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Chemical genetic activation of the cholinergic basal forebrain hippocampal circuit rescues memory loss in Alzheimer’s disease
Liu W, Li J, Yang M, Ke X, Dai Y, Lin H, Wang S, Chen L, Tao J (2022) Chemical genetic activation of the cholinergic basal forebrain hippocampal circuit rescues memory loss in Alzheimer’s disease. Alzheimers Res Ther 14(1):53. doi: 10.1186/s13195-022-00994-w
Related Products: 192-IgG-SAP (Cat. #IT-01)
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Saporin as a commercial reagent: its uses and unexpected impacts in the biological sciences-tools from the plant kingdom
Ancheta LR, Shramm PA, Bouajram R, Higgins D, Lappi DA (2022) Saporin as a commercial reagent: its uses and unexpected impacts in the biological sciences-tools from the plant kingdom. Toxins (Basel) 14(3):184. doi: 10.3390/toxins14030184 PMID: 35324681
Summary: Saporin is a ribosome-inactivating protein that can cause inhibition of protein synthesis and causes cell death when delivered inside a cell. Development of commercial Saporin results in a technology termed ‘molecular surgery’, with Saporin as the scalpel. Its low toxicity (it has no efficient method of cell entry) and sturdy structure make Saporin a safe and simple molecule for many purposes. The most popular applications use experimental molecules that deliver Saporin via an add-on targeting molecule. These add-ons come in several forms: peptides, protein ligands, antibodies, even DNA fragments that mimic cell-binding ligands. Cells that do not express the targeted cell surface marker will not be affected. This review will highlight some newer efforts and discuss significant and unexpected impacts on science that molecular surgery has yielded over the last almost four decades. There are remarkable changes in fields such as the Neurosciences with models for Alzheimer’s Disease and epilepsy, and game-changing effects in the study of pain and itch. Many other uses are also discussed to record the wide-reaching impact of Saporin in research and drug development.
Effects of age on sexually dimorphic food protection behavior associated with hippocampal cholinergic deafferentation.
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)
A brief history of saporin and its contributions to neuroscience
Shramm PA, Ancheta LR, Bouajram R, Lappi DA (2021) A brief history of saporin and its contributions to neuroscience. Neuroscience 2021 Abstracts J002.11. Society for Neuroscience, Virtual.
Summary: When investigating the origins of targeted toxins (a drug, therapy, or scientific tool directed to a unique extracellular target), an appropriate place to begin is with the Nobel Prize-winning work of Paul Ehrlich and his concept of the “magic bullet.” Over 100 years later, the use of targeted toxins to perform molecular neurosurgery has become a vital practice that allows researchers to observe changes in organisms after eliminating a neuronal population. A prime example of this practice is the specific targeting of cholinergic neurons in the basal forebrain to mimic Alzheimer’s disease (AD). The research tool designed for this purpose is 192-IgG-Saporin, an antibody conjugated to the ribosome-inactivating protein (RIP) Saporin. Researchers have used this targeted toxin for over 30 years. A 2019 publication by Verkhratsky et al. reviews AD models and states this is the only lesion model that specifically targets cholinergic neurons. In 1983, during a quest to find the optimal payload for a targeted toxin, Fiorenzo Stirpe and colleagues discovered Saporin, a plant protein isolated from the common soapwort plant Saponaria officinalis. Unlike ricin and abrin, Saporin does not have a binding chain and cannot enter a cell on its own. Scientists have devised new ways to use Saporin to advance their research and drug development activities. Just a few examples include: 1. A novel suicide gene therapy approach that uses a vector encoding a double-stranded DNA aptamer to deliver the gene encoding Saporin, 2. Delivery of Saporin encapsulated in a nanotechnology system for development of cancer treatments, 3. A deeper understanding of the difference between pain and itch and the relevant pathways, and 4. Development of a stable epilepsy animal model that is used for screening specific treatments that will lead to micro-methods to eliminate the disease. This review will focus on Saporin as the payload delivered to cells. Targeted toxins (typically targeted by an antibody or peptide chemically linked or genetically fused) provide robust tools for neuroscience where ablation of specific neuronal populations is used to study behavior and function. Saporin is an ideal molecule because of its extreme resistance to high temperatures and denaturation, retention of catalytic activity after conjugation, and lack of a binding chain to allow entrance to the cytoplasm of cells on its own. As a result, it is one of the most studied RIPs used for its vigorousness, potency, safety, and ease of use in the laboratory. The information presented will shed light on the history of Saporin, current applications, and what the future holds for this protein in the neuroscience field.
Related Products: Saporin (Cat. #PR-01)
Toxic substance-induced hippocampal neurodegeneration in rodents as model of Alzheimer’s dementia
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)
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.
