targeted-toxins

Li Y, Hollis E (2021) Basal forebrain cholinergic neurons selectively drive coordinated motor learning in mice. J Neurosci 41(49):10148-10160. doi: 10.1523/JNEUROSCI.1152-21.2021 PMID: 34750228

Related Products: NGFr (mu p75) Rabbit Polyclonal, affinity-purified (Cat. #AB-N01AP), mu p75-SAP (Cat. #IT-16)

Bortz J, Klatt KC, Wallace TC (2021) Perspective: Estrogen and the risk of cognitive decline: a missing choline(rgic) link?. Adv Nutr 13(2):376-387. doi: 10.1093/advances/nmab145

Objective: Explore the relationship between cognitive aging and sex hormones, the cholinergic system, and choline as an essential nutrient.

Summary: This perspective identifies numerous areas for future preclinical and clinical research, highlighting the need for randomized controlled trials in postmenopausal women to assess the impact of choline supplementation on cognitive decline, with appropriate consideration of the estrogen availability, critical windows, dose, and PEMT genotype.

Usage: The authors reference a publication about the effects of estrogen on cognitive improvements where 192-IgG-SAP was used as a specific cholinergic system lesioning tool.

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

See Also:

• Gibbs RB Basal forebrain cholinergic neurons are necessary for estrogen to enhance acquisition of a delayed matching-to-position T-maze task. Horm Behav 42(3):245-257, 2002.
• Gibbs RB et al. Donepezil plus estradiol treatment enhances learning and delay-dependent memory performance by young ovariectomized rats with partial loss of septal cholinergic neurons. Horm Behav 59(4):503-511, 2011.

Kunimura K, Fukui Y (2021) The molecular basis for IL-31 production and IL-31-mediated itch transmission: from biology to drug development. Int Immunol 33(12):731-736. doi: 10.1093/intimm/dxab065

Objective: To investigate the molecular mechanisms of how IL-31 is produced in helper T cells upon stimulation and transmits the itch sensation to the brain.

Summary: This review highlights recent findings that show the functional significance of endothelial PAS domain 1 (EPAS1) and neurokinin B (NKB) in the IL-31-induced itch sensation.

Usage: Neurons expressing the Nppb receptor were specifically ablated by intrathecal injection of Nppb-SAP. Treatment with Bombesin-SAP reduced IL-31-induced scratching.

See: Sakata D et al. Selective role of neurokinin B in IL-31–induced itch response in mice. J Allergy Clin Immunol 144(4):1130-1133, 2019.

Related Products: Bombesin-SAP (Cat. #IT-40), Nppb-SAP (Cat. #IT-69)

Dobryakova YV, Spivak YS, Zaichenko MI, Koryagina AA, Markevich VA, Stepanichev MY, Bolshakov AP (2021) Intrahippocampal adeno-associated virus-mediated overexpression of nerve growth factor reverses 192IgG-saporin-induced impairments of hippocampal plasticity and behavior. Front Neurosci 15:745050. doi: 10.3389/fnins.2021.745050

Objective: Determine any beneficial effects of adeno-associated virus (AAV)-mediated overexpression of nerve growth factor (NGF) in the hippocampus of rats with cholinergic loss.

Summary: 192-IgG-SAP was used to induce a rat animal model of cholinergic deficit. The authors concluded that NGF overexpression in the hippocampus after cholinergic loss induces beneficiall effects which are not related to maintenance of cholinergic function.

Usage: 1.5 mg of 192-IgG-SAP was injected into the medial septum area.

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

Nguyen KL, Lamerand SR, Deshpande RP, Taylor BK (2021) Contribution of small diameter non-peptidergic primary afferent neurons to central neuropathic pain in a new, more clinically relevant mouse model of multiple sclerosis. Neuroscience 2021 Abstracts P377/07. Society for Neuroscience, Virtual.

