Alzheimer’s Disease
binds selectively and irreversibly to low-affinity nerve growth factor receptor
interrupting cholinergic neuronal protein synthesis.”
“Anti-DBH-SAP allows a selective and gradual lesioning of noradrenergic neurones in the brain stem nucleus locus coeruleus, the primary site of noradrenaline production in the CNS.”
Verkhratsky A, Parpura V,
Rodriguez-Arellano J, & Zorec R. (2019). Astroglia in Alzheimer’s
Disease. In A Verkhratsky, M
Ho, R Zorec
& V Parpura
in Neurodegenerative Diseases (Vol. Advances in Experimental Medicine
and Biology, vol 1175, pp. 273-324). Singapore: Springer.
Summary: 192-IgG-SAP binds selectively and irreversibly to low-affinity nerve growth factor receptor interrupting cholinergic neuronal protein synthesis was employed. Anti-DBH-SAP binds dopamine-β-hydroxylase, which is not only localized mainly in the cytosol, but also at the plasma membrane surface of noradrenergic neurons. Anti-DBH-SAP produced specific and dose-dependent depletions of locus coeruleus neurons, with no effects on other cholinergic, dopaminergic or serotonergic neuronal populations. The possibility to induce a partial or total noradrenergic loss (by varying the injected dose) makes this immunotoxic approach an ideal model to study events within the noradrenergic projection system, as they occur during age-related demise of locus coeruleus in humans.
Congratulations to Dr. Argyle Bumanglag and the team at University of Florida for the important work they presented using SSP-SAP to create an animal model of temporal lobe epilepsy.
Injections of SSP-SAP into the hippocampus of a rat causes acute hippocampal injury, permanent dentate granule cell-onset epilepsy, and hippocampal sclerosis that closely resembles the selective hippocampal pathology exhibited by patients diagnosed with TLE. The rats are chronically epileptic, with data going out a year for lesioned animals.
Also see the recent publication:
Chun E, Bumanglag AV, Burke SN, & Sloviter RS. Targeted hippocampal GABA neuron ablation by Stable Substance P–saporin causes hippocampal sclerosis and chronic epilepsy in rats. (2019). Epilepsia, 60 (5):e52-e57.
Objective: Hippocampal GABA neurons were targeted for selective elimination to determine whether a focal hippocampal GABAergic defect in an otherwise normal brain can initiate cryptogenic temporal lobe epilepsy with hippocampal sclerosis. Summary: Hippocampal GABAergic dysfunction is epileptogenic and can produce the defining features of cryptogenic temporal lobe epilepsy. Dose: Intrahippocampal injections of SSP-SAP (0.4 ng/10 nL) were performed using a 0.5-μL Neuros Syringe lowered into four hippocampal sites along both the transverse and longitudinal hippocampal axes bilaterally.
bind to your primary antibody via a secondary antibody or Streptavidin cross-linked
to a pH-dependent fluorescent reporter.
This fluorescent reporter increases intensity as the pH of its
surroundings becomes more acidic, as evident when exposed to the environment
inside a cell.
SLC46A3 as a Potential Predictive Biomarker for Antibody-Drug Conjugates Bearing Noncleavable Linked Maytansinoid and Pyrrolobenzodiazepine Warheads. Kinneer K, et al. Clin Cancer Res, 24 (24):6570-6582, 2018.
Objective: To develop biomarkers to uncover the underlying mechanism of resistance by certain cell lines for ADCs.
Summary: Loss of SLC46A3 expression was found to be a mechanism of innate and acquired resistance to ADCs bearing DM1 and SG3376.
Dose: For Lysosomal trafficking, ADCs were labeled with Fab-pHast human (Cat. #PH-01). Cells were incubated with 3 mg/mL of labeled ADCs at 37°C for desired time points and fluorescence quantified by flow cytometry.
pHast Ab Internalization Assay Parental HEK-293 cells, and HEK-293 cells transfected with the p75 receptor, were plated in a 96-well plate overnight. Titrated 192-IgG antibody (Cat. #AB-N43) was incubated at RT with 50 nM of Fab-pHast Mouse (Cat. PH-02) for 20 min prior to addition to cells. Plates were incubated overnight to allow maximum internalization, but a few hours is sufficient for detection.
Objective: To examine the effects of clinical candidate, 17v on sleep/wake activity in Orexin-SAP lesioned male Wistar rats. Summary: 17v demonstrated high receptor occupancy and marked wake-promoting effects with decreased rapid-eye-movement sleep in Orexin-SAP lesioned rats supporting its potential therapeutic utility in treating human sleep disorders. Dose: Intracerebral injections of Orexin-SAP (100 ng/0.5 μl) in lateral hypothalamus of rats produce selective disruption of neurons containing orexin-B receptors and produces symptoms that are characteristic of narcolepsy.
Leptin receptor-expressing neurons in the ventromedial nucleus of the hypothalamus contribute to weight loss caused by fourth ventricle leptin infusions. (2019). Am J Physiol Endocrinol Metab PMID: 31361549 Seamon M, Ahn W, Li A-J, Ritter S, & Harris RBS.
Objective: To test the importance of VMH leptin responsiveness in mediating weight loss caused by fourth ventricle leptin infusion. Summary: Leptin did not inhibit food intake and respiratory exchange ratio in rats treated with Leptin-SAP. VMH leptin receptors do not play a significant role in maintaining energy balance in basal conditions, but limit weight gain during positive energy balance. Dose: Bilateral VMH 75-nl injections of 260 ng/ml of Leptin-SAP or Blank-SAP.
Neuroprotective Effects of Exercise on the Morphology of Somatic Motoneurons Following the Death of Neighboring Motoneurons. (2019). Chew C, & Sengelaub DR. Neurorehabil Neural Repair, epub ahead of print 1545968319860485.
Objective: To explore whether exercise shows the same neuroprotective effect on induced dendritic atrophy as that seen with androgen treatment. Summary: Exercise following neural injury exerts a protective effect on motoneuron dendrites comparable to that seen with exogenous androgen treatment. Dose: Motoneurons innervating the left vastus medialis muscle were selectively killed by intramuscular injection of CTB-SAP (2 μL, 0.1%). Saporin injection reduced the weight of the vastus medialis muscle; exercise had no effect on muscle weight.