References

Qiu M, Li J, Tan L, Zhang M, Zhou G, Zeng T, Li A (2018) Targeted ablation of distal cerebrospinal fluid-contacting nucleus alleviates renal fibrosis in chronic kidney disease. Front Physiol 9:1640. doi: 10.3389/fphys.2018.01640

Objective: To test the hypothesis that distal cerebrospinal fluid-contacting nucleus (dCSF-CNs) might affect the renin-angiotensin system (RAS) in kidney injury progression.

Summary: Less CTB-labeled neurons were found in dCSF-CNs of CTB-SAP-treated rats. Meanwhile, CTB-SAP downregulated AGT, Ang II, AT1R, NOX2, catalase, MCP-1, IL-6, fibronectin, and collagen I, and upregulated ACE2 and Mas receptor. Targeted dCSF-CNs ablation could alleviate renal inflammation and fibrosis in chronic kidney injury.

Usage: CTB-SAP (500 ng) into the lateral ventricles over a 3-min period.

Related Products: CTB-SAP (Cat. #IT-14)

Bailey D, Catron M, Kovtun O, Macdonald R, Zhang Q, Rosenthal S (2018) Single quantum dot tracking reveals serotonin transporter diffusion dynamics are correlated with cholesterol-sensitive threonine 276 phosphorylation status in primary midbrain neurons. ACS Chem Neurosci 9:2534-2541. doi: 10.1021/acschemneuro.8b00214 PMID: 29787674

Objective: Visualizing SERT behavior at the single molecule level in endogenous systems remains a challenge. The authors utilize quantum dot (QD) single particle tracking (SPT) to capture SERT dynamics in primary rat midbrain neurons.

Summary: Results provide new insights into endogenous neuronal SERT mobility and its associations with membrane cholesterol and SERT phosphorylation status.

Usage: Live Cell QD Tracking – Cells were incubated with 5 μg/mL primary SERT antibody in warm fluorescent media at 37 °C and 5% CO2 for 6 min.

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Manzuoerh R, Farahpour MR, Oryan A, Sonboli A (2019) Effectiveness of topical administration of Anethum graveolens essential oil on MRSA-infected wounds. Biomed Pharmacother 109:1650-1658. doi: 10.1016/j.biopha.2018.10.117 PMID: 30551419

Usage: immunohistochemistry (1:500)

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Seel S, Eacott M, Langston R, Easton A (2018) Cholinergic input to the hippocampus is not required for a model of episodic memory in the rat, even with multiple consecutive events. Behav Brain Res 354:48-54. doi: 10.1016/j.bbr.2017.06.001

Summary: The authors use 192-IgG-SAP (Cat. #IT-01) to examine episodic memory. Continual trials versions of an episodic memory task are unimpaired by cholinergic lesions of the medial septum. In contrast continual trial versions of a location-context (where-which) task are impaired in the same animals. The results replicate the effects of lesions on one-trial a day versions of the same tasks. Increasing the amount of interference between trials by increasing the overlap of features in consecutive events has no effect on the behavioural outcome of these lesions. The result is interpreted in light of models of acetylcholine function centered around pattern separation.

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

Shibata S, Hayashi R, Okubo T, Kudo Y, Katayama T, Ishikawa Y, Toga J, Yagi E, Honma Y, Quantock AJ, Sekiguchi K, Nishida K (2018) Selective laminin-directed differentiation of human induced pluripotent stem cells into distinct ocular lineages. Cell Rep 25:1668-1679. doi: 10.1016/j.celrep.2018.10.032 PMID: 30404017

Usage: Immunostaining, flow cytometry

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Ueda H, Neyama H, Nagai J, Matsushita Y, Tsukahara T, Tsukahara R (2018) Involvement of lysophosphatidic acid-induced astrocyte activation underlying the maintenance of partial sciatic nerve injury-induced neuropathic pain. Pain 159:2170-2178. doi: 10.1097/j.pain.0000000000001316

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Moreno-Rodriguez M, Martinez-Gardeazabal J, Llorente-Ovejero A, Lombardero L, Manuel I, Rodriguez-Puertas R (2018) Learning and memory improvement mediated by CB1 cannabinoid receptors in animal models of cholinergic dysfunction. Neuroscience 2018 Abstracts 049.05 / S3. Society for Neuroscience, San Diego, CA.

