References

Fitzpatrick MJ, Krizan J, Hsiang JC, Shen N, Kerschensteiner D (2024) A pupillary contrast response in mice and humans: Neural mechanisms and visual functions. Neuron doi: 10.1016/j.neuron.2024.04.012 PMID: 38697114

Objective: To show that temporal contrast drives pupil constriction through a cell-type-specific retinal circuit in mice and humans.

Summary: The pupillary contrast response enhances high spatial frequency contrast in retinal images and improves visual acuity.

Usage: Immunohistochemistry (1:2000) (Cat: AB-N38).

Related Products: Melanopsin Rabbit Polyclonal (Cat. #AB-N38)

Dyer B, Yu SO, Lane Brown R, Lang RA, D’Souza SP (2024) A new Opn4cre recombinase mouse line to target intrinsically photosensitive retinal ganglion cells (ipRGCs). bioRxiv doi: 10.1101/2024.04.16.589750

Objective: To generate a new Opn4cre knock-in allele [Opn4cre(DSO)], in which cre is placed immediately downstream of the Opn4 start codon.

Summary: The Opn4cre(DSO) mouse line improves the specificity of ipRGC labeling, enabling the targeted study of these cells in relation to light-regulated behaviors and physiology.

Usage: Histology and immunofluorescence.

Related Products: Melanopsin Rabbit Polyclonal, affinity-purified (Cat. #AB-N39)

Zuppone S, Zarovni N, Noguchi K, Loria F, Morasso C, Lõhmus A, Nakase I, Vago R (2024) Novel loading protocol combines highly efficient encapsulation of exogenous therapeutic toxin with preservation of extracellular vesicles properties, uptake and cargo activity. Discov Nano 19(1):76. doi: 10.1186/s11671-024-04022-8 PMID: 38691254

Objective: Extracellular vesicles (EVs) have been investigated as carriers of biological therapeutics such as proteins and RNA as well as small-molecule drugs. The objective was to test a strategy of EV loading based on temporary pH alteration through incubation of EVs with alkaline sodium carbonate, which results in conspicuous exogenous molecule incorporation.

Summary: The encapsulated saporin resulted protected from degradation and was efficiently conveyed to receiving cancer cells and triggered cell death. EV-delivered saporin was more cytotoxic compared to the free toxin. This approach allows both the structural preservation of vesicle properties and the transfer of protected cargo in the context of drug delivery.

Usage: Authors used fluorescently labeled saporin, SAP-FITC, and a nano-sized EV-to-cargo ratio of 1:1.5 (w:w).

Related Products: Saporin Goat Polyclonal, affinity-purified FITC-labeled (Cat. #AB-15AP-FL)

Aerts EG (2024) Estradiol’s role in timely puberty onset in the ewe. Western Virginia Univ

Objective: To investigate the role of arcuate nucleus KNDy (kisspeptin/neurokinin B/dynorphin) neurons in regulating the timing of puberty onset and estradiol (E2) sensitivity in female sheep.

Summary: Ablation of approximately 75% of KNDy neurons using NKB-SAP in the arcuate nucleus significantly delayed puberty onset and blunted the luteinizing hormone (LH) surge, demonstrating that KNDy neurons are critical for timely puberty in ewes. However, animals retained the ability to respond to NK3R agonist senktide, suggesting upstream populations may mediate estradiol negative feedback.

Usage: NKB-SAP (IT-63) was bilaterally injected into the arcuate nucleus (1 µg/side in 1 µL) to ablate NK3R-expressing KNDy neurons and evaluate their role in pubertal timing and LH regulation.

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

Chen S (2024) Nanocapsule-based prodrugs for targeted treatment of AIDS-associated non-hodgkin lymphoma. Univ California Thesis.

Objective: To propose a novel nanocapsule based platform that encapsulates the native drugs using various monomers and crosslinkers through free radical polymerization.

Summary: This encapsulation technology modifies the surface properties of the encapsulated drugs, enhancing their penetration into deeper tumor tissues and across the blood-brain barrier (BBB). Moreover, it significantly improves the stability of the drugs in vivo, protecting them from rapid degradation or clearance by the immune system. By adjusting the composition of the monomers and crosslinkers, the surface charge, hydrophobicity, and size of the nanocapsules can be finely tuned to maximize their efficacy in reaching and penetrating the target tissues.

Usage: Conjugation of ch128.1Av (anti-TfR1 IgG3-avidin fusion protein) with biotinylated saporin 6 (b-SO6) to eliminate malignant cells, including NHL malignancies. However, safe systemic delivery of ch128.1Av/b-SO6 is limited by its non-specific toxicity to normal cells expressing TfR1.

Related Products: MonoBiotin-ZAP (Cat. #BT-ZAP)

Thomson AC (2024) Puberty-Associated Changes in Kiss1r, MC3R, and MC4R in the Ewe. West Virgina University

Objective: To examine kisspeptin receptor (Kiss1r) mRNA expression in gonadotropin releasing hormone (GnRH) neurons and melanocortin 3 and 4 receptor (MC3R/MC4R) expression in kisspeptin neurons across pubertal development.

Summary: Kiss1r expression in GnRH neurons increased with development. In the arcuate nucleus (ARC), the proportion of kisspeptin neurons expressing MC3R, but not MC4R, also rose, though MC3R signal intensity remained unchanged. ARC Kiss1r expression did not vary. Findings support increased GnRH neuron sensitivity to kisspeptin and aMSH as part of the pubertal neurocircuitry.

