targeted-toxins

Aerts EG, Griesgraber MJ, Shuping SL, Bowdridge EC, Hardy SL, Goodman RL, Nestor CC, Hileman SM (2024) The effect of NK3-Saporin injection within the arcuate nucleus on puberty, the LH surge, and the response to Senktide in female sheep. Biol Reprod 110(2):275-287. doi: 10.1093/biolre/ioad147 PMID: 37930247

Objective: To investigate the role of NKB-SAP (NK3-SAP) in the arcuate nucleus on the timing of puberty, the LH surge, and the response to the NK3R agonist senktide in female sheep.

Summary: This study explores how the ablation of NK3R-containing neurons in the arcuate nucleus affects puberty onset and reproductive hormone dynamics in female sheep. The findings demonstrate that NK3-SAP injections significantly delay puberty, reduce the amplitude of the LH surge, and alter the response to senktide, underscoring the critical role of NK3R-containing neurons in reproductive function.

Usage: Prepubertal ewes received 1 μL (0.7 μg) of NKB-SAP (NK3-SAP) [IT-63] or Blank-SAP (IT-21) injections aimed at the arcuate (ARC) nucleus to ablate neurons expressing NK3R.

Related Products: NKB-SAP (Cat. #IT-63), Blank-SAP (Cat. #IT-21)

Abdolvahab MH, Karimi P, Mohajeri N, Abedini M, Zare H (2024) Targeted drug delivery using nanobodies to deliver effective molecules to breast cancer cells: The most attractive application of nanobodies. Cancer Cell Int 24(1):67. doi: 10.1186/s12935-024-03259-8 PMID: 38341580

Objective: Using nanobodies to deliver saporin to breast cancer cells.

Summary: Through the binding of saporin to a nanobody, a fragment of an antibody, breast cancer cells that over-express Her2 can be targeted and eliminated. Binding of saporin in nanoparticles to 11A4 nanobody (anti-HER2 receptor) showed dose-dependent cytotoxicity against SK-BR-3 cells when tested. Photochemical internalization of saporin loaded nanoparticles also demonstrated dose-dependent cytotoxicty in SK-BR-3 breast cancer cells.

Related Products: Trastuzumab (Anti-HER2)-SAP (Cat. #BETA-038)

See Also:

• Martínez-Jothar L, Beztsinna N, van Nostrum CF, Hennink WE, Oliveira S (2019) Selective Cytotoxicity to HER2 Positive Breast Cancer Cells by Saporin-Loaded Nanobody-Targeted Polymeric Nanoparticles in Combination with Photochemical Internalization. Mol Pharm 16(4):1633-1647. doi: 10.1021/acs.molpharmaceut.8b01318 PMID: 30817164

Martínez-Gardeazabal J, Moreno-Rodríguez M, Llorente-Ovejero A, González de San Román E, Lombardero L, Bengoetxea de Tena I, Sustacha J, Matute C (2024) Cell lipotypes localization in brain by mass spectrometry imaging. bioRxiv doi: 10.1101/2024.02.02.578599

Objective: Characterizing the type of different central nervous system cells via mass spectrometry of their component lipids.

Summary: Different varieties of cells in the central nervous system perform different functions and, as a consequence, have different compositions. Using purified rat cell cultures of neurons, astrocytes, oligodendrocytes, microglia, and choroid plexus cells, a model was constructed to identify the localization of any brain cell through mass spectrum imaging of the lipid composition.

Usage: Injected 192-IgG-SAP (130 ng/µl) into the nucleus basalis magnocellularis (nbM) of rats.

Related Products: 192-IgG-SAP (Cat. #IT-01)

Björklund A, Barker RA (2024) The basal forebrain cholinergic system as target for cell replacement therapy in Parkinson’s disease. Brain awae026. doi: 10.1093/brain/awae026 PMID: 38279949

Objective: Review the use of cholinergic cell replacement as a potential therapeutic strategy in Parkinson’s Disease (PD) and how rodent models of PD-like cognitive decline can be used by analyzing rodent and primate studies.

