References

Kucinski A (2015) Featured Article: Impairments in gait, posture and complex movement control in rats modeling the multi-system, cholinergic-dopaminergic losses in Parkinson’s Disease. Targeting Trends 16(1)

Related Products: 192-IgG-SAP (Cat. #IT-01), Anti-ChAT-SAP (Cat. #IT-42)

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See Also:

• Phillips K et al. Impairments in gait, posture and complex movement control in rats modeling the multi-system, cholinergic-dopaminergic losses in PD. Neuroscience 2014 Abstracts 692.21, 2014. Society for Neuroscience, Washington, DC

Devesa I, Ferrándiz-Huertas C, Mathivanan S, Wolf C, Luján R, Changeux J, Ferrer-Montiel A (2014) αCGRP is essential for algesic exocytotic mobilization of TRPV1 channels in peptidergic nociceptors. Proc Natl Acad Sci U S A 111:18345-18350. doi: 10.1073/pnas.1420252111

Summary: The sensitization of transient receptor potential vanilloid 1 (TRPV1) can lead to the development and maintenance of chronic pathological pain conditions. In this work the authors determined that TRPV1 receptors use membrane insertion mechanisms in order to potentiate neuronal excitability. In order to specifically link this activity to peptidergic neurons the authors treated rat primary dorsal root ganglion cultures with 10 mM rIB4-SAP (Cat. #IT-10) to deplete the non-peptidergic neurons.

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

Ehrlich D, Wang B, Lu W, Dowling P, Yuan R (2014) Intratumoral anti-HuD immunotoxin therapy for small cell lung cancer and neuroblastoma. J Hematol Oncol 7:91. doi: 10.1186/s13045-014-0091-3

Summary: HuD protein is a 40-kDa neuronal RNA-binding protein that is expressed in 100% of small cell lung cancer (SCLC) tumor cells. An anti-HuD monoclonal was biotinylated and combined with Streptavidin-ZAP (Cat. #IT-27); this conjugate was tested both in vitro and in vivo. Anti-HuD-SAP eliminated NCI-H69 and Neuro-2a cells at an EC50 of <0.5 μg/ml. 1 mg/kg of the conjugate injected directly into subcutaneous tumors generated in mice resulted in a temporary lack of tumor growth or regression of the tumor. The results demonstrate the potential of HuD as a therapeutic target for SCLC and neuroblastoma.

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

Keimpema E, Zheng K, Barde SS, Berghuis P, Dobszay MB, Schnell R, Mulder J, Luiten PG, Xu ZD, Runesson J, Langel U, Lu B, Hokfelt T, Harkany T (2014) GABAergic terminals are a source of galanin to modulate cholinergic neuron development in the neonatal forebrain. Cereb Cortex 24(12):3277-3288. doi: 10.1093/cercor/bht192

Summary: In this work the authors sought to clarify the role of galanin during brain development. Several different techniques were used including the use of Galanin-SAP (Cat. #IT-34) on primary cell cultures from the fetal forebrains of rats. Cultured basal forebrain neurons were exposed to 5 ng/ml of Galanin-SAP for 8 hours, and cell death was assessed after 72 hours. Cholinergic cells were killed by Galanin-SAP, indicating that these neurons can use extracellular galanin-2 receptors to facilitate development.

Related Products: Galanin-SAP (Cat. #IT-34)

Sato M, Inada E, Saitoh I, Matsumoto Y, Ohtsuka M, Miura H, Nakamura S, Sakurai T, Watanabe S (2015) A combination of targeted toxin technology and the piggyBac-mediated gene transfer system enables efficient isolation of stable transfectants in nonhuman mammalian cells. Biotechnol J 10:143-153. doi: 10.1002/biot.201400283

Summary: In this work the authors developed a new transfection strategy that takes advantage of the fact that many cell lines endogenously express α-1,3-galactosyltransferase (α-Gal), the target of rIB4-SAP (Cat. #IT-10). After transfection low expressing or non-transfected cells are killed by an application of rIB4-SAP at 80 μg/ml for 2 hours. The surviving cells eventually express α-Gal again, and require no selective agent to maintain expression of the gene of interest. These transfected cells can be transfected again using the same method.

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

Read the featured article in Targeting Trends.

Pergolizzi J, Gharibo C, Ho K (2015) Treatment considerations for cancer pain: A global perspective. Pain Pract 15:778-792. doi: 10.1111/papr.12253

Summary: This review discusses the treatment of cancer pain, addressing various aspects of the overall picture, such as early pain treatment to reduce central sensitization and chronic pain, pain assessment tools, and guidelines for treating specific populations of patients. Some of the current tools for pain management are discussed, including SP-SAP, which is currently in clinical trials as a cancer pain therapeutic.

Related Products: SP-SAP (Cat. #IT-07)

Feetham C, Barrett-Jolley R (2014) NK1-receptor-expressing paraventricular nucleus neurones modulate daily variation in heart rate and stress-induced changes in heart rate variability. Physiol Rep 2:e12207. doi: 10.14814/phy2.12207

Summary: Neurons in the paraventricular nucleus (PVN) project to the medulla and spinal cord, regulating heart rate and blood pressure. Although the activity of these neurons becomes elevated during heart failure, their role in overall cardiovascular control is unclear. The authors lesioned the PVN of rats with 2 ng injections of SSP-SAP (Cat. #IT-11). Heart rate variability during the experiment was measured using a high/low frequency ratio in response to psychological stress. The variability response of lesioned rats was lower than that of controls, and a shift in daily heart rate variation was seen as well. The authors conclude that neurokinin-1 expressing neurons in the PVN couple the cardiovascular system to the daily heart rate as well as the sympathetic response to psychological stress.

Related Products: SSP-SAP (Cat. #IT-11)

Cetas J, McFarlane R, Kronfeld K, Smitasin P, Liu J, Raskin J (2015) Brainstem opioidergic system is involved in early response to experimental SAH. Transl Stroke Res 6:140-147. doi: 10.1007/s12975-014-0378-2

Objective: To determine the cause of poor long-term outcomes after Subarachnoid hemorrhage (SAH).

Summary: Failure of the RVM μ-opioid receptor cells to initiate the compensatory CBF response sets the stage for acute and delayed ischemic injury following SAH.

Usage: To lesion medullary neurons expressing the μ-opioid receptor, Dermorphin–SAP was microinjected as a bilateral dose of 0.5 pmol in 500 nL per side (1 pmol in 1 μL total dose and injection volume). Blank–SAP or vehicle was injected in equal volumes and dose as controls.

Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12), Blank-SAP (Cat. #IT-21)

Nair DV, Al-Badri MM, Peng H, Schenkman N, Pacheco-Quinto J, Eckman CB, Iacono D, Eckman EA (2014) Chronic oxotremorine treatment ameliorates depressive phenotype in a rodent model of Alzheimer’s disease. Neuroscience 2014 Abstracts 670.03. Society for Neuroscience, Washington, DC.

Summary: Alzheimer’s disease (AD) is a progressive neurodegenerative condition that is characterized by changes to brain structure and function. It is estimated that depression and other neuropsychiatric symptoms occur in up to 90% of AD patients, yet the neurobiological basis of these symptoms and their influence on the clinical course of AD remain unclear. Using a rat model of AD-like basal forebrain cholinergic cell loss, our lab has previously shown that central administration of a muscarinic receptor agonist, oxotremorine, for 4 weeks could induce hippocampal neurogenesis and reverse the spatial working memory deficit triggered by cholinergic denervation. Preliminary experiments conducted with this model in our lab also revealed a depressive phenotype emerging between 11 and 15 weeks after cholinergic denervation. The depressive phenotype was detected using a sucrose consumption test and further confirmed by forced swim test. The goal of the present study was to determine whether effects of chronic oxotremorine treatment could ameliorate the depressive phenotype observed after selective cholinergic cell loss in the basal forebrain. Adult female Sprague Dawley rats were injected intracerebroventricularly (icv) with the immunotoxin 192-IgG-saporin (SAP), to induce AD-like basal forebrain cholinergic cell loss. After a 5 week recovery period, the rats then received 8 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. Biochemical analysis of a range of markers including tryptophan hydroxylase, the rate limiting enzyme for synthesis of serotonin, was performed after extraction of the brains following the behavioral tests. Results of these experiments demonstrate that oxotremorine treatment prevents the development of the depressive phenotype in SAP-lesioned rats. A number of oxotremorine-treated rats showed increases in tryptophan hydroxylase, suggesting a possible mechanism for the improved behavioral phenotype Based on these data, we propose that 192-IgG saporin lesioned rats may be an effective model for studying the pathophysiology and therapeutic modulation of age- and neurodegeneration-related neuropsychiatric symptoms such as depression.

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

Phillips K, Kucinski A, Albin R, Sarter M (2014) Impairments in gait, posture and complex movement control in rats modeling the multi-system, cholinergic-dopaminergic losses in PD. Neuroscience 2014 Abstracts 692.21. Society for Neuroscience, Washington, DC.

Summary: In addition to striatal dopamine loss, degeneration of cholinergic neurons in the basal forebrain (BF) and the brainstem pedunculopontine nucleus (PPN) were documented in patients with Parkinson’s disease (PD). Loss of cholinergic projections to cortical, thalamic and midbrain regions have been associated with impairments in gait and postural control and a propensity for falls. We previously demonstrated that loss of cortical cholinergic inputs and the resulting impairments in attentional control ‘unmask’ gait and postural risk factors and thus yielded falls in rats with striatal dopamine loss (Kucinski et al., 2013). For this research we developed a new behavior task for the assessment of gait, postural control, and fall propensity (Michigan Complex Motor Control Task; MCMCT). Here, to determine the contributions of the PPN cholinergic projection system to complex movement control, we also lesioned the cholinergic pars compacta (posterior) division of the PPN by infusing anti-ChAT saporin-coupled immunotoxin. Rats received these lesions either in combination with BF cholinergic (192-IgG-saporin) or dorsomedial striatal dopamine loss (6-OHDA), or all three lesions together (“triples”). MCMCT performance by triples was characterized by more falls than in rats with just PPN lesions, PPN plus striatal dopamine loss, or rats with loss of both BF and PPN cholinergic neurons. High fall rates in triples persisted throughout the 20-day MCMCT testing sequence, indicating that daily practice did not improve the interactions between loss of attentional control and gait and postural deficits that underlie falls. Interestingly, combined loss of BF and PPN cholinergic neurons increased falls relative to controls and single lesions, suggesting that ascending cholinergic PPN loss sufficiently dysregulates striatal dopamine input for BF cholinergic cell loss to ‘unmask’ the impact of the former on striatal dysfunction. Finally, PPN cholinergic cell loss resulted in ballistic postural (recovery) movements and slip-triggered switches to asymmetrical gait. Such behavior was previously observed in rats after electrolytic lesions of the PPN region, considered a model of “Parkinsonian festination” (Cheng et al., 1981) and it may assist in maintaining balance by stabilizing the center of gravity. Collectively, our findings support the hypothesis that PPN cholinergic projections contribute to the mediation of gait symmetry and postural control, and when lesioned in combination with forebrain cholinergic and dopaminergic system, results in profound impairments in the control of complex movements. This research was supported by the Michael J. Fox Foundation.

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

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