Usage: Author references prior studies. Deletion of about 75% of KNDy neurons through targeted NKB-SAP (IT-63) injections significantly delayed puberty onset. Reduction of Kiss1r expression in the ARC via targeted injection of a Kisspeptin-SAP (IT-102) conjugate disrupted pulsatile LH release and blocked the LH surge.

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

See Also:

• Aerts EG et al. 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, 2024.

Kudsi SQ, Viero FT, Pereira LG, Trevisan G (2024) Involvement of the transient receptor channels in preclinical models of musculoskeletal pain. Curr Neuropharmacol 22(1):72-87. doi: 10.2174/1570159X21666230908094159 PMID: 37694792

Objective: To provide an updated view of the most studied preclinical models of muscle hyperalgesia and the role of transient receptor potential (TRP) in these models.

Summary: The participation of TRPV1, TRPA1, and TRPV4 in different models of musculoskeletal pain was evaluated using pharmacological and genetic tools. All the studies detected the antinociceptive effect of respective antagonists or reduced nociception in knockout mice. Hence, TRPV1, TRPV4, and TRPA1 blockers could potentially be utilized in the future for inducing analgesia in muscle hypersensitivity pathologies.

Usage: NK1-expressing neurons were ablated by SP-SAP (neurotoxin saporin conjugated to substance P) to Vc, and the ablation of NK1-expressing second-order neurons reduced the MGS and bite force nociceptive behaviors.

Related Products: SP-SAP (Cat. #IT-07)

See Also:

• Wang S, Lim J, Joseph J, Wang S, Wei F, Ro JY, Chung MK. Spontaneous and Bite-Evoked Muscle Pain Are Mediated by a Common Nociceptive Pathway With Differential Contribution by TRPV1. J Pain. 2017 Nov;18(11):1333-1345. doi: 10.1016/j.jpain.2017.06.005. Epub 2017 Jun 29. PMID: 28669862

Kolster MK (2024) Cleavable peptide-triterpene conjugates for improved gene delivery. Univ Berlin Thesis.

Objective: To use SO1861, a saponin triterpene, conjugated to a Saporin-encoding gene to target in vivo mice tumors.

Summary: Targeted nanoplexes containing covalently conjugated SO1861 were prepared by incorporation of a targeting peptide and tested in vivo in an allograft tumor model in mice. Using a suicide gene vector encoding the cytotoxic protein saporin, treatment with targeted SO1861-containing nanoplexes was observed to slow tumor growth and improve survival compared to vehicle control.

Usage: Saporin-nanocomplexes were intravaneuously injected into mice to determine transfection efficiency.

Related Products: Saporin (Cat. #PR-01)

Morroni F, Caccamo A (2024) Advances and Challenges in Gene Therapy for Alzheimer’s Disease. J Alzheimers Dis 101(s1):S417-S431. doi: 10.3233/JAD-230783 PMID: 39422937

Objective: Provide an overview of clinical and preclinical studies where gene therapy techniques have been utilized in the context of Alzheimer’s Disease (AD), highlighting their potential as novel therapeutic strategies.

Summary: Gene therapy offers the potential for long-term benefits by providing sustained therapeutic effects. By modifying or replacing faulty genes, it may slow down or halt the progression of AD. Vector-based genetic therapies have demonstrated promising results in mouse models, but face hurdles such as managing risks associated with vectors and delivery methods.

Usage: Rats with cholinergic deficit were induced by intraseptal injection of 192-IgG-SAP (IT-01).

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

See Also:

• Dobryakova YV et al. Intrahippocampal adeno-associated virus-mediated overexpression of nerve growth factor reverses 192IgG-saporin-induced impairments of hippocampal plasticity and behavior. Front Neurosci 15:745050, 2021.

Souza GMPR, Abbott SBG (2024) Loss-of-function of chemoreceptor neurons in the retrotrapezoid nucleus: What have we learned from it?. Respir Physiol Neurobiol 322:104217. doi: 10.1016/j.resp.2024.104217 PMID: 38237884

Objective: To discuss the current definition of chemoreceptor neurons in the retrotrapezoid nucleus (RTN) and describe how this definition has evolved over time.

Summary: Studies offer evidence that RTN neurons are indispensable for the central respiratory chemoreflex in mammals and exert a tonic drive to breathe at rest. Moreover, RTN has an interdependent relationship with oxygen sensing mechanisms for the maintenance of the neural drive to breathe and blood gas homeostasis. Collectively, RTN neurons are a genetically-defined group of putative central respiratory chemoreceptors that generate CO2-dependent drive that supports eupneic breathing and stimulates the hypercapnic ventilatory reflex.

Usage: One widely adopted approach to eliminate RTN neurons utilizes local microinjections of the ribosomal-toxin Saporin conjugated to the analogue of substance-P (SSP-SAP),which results in cell death of neurokinin receptor 1-expressing neurons in a concentration-dependent manner.

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

See Also:

• Nattie EE et al. Substance P-saporin lesion of neurons with NK1 receptors in one chemoreceptor site in rats decreases ventilation and chemosensitivity. J Physiol 544(Pt 2):603-616, 2002.
• Souza GMPR et al. Breathing regulation and blood gas homeostasis after near complete lesions of the retrotrapezoid nucleus in adult rats. J Physiol 596(13):2521-2545, 2018.
• Takakura AC et al. Phox2b-expressing retrotrapezoid neurons and the integration of central and peripheral chemosensory control of breathing in conscious rats. Exp Physiol 99(3):571-585, 2014.
• Takakura AC et al. Selective lesion of retrotrapezoid Phox2b-expressing neurons raises the apneic threshold in rats. J Physiol 586:2975-2991, 2008.