References

Yaksh TL, dos Santo G, Lemes J, Malange K (2023) Neuraxial drug delivery in pain management: An overview of past, present, and future. Anaesthesiology 37(2):243-265. doi: 10.1016/j.bpa.2023.04.003 PMID: 37321769

Objective: Review of neuraxial therapeutic delivery platforms for pain management and the regulation caused by pharmacological targeting of dorsal root ganglion and dorsal horn systems.

Summary: Studies have shown modulation by spinal opiates, but subsequent work reveals the complexity of the neuraxial system. Various delivery platforms, such as viral transfection, antisense and targeted neurotoxins give evidence to approaches to selectively address the acute and chronic pain phenotype. Substance P-Saporin is discussed as a method to lesion NK1R-containing neurons for the treatment of chronic pain.

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

See Also:

• Wiese AJ et al. Intrathecal substance p-saporin in the dog: distribution, safety, and spinal neurokinin-1 receptor ablation. Anesthesiology 119(5):1163-1177, 2013.
• Brown DC et al. Intrathecal substance p-saporin in the dog: efficacy in bone cancer pain. Anesthesiology 119(5):1178-1185, 2013.
• Wiley RG Substance P receptor-expressing dorsal horn neurons: Lessons from the targeted cytotoxin, substance P-saporin. Pain 136:7-10, 2008.

Wu D, Yu N, Gao Y, Xiong R, Liu L, Lei H, Jin S, Liu J, Liu Y, Xie J, Liu E, Zhou Q, Liu Y, Li S, Wei L, Lv J, Yu H, Zeng W, Zhou Q, Xu F, Luo MH, Zhang Y, Yang Y, Wang JZ (2023) Targeting a vulnerable septum-hippocampus cholinergic circuit in a critical time window ameliorates tau-impaired memory consolidation. Mol Neurodegener 18(1):23. doi: 10.1186/s13024-023-00614-7 PMID: 37060096

Objective: There is an urgent need to study the targeting strategy for the MS-hippocampus cholinergic pathway to rescue tau-impaired memory.

Summary: Abnormal tau accumulation and cholinergic degeneration are hallmark pathologies in the brains of patients with Alzheimer’s disease (AD). However, the sensitivity of cholinergic neurons to AD-like tau accumulation and strategies to ameliorate tau-disrupted spatial memory in terms of neural circuits still remain elusive. The authors found that cholinergic neurons with an asymmetric discharge characteristic in the MS-hippocampal CA1 pathway are vulnerable to tau accumulation. Photoactivating MS-CA1 cholinergic inputs within a critical 3 h time window during memory consolidation efficiently improved tau-induced spatial memory deficits in a theta rhythm dependent manner. 192-IgG-Saporin was used to create an Alzheimer’s Disease animal model.

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

See Also:

• Dornan WA et al. Comparison of site-specific injections into the basal forebrain on water maze and radial arm maze performance in the male rat after immunolesioning with 192 IgG saporin. Behav Brain Res 82:93-101, 1996.

Singh SA, Vellapandian C (2023) The promising guide to LC–MS analysis and cholinesterase activity of Luffa cylindrica (L.) fruit using in vitro and in-silico analyses. Futur J Pharm Sci 9:33. doi: 10.1186/s43094-023-00478-0

Objective: Identify and analyze the extract of the plant Luffa cylindrica for bioactive and biochemical properties, particularly as it relates to bioactivity in neurological diseases.

Summary: Luffa cylindrica contains a total of 80 compounds that were identified in the ethanolic extract from LC–MS analysis. The bioactive compounds were screened for activity in receptors responsible for causing oxidative stress-associated Alzheimer’s disease. Perlolyrine was chosen to perform in-silico docking. An in vitro activity of cholinesterase showed highest inhibition at 500 μg/ml. In-silico docking of perlolyrine showed better binding affinity and score. Results revealed that out of 10 docked receptors, amyloid beta showed the highest binding affinity with an energy of −46.1 kcal/mol showing promising drug for Alzheimer’s disease. The study reports the presence of a promising, bioactive compound (perlolyrine) with promisng applications in vivo, oxidative stress-related Alzheimer’s disease.