Summary: Although therapies targeting the cholinergic system have so far been focused mainly on patients with Alzheimer´s disease, PD with dementia may be a more relevant condition. In PD with dementia the Basal Forebrain system undergoes progressive degeneration, and the magnitude of cholinergic cell loss has been shown to correlate with the level of cognitive impairment. Thus, cell therapy aimed to replace the lost basal forebrain cholinergic neurons represents an interesting strategy to combat some of the major cognitive impairments in patients with PD dementia.

Usage: Rats were given 192-IgG-SAP (IT-01), 0.2-0.4 μg, delivered as a single 0.3-1.0 μl injection into either the substantia innominate/nucleus basalis of Meynert (SI/NBM) or the medial septum/ventral diagonal band (MS/VDB).

Related Products: 192-IgG-SAP (Cat. #IT-01)

Bernabe CS, Caliman IF, de Abreu ARR, Molosh AI, Truitt WA, Shekhar A, Johnson PL (2024) Identification of a novel perifornical-hypothalamic-area-projecting serotonergic system that inhibits innate panic and conditioned fear responses. Transl Psychiatry 14(1):60. doi: 10.1038/s41398-024-02769-3 PMID: 38272876

Objective: To investigate the role of serotonergic inputs from the raphe nuclei to the perifornical hypothalamic area (PFA) in regulating panic and fear responses.

Summary: This study identifies a novel serotonergic system projecting to the PFA that inhibits innate panic and conditioned fear responses. The findings suggest that serotonergic inputs from the lateral wings of the dorsal and median raphe nuclei to the PFA represent a panic/fear-off circuit, which could also play a role in modulating reward behaviors.

Usage: Each rat (Adult Sprague-Dawley; 300–350 g) received two bilateral microinjections per site (100 nl each, 1 μM in ACSF) of either Anti-SERT-SAP (IT23) or the control Mouse IgG-SAP (IT-18) via an injector that was connected to bilateral guide-cannulas implanted into the PFA.

Related Products: Anti-SERT-SAP (Cat. #IT-23), Mouse IgG-SAP (Cat. #IT-18)

Fulton S, Horn CC, Zhang C (2024) Characterizing a new tool to manipulate area postrema GLP1R+ neurons across species. Physiol Behav 114474. doi: 10.1016/j.physbeh.2024.114474 PMID: 38272107

Objective: Characterize the ligand exenatide conjugated to saporin as a tool to ablate GLP1 receptor-expressing cells from human, mice, and shrews, a small animal model capable of emesis (vomiting).

Summary: Nausea is a distressing sensation that is a common side effect of many medications. Nausea and emesis are among the top adverse side effects of glucagon-like peptide-1 (GLP1) receptor (GLP1R) agonists-based medications to treat type 2 diabetes and obesity. The area postrema is a brain structure that mediates nausea effects. The authors provide characterization of Ex4-SAP (GLP-1-SAP) to specifically ablate GLP1R-expressing HEK293T cells in vitro and in area postrema neurons in mice and house musk shrews in vivo.

Usage: C57BL-6J mice were injected with Ex4-SAP (IT-90) or Blank-Streptavidin-SAP at 200 ng/ul, in a total of 400 nl at a rate of 2 nl/second. Musk shrews were injected with Ex4-SAP (IT-90) or Blank-Streptavidin-SAP at 500 ng/ul, in a total of 200 nl at a rate of 2 nl/second.

Related Products: Ex4-SAP (GLP-1-SAP) (Cat. #IT-90), Blank-Streptavidin-SAP (Cat. #IT-27B)

Janes TA, Cardani S, Saini JK, Pagliardini S (2024) Etonogestrel promotes respiratory recovery in an in vivo rat model of central chemoreflex impairment. Acta Physiol (Oxf) e14093. doi: 10.1111/apha.14093 PMID: 38258900

Objective: Examine the use of progestins and synthetic progestins in the stimulation of breathing, especially after chemoreflexive impairment.

