References

Bohl JM, Hassan AR, Sharpe ZJ, Kola M, Shehu A, Beaudoin DL, Ichinose T (2025) Pivotal roles of melanopsin containing retinal ganglion cells in pupillary light reflex in photopic conditions. 19:1547066. doi: 10.3389/fncel.2025.1547066 PMID: 39990971

Objective: To examine the roles of intrinsically photosensitive retinal ganglion cells (ipRGCs) in the pupillary light reflex (PLR) by ablating photoreceptors using N-nitroso-N-methylurea (MNU).

Summary: Results suggest that ipRGCs primarily contribute to the PLR at a high light intensity, which does not agree with the previous results shown by mutant mouse models. The results indicate that the melanopsin response in ipRGCs generate fast and robust PLR when induced by high light.

Usage: Retinal whole mount preparations were fixed using 4% paraformaldehyde and blocked with 10% normal donkey serum and 0.5% Triton-X in PBS (PBS-T). Melanopsin antibody (AB-N39) was used at 1:5000 in PBS-T and was incubated for 3 days at 4°C, followed by Alexa568 donkey-anti-rabbit for 2 h.

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

Rahhal N, Rentzsch M, Seiser S, Freystätter C, Elbe-Bürger A, Rademacher C (2025) Targeted delivery of cytotoxic proteins via lipid-based nanoparticles to primary Langerhans cells. Nanoscale doi: 10.1039/d4nr03638g PMID: 39775685

Summary: Saporin was used as a model protein to showcase the potential of delivering intact proteins to Langerhans cells. Authors observed specific killing of cells expressing langerin in vitro, and in primary Langerhans cells isolated from mouse and human skin ex vivo with minimal off target effects.

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

Vringer M, Zhou J, Gool JK, Bijlenga D, Lammers GJ, Fronczek R, Schinkelshoek MS (2024) Recent insights into the pathophysiology of narcolepsy type 1. Sleep Med Rev 78:101993. doi: 10.1016/j.smrv.2024.101993 PMID: 39241492

Objective: To focus on recent insights into Narcolepsy type 1 (NT1) pathophysiology, discussing structural and functional changes, immune system involvement, genetic findings, and future perspectives for the pathophysiology and treatment options.

Summary: Narcolepsy type 1 (NT1) is one of the central disorders of the hypersomnolence and results from hypocretin (Hcrt, also nown as orexin) deficiency in the brain. The development of HcrtR2-specific or dual HcrtR1 and HcrtR2 agonists, has shown promising results in pre-clinical and clinical trials. These agonists can potentially become the first drugs to directly target the Hcrt system and replace the shortage of Hcrt in NT1.

Usage: Hcrt-2 conjugated to the ribosome-inactivating toxic protein saporin (Orexin-SAP, Cat #IT-20) eliminated up to 90% of Hcrt neurons but also caused significant loss of neighboring neuronal cells, such as Melanin-concentrating hormone (MCH) neurons.

Related Products: Orexin-B-SAP (Cat. #IT-20)

Wang D, Wei SN, Zhang L, Lang ZC, Wang SN, Cheng B, Lu Y, Wang X, Wang W, Li FS, Zhang H (2024) Impaired basal forebrain cholinergic neuron gdnf signaling contributes to perioperative sleep deprivation–induced chronicity of postsurgical pain in mice through regulating cholinergic neuronal activity, apoptosis, and autophagy. CNS Nerusci Ther doi: 10.1111/cns.70147 PMID: 39639706

Objective: This study investigated the roles of lateral basal forebrain glial cell line–derived neurotrophic factor (GDNF). The authors researched GDNF and the associated signaling and cholinergic neuron activity, apoptosis, and autophagy dysfunction in sleep deprivation–induced increased risk of chronic postsurgical pain (CPSP) in mice.

Summary: Perioperative sleep deprivation promotes chronicity of postsurgical pain possibly through decreasing basal forebrain GDNF signaling and causing cholinergic neuronal apoptosis and autophagy dysfunction.

Usage: To ablate the basal forebrain cholinergic neurons, 0.4μg/μL of mu p75-SAP (IT-16) in 0.6μL phosphate-buffered saline was used 3 weeks before the Skin/Muscle Incision and Retraction modeling.

Related Products: mu p75-SAP (Cat. #IT-16)

Lewis RD, Keilholz AN, Smith CL, Burd EA, Nichols NL (2024) Spinal TNF-α receptor 1 is differentially required for phrenic long-term facilitation (pLTF) over the course of motor neuron death in adult rats. Front Physiol 15 doi: 10.3389/fphys.2024.1488951 PMID: 39703667

Objective: To study the impact motor neuron death has on the output of surviving phrenic motor neurons as well as the compensatory mechanisms that are recruited.

Summary: Results revealed that TNFR1 expression was increased on phrenic motor neurons of 28d CTB-SAP rats, and that astrocytes were increased and exhibited reactive morphology in the phrenic motor nucleus of CTB-SAP rats. This work suggests that TNFR1 could be used as a potential therapeutic agent in CTB-SAP rats and patients with respiratory motor neuron disease.

Usage: Intrapleural injection of CTB-SAP (25μg dissolved in PBS) to target respiratory motor neurons.

Related Products: CTB-SAP (Cat. #IT-14)

Shivakumar AB, Mehak SF, Gupta A, Gangadharan G (2024) Medial septal cholinergic neurotransmission is essential for social memory in mice. Prog Neuropsychopharmacol Biol Psychiatry 136:111207. doi: 10.1016/j.pnpbp.2024.111207 PMID: 39615870

Objective: To identify the physiological link between medial septal dependent cholinergic theta oscillations in the hippocampus and social memory behavior.

Summary: Selective ablation of cholinergic neurons in the medial septum (MS) impaired social memory in mice, while their sociability and social novelty remained intact. Additionally, these mice showed an attenuation of cholinergic theta oscillations (3–7Hz) in the hippocampal dorsal CA2 (dCA2) region. Furthermore, enhancing dCA2 theta oscillations by elevating cholinergic signaling using acetylcholinesterase inhibitor rescued social memory deficit. Together, these results indicate that 1) medial septal cholinergic neurons are essential for modulating social memory and 2) cholinergic hippocampal theta oscillations contribute to social memory processes.

Usage: Ablation of cholinergic neurons in the MS using mu-p75-SAP (IT-16, 0.2μg/0.5μl).

Related Products: mu p75-SAP (Cat. #IT-16)

Morishata Y, Fuentes I, Gonzalez-Salinas S, Favate J, Mejaes J, Zushida K, Nishi A, Hevi C, Goldsmith N, Buyske S, Sillivan SE, Miller CA, Kandel ER, Uchida S, Shah P, Alarcon JM, Barker DJ, Shumyatsky GP (2024) Dopamine release and dopamine-related gene expression in the amygdala are modulated by the gastrin-releasing peptide in opposite directions during stress-enhanced fear learning and extinction. Molexular Psychiatry doi: 10.1038/s41380-024-02843-8 PMID: 39580604

Objective: To investigate neural circuits serving the dopamine function for fear extinction and PTSD.

Summary: Results demonstrate that gastrin-releasing peptide regulates dopamine function in stress-enhanced fear processing and identifies Grp as the first gene known to regulate dopaminergic control of fear extinction.

Usage: Bombesin-SAP (IT-40) or Blank-SAP (IT-21) (80 ng/µl) dissolved in saline were injected bilaterally into the basolateral amygdala (AP: -2.0 mm, ML: ±3.25 mm, DV: -4.3 mm) in 0.3 µl volume.

Related Products: Bombesin-SAP (Cat. #IT-40), Blank-SAP (Cat. #IT-21)

Sun Y, Wu X, Li J, Radiom M, Mezzenga R, Verma CS, Yu J, Miserez A (2024) Phase-separating peptide coacervates with programmable material properties for universal intracellular delivery of macromolecules. Nat Commun 15(1):10094. doi: 10.1038/s41467-024-54463-z PMID: 39572548

Objective: To systematically manipulate the sequence of Phase-separating peptides (PSPs) to unravel the relationships between their molecular structure, the physical properties of the resulting coacervate microdroplets (CMs), and their delivery efficacy.

Summary: A few amino acid alterations are sufficient to modulate the viscoelastic properties of CMs towards either a gel-like or a liquid-like state as well as their binding interaction with cellular membranes, collectively enabling to tune the kinetics of intracellular cargo release. The authors also demonstrated that the optimized PSPs CMs display excellent transfection efficiency in hard-to-transfect cells such as primary fibroblasts and immune cells.

Usage: The cytotoxicity of the saporin-loaded (at various concentrations) or pristine CMs were evaluated using the Cell Counting Kit-8 (CCK-8).

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

Park HB, Kim KH, Kim JH, Kim SI, Oh YM, Kang M, Lee S, Hwang S, Lee H, Lee T, Park S, Lee JE, Jeong GR, Lee DH, Youn H, Choi EY, Son WC, Chung SJ, Chung J, Choi K (2024) Improved safety of chimeric antigen receptor T cells indirectly targeting antigens via switchable adapters. Nat Commun 15(1):9917. doi: 10.1038/s41467-024-53996-7 PMID: 39557825

Objective: To show that switchable CAR-T cells with a tumor targeting adaptor can mitigate on-target off-tumor toxicity against a low selectivity tumor antigen that cannot be targeted by conventional CAR-T cells, such as CD40.

Summary: The system is composed of anti-cotinine murine CAR-T cells and cotinine-labeled anti-CD40 single chain variable fragments (scFv), with which the authors show selective tumor killing while sparing CD40-expressing normal cells including macrophages in a mouse model of lymphoma. The authors evaluated whether Cot CAR-T cells could be depleted by Cot-saporin in vivo in an allogeneic CAR-T cell transfer model. When Balb/C mice transplanted with B6 bone marrow cells were injected with B6 Cot CAR-T cells, the transferred Cot CAR-T cells expanded in the peripheral blood in response to Balb/C alloantigen. However, when Cot-saporin was administered during this expansion phase, the Cot CAR-T cells failed to expand and were subsequently eliminated in the blood. Thus, Cot-saporin-mediated CotCAR-T cell suicide was confirmed in vitro and in vivo.

Usage: in vitro Cot CAR-T cell depletion by cotinine-drug conjugates: Peptides were incubated with saporin-labeled streptavidin (IT-27) at a molar ratio of 4:1 to generate cotinine-saporin conjugate (Cot-saporin). For Cot-saporin-dependent cytotoxicity assays on Cot CAR-T cells, a 1:1 mixed population (50,000 cells each) of Cot CAR-T cells (target cells) and control T cells (bystander non-CAR-T cells) were incubated with various doses of Cot-saporin for 48 h in medium containing human IL-2. Seven days after CAR-T cell transfer, Cot-saporin was administered intraperitoneally three times at 3-day intervals.

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

Ammar AO (2024) Involvement of peptidergic Edinger-Westphal nucleus in the neurobiology of migraine and acute alcohol exposure. Univ Pecs Thesis.

Objective: To confirm the role of Edinger-Westphal nucleus/urocortin1 (EWcp/UCN1) neurons in migraine. They hypothesized that selective ablation of EWcp/UCN1 neurons will influence the migraine-related behaviors induced by CGRP.

Summary: Upon selective ablation of EWcp/UCN1 neurons, authors examined the migraine-related behaviors in response to calcitonin gene-related peptide (CGRP) treatment. Leptin-SAP treatment significantly reduced the number of UCN1 immunoreactive neurons in the EWcp compared to naïve mice. Before ablation of EWcp/UCN1 neurons, CGRP treatment significantly reduced the periorbital withdrawal threshold compared to saline.

Usage: For selective UCN1 neuron ablation, 50 nl of Leptin-SAP was microinjected into the rostral and caudal parts of the EWcp area.

Related Products: Leptin-SAP (Cat. #IT-47)