Meng J, Chen W, Wang J (2020) Intervening B-type natriuretic peptide signaling for controlling chronic itch. Brit J Pharmacol 177(5):1025-1040. doi: 10.1111/bph.14952
Objective: Review of recent findings used to examine the role of B-type natriuretic peptide (BNP) in itch transduction and the modulation of other pururitic proteins.
Summary: Mice treated with Nppb-SAP ablated 70% of the BNP receptor-positive neurons in the spinal cord.
Srikanthan MA, Humbert O, Haworth KG, Ironside C, Rajawat YS, Blazar BR, Palchaudhuri R, Boitano AE, Cooke MP, Scadden DT, Kiem HP (2020) Effective multi-lineage engraftment in a mouse model of fanconi anemia using non-genotoxic antibody-based conditioning. Mol Ther Methods Clin Dev 17:455-464. doi: 10.1016/j.omtm.2020.02.001 PMID: 32226796
Objective: To utilize antibody-drug conjugates (ADC) as an alternative conditioning regimen in a Fanconi anemia (FA) mouse model of autologous transplantation.
Summary: Antibody conjugates targeting hematopoietic cells are an emerging non-genotoxic method of promoting engraftment of transplanted cells while maintaining intact marrow cellularity. FANCA knockout mice were conditioned with either Anti-CD45-SAP or Anti-CD117-SAP prior to receiving whole marrow from a heterozygous healthy donor. Bone marrow and peripheral blood analysis revealed equivalent levels of donor engraftment, with minimal toxicity in ADC-treated groups as compared with cyclophosphamide-treated control.
Usage: Anti-CD45-SAP (3 mg/kg total complex) or Anti-CD117-SAP (1.5 mg/kg total complex) via tail vein injection.
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).
Liu X, Miao XH, Liu T (2020) More than scratching the surface: recent progress in brain mechanisms underlying itch and scratch. Neurosci Bull 36(1):85-88. doi: 10.1007/s12264-019-00352-1
Summary: The discovery of descending neural circuitry to drive the itch-scratching cycle may provide potential therapeutic targets in the central nervous system for the management of chronic itch.
Usage: To ablate the spinal GRPR+ neurons, mice were intrathecally injected with Bombesin-SAP or Blank-SAP (400 ng/5 mL).
Seven YB, Simon AK, Sajjadi E, Zwick A, Satriotomo I, Mitchell GS (2020) Adenosine 2A receptor inhibition protects phrenic motor neurons from cell death induced by protein synthesis inhibition. Exp Neurol 323:113067. doi: 10.1016/j.expneurol.2019.113067
Objective: To test the hypothesis that A2A receptor antagonism promotes phrenic motor neuron survival and preserves diaphragm function when faced with toxic, neurodegenerative insults that lead to phrenic motor neuron death.
Summary: The authors utilized a novel neurotoxic model of respiratory motor neuron death using intrapleural injections of CTB-SAP. A2A receptors contribute to neurotoxic phrenic motor neuron death, an effect mitigated by A2A receptor antagonism.
Usage: Intrapleural administration of CTB-SAP (25 μg per side) causes: 1) profound phrenic motor neuron death (~5% survival); 2) ~7-fold increase in phrenic motor neuron A2A receptor expression prior to cell death; and 3) diaphragm muscle paralysis (inactive in most rats; ~7% residual diaphragm EMG amplitude during room air breathing).
Patrone LGA, Capalbo AC, Marques DA, Bícego KC, Gargaglioni LH (2020) An age- and sex-dependent role of catecholaminergic neurons in the control of breathing and hypoxic chemoreflex during postnatal development. Brain Res 1726:146508. doi: 10.1016/j.brainres.2019.146508
Objective: To discover the role of brainstem catecholaminergic (CA) neurons in the hypoxic ventilatory response (HVR).
Summary: Brainstem CA neurons modulate the HVR during the postnatal phase, and possibly thermoregulation during hypoxia.
Usage: Evaluation of brainstem CA neurons in the HVR during postnatal development in male and female rats through specific cell depletion with Anti-DBH-SAP (420 ng/nL) injected in the fourth ventricle.
Díaz HS, Andrade DC, Toledo C, Pereyra KV, Schwarz KG, Díaz-Jara E, Lucero C, Arce-Álvarez A, Schultz HD, Silva JN, Takakura AC, Moreira TS, Marcus NJ, Del Rio R (2020) Episodic stimulation of central chemoreceptor neurons elicits disordered breathing and autonomic dysfunction in volume overload heart failure. Am J Physiol Lung Cell Mol Physiol 318(1):L27-L40. doi: 10.1152/ajplung.00007.2019
Objective: To determine the role of the central chemoreflex in the development of respiratory and autonomic dysfunction in volume overload heart failure (HF).
Summary: Episodic hypercapnic stimulation triggers ventilatory plasticity and elicits cardiorespiratory abnormalities in HF that are largely dependent on retrotrapezoid nucleus (RTN) chemoreceptor neurons.
Usage: Bilateral injections of SSP-SAP, 0.6 ng/30 nL, into the RTN were administered to destroy chemoreceptor neurons.
Shin J, Kong C, Lee J, Choi BY, Sim J, Koh CS, Park M, Na YC, Suh SW, Chang WS, Chang JW (2019) Focused ultrasound-induced blood-brain barrier opening improves adult hippocampal neurogenesis and cognitive function in a cholinergic degeneration dementia rat model. Alzheimers Res Ther 11(1):110. doi: 10.1186/s13195-019-0569-x
Objective: To investigate the decrease of adult hippocampal neurogenesis (AHN) in Alzheimer’s disease (AD).
Summary: This work studied the effect of FUS on AHN in a cholinergic degeneration rat model of dementia.
Usage: 192-IgG-SAP was injected bilaterally into the lateral ventricle (4 μl at a concentration of 0.63 μg/μl at a rate of 1 μl/min).
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).
Rizvanovic H, Pinheiro AD, Kim K, Thomas J (2019) Chlorotoxin conjugated with saporin reduces viability of ML-1 thyroid cancer cells in vitro. bioRxiv 885483. doi: 10.1101/2019.12.20.885483
Objective: To determine whether Chlorotoxin-conjugated Saporin (CTX-SAP) would inhibit the growth of aggressive thyroid cancer cell lines expressing MMP-2.
Summary: This in vitro study demonstrated the efficacy of a CTX-SAP conjugate in reducing the viability of ML-1 thyroid cancer cells in a dose dependent manner.
Usage: There was a statistically significant reduction in cell viability with increasing concentrations of the CTX-SAP conjugate (biotinylated Chlorotoxin mixed with Streptavidin-ZAP). The cell viability of ML-1 cells was decreased by 49.77% with the treatment of 600 nM of CTX-SAP (F=44.24). Unconjugated Chlorotoxin or Saporin had no significant effect on cell viability a using similar assay.