Summary: Central CO2 chemoreflex is important for respiratory control. The retrotrapezoid nucleus is involved in CO2 chemosensitivity where its removal or inhibition attenuates CO2 chemoreflexes and diminishes restful breathing. Progesterone stimulates restful breathing and CO2 chemoreflexes. The authors investigated whether acute or chronic administration of the progestinic drug, etonogestrel, could help in the recovery of respiratory chemoreflexes following lesion of the retrotrapezoid nucleus via a SP-SAP.

Usage: Rats were injected with 26-43.3 ng/ul of SP-SAP (IT-11) or 46.7 ng/ul of Blank-SAP (IT-21), with 150 nl per injection.

Related Products: SSP-SAP (Cat. #IT-11), Blank-SAP (Cat. #IT-21)

Donovan LJ, Bridges CM, Nippert AR, Wang M, Wu S, Forman TE, Haight ES, Huck NA, Bond SF, Jordan CE, Gardner AM, Nair RV, Tawfik VL (2024) Repopulated spinal cord microglia exhibit a unique transcriptome and contribute to pain resolution. Cell Rep 43(2):113683. doi: 10.1016/j.celrep.2024.113683 PMID: 38261512

Objective: To study the role of microglia in pain resolution and determine if repopulated microglia actively resolve pain or initiate the transition from acute to chronic pain.

Summary: Pain resolution coincides with microglial repopulation in the spinal cord rather than depletion. Repopulated microglia exhibit unique gene expressions related to phagocytosis and stress response in mice. The study identified potential targets for developing microglial-targeted pain therapeutics by comparing mouse and human spinal cord microglial datasets.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)

See Also:

• Echeverry S et al. Spinal microglia are required for long-term maintenance of neuropathic pain. Pain 158:1792-1801, 2017.
• Sorge R et al. Different immune cells mediate mechanical pain hypersensitivity in male and female mice. Nat Neurosci 18:1081-1083, 2015.

Masmudi-Martín M, López-Aranda MF, Navarro-Lobato I, Khan ZU (2024) A role of frontal association cortex in long-term object recognition memory of objects with complex features in rats. Eur J Neurosci 59(7):1743-1752. doi: 10.1111/ejn.16243 PMID: 38238909

Objective: Provide evidence that the frontal association cortex and not the Perirhinal cortex is essential for object recognition memory (ORM) of objects with complex features.

Summary: The Perirhinal cortex is a brain area that has been seen as being crucial for ORM. However, the authors challenge that thought by using an ORM enhancer named RGS14414. Used as a tool, expression of it in rat brain frontal association cortex induced the formation of long-term complex ORM whereas the expression of the enhancer in Perirhinal cortex didn’t illicit the same effect. The authors also showed that expression of the enhancer in Perirhinal cortex instead caused formation of ORM of objects with only simple features. Furthermore, the selective elimination of frontal association cortex neurons via OX7-SAP (IT-02) completely removed the formation of complex ORM.

Usage: OX7-SAP (IT-02) was injected into the frontal association cortex of rats at a dose of 0.2 ug in 1 ul.

Related Products: OX7-SAP (Cat. #IT-02)

Ivanova D, O’Byrne KT (2024) New methods to investigate the GnRH pulse generator. J Mol Endocrinol 72(2):e230079. doi: 10.1530/JME-23-0079 PMID: 38085702

Objective: To review the latest methodologies and insights into the GnRH pulse generator and its role in regulating reproductive hormone secretion.

Summary: The paper discusses recent advancements in understanding the GnRH pulse generator and its role in reproductive hormone secretion. It highlights the involvement of kisspeptin/neurokinin B/dynorphin (KNDy) neurons and the use of advanced techniques like genetic mouse models, electrophysiology, optogenetics, and calcium imaging. These findings enhance our comprehension of the KNDy network’s oscillatory behavior and its regulation by gonadal steroids, which is crucial for developing better infertility treatments.

Related Products: NKB-SAP (Cat. #IT-63)

See Also:

• Helena C et al. KNDy neurons modulate the magnitude of the steroid-induced luteinizing hormone surges in ovariectomized rats. Endocrinology 156:4200-4213, 2015.