References

Schwarz KG, Pereyra KV, Diaz-Jara E, Vicencio SC, Del Rio R (2024) Brainstem C1 neurons mediate heart failure decompensation and mortality during acute salt loading. Cardiovascular Research doi: 10.1093/cvr/cvae261 PMID: 39775485

Objective: To test whether rostral ventrolateral medulla (RVLM) C1 neurons drive cardiorespiratory decompensation, and ultimately lead to sudden death in heart failure (HF) rats.

Summary: The results strongly suggest that RVLM C1 neurons contribute to acute HF decompensation during salt loading by a mechanism encompassing further increases in sympathetic outflow and hypoxia-related breathing disorder.

Usage: Bilateral injections of anti-dopamine-β-hydroxylase conjugated with saporin toxin (Anti-DBH-SAP; 7.5 ng/100 nl of sterile saline solution) were delivered to the RVLM-C1 region using the stereotaxic coordinates.

Related Products: Anti-DBH-SAP (Cat. #IT-03)

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)

Lv X, Martin J, Hoover H, Joshi B, Wilkens M, Ullisch DA, Leibold T, Juchum JS, Revadkar S, Kalinovska B, Keith J, Truby A, Liu G, Sun E, Haserick J, DeGnore J, Conolly J, Hill AVS, Baldoni J, Kensil C, Levey D, Spencer AJ, Gorr G, Findeis M, Tanne A (2024) Chemical and biological characterization of vaccine adjuvant QS-21 produced via plant cell culture. iScience 27(3):109006. doi: 10.1016/j.isci.2024.109006 PMID: 38361610

Objective: To report for the first time successful plant cell culture production of Quillaja saponaria (QS)-21 having structural, chemical, and biological properties similar to the bark-extracted product.

Summary: The data demonstrate that cell culture is a sustainable alternative to natural resources to produce QS-21 as an adjuvant. In this proof-of-concept approach, it’s shown that the chemical, biochemical, and biophysical equivalence of bark extract and cell culture-derived QS-21 translate into conserved biological and adjuvant properties both in vitro and in vivo.

Usage: Pseudo cross-presentation assays (25 ng/mL Saporin).

Related Products: Saporin (Cat. #PR-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.

Zhao Q, Zong H, Zhu P, Su C, Tang W, Chen Z, Jin S (2024) Crosstalk between colorectal CSCs and immune cells in tumorigenesis, and strategies for targeting colorectal CSCs. Exp Hematol Oncol 13(1):6. doi: 10.1186/s40164-024-00474-x PMID: 38254219

Summary: Cancer immunotherapy has become a promising strategy in the treatment of colorectal cancer, and relapse after tumor immunotherapy. Cancer stem cells (CSCs) have the capabilities of self-renewal and differentiation and are also resistant to the traditional therapies of radiotherapy and chemotherapy. The authors review strategies for targeting colorectal CSCs, where one method described uses a biotinylated antibody against EpCAM (clone 3-171) conjugated to saporin via Streptavidin-ZAP (IT-27).

Related Products: Streptavidin-ZAP (Cat. #IT-27)

See Also:

• Lund K et al. The novel EpCAM-targeting monoclonal antibody 3-17I linked to saporin is highly cytotoxic after photochemical internalization in breast, pancreas and colon cancer cell lines. MAbs 6(4):1038-1050, 2014.

Bogen O, Araldi D, Sucher A, Kober K, Ohara PT, Levine JD (2024) Isolectin B4 (IB4)-conjugated streptavidin for the selective knockdown of proteins in IB4-positive (+) nociceptors. Mol Pain doi: 10.1177/17448069241230419 PMID: 38246917

Objective: To address the need for selective transfection methods, the authors covalently linked isolectin B4 (IB4) to streptavidin and analyzed whether it could be used to study protein function in IB4(+)-nociceptors

Summary: Rats treated intrathecally with IB4-conjugated streptavidin complexed with biotinylated antisense oligonucleotides for protein kinase C epsilon (PKCε) mRNA werefound to have: (a) less PKCε in dorsal root ganglia (DRG), (b) reduced PKCε expression in IB4(+) but not IB4(–) DRG neurons, and (c) fewer transcripts of the PKCε gene in the DRG. This knockdown in PKCε expression in IB4(+) DRG neurons is sufficient to reverse hyperalgesic priming, a rodent model of chronic pain that is dependent on PKCε in IB4(+)- nociceptors.

Usage: For each intrathecal injection 2.3μL IB4-streptavidin (30 pmol of conjugate with 120 pmol of biotin binding sites), 1.2μL biotinylated ODN (c = 100 pmol/μl) and 16.5μL PBS were mixed (injection volume = 20μL),

Related Products: Streptavidin-ZAP (Cat. #IT-27), IB4-SAP (Cat. #IT-10)

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)