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

See Also:

• Santosh et al (2015) Mechanism of Anti-HIV Activity of Ribosome Inactivating Protein, Saporin. Protein & Peptide Letters. 22(6): 497-503. doi: 10.2174/0929866522666150428120701

Karthikeyan R, Davies WIL, Gunhaga L (2023) Non-image-forming functional roles of OPN3, OPN4 and OPN5 photopigments. J Photochem Photobiol 15:100177. doi: 10.1016/j.jpap.2023.100177

Objective: To review recent studies that focus on the non-image-forming functional roles of the OPN3, OPN4, and OPN5 photopigments.

Summary: This publication explores the non-image-forming functions of OPN3, OPN4, and OPN5 photopigments, highlighting their roles in various physiological processes such as regulation of circadian rhythms, pupillary light responses, modulation of sleep, mood, and hormone secretion, providing insights into the diverse functions of these photopigments beyond vision.

Related Products: Melanopsin-SAP (Cat. #IT-44)

Ren X, Liu S, Virlogeux A, Kang SJ, Brusch J, Liu Y, Dymecki SM, Han S, Goulding M, Acton D (2023) Identification of an essential spinoparabrachial pathway for mechanical itch. Neuron 30:S0896-6273. doi: 10.1016/j.neuron.2023.03.013 PMID: 37023756

Objective: Study pathways of mechanical and chemical itch.

Summary: Mechanical and chemical itch are controlled by separate pathways within the body. Gpr83ligand PEN peptide conjugated to saporin (PEN-SAP) was used to selectively ablate CAlcrl projection neurons, alleviating mechanical itch sensitivity in wild-type mice. Substance-P saporin (SSP-SAP) was injected into mice and used as a negative control for the ablation of itch-sensitive neurons in the areas targeted. The ablated mice maintained mechanical itch sensitivity.

Usage: Intrathecal injections of SSP-SAP (IT-11; 100 ng/10 ml 0.9% sterile saline), biotinylated Gpr83 ligand (PEN) conjugated to Strepavidin-ZAP (IT-27), PEN-SAP, 3 ug/10 ml, 0.9% sterile saline, or control Blank-SAP (IT-21) in mice.

Related Products: SSP-SAP (Cat. #IT-11), Streptavidin-ZAP (Cat. #IT-27), Blank-SAP (Cat. #IT-21)

Son H, Shin J, Park J (2023) Recent progress in nanomedicine-mediated cytosolic delivery. RSC Adv 13(15):9788-9799. doi: 10.1039/D2RA07111H PMID: 36998521

Summary: Cytosolic delivery of drugs, like saporin, through nanocapsules offers ways to move proteins through the body with greater specificity and efficacy. A nanoparticle that released a modified saporin protein at pH conditions correlative conditions to a tumor micro-environment was discussed as a model to deliver peptide-drugs to the cytosol.

Nestor CC, Merkley CM, Lehman MN, Hileman SM, Goodman RL (2023) KNDy neurons as the GnRH pulse generator: Recent studies in ruminants. Peptides 164:171005. doi: 10.1016/j.peptides.2023.171005 PMID: 36990389

Objective: This publication aims to summarize and provide an overview of recent studies investigating the role of KNDy neurons as the pulse generator for gonadotropin-releasing hormone (GnRH) release in ruminants.

Summary: Recent studies in ruminants, specifically sheep and cows, have investigated the role of KNDy neurons in driving the pulsatile release of GnRH. These studies have demonstrated the rhythmic electrical activity of KNDy neurons, coinciding with the pulsatile secretion of GnRH in ewes, suggesting their central role as the pulse generator. Additionally, the expression patterns of genes related to KNDy neurons and GnRH pulsatility have been examined in cows, revealing variations throughout the estrous cycle and indicating a potential involvement of KNDy neurons in regulating GnRH release in this species. These findings contribute to our understanding of reproductive physiology in ruminants and have implications for both animal and human reproductive health.

