control-conjugates

Cusulin C, Monni E, Ahlenius H, Wood J, Brune J, Lindvall O, Kokaia Z (2012) Embryonic stem cell-derived neural stem cells fuse with microglia and mature neurons. Stem Cells 30:2657-2671. doi: 10.1002/stem.1227

Summary: The fusogenic role of microglia could be even more important after NSC transplantation into brains affected by neurodegenerative diseases associated with microglia activation.

Usage: Primary Cells and NS Cell Coculture. Seven to twelve days after plating primary cells, NS cells were plated on top (10,000 cells per cm2)  for 1–3 days. Rat primary cells were treated with 10 nM Mac-1-SAP or Mouse IgG-SAP during the 5 days prior to the coculture, and analyzed 3 days thereafter.

Related Products: Mac-1-SAP rat (Cat. #IT-33), Mouse IgG-SAP (Cat. #IT-18)

Kato J, O’Donnell RT, Abuhay M, Tuscano JM (2012) Efficacy and toxicity of a CD22-targeted antibody-saporin conjugate in a xenograft model of non-Hodgkin’s lymphoma. Oncoimmunology 1(9):1469-1475. doi: 10.4161/onci.21815

Summary: CD22 is a B-cell-specific antigen found on many B-cell malignancies. It is not expressed by stem cell precursors, and is rapidly internalized when bound by an antibody. In this work, the authors use a custom conjugate of anti-CD22 (mAb HB22.7) and saporin in a cytotoxicity assay on non-Hodgkin’s lymphoma cell lines, as well as in a mouse tumor model. The dosing for the tumor model was 1 mg conjugate per kg of animal. Mouse IgG-SAP (Cat. #IT-18) was used as a control. The results indicate that CD22 is a potential therapeutic target for cancer therapy.

Related Products: Mouse IgG-SAP (Cat. #IT-18), Custom Conjugates

Mittelman-Smith MA, Williams H, Krajewski-Hall SJ, McMullen NT, Rance NE (2012) Role for kisspeptin/neurokinin B/dynorphin (KNDy) neurons in cutaneous vasodilatation and the estrogen modulation of body temperature. Proc Natl Acad Sci U S A 109(48):19846-19851. doi: 10.1073/pnas.1211517109

Summary: Menopause is marked by estrogen withdrawal, and also by hot flushes. Given the fact that hypothalamic levels of kisspeptin/neurokinin B/dynorphin (KNDy) neurons are significantly altered in menopause, the authors investigated whether these neurons are involved in the generation of flushes. Rats received bilateral injections of NK3-SAP (Cat. #IT-63) into the arcuate nucleus – a total of 40 ng. Blank-SAP (Cat. #IT-21) was used as control. The data indicate that KNDy neurons promote cutaneous vasodilation, and play a role in 17β-estradiol modulation of body temperature, supporting the hypothesis that these neurons could play a role in the generation of hot flushes.

Related Products: NKB-SAP (Cat. #IT-63), Blank-SAP (Cat. #IT-21)

Kerbler GM, Hamlin AS, Pannek K, Kurniawan ND, Keller MD, Rose SE, Coulson EJ (2013) Diffusion-weighted magnetic resonance imaging detection of basal forebrain cholinergic degeneration in a mouse model. Neuroimage 66C:133-141. doi: 10.1016/j.neuroimage.2012.10.075

Summary: The authors examined the effectiveness of diffusion MRI using diffusion tensor imaging (DTI) and probabilistic tractography in detecting cholinergic loss in a mouse model. Mice received bilateral 0.2-μg icv injections of mu p75-SAP (Cat. #IT-16). Rabbit IgG-SAP (Cat. #IT-35) was used as control. The animals were then examined using DTI. The data indicate that DTI is a valid technique for assessment of cholinergic loss in septo-hippocampal tracts as a result of Alzheimer’s disease.

Related Products: mu p75-SAP (Cat. #IT-16), Rabbit IgG-SAP (Cat. #IT-35)

Krajewski-Hall SJ, Mittelman-Smith MA, Williams H, Lafrance KJ, Mcmullen NT, Rance NE (2012) A role for kisspeptin/neurokinin B/dynorphin (KNDy) neurons in the regulation of estrous cycles and the estrogen modulation of body temperature. Neuroscience 2012 Abstracts 585.02. Society for Neuroscience, New Orleans, LA.

Summary: We have recently described a method to selectively ablate kisspeptin/neurokinin B/dynorphin (KNDy) neurons using stereotaxic injections of NK3-SAP, a neurokinin 3 receptor agonist conjugated to saporin (Mittelman-Smith, Endocrinology, 2012). These studies revealed a critical role for arcuate KNDy neurons in tonic gonadotropin secretion, the rise in serum LH after ovariectomy and estrogen modulation of body weight. Here we determine the effects of KNDy neuron ablation on estrous cycles and the estradiol modulation of body temperature. In the first study, stereotaxic injections of NK3-SAP or Blank-SAP were made in the arcuate nucleus of ovary-intact, adult female rats. Rats with nearly complete KNDy-neuron ablation (verified by NKB immunohistochemistry) exhibited constant diestrus and ovarian atrophy, confirming the importance of these neurons in reproductive regulation. In a second experiment, we evaluated the effects of KNDy neuron ablation on the thermoregulatory axis in rats that were ovariectomized (OVX) and then treated with 17β-estradiol (E2). Tail skin temperatures (TSKIN) and core temperatures (TCORE) were recorded in rats throughout the light/dark cycle and during exposure to different ambient temperatures (TAMBIENT) in an environmental chamber. Notably, the average TSKIN of KNDy-ablated rats was consistently lower than control rats, indicative of lower levels of cutaneous vasodilatation. Moreover, KNDy neuron ablation blocked the reduction of TSKIN by E2 that occurred during the light phase in the environmental chamber, but did not affect the E2 suppression of TSKIN during the dark phase. At a high TAMBIENT of 33 C, the mean TCORE of OVX control rats increased to 39.0 C, and was reduced by E2 replacement. In contrast, at this high TAMBIENT, the average TCORE of OVX, KNDy-ablated rats was lower than OVX control rats, and TCORE was not altered by E2 replacement. Because KNDy neurons exhibit dramatic changes in morphology and gene expression in postmenopausal women, we have hypothesized these neurons contribute to the generation of hot flushes. These studies support this hypothesis by providing the first evidence that KNDy neurons participate in the E2 modulation of body temperature and promote cutaneous vasodilatation, one of the cardinal signs of a hot flush.

