control-conjugates

Fricks-Gleason AN, Keefe KA (2013) Evaluating the role of neuronal nitric oxide synthase-containing striatal interneurons in methamphetamine-induced dopamine neurotoxicity. Neurotox Res 24(2):288-297. doi: 10.1007/s12640-013-9391-6

Summary: Using the fact that neuronal nitric oxide synthase (nNOS)-containing neurons in the striatum express the substance P receptor, the authors injected four locations in the striatum with 3 ng each of SSP-SAP (Cat. #IT-11). Blank-SAP (Cat. #IT-21) was used as a control. Although there was a significant loss of nNOS-containing neurons, the lesions did not attenuate NO production.

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

Hamlin AS, Windels F, Boskovic Z, Sah P, Coulson EJ (2013) Lesions of the basal forebrain cholinergic system in mice disrupt idiothetic navigation. PLoS One 8(1):e53472. doi: 10.1371/journal.pone.0053472

Summary: Alzheimer’s disease patients perform poorly on spatial navigation tests requiring either distal cues (allothetic) or body-centered cues (idiothetic). The authors used 0.2 μg bilateral infusions of mu p75-SAP (Cat. #IT-16) into the lateral ventricles