Summary: Over 50% of multiple sclerosis (MS) patients suffer from neuropathic pain (MSNP). Current treatments give inadequate relief due to incomplete understanding of underlying mechanisms. Recent electrophysiological recordings of primary afferent neurons (PAN) in the dorsal root ganglion (DRG) following experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, revealed increased afterhyperpolarization in small-diameter fibers. These data form the premise of our goal to understand the contribution of small-diameter (peptidergic or non-peptidergic) PANs to MSNP. Arguably the most common method to induce EAE is administration of myelin oligodendrocyte glycoprotein (MOG) to generate an autoimmune response targeting the myelin sheath. A MOG fragment is typically given with two adjuvants: complete Freund’s adjuvant (CFA) to boost immunogenicity and pertussis toxin (PTX) to breakdown the blood-brain barrier and facilitate CNS immune cell infiltration. However, PTX can disrupt G-protein coupled receptors, cause pain, and alter autoimmune response gene expression. In 10-week-old C57BL/6 mice, we conducted the first rigorous comparison of a classic PTX EAE model with the novel non-PTX (nPTX) EAE model. We found that both PTX and nPTX EAE mouse models showed the same degree of: 1) motor deficits; 2) plantar hindpaw mechanical and cold hypersensitivity (except cold hypersensitivity resolved more quickly after PTX EAE than nPTX EAE); and 3) lumbar spinal cord demyelination. Unlike most rodent models of MS including PTX EAE, the nPTX EAE group exhibited somatosensory cortex demyelination, a core feature of MS in human patients and cold hypersensitivity. We suggest nPTX EAE to be the most clinically relevant rodent model available to study not only MSNP, but MS in general. To evaluate the contribution of peptidergic and non-peptidergic neurons to MSNP, we induced nPTX EAE. After 12 days we administered capsaicin (10µg/mouse, i.t.) or IB4-saporin (1.5µg/mouse, i.t.) to primarily ablate peptidergic or nonpeptidergic C-fibers, respectively. Ablation efficacy was successfully confirmed with dramatic loss in DRG of TRPV1/CGRP immunoreactivity (peptidergic C-fibers) following capsaicin, and IB4 immunoreactivity (nonpeptidergic C-fibers) following IB4-saporin. IB4-saporin, but not capsaicin, partially reduced mechanical hypersensitivity and reversed cold hypersensitivity within 9 days. These data suggest nonpeptidergic but not peptidergic C-fibers contribute to MSNP. Our next studies will use genetic knockout, chemogenetic, and optogenetic strategies using MrgprdCreER mice to modulate the activity of nonpeptidergic C-fibers.

Related Products: IB4-SAP (Cat. #IT-10)

Read the featured article in Targeting Trends.

Ahn J, Christy DJ, Horner K (2021) The role of the patch compartment of striatum in reward-driven behaviors. Neuroscience 2021 Abstracts P747/06. Society for Neuroscience, Virtual.

Summary: The striatum is a neural structure that plays a critical role in cognitive functions, behavioral decision-making, and reward generation. The striatum exhibits a heterogeneous composition, containing neurons belonging to the patch compartment—which is thought to be involved in habitual reward-related behaviors—surrounded by neurons belonging to the matrix compartment—which is thought to be involved in adaptive motor control. Additionally, the striatum is further subdivided into the dorsolateral striatum (DLS) and the dorsomedial striatum (DMS), each with their own patch and matrix compartments. The DMS has been associated with goal-oriented behavior seen during the initial stages of addiction. Conversely, the DLS has been associated with habitual behaviors seen during late-stage addictive behaviors that are inflexible. It is thought that drug addiction is initially mediated by the DMS before DLS activity becomes predominant. Previously, it has been shown that the patch compartment of the DLS is necessary for development of habitual behavior, but the role of the patch compartment of the DMS is less clear. Our study intends to demonstrate that selective ablation of DMS patch compartment neurons will result in a negative impact on the initial development of reward-driven behaviors during the early stages of drug addiction. Since patch compartment neurons express a high level of mu opioid receptors compared to the surrounding matrix, we used dermorphin-saporin, a toxin that selectively destroys mu opioid receptor-containing neurons to target patch compartment neurons in the DMS and DLS for ablation. Following infusion in the DMS or DLS with dermorphin-saporin (17 ng/μl) or vehicle, rats were trained to self-administer cocaine (0.4 mg/kg/infusion) on progressive ratio schedule of reinforcement, starting with fixed ratio of 1 and ending with a fixed ratio of 5. Ablation of the patch compartment altered the level of responding for cocaine as the schedule of reinforcement became progressively labor-intensive. These data suggest that the patch compartment contributes to reward-driven behaviors.

Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12)

Osterlund Oltmanns JR, Schaeffer EA, Blackwell AA, Pietrucha SA, Yang H, Tasi S, Kartje GL, Wallace D (2021) Effects of age on sexually dimorphic food protection behavior associated with hippocampal cholinergic deafferentation. Neuroscience 2021 Abstracts P210.07. Society for Neuroscience, Virtual.

Summary: Loss of hippocampal cholinergic projection originating from basal forebrain structures has been associated with the progression of Dementia of the Alzheimer’s Type. The role of these fibers in information processing deficits has been debated; however, spontaneous behaviors such as food protection have been observed to dissociate the contributions of hippocampal and cortical cholinergic function. Sexual dimorphism and age are critical factors in the progression of neurodegenerative disorders, yet these factors have not been evaluated in food protection behavior. The current study infused the immunotoxin 192-IgG-Saporin bilaterally into the medial septum to produce selective cholinergic deafferentation of the hippocampal formation. Female and male rats received infusion of the immunotoxin at either three or 18 months of age. Testing in the in the food protection paradigm began six weeks after the surgery. During the five days of testing, rats received two food protection sessions. Each of these sessions involved the rat (dodger) being placed in a transparent cylinder with a same sex conspecific (robber). The dodger was given a one-gram food item to consume, while the robber made multiple attempts to obtain the food item. The number, success rate, and type of food protection behaviors were recorded across all food protection sessions. Rats also received a third session each day in which the latency to consume the food item was recorded in the absence of the conspecific. Preliminary results indicate that sex and age interact with cholinergic hippocampal deafferentation to influence the organization of food protection behaviors. These observations establish a foundation for future work investigating novel therapeutic interventions that target neuroplasticity within spared cholinergic systems.

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

Walker J, Kim T, Giszter S, Detloff MR (2021) Nociception impedes grasping recovery in the spinal cord injured rat. Neuroscience 2021 Abstracts P372.04. Society for Neuroscience, Virtual.

Related Products: IB4-SAP (Cat. #IT-10)

Nurmasitoh T, Sari DCR, Susilowati R (2021) Toxic substance-induced hippocampal neurodegeneration in rodents as model of Alzheimer’s dementia. Open Access Maced J Med Sci [Internet] 9(F):523.

Summary: In this review, the authors discussed hippocampal neurodegeneration rodent animal models of Alzheimer’s Dementia and their induction via a toxic substance. Between 2016-2021, 80 studies were reported with 17 different modeling techniques mentioned.

Usage: 192-IgG-Saporin was referenced using intracerebroventricular injection (ICV) as the route of administration where the parameters studied included, neurotrophic factors, cholinergic activity and neuro-degeneration markers.

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

Available here

See Also:

• Gelfo F et al. Chronic lithium treatment in a rat model of basal forebrain cholinergic depletion: Effects on memory impairment and neurodegeneration. J Alzheimers Dis 56:1505-1518, 2017.
• Volobueva MN et al. Intracerebroventricular administration of 192IgG-saporin alters the state of microglia in the neocortex. Neurochem J 14(1):37-42, 2020.
• Shin J et al. Focused ultrasound-induced blood-brain barrier opening improves adult hippocampal neurogenesis and cognitive function in a cholinergic degeneration dementia rat model. Alzheimers Res Ther 11(1):110, 2019.

Wong JJW, Selbo PK (2021) Light-controlled elimination of PD-L1+ cells. J Photochem Photobiol B 225:112355. doi: 10.1016/j.jphotobiol.2021.112355

Objective: To investigate novel strategies that simultaneously target both tumor cells and immunosuppressive cells in the tumor microenvironment. The focus was on the evaluation in vitro of Anti-PD-L1-SAP combined with photochemical internalization (PCI) as a therapeutic strategy to target and eliminate PD-L1 expressing tumor and immunosuppressive cells.

Summary: The authors show that the intracellular light-controlled drug delivery method induces specific and strongly enhanced cytotoxic effects of Anti-PD-L1-SAP in the PD-L1+ triple-negative breast cancer MDA-MB-231 cell line, while no enhanced efficacy was obtained in the PD-L1 negative control cell line MDA-MB-453. 

Usage: Anti-PD-L1-SAP and Streptavidin-ZAP (Control) were used in a cytotoxicity assay.

Related Products: Anti-PD-L1-SAP (Cat. #IT-45), Streptavidin-ZAP (Cat. #IT-27)