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).
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.
Souza GMPR, Stornetta RL, Stornetta DS, Abbott SBG, Guyenet PG (2019) Contribution of the retrotrapezoid nucleus and carotid bodies to hypercapnia- and hypoxia-induced arousal from sleep. J Neurosci 39(49):9725-9737. doi: 10.1523/JNEUROSCI.1268-19.2019
Objective: To examine the contribution of two lower brainstem nuclei that could be implicated in CO2 and hypoxia-induced arousal.
Summary: RTN, a brainstem nucleus that mediates the effect of brain acidification on breathing, also contributes to arousal elicited by CO2 but not hypoxia.
Usage: To ablate the retrotrapezoid nucleus (RTN), SSP-SAP was administered (2.4 ng) through bilateral injections via a dorsal craniotomy.
Thorsdottir D, Cruickshank NC, Einwag Z, Hennig GW, Erdos B (2019) BDNF downregulates β-adrenergic receptor-mediated hypotensive mechanisms in the paraventricular nucleus of the hypothalamus. Am J Physiol Heart Circ Physiol 317(6):H1258-H1271. doi: 10.1152/ajpheart.00478.2019
Objective: To determine whether BDNF increases blood pressure in part by diminishing inhibitory hypotensive input from nucleus of the solitary tract (NTS) catecholaminergic neurons projecting to the PVN.
Summary: BDNF, a key hypothalamic regulator of blood pressure, disrupts catecholaminergic signaling between the NTS and the PVN by reducing the responsiveness of PVN neurons to inhibitory hypotensive β-adrenergic input from the NTS.
Usage: Bilateral NTS injections of sterile PBS (for control) or Anti-DBH-SAP (22 ng).
