References

Nair DV, Al-Badri MM, Peng H, Pachego-Quinto J, Eckman CB, Iacono D, Eckman EA (2015) Preliminary investigation on the antidepressive effect of chronic oxotremorine treatment in a rodent model of Alzheimer’s disease. Neuroscience 2015 Abstracts 40.29/C34. Society for Neuroscience, Chicago IL.

Summary: Alzheimer’s disease (AD) is a progressive neurodegenerative disease and the rate of progression varies from individual to individual. A great deal of evidence supports the idea that depression and other neuropsychiatric conditions co-exist with cognitive decline. However, the neurobiological basis of these symptoms and their influence on the clinical course of AD remain unclear. Our lab has shown previously that the 192-IgG saporin rat model of AD-like basal forebrain cholinergic cell loss exhibits a depression-like phenotype that develops months after the well-described impairment in spatial working memory. Furthermore, we have shown that chronic intracerebroventricular administration of the muscarinic agonist oxotremorine reverses both spatial working memory deficits and the depression-like behavior triggered by cholinergic denervation, and induces hippocampal neurogenesis. Current experiments are focused on determining additional pathological correlates of depression in this model and how they may be modulated by muscarinic agonists. To induce AD-like basal forebrain cholinergic cell loss, adult female Sprague Dawley rats were injected intracerebroventricularly (icv) with the immunotoxin 192-IgG-saporin (SAP) or saline as control (SHAM). After a 5 week recovery period, the rats received either 2 or 6 weeks of icv infusion of either oxotremorine or vehicle (saline) via osmotic minipump. Behavioral testing to assess the depressive phenotype was carried out using the sucrose consumption test every 2 weeks during oxotremorine treatment. The phenotype was further confirmed by forced swim test. The levels of ChAT, tryptophan hydroxylase (TPH), muscarinic receptors and FosB and ΔFosB were assessed in the hippocampus, basal forebrain, and orbitofrontal cortex by western blot and immunohistochemistry. Our preliminary results show increases in TPH, M1 receptors and FosB in the hippocampus, basal forebrain, and orbitofrontal cortex of a subset of treated animals, but no changes ChAT or ΔFosB. Further experiments are in progress to determine if there are changes in the expression of these and additional proteins in other brain regions including the nucleus accumbens, an area involved in activational aspects of motivation which also contributes to behavioral disorders such as to depression. The results of these studies may provide new insight in understanding the molecular basis of depression and antidepressant action of oxotremorine thereby defining new targets for possible therapeutic intervention for depressive symptoms in AD.

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

Pittenger CJ (2015) Modeling Tourette syndrome pathophysiology through targeted manipulation of striatal interneurons. Neuroscience 2015 Abstracts 6.07. Society for Neuroscience, Chicago IL.

Summary: Postmortem studies of Tourette syndrome patients has revealed a reduction in the number of specific striatal interneurons. The authors explored the hypothesis that this neuronal deficit is enough to produce the symptoms of Tourette syndrome in mice. Animals received 90-ng injections of Anti-ChAT-SAP (Cat. #IT-42) into the striatum. Rabbit IgG-SAP (Cat. #IT-35) was used as a control. The data suggest that loss of the striatal interneurons is enough to produce some, but not all, of the symptoms caused by Tourette syndrome.

Related Products: Anti-ChAT-SAP (Cat. #IT-42), Rabbit IgG-SAP (Cat. #IT-35)

See Also:

• Xu M et al. Targeted ablation of cholinergic interneurons in the dorsolateral striatum produces behavioral manifestations of Tourette syndrome. Proc Natl Acad Sci U S A 112:893-898, 2015.

Zhou N, Hao Z, Zhao X, Maharjan S, Zhu S, Song Y, Yang B, Lu L (2015) A novel fluorescent retrograde neural tracer: cholera toxin B conjugated carbon dots. Nanoscale 7(38:15635-15342. doi: 10.1039/c5nr04361a PMID: 26285001

Related Products: Cholera Toxin B, Recombinant (Cat. #PR-14)

Pires E, D’Souza R, Needham M, Herr A, Jazaeri A, Li H, Stoler M, Anderson-Knapp K, Thomas T, Mandal A, Gougeon A, Flickinger C, Bruns D, Pollok B, Herr J (2015) Membrane associated cancer-oocyte neoantigen SAS1B/ovastacin is a candidate immunotherapeutic target for uterine tumors. Oncotarget 6:30194-30211. doi: 10.18632/oncotarget.4734

Summary: Ovastatin is a zinc matrix metallo-proteinase thought to play roles in sperm-egg interaction and the prevention of polyspermy in eutherians. This protein is not found in normal adult tissues, but is expressed by uterine carcinosarcomas. The authors investigated the possibility of targeting ovastatin as a tumor surface neoantigen for therapeutic purposes. SNU539 cells, a uterine malignant mixed Müllerian tumor-derived cell line, were challenged with 1 μM, 0.1 μM, and 0.01 μM rabbit polyclonal anti-ovastatin coupled to 5.42 nM Fab-ZAP rabbit (Cat. #IT-57). Rabbit IgG-SAP (Cat. #IT-35) was used as a control. The results indicate that for this form of uterine cancer, ovastatin is a viable therapeutic target.

Related Products: Fab-ZAP rabbit (Cat. #IT-57), Rabbit IgG-SAP (Cat. #IT-35)

Aoki S, Wickens JR (2015) Featured Article: A specific immunotoxin elucidates a causal role of striatal cholinergic system in behavioral flexibility. Targeting Trends 16(4)

Related Products: Anti-ChAT-SAP (Cat. #IT-42)

Read the featured article in Targeting Trends.

See Also:

• Aoki S et al. Role of Striatal Cholinergic Interneurons in Set-Shifting in the Rat. J Neurosci 35:9424-9431, 2015.

Aicher S, Hermes S, Hegarty D (2015) Denervation of the lacrimal gland leads to corneal hypoalgesia in a novel rat model of aqueous dry eye disease. Invest Ophthalmol Vis Sci 56:6981-6989. doi: 10.1167/iovs.15-17497

Summary: One result of functional disruption of the tear gland is dry eye disease (DED), which represents a group of disorders rather than a singular one. DED manifests itself in altered responses to noxious corneal stimulation, but many of these patients do not actually have dry eyes or tear gland dysfunction. In order to investigate what circuits are involved in DED the authors created two models, one of which used the ablation of p75 receptor-expressing neurons innervating the extraorbital lacrimal gland. Rats received 2.5 μg of 192-IgG-SAP (Cat. #IT-01) directly into the left extraorbital lacrimal gland. Tear production in the lesioned animals was normal, and responses to noxious cold stimuli were impaired. This accompanied by unchanged fiber density indicates that the nociceptive signaling was affected on a molecular level.

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

Devoto P, Flore G, Saba P, Frau R, Gessa G (2015) Selective inhibition of dopamine-beta-hydroxylase enhances dopamine release from noradrenergic terminals in the medial prefrontal cortex. Brain Behav 5:e00393. doi: 10.1002/brb3.393

Summary: Dopamine-beta-hydroxylase (DBH) is a neuronal enzyme that is a potential target for the treatment of cocaine abuse, alcohol dependence, and eating disorders. Here the authors administered 5 μg of icv Anti-DBH-SAP (Cat. #IT-03) to rats, and assessed the effect of the dopaminergic lesion on levels of extracellular dopamine. Mouse IgG-SAP (Cat. #IT-18) and saporin (Cat. #PR-01) were used as controls. Extracellular levels of dopamine were significantly increased in both lesioned animals and those treated with the DBH inhibitor nepicastat. Clonadine could reverse the nepicastat effect, but not the effect of Anti-DBH-SAP treatement. The data demonstrate a mechanism for the synergistic effect of cocaine on nepicastat-induced dopamine release.

Related Products: Anti-DBH-SAP (Cat. #IT-03), Mouse IgG-SAP (Cat. #IT-18), Saporin (Cat. #PR-01)

Werner A, Iwasaki S, McGourty CA, Medina-Ruiz S, Teerikorpi N, Fedrigo I, Ingolia NT, Rape M (2015) Cell-fate determination by ubiquitin-dependent regulation of translation. Nature 525(7570):523-527. doi: 10.1038/nature14978 PMID: 26399832

Usage: Immunofluorescence 1:100

Related Products: NGFr (ME20.4, p75) Mouse Monoclonal (Cat. #AB-N07)

Cao Q, Lu J, Li Q, Wang C, Wang X, Lee V, Wang C, Nguyen H, Zheng G, Zhao Y, Alexander S, Wang Y, Harris D (2016) CD103+ dendritic cells elicit CD8+ t cell responses to accelerate kidney injury in adriamycin nephropathy. J Am Soc Nephrol 27:1344-1360. doi: 10.1681/ASN.2015030229

Summary: Although it is known that dendritic cells (DCs) are involved in chronic kidney disease, it is not well understood how they either resolve or aggravate the condition. CD103+ dendritic cells in particular, are known to maintain tolerance through interaction with regulatory T cells, as well as protect against infection through interactions with CD8+ T cells. In this work the authors depleted CD103+ DCs by administering 1 mg/kg of anti-CD103-SAP (Cat. #IT-50) to the intraperitoneal space of mice subject to adriamycin nephropathy. Rat IgG-SAP (Cat. #IT-17) was used as a control. Elimination of the CD103+ DCs attenuated the kidney injury, indicating that in murine chronic kidney disease CD103+ DCs are pathogenic rather than therapeutic.

Related Products: Anti-CD103-SAP (Cat. #IT-50), Rat IgG-SAP (Cat. #IT-17)

Damelin M, Bankovich A, Park A, Aguilar J, Anderson W, Santaguida M, Aujay M, Fong S, Khandke K, Pulito V, Ernstoff E, Escarpe P, Bernstein J, Pysz M, Zhong W, Upeslacis E, Lucas J, Lucas J, Nichols T, Loving K, Foord O, Hampl J, Stull R, Barletta F, Falahatpisheh H, Sapra P, Gerber H, Dylla S (2015) Anti-EFNA4 calicheamicin conjugates effectively target triple-negative breast and ovarian tumor-initiating cells to result in sustained tumor regressions. Clin Cancer Res 21:4165-4173. doi: 10.1158/1078-0432.CCR-15-0695

Summary: Triple-negative breast cancer (TNBC) is characterized by tumors lacking HER2, estrogen receptor, and progesterone receptor. TNBC has proved to be very difficult to treat, in large part because of the absence of consensus targets on the surface of the tumor cells. In this work the authors empirically established a set of surface markers associated with TNBC tumor initiating cells, as produced by patient-derived xenografts. Ephrin-A4 was selected as a therapeutic target, and a cell line transfected with the ephrin-A4 gene was challenged with two versions of biotinylated anti-ephrin-A4 coupled to Streptavidin-ZAP (Cat. #IT-27). Both the mouse monoclonal and the humanized antibodies reach an EC50 of 10 ng/ml, indicating that ephrin-A4 has promise as a therapeutic target for TNBC.

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