Tart cherry extract and omega fatty acids reduce behavioral deficits, gliosis, and amyloid-beta deposition in the 5xFAD mouse model of Alzheimer’s disease
Bowers Z, Maiti P, Bourcier A, Morse J, Jenrow K, Rossignol J, Dunbar GL (2021) Tart cherry extract and omega fatty acids reduce behavioral deficits, gliosis, and amyloid-beta deposition in the 5xFAD mouse model of Alzheimer’s disease. Brain Sci 11(11):1423. doi: 10.3390/brainsci11111423 PMID: 34827424
Objective: To assess the efficacy of Total Body Rhythm (TBR) for treating behavioral and neuropathological deficits in the 5xFAD model of AD.
Summary: The combination of tart cherry extract and omega fatty acids in TBR can reduce AD-like deficits in 5xFAD mice.
Usage: Previous work demonstrated that TBR can prevent loss of body weight in a mu p75-SAP mouse model of AD.
Related Products: mu p75-SAP (Cat. #IT-16)
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Engrafted stem cell therapy for Alzheimer’s disease: A promising treatment strategy with clinical outcome
Salwa, LK (2021) Engrafted stem cell therapy for Alzheimer’s disease: A promising treatment strategy with clinical outcome. J Control Release 338:837-857. doi: 10.1016/j.jconrel.2021.09.007
Objective: This review provides a detailed update on stem cell therapy (SCT) for Alzheimer’s Disease (AD)
Summary: What future holds for SCT in the treatment of AD is summarized
Usage: Liu et al. injected 1.5 μg of mu p75-SAP into the medial septum.
Read the featured article in Targeting Trends.
Related Products: mu p75-SAP (Cat. #IT-16)
Overexpression of nerve growth factor in the hippocampus induces behavioral changes in rats with 192IgG-saporin-induced cholinergic deficit
Dobryakova YV, Zaichenko MI, Spivak YS, Stepanichev MY, Markevich VA, Bolshakov AP (2021) Overexpression of nerve growth factor in the hippocampus induces behavioral changes in rats with 192IgG-saporin-induced cholinergic deficit. Neurochem J 15:273-281. doi: 10.1134/S1819712421030028
Summary: Degeneration of septal cholinergic neurons caused by the immunotoxin 192-IgG-SAP produces a model of the pathological state that occurs in Alzheimer’s Disease. This study investigated whether overexpression of NGF in the hippocampus, where septal neurons send their projections, may reduce the consequences of this damage. Data suggest that NGF overexpression in the hippocampus of rats may partly compensate some 192 IgG-SAP-induced impairments related to cholinergic deficit.
Usage: 192-IgG-SAP or an equivalent volume of PBS (4 µg/site) was administered bilaterally into the ventricles.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Cholinergic modulation of sensory processing in awake mouse cortex
Jimenez-Martin J, Potapov D, Potapov K, Knöpfel T, Empson RM (2021) Cholinergic modulation of sensory processing in awake mouse cortex. Sci Rep 11(1):17525. doi: 10.1038/s41598-021-96696-8
Objective: To decipher the timing and significance of acetylcholine actions.
Summary: Study provides new insights into how the cortex processes sensory information and how loss of acetylcholine, for example in Alzheimer’s Disease, disrupts sensory behaviours.
Usage: Focal cortical injection of mu p75-SAP or Rabbit IgG-SAP (1.7 mg/ml, 0.3 µl total volume, rate 0.075 µl/minute).
Related Products: mu p75-SAP (Cat. #IT-16), Rabbit IgG-SAP (Cat. #IT-35)
Therapeutic agent delivery across the blood-brain barrier using focused ultrasound
McMahon D, O’Reilly MA, Hynynen K (2021) Therapeutic agent delivery across the blood-brain barrier using focused ultrasound. Annu Rev Biomed Eng 23:89-113. doi: 10.1146/annurev-bioeng-062117-121238 PMID: 33752471
Summary: Review of the use of focused ultrasound, in combination with circulating microbubbles, can be used to transiently and noninvasively increase cerebrovascular permeability with a high level of spatial precision. For minutes to hours following sonication, drugs can be administered systemically to extravasate in the targeted brain regions and exert a therapeutic effect, after which permeability returns to baseline levels.
Usage: Shin et al. reported improved spatial memory following FUS+MB exposure in a rat model of cholinergic neuron degeneration. 192-IgG-SAP was injected bilaterally into the lateral ventricle (4 μl at a concentration of 0.63 μg/μl at a rate of 1 μl/min).
Related Products: 192-IgG-SAP (Cat. #IT-01)
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