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Towards astroglia-based noradrenergic hypothesis of Alzheimer’s disease
Leanza G, Zorec R (2023) Towards astroglia-based noradrenergic hypothesis of Alzheimer’s disease. Function (Oxf) 4(1):zqac060., IT. doi: 10.1093/function/zqac060 PMID: 36590326
Summary: These results indicate a prominent role of NA-neurons vs. ACh neurons in impairments of working memory, relevant for AD, and are consistent with an astrocyte-specific metabolic impairment in a mouse model of intellectual disability.
Usage: Bilateral icv injection of 192-IgG-SAP and/or Anti-DBH-SAP
Related Products: 192-IgG-SAP (Cat. #IT-01), Anti-DBH-SAP (Cat. #IT-03)
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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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)
Neurotoxic effects, mechanisms, and outcome of 192 IgG-Saporin lesions.
Petrosini L, De Bartolo P, Cutuli D (2021) Neurotoxic effects, mechanisms, and outcome of 192 IgG-Saporin lesions. RM Kostrzewa (Ed.): Handbook of Neurotoxicity . Springer, Cham doi: 10.1007/978-3-030-71519-9_79-1
Summary: 192-IgG-saporin selectively destroys basal forebrain cholinergic neurons that provide cholinergic input to the hippocampus, entire cortical mantle, amygdala, and olfactory bulb. Immunotoxic lesions by 192-IgG-saporin represent a valid animal model of Alzheimer’s disease, given the degeneration of basal cholinergic system present in this pathology. The selective lesioning of cholinergic innervation by means of 192-IgG-saporin (injected i.p. or i.c.v.) is able to interfere with experience-dependent plasticity.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Reversal of object recognition memory deficit in perirhinal cortex-lesioned rats and primates and in rodent models of aging and alzheimer’s diseases.
Masmudi-Martín M, Navarro-Lobato I, López-Aranda MF, Browning PGF, Simón A-M, López-Téllez JF, Jiménez-Recuerda I, Martîn-Montañez E, Pérez-Mediavilla A, Frechilla D, Baxter MG, Khan ZU (2020) Reversal of object recognition memory deficit in perirhinal cortex-lesioned rats and primates and in rodent models of aging and alzheimer’s diseases. Neuroscience 448:287-298. doi: 10.1016/j.neuroscience.2020.08.039
Objective: To determine if Object Recognition Memory (ORM) can be restored.
Summary: Memory-deficient rats were generated by induction of lesions to the perirhinal cortex (PRh) through an injection of OX7-SAP. Expression of regulator of G-protein signaling 14 of 414 amino acids (RGS14414) restored ORM in memory-deficient PRh-lesioned rats and nonhuman primates. This treatment was sufficient for full recovery of ORM in rodent models of aging and Alzheimer’s disease.
Usage: Rats were injected with OX7-SAP (0.9 mg in 1ml) in the PRh of the brain.
Related Products: OX7-SAP (Cat. #IT-02)
Saporin from Saponaria officinalis as a tool for experimental research, modeling, and therapy in neuroscience.
Bolshakov AP, Stepanichev MY, Dobryakova YV, Spivak, YS, Markevich, VA (2020) Saporin from Saponaria officinalis as a tool for experimental research, modeling, and therapy in neuroscience. Toxins (Basel) 12(9):546. doi: 10.3390/toxins12090546
Summary: A review of studies where saporin-based conjugates were used to analyze cell mechanisms of sleep, general anesthesia, epilepsy, pain, and development of Parkinson’s and Alzheimer’s diseases.
Related Products: Targeted Toxins
Identification of multiple targets in the fight against Alzheimer’s disease
Giannoni P, Fossati S, Claeysen S, Marcello E, eds (2020) Identification of multiple targets in the fight against Alzheimer’s disease. Front Aging Neurosci 12:169. doi: 10.3389/fnagi.2020.00169
Summary: A collection of 20 articles that depict a broad representation of the most impactful advances in Alzheimer’s disease (AD) comprehension and therapeutic openings.
Related Products: 192-IgG-SAP (Cat. #IT-01), mu p75-SAP (Cat. #IT-16)
Focused ultrasound-induced blood-brain barrier opening improves adult hippocampal neurogenesis and cognitive function in a cholinergic degeneration dementia rat model.
Shin J, Kong C, Lee J, Choi BY, Sim J, Koh CS, Park M, Na YC, Suh SW, Chang WS, Chang JW (2019) 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. doi: 10.1186/s13195-019-0569-x
Objective: To investigate the decrease of adult hippocampal neurogenesis (AHN) in Alzheimer’s disease (AD).
Summary: This work studied the effect of FUS on AHN in a cholinergic degeneration rat model of dementia.
Usage: 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)
Astroglia in Alzheimer’s Disease.
Verkhratsky A, Parpura V, Rodriguez-Arellano J, Zorec R (2019) Astroglia in Alzheimer’s Disease. (eds. Verkhratsky A, Ho M, Zorec R, Parpura V). In: Advances in Experimental Medicine and Biology: Neuroglia in Neurodegenerative Diseases. 1175:273-324. Springer, Singapore. doi: 10.1007/978-981-13-9913-8_11
Summary: A review of the tools for creating animal models of Alzheimer’s Disease. 192-IgG-SAP binds selectively and irreversibly to low-affinity nerve growth factor receptor interrupting cholinergic neuronal protein synthesis was employed. Anti-DBH-SAP binds dopamine-β-hydroxylase, which is not only localized mainly in the cytosol, but also at the plasma membrane surface of noradrenergic neurons. Anti-DBH-SAP produced specific and dose-dependent depletions of locus coeruleus neurons, with no effects on other cholinergic, dopaminergic or serotonergic neuronal populations. The possibility to induce a partial or total noradrenergic loss (by varying the injected dose) makes this immunotoxic approach an ideal model to study events within the noradrenergic projection system, as they occur during age-related demise of locus coeruleus in humans.
Related Products: 192-IgG-SAP (Cat. #IT-01), Anti-DBH-SAP (Cat. #IT-03)
3D reconstruction of the neurovascular unit reveals differential loss of cholinergic innervation in the cortex and hippocampus of the adult mouse brain.
Nizari S, Carare RO, Romero IA, Hawkes CA (2019) 3D reconstruction of the neurovascular unit reveals differential loss of cholinergic innervation in the cortex and hippocampus of the adult mouse brain. Front Aging Neurosci 11:172. doi: 10.3389/fnagi.2019.00172
Objective: To further characterize the effect of the loss of cholinergic innervation on the NVU (neurovascular unit) in Alzheimer’s Disease.
Summary: Significantly less ChAT staining was detected in the medial septum of saporin-treated mice at 45 days post-surgery. This was accompanied by a significant decrease in cholinergic nerve fiber density in the hippocampus and the cortex. As expected, p75 NTR-negative neurons in the striatum were not affected by mu p75-SAP treatment.
Usage: In this study, the mu-p75-SAP was used to induce death of basal forebrain cholinergic neurons and their fiber projections. mu p75-SAP 0.5 µL (0.596 µg/µL) or 0.9% saline (n = 19) was injected into each ventricle.
Related Products: mu p75-SAP (Cat. #IT-16)
Removal of p75 neurotrophin receptor expression from cholinergic basal forebrain neurons reduces amyloid-β plaque deposition and cognitive impairment in aged APP/PS1 mice.
Qian L, Milne MR, Shepheard S, Rogers ML, Medeiros R, Coulson EJ (2019) Removal of p75 neurotrophin receptor expression from cholinergic basal forebrain neurons reduces amyloid-β plaque deposition and cognitive impairment in aged APP/PS1 mice. Mol Neurobiol 56(7):4639-4652. doi: 10.1007/s12035-018-1404-2
Objective: To investigate the contribution of CBF neuronal p75NTR to the progression of Alzheimer’s Disease
Summary: Data indicate that a direct interaction between CBF-expressed p75NTR and Aβ does not contribute significantly to the regulation of Aβ load.
Usage: To lesion CBF neurons, a single infusion of mu p75-SAP or control Rabbit IgG-SAP (0.4 mg/ml) was stereotaxically-injected into the basal forebrain.
Related Products: mu p75-SAP (Cat. #IT-16), Rabbit IgG-SAP (Cat. #IT-35)
Atopic dermatitis linked cytokine interleukin-31 induced itch mediated via a neuropeptide natriuretic polypeptide b
Pitake S, Ralph PC, DeBrecht J, Mishra SK (2018) Atopic dermatitis linked cytokine interleukin-31 induced itch mediated via a neuropeptide natriuretic polypeptide b. Acta Derm Venereol 98:795-796. doi: 10.2340/00015555-2977
Objective: To determine if NPPB is involved as a neuropeptide in IL-31-mediated itch in atopic dermatitis (AD) via natriuretic polypeptide receptor A (NPRA) in the spinal cord.
Summary: This study reveals an important role of neuropeptide NPPB in AD that could provide a therapeutic target for alleviating chronic itch associated with AD.
Usage: To further demonstrate the IL-31-mediated itch response by NPRA receptors expressed in the spinal cord, Nppb-SAP (5 μg) was used to eliminate neurons expressing NPRA receptors in the spinal cord.
Related Products: Nppb-SAP (Cat. #IT-69)
Noradrenergic hypothesis linking neurodegeneration-based cognitive decline and astroglia.
Leanza G, Gulino R, Zorec R (2018) Noradrenergic hypothesis linking neurodegeneration-based cognitive decline and astroglia. Front Mol Neurosci 11:254. doi: 10.3389/fnmol.2018.00254
Objective: To examine noradrenergic dysfunction in AD-related cognitive decline in humans and its potential involvement in AD pathology and disease progression.
Summary: The authors discuss noradrenergic dysfunction in AD-related cognitive decline. The research focuses on animal models to allow the validation of the noradrenergic hypothesis of AD, including those based upon the Anti-DBH-SAP-mediated ablation of LC. The article also addresses how astrocytes may participate in the regulation of neurogenesis, a new strategy for preventing LC neuron loss.
Usage: DBH (–/–) knockout mice do not seem to offer the possibility to obtain partial or graded neurotransmitter depletions. In light of these limitations, the authors used Anti-DBH-SAP which is able to target noradrenergic neurons in the LC with unprecedented selectivity and efficiency. Anti-DBH-SAP was injected bilaterally into the LC.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Essential role of hippocampal noradrenaline in the regulation of spatial working memory and TDP‐43 tissue pathology
Pintus R, Riggi M, Cannarozzo C, Valeri A, de Leo G, Romano M, Gulino R, Leanza G (2018) Essential role of hippocampal noradrenaline in the regulation of spatial working memory and TDP‐43 tissue pathology. J Comp Neurol 526:1131-1147. doi: 10.1002/cne.24397
Objective: To determine the noradrenergic contribution to cognitive and histopathological changes in Alzheimer’s Disease.
Summary: Integrity of ascending noradrenergic inputs to the hippocampus may be required for the regulation of specific aspects of learning and memory and to prevent TDP-43 tissue pathology.
Usage: Anti-DBH-SAP was used at a dose of 0.50 µg dissolved in sterile PBS.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Ontogenetic and phylogenetic approaches for studying the mechanisms of cognitive dysfunctions
Zhuravin IA, Dubrovskaya NM, Tumanova NL, Vasilev DS, Nalivaeva NN (2018) Ontogenetic and phylogenetic approaches for studying the mechanisms of cognitive dysfunctions. Evolutionary Physiology and Biochemistry – Advances and Perspectives: InTech 714-741. doi: 10.5772/intechopen.73666
Summary: The effectiveness of the studies of the pathogenesis of AD and search for the strategies of its prevention and treatment depend on appropriate modeling of the pathological conditions in the brain leading to AD. Traditionally, the main focus on designing animal models of AD was related to the identification of brain areas and mediator systems related to memory. One model employed injections of a monoclonal antibody against growth factor receptor conjugated with saporin (192 IgG-saporin), which also resulted in the loss of cholinergic neurons and cognitive disorder
Related Products: 192-IgG-SAP (Cat. #IT-01)
Impact of chronic stress on the spatial learning and GR-PKAc-NF-κB signaling in the hippocampus and cortex in rats following cholinergic depletion.
Lee S, Cho W, Lee Y, Han J (2018) Impact of chronic stress on the spatial learning and GR-PKAc-NF-κB signaling in the hippocampus and cortex in rats following cholinergic depletion. Mol Neurobiol 55:3976-3989. doi: 10.1007/s12035-017-0620-5
Objective: Examine the effects of chronic stress on cognitive status and GR-PKAc-NF-κB signaling in rats with a loss of cholinergic input to the hippocampus and cortex.
Summary: The activation of NF-κB induced by cholinergic depletion appears to be aggravated by chronic stress, and this might explain the increased susceptibility of patients with Alzheimer’s disease to stress since activation of NF-κB is associated with stress.
Usage: Male Sprague-Dawley rats received injections of 192 IgG-SAP dissolved in sterile 0.01 M PBS) at a concentration of 0.25 μg/μl.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Lipid mapping of the rat brain for models of disease.
Martínez-Gardeazabal J, González de San Román E, Moreno-Rodríguez M, Llorente-Ovejero A, Manuel I, Rodríguez-Puertas R (2017) Lipid mapping of the rat brain for models of disease. Biochim Biophys Acta Biomembr 1859:1548-1557.. doi: 10.1016/j.bbamem.2017.02.011
Objective: To map the spatial distribution of different lipid species in the rat central nervous system (CNS) using IMS to find a possible relationship between anatomical localization and physiology. The data obtained were subsequently applied to a model of neurological disease, the 192IgG-saporin lesion model of memory impairment.
Summary: The specific distribution of different lipids supports their involvement not only in structural and metabolic functions but also as intracellular effectors or specific receptor ligands and/or precursors. Moreover, the specific localization in the CNS described here will enable us to analyze lipid distribution to identify their physiological conditions in rat models of neurodegenerative pathologies, such as Alzheimer’s disease.
Usage: 192 IgG-SAP in aCSF (135 ng/1 μl/hemisphere; 0.25 μl/min) was administered.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Nonamyloidogenic processing of amyloid beta precursor protein is associated with retinal function improvement in aging male APP
Joly S, Lamoureux S, Pernet V (2017) Nonamyloidogenic processing of amyloid beta precursor protein is associated with retinal function improvement in aging male APP. Neurobiol Aging 53:181-191. doi: 10.1016/j.neurobiolaging.2017.02.004 PMID: 28262325
Objective: To determine amyloid beta role in the aging retina in Alzheimer’s Disease
Summary: Retinal-specific processing of amyloid may confer protection against AD and selectively preserve cone-dependent vision during aging.
Usage: Immunohistochemistry 1:1000
Related Products: Melanopsin Rabbit Polyclonal (Cat. #AB-N38)