References

Gamage R, Rossetti I, Niedermayer G, Münch G, Buskila Y, Gyengesi E. (2023) Chronic neuroinflammation during aging leads to cholinergic neurodegeneration in the mouse medial septum. J Neuroinflammation 20(1):235. doi: 10.1186/s12974-023-02897-5 PMID: 37833764

Summary: This publication presents the findings of studies on age-related cholinergic decline. The authors mention a diffusion MRI study that documented a 25% reduction in the BFCN (Basal Forebrain Cholinergic Neurons) population and a significant loss of terminal cholinergic projections in the hippocampus after inducing selective BFCN degeneration in mice using mu p75-SAP.

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

See Also:

• Kerbler GM et al. Diffusion-weighted magnetic resonance imaging detection of basal forebrain cholinergic degeneration in a mouse model. Neuroimage 66C:133-141, 2013.

Münzberg H, Berthoud HR, Neuhuber WL (2023) Sensory spinal interoceptive pathways and energy balance regulation. Mol Metab 78:101817. doi: 10.1016/j.molmet.2023.101817 PMID: 37806487

Objective: To review and discuss the roles of spinal sensory pathways, specifically dorsal root ganglia (DRG) afferents, in energy balance regulation, highlighting their contributions to metabolic homeostasis in health and disease.

Summary: This comprehensive review explores the emerging significance of spinal sensory neurons, beyond traditional gut-brain and adipose tissue-to-brain signaling pathways, in regulating energy intake and metabolism. It delves into the anatomy and functions of spinal sensory pathways, emphasizing the potential of DRG afferents in providing metabolic information to the brain. The review suggests that identifying specific DRG neurons and understanding their molecular mechanisms are crucial steps toward developing targeted therapies for metabolic diseases, such as obesity, diabetes, and cancer.

Usage: The publication references that CCK-SAP (IT-31) injected into the nodose ganglia of mice and rats selectively ablates vagal afferent neurons expressing CCKA receptors.

Related Products: CCK-SAP (Cat. #IT-31)

See Also:

• Diepenbroek C et al. Validation and characterization of a novel method for selective vagal deafferentation of the gut. Am J Physiol Gastrointest Liver Physiol 313:G342-G352, 2017.

Campideli-Santana AC, da Costa Silva KS, Araújo-Lopes R, Antunes LM, Szawka RE (2023) Submaximal loss of KNDy neurons accelerates and amplifies pulsatile LH secretion in female rats. J Endocrine Society 7(S1):bvad114.1214. doi: 10.1210/jendso/bvad114.1214

Objective: To investigate the impact of the submaximal loss of KNDy neurons on the pulsatile secretion of luteinizing hormone (LH) in female rats.

Summary: The study found that a partial loss of these neurons led to irregular estrous cycles and increased frequency and amplitude of LH pulses. This suggests a new role for KNDy neurons in moderating LH pulse frequency and amplitude in ovary-intact animals, with implications for early antral follicle recruitment.

Usage: Adult female rats underwent a neurochemical ablation of KNDy neurons via intra-ARC stereotaxic injections of NKB-SAP (IT-63), while control animals received Blank-SAP (IT-21).

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

Aquino NSS, Campideli-Santana AC, Antunes LM, Araújo-Lopes R, da Costa Silva KS, Costa Henriques P, de Oliveira Gusmão D, Bernuci MP, Szawka RE, dos Reis AM (2023) Partial loss of KNDy neurons in prenatally androgen treated female rats alters the LH secretion and ovarian morphology in a model of polycystic ovary syndrome. J Endocrine Society 7(S1):bvad114.1215. doi: 10.1210/jendso/bvad114.1215

Objective: To examine the impact of partial loss of KNDy neurons in prenatally androgen-treated female rats on luteinizing hormone (LH) secretion and ovarian morphology, as a model of polycystic ovary syndrome (PCOS).

Summary: The study found that the ablation of KNDy neurons resulted in increased LH pulse amplitude and mean LH levels without affecting pulse frequency, and partially restored the number of primordial follicles, suggesting KNDy neurons’ role in modulating LH release and ovarian reserve in PCOS.

Usage: Intra-ARC stereotaxic injections of the neurokinin-3 receptor agonist conjugated with Saporin (NKB-SAP, IT-63) to induce the lesion of KNDy neurons. Blank-SAP (IT-21) was used as a control.

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

Nie Y, Liang J, Sun J, Li J, Zhai X, Zhao P (2023) Orexin A alleviates LPS-induced acute lung injury by inhibiting macrophage activation through JNK-mediated autophagy. Int Immunopharmacol 124(Pt B):111018. doi: 10.1016/j.intimp.2023.111018 PMID: 37801969

Objective: To investigate the crosstalk between the central nervous system and immune response through the inflammatory response caused by lung injury.

Summary: By modeling acute respiratory distress in mice, the role of orexin-A and orexin-B was investigated through their inflammatory response. Orexin neurons were eliminated through lesions with Orexin-B-SAP (IT-20). Inflammatory cell infiltration and pro-inflammatory cytokines generation were aggravated after orexin neurons were ablated.

Usage: Mice were injected in the bilateral hypothalamus with 1 μL of Orexin-B-SAP (0.36 μg/μL) using a permanent stainless steel internal cannula connected at a speed of 16.5 ng/23 nl/second.

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

Goodman RL, Moore AM, Onslow K, Hileman SM, Hardy SL, Bowdridge EC, Walters BA, Agus S, Griesgraber MJ, Aerts EG, Lehman MN, Coolen LM (2023) Lesions of kndy and kiss1r neurons in the arcuate nucleus produce different effects on lh pulse patterns in female sheep. Endocrinology 164(11):bqad148. doi: 10.1210/endocr/bqad148 PMID: 37776515

Objective: To test the functional role of ovine KNDy neurons in pulse generation and identify the roles of nearby Kiss1 receptor (Kiss1R)-containing cells.

Summary: Injection of NK3-SAP (NKB-SAP) ablated over 90% of the KNDy cells, Kiss-SAP lesioned about two-thirds of the Kiss1R population. This led to a significant decrease in LH pulse amplitude and altering LH pulse patterns. NK3-SAP increased the interpulse interval without affecting the regularity of LH pulses, whereas Kiss-SAP disrupted their regular hourly occurrence but not the interpulse interval. The findings suggest that KNDy neurons are critical for GnRH pulse generation in ewes, while ARC Kiss1R cells support the amplitude and regularity of these pulses, possibly as part of a positive feedback loop involving GABA or glutamate.

Usage: Saporin conjugates were injected into the arcuate nucleus. Kiss-SAP (kisspeptin54-SAP) was diluted to 700 ng/μL in PBS immediately before use. In preliminary work to test the effectiveness of Kiss-SAP, a single unilateral injection (1 μL of 700 ng/μL) of this conjugate was made in the preoptic area of 3 ewes. The contralateral side was used as control and either received no injections or Blank-SAP (1 μL of 700 ng/μL) (IT-21).

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

Gao Q, Zhang Y, Wang X, Wang R, Zhang L (2024) Regulation of nociception threshold by norepinephrine through adrenergic α2 receptor in rat models of Parkinson’s disease. CNS Neurosci Ther 30(3):e14446. doi: 10.1111/cns.14446 PMID: 37721421

Objective: To investigate the effect of norepinephrine on the activation of brain cells through adrenergic α2 receptor, to regulate the nociception threshold in a 6-OHDA-induced animal model of Parkinson’s disease (PD).

Summary: The change of norepinephrine content can affect the activation of prefrontal and cingulate gyrus glial cells and participate in the regulation of nociception threshold in PD rats. Adrenergic α2 receptor agonist and central presynaptic membrane α2 receptor blocker both affect cell activation and improve hyperalgesia.

Usage: 4 μL of Anti-DBH-saporin was injected into the right lateral ventricle (1.25 μg/μL, 0.9% NaCl dilution), and injected at the rate of 1 μL/min.

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

Kubeil M, Suzuki Y, Casulli MA, Kamal R, Hashimoto T, Bachmann M, Hayashita T, Stephan H (2023) Exploring the potential of nanogels: From drug carriers to radiopharmaceutical agents. Adv Healthc Mater e2301404. doi: 10.1002/adhm.202301404 PMID: 37717209

Summary: This review provides a brief overview of current developments of nanogels in the fields of drug delivery, therapeutic applications, tissue engineering and sensor systems. The authors described one development using saporin. Mimicking the function of molecular chaperones, Kawasaki et al. created magnetic in vivo protein transport nanogels with encapsulated iron oxide nanoparticles. The nanogels also contained saporin, which was rapidly released by an exchange reaction with serum protein. The evaluation using an oral cancer model revealed a reduction in tumor volume and suppression of tumor regrowth, with no change in body weight.

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

See Also:

• Kawasaki R et al. (2021) Magnetically navigated protein transduction in vivo using iron oxide-nanogel chaperone hybrid. Adv Healthc Mater 10(9):e2001988. doi: 10.1002/adhm.202001988 PMID: 33694289

Thongchot S, Aksonnam K, Thuwajit P, Yenchitsomanus PT, Thuwajit C (2023) Nucleolin‑based targeting strategies in cancer treatment: Focus on cancer immunotherapy (Review). Int J Mol Med 52(3):81. doi: 10.3892/ijmm.2023.5284 PMID: 37477132

Objective: The authors review the mechanisms through which the multiple functions of NCL can participate in the progression of cancer. In addition, the studies that define the utility of NCL‑dependent anticancer therapies are summarized, with specific focus being paid to cancer immunotherapeutic approaches.

Summary: NCL is a multifunctional protein abundantly distributed in the nucleus, cytoplasm and cell membrane. It influences carcinogenesis, and the proliferation, survival and metastasis of cancer cells, leading to cancer progression. The overexpression of nucleolin (NCL) in a number of types of cancer provides an attractive antigen target for the development of novel anticancer immunotherapeutic treatments.

Usage: The mice were treated with 0.5 mg/kg body weight of SAP-N6L via intraperitoneal injection.

See Also:

• Dhez AC et al. Targeted therapy of human glioblastoma via delivery of a toxin through a peptide directed to cell surface nucleolin. J Cell Physiol 233(5):4091-4105, 2018.

Marquez J (2023) PTGFRN as a target for antibody-drug conjugate (ADC) development in mesothelioma and medulloblastoma. Univ Maryland Baltimore Thesis.

Objective: To investigate the role of Prostaglandin F2 Receptor Negative (PTGFRN) regulator in cancer progression and develop an antibody-drug conjugate (ADC) targeting PTGFRN for the treatment of mesothelioma and pediatric medulloblastoma.

Summary: This dissertation explores the expression and function of PTGFRN in mesothelioma and pediatric medulloblastoma, identifying its association with aggressive cancer phenotypes. The study further develops a potent ADC using a PTGFRN-specific monoclonal antibody conjugated to the cytotoxic compound Duocarmycin, demonstrating significant anti-cancer efficacy in both in vitro and in vivo models .

Usage: Both a custom direct conjugate and Fab-ZAP Mouse (IT-48) were used (up to 10 nM) on transfected HEK-293A cells.

Related Products: Fab-ZAP mouse (Cat. #IT-48), Custom Conjugates