Related Products: NKB-SAP (Cat. #IT-63), Blank-SAP (Cat. #IT-21)

Kato J, Satake N, O’Donnell RT, Abuhay M, Lewis C, Tuscano JM (2013) Efficacy of a CD22-targeted antibody-saporin conjugate in a xenograft model of precursor-B cell acute lymphoblastic leukemia. Leuk Res 37(1):83-88. doi: 10.1016/j.leukres.2012.09.010

Summary: Most cases of acute lymphoblastic leukemia (ALL) are of B-cell lineage. Although children with ALL have a high survival rate, there is a subset of children with a much lower survival rate, and long-term side effects from treatment are problematic. CD22 has been suggested as a therapeutic target because it is not present on hematopoietic stem cells, therefore allowing regeneration of normal B cells following depletion of malignant B cells. The authors used a custom conjugate of the antibody HB22.7 and saporin to demonstrate specific toxicity against pre-B ALL cell lines. Mouse IgG-SAP (Cat. #IT-18) was used as a control.

Related Products: Mouse IgG-SAP (Cat. #IT-18), Custom Conjugates

Laplante F, Zhang ZW, Huppe-Gourgues F, Dufresne MM, Vaucher E, Sullivan RM (2012) Cholinergic depletion in nucleus accumbens impairs mesocortical dopamine activation and cognitive function in rats. Neuropharmacology 63(6):1075-1084. doi: 10.1016/j.neuropharm.2012.07.033

Summary: Current thought is that loss of cholinergic function in the nucleus accumbens (N.Acc) is associated with schizophrenia. This deficit is accompanied by low dopaminergic activity in the prefrontal area, which adversely affects working memory. Rats received bilateral injections totaling 500 ng of anti-ChAT-SAP (Cat. #IT-42) into the N.Acc; rabbit IgG-SAP (Cat. #IT-35) was used as a control. Lesioned animals had markedly reduced mesocortical dopamine activation, which corresponded with cognitive impairments. The data suggest that loss of cholinergic neurons in the N.Acc causes loss of dopamine function in the mesocorticolimbic system.

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

Coolen LM (2012) Featured Article: A pivotal role of lumbar spinothalamic cells in regulation of ejaculation via intraspinal connections. Targeting Trends 13(3)

Related Products: SSP-SAP (Cat. #IT-11), Blank-SAP (Cat. #IT-21)

Read the featured article in Targeting Trends.

See Also:

• Staudt MD et al. A Pivotal Role of Lumbar Spinothalamic Cells in the Regulation of Ejaculation via Intraspinal Connections. J Sex Med 9(9):2256-2265, 2012.

Mishra SK, Holzman S, Hoon MA (2012) A nociceptive signaling role for neuromedin B. J Neurosci 32(25):8686-8695. doi: 10.1523/JNEUROSCI.1533-12.2012

Summary: Previous work suggests that neuromedin B (NMB) is involved in nociception. Direct injection of the peptide causes nociceptive sensitization, while NMB antagonists attenuate sensitization in reponse to nerve stimulation with mustard oil. Specific subsets of dorsal horn interneurons were eliminated by administering either 10 μg of the custom conjugate neuromedin B-SAP, 0.13 μg of SSP-SAP (Cat. #IT-11), or 1.3 μg of bombesin-SAP (Cat. #IT-40). Blank-SAP (Cat. #IT-21) was used as a control. The data indicate that NMB may be involved in the perception of thermal sensation, but not mechanical or pruritic sensation.

Related Products: NMB-SAP (Cat. #IT-70), SSP-SAP (Cat. #IT-11), Bombesin-SAP (Cat. #IT-40), Blank-SAP (Cat. #IT-21)

Li AJ, Wiater MF, Oostrom MT, Smith BR, Wang Q, Dinh TT, Roberts BL, Jansen HT, Ritter S (2012) Leptin-sensitive neurons in the arcuate nuclei contribute to endogenous feeding rhythms. Am J Physiol Regul Integr Comp Physiol 302(11):R1313-26. doi: 10.1152/ajpregu.00086.2012

Summary: It is clear that the arcuate nucleus (Arc) plays an important role in the generation of feeding rhythms. To clarify how this region modulates signals governing food intake the authors took advantage of the Arc mediation of leptin. Rats received bilateral injections of leptin-SAP (Cat. #IT-47, 56.5 ng per dose) into each Arc. Blank-SAP (Cat. #IT-21) was used as a control. The lesioned animals quickly became obese and displayed arrhythmic eating patterns under normal light conditions. The results indicate that lesioned neurons in the Arc as well as those in the suprachiasmatic nuclei are required for maintenance of feeding rhythms controlled by photic cues.

Related Products: Leptin-SAP (Cat. #IT-47), Blank-SAP (Cat. #IT-21)