Summary: The selective vulnerability of the basal forebrain cholinergic system (BFCS) is responsible for most of the clinical alterations in learning and memory processes that are characteristic of the Alzheimer’s disease (AD). The loss of cholinergic neurons and muscarinic receptors (MR) in the nucleus basalis of Meynert have been reported in AD. The endocannabinoid system is a neuromodulator of the BFCS, but there are controversial reports regarding the cannabinoid effects in learning and memory processes. The animal models of cholinergic impairment mimic the main histopathological and behavioral effects observed in patients. The MR antagonism, e.g. using scopolamine (SCOP), is used as a model of amnesia in rodents. The intraparenchymal administration of 192-IgG-saporin (SAP) in the nucleus basalis magnocellularis eliminates cholinergic neurons leading to learning and memory deficits. Then, the present study evaluates the modulation of spatial and working memory with the Barnes Maze following a subchronic treatment with a low dose (0.5 mg/kg) of WIN55,212-2 (WIN) in both the SCOP and SAP models of learning and memory deficit. In the SCOP model, the administration of WIN protects learning and memory impairment during the probe trial, recorded as the time spent in the target quadrant (WIN + SCOP: 78 ± 13 sec vs VEH + SCOP: 45 ± 3 sec; p < 0.001). A similar effect of the treatment was observed in the SAP model (SAP: 50 ± 3 sec vs SAP + WIN: 82 ± 7 sec; p < 0.001). This effect was specifically mediated by CB1 receptors, since it was blocked by the co-administration of the specific CB1 antagonist, SR141716A (0.5 mg/kg) (SAP: 49 ± 3 sec vs SAP + WIN + SR: 48 ± 5 sec). However, higher doses of WIN (3 mg/kg) induced negative effects in learning and memory in control (C) rats, but positive and comparable to the lower dose in the SAP model (C: 89 ± 3 sec, C + WIN-3 mg/kg: 48 ± 3 sec; SAP: 49 ± 3; SAP + WIN-3 mg/kg: 80 ± 12 sec; p < 0.001). The CB1 receptor activation by low doses of the cannabinoid agonist WIN are able to block the amnesic effects induced by SCOP and also the learning and memory impairment produced by the BFCS pathway degeneration. CB1 agonists could contribute to improve the clinical symptoms of AD. International application patent PCT/EP2018/054525.

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

Kong C, Shin J, Lee J, Koh C, Sim J, Na Y, Chang W, Chang J (2018) Improvements of cognitive function by focused ultrasound associated with adult hippocampal neurogenesis in immunotoxin 192-Saporin rat model of cholinergic degeneration. Neuroscience 2018 Abstracts 174.27 / JJJ31. Society for Neuroscience, San Diego, CA.

Summary: Introduction: Alzheimer’s disease is irreversible, progressive neurodegenerative disorder that destroys memory and cognitive function. Recently, focused ultrasound (FUS) has been demonstrated that FUS-mediated BBB opening induces an increase in hippocampal neurogenesis in adult rodents. In this study, we investigated the effects of FUS on memory and cognitive function after 192 IgG-saporin lesion. Materials and Methods: The present study utilized adult male Sprague-Dawley rats (200-250 g). Animals were divided into the three groups: Sham group (PBS injection), Lesion group (saporin injection), FUS group (saporin + FUS treatment). Lesion groups were injected bilaterally into the lateral ventricle. Rats were sonicated using a single-element transducer with microbubble. The acoustic parameters used for each sonication are: pressure amplitude 0.3 MPa, pulse length 10 ms, burst repetition frequency 1 Hz, and a duration of 120 s. BrdU was intraperitoneally injected two times per day for 4 consecutive days starting 24 hours after sonication. Two weeks after IgG-saporin administration, spatial memory was tested with the Morris water maze training. Results: In the water maze test, the FUS groups were significantly increased in number of crossing and platform zone, compared to the lesion group. We confirmed that the number of BrdU+, DCX+, and NeuN+ were significantly increased in the dentate gyrus following FUS sonication, compared to the lesion groups. Also, we found that the expression level of BDNF and TrkB increased in FUS group. Conclusion: Our results suggest that FUS treatments led to spatial memory improvement in cholinergic deficits rat model. Therefore, this provides evidence that the behavior changes may be mediated by increased acetylcholine activity and neuronal plasticity. Furthermore, FUS may represent a promising treatment for neurodegenerative disease, including Alzheimer’s disease because neurogenesis is associated with memory and cognitive function.

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

Ancheta L, Bouajram R, Lappi DA (2018) Screening targeting agents and their cell surface biomarkers for high specificity and rapid internalization via cell death and fluorescence. Neuroscience 2018 Abstracts 128.20 / M17. Society for Neuroscience, San Diego, CA.

Summary: Some of the most recent successes in the treatment of cancers or research into passive immunotherapies for neurodegenerative diseases, employ the use of antibodies. These treatments utilize antibodies that either: 1) interfere with cell surface proteins responsible for tumor cell proliferation, 2) act as immune checkpoint inhibitors, or 3) are re-engineered to allow transport of other molecules across the blood-brain barrier (BBB). There are a growing number of antibody and small molecule therapeutic candidates and this demands a quick and efficient technique to screen for biomarkers that internalize effectively upon binding. The method described provides for the efficient determination of internalization of cell surface biomarkers upon binding of antibodies or peptides. This one-step, robust method uses a targeting agent combined with both a fluorescent reporter and a cytotoxic payload. The construct that makes this method effective was formed by cross-linking a fluorescent reporter, in this case fluorescein (FITC) and streptavidin to the ribosome-inactivating protein, Saporin. The conjugate used in screening potential therapeutics is a mixture of a biotinylated targeting agent mixed in a 1:1 molar ratio with FITC-labeled Streptavidinylated-Saporin. The method provides a definitive assay readout: fluorescence within 1 hour and cell death in 72 hours. This method is designed for rapid screening, in a quick and reproducible manner, for specificity and internalization in various cell types to explore suitability of candidates as therapeutics.

Related Products: Streptavidin-ZAP (Cat. #IT-27), FITC-Streptavidin-ZAP (Cat. #IT-85)

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See Also:

• Tan HL et al. Conservation of oncofetal antigens on human embryonic stem cells enables discovery of monoclonal antibodies against cancer. Sci Rep 8:11608, 2018.
• Yuan X et al. Characterization of the first fully macropinocytosing human antibodies human anti-TEM1 scFv in models of solid tumor imaging and immunotoxin-based therapy. Cancer Immunol Immunother 66:367-378, 2017.
• Forsyth PA et al. p75 neurotrophin receptor cleavage by α- and γ-secretases is required for neurotrophin-mediated proliferation of brain tumor-initiating cells. J Biol Chem 289(12):8067-8085, 2014.
• Thakkar JP et al. Epidemiologic and molecular prognostic review of glioblastoma. Cancer Epidemiol Biomarkers Prev 23(10):1985-1996, 2014.
• Kohls M Evaluate Potential Targeting Molecules. Nature Methods , 2006.

McGaughy JA, Hutchins DJ, Pimentel AJ, Pimentel CS, Swaine JA (2018) Dissociable effects of noradrenergic and cholinergic lesions of anterior cingulate cortex on distractibility. Neuroscience 2018 Abstracts 238.14 / ZZ15. Society for Neuroscience, San Diego, CA.

Summary: Prior data from our lab and others has shown that that the anterior cingulate cortex (ACC) of the rat is critically involved in many aspects of executive function and cognitive control. Previously, we have shown that excitotoxic lesions of the ACC produced deficits in the ability of male rats to filter salient distractors. Additionally, these same subjects were unable to reverse reinforcement contingencies when tested with complex stimuli (Newman and McGaughy 2011). These deficits in filtering were not attributable to impairments in conditional discrimination learning, impairments in reversal learning with uni-dimensional stimuli or a general distractibility to conspicuous, irrelevant stimuli. In the present study, male, Long-Evans rats were used to determine if lesions to the noradrenergic or cholinergic afferents to ACC could recapitulate the effects of excitotoxic lesions in the same area. Lesions were produced by infusion into rostral ACC of dopamine β hydroxylase saporin or 192 IgG-saporin to deplete norepinephrine or acetylcholine, respectively. After two weeks of recovery from surgery, rats were tested in an intradimensional/extradimensional set-shifting task. This test was selected because of it’s utility in translational neuroscience and it’s sensitivity to several aspects of executive function including susceptibility to salient distractors, the ability to form an attentional set, the ability to shift an attentional set and reversal learning. Preliminary data show that noradrenergic, but not cholinergic lesions recapitulate some, but not all, of the impairments found after excitotoxic lesion of ACC. Specifically noradrenergic lesioned rats were more susceptible to salient distractors than sham-lesioned rats. In contrast to the effects of excitotoxic lesions, noradrenergic lesions did not impair the ability to reverse reinforcement contingencies when using complex stimuli containing salient, irrelevant stimulus dimensions. The extent of the lesions to ACC were assessed using markers for norepinephrine transporters and acetylcholinesterase. Together these data support the hypothesis that norepinephrine in the ACC is critically involved in the ability to filter salient distractors. The significance of these findings will be discussed in terms of the relevance of these data to the treatment of several neuropsychiatric disorders including attention deficit hyperactivity disorder, depression and addiction.

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