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

Konturek-Ciesla A, Dhapola P, Zhang Q, Säwén P, Wan H, Karlsson G, Bryder D (2023) Temporal multimodal single-cell profiling of native hematopoiesis illuminates altered differentiation trajectories with age. Cell Rep 42(4):112304. doi: 10.1016/j.celrep.2023.112304 PMID: 36961818

Objective: Using single-cell transcriptome and epitope profiling to study hematopoiesis and the effects from aging.

Summary: The contribution from Hematopoietic stem cells (HSCs) to mature blood cells decline with age. The authors used transcriptome and epitope profiling to reconstruct early hematopoiesis and assessed HSC-specific lineage tracing. Their analysis identified previously uncharacterized cell populations which included multipotent progenitor cells (MPP) Ly-1 and Ly-II. Flt3 is a marker indicative of early differentiation found on MPP cells and was targeted for elimination via an antibody to Flt3 combined with Streptavidin-ZAP. This cell depletion provided evidence for the lack of self-renewal of Ly-1 and Ly-II cells in a transplantation setting and suggests that they need to be continuously replenished by upstream HSPCs.

Usage: Biotinylated anti-CD135 (clone A2F10) was combined with Streptavidin-ZAP at a 1:1 molar ratio, diluted in PBS to 0.2 mg/ml and injected into mice at 3 mg/kg.

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

Donertas-Ayaz B, Caudle RM (2023) Locus coeruleus-noradrenergic modulation of trigeminal pain: Implications for trigeminal neuralgia and psychiatric comorbidities. Neurobiol Pain 13:100124. doi: 10.1016/j.ynpai.2023.100124 PMID: 36974102

Objective: To summarize the knowledge about the involvement of noradrenaline in acute and chronic trigeminal pain conditions and how the activity of the locus coeruleus (LC) noradrenergic neurons changes in response to acute and chronic pain conditions and how these changes might be involved in pain-related comorbidities including anxiety, depression, and sleep disturbance.

Summary: LC inhibition of nociceptive transmission in acute pain and in longterm neuropathic pain increases the tonic activity of LC-NA neurons. These changes may contribute to impaired descending pain modulation and pain-related comorbidities such as depression, anxiety, and sleep disorders.

Usage: Elimination of NA neurons via injection of anti-dopamine β-hydroxylase-saporin (Anti-DBH-SAP) into the lateral ventricle and trigeminal brainstem nuclei three weeks after infraorbital nerve injury attenuated mechanical allodynia

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

Zaichenko MI, Philenko P, Sidorina V, Grigoryan GA (2023) Acute and chronic lipopolysaccharide-induced stress changes expression of proinflammatory cytokine genes in the rat brain region-specifically and affects learning and memory. Biochemistry Moscow 88:526-538. doi: 10.1134/S0006297923040089 PMID: 37080938

Objective: Goal of the work was to conduct comparative analysis of the effects of acute and chronic lipopolysaccharide- induced stress on the behavior of rats in the Morris water maze test and on expression of mRNA of proinflammatory cytokines and BDNF in different brain structures.

Summary: Chronic stress, depression, and other neuropsychiatric disorders have been often associated with inflammation processes and activity of the brain immune system. In order to investigate association of neuroinflammation with such disorders the model of proinflammatory bacterial lipopolysaccharide intoxication was used. In the experiments with rats, acute lipopolysaccharide (LPS)-induced stress improved learning in the Morris water maze and caused substantial increase of the TNF-α and IL-1β mRNA concentrations in the hippocampus and amygdala, but not in the frontal lobe in comparison with the control animals. Hprt and Ywhaz genes were selected for use as molecular biology reference genes based on the analysis of the rat hippocampus transcriptome from the work done by Dobryakova, Y.V. et. al (2018) Intracerebroventricular administration of 192IgG-saporin alters expression of microglia-associated genes in the dorsal but not ventral hippocampus.

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

See Also:

• Dobryakova YV et al. Intracerebroventricular administration of 192IgG-saporin alters expression of microglia-associated genes in the dorsal but not ventral hippocampus. Front Mol Neurosci 10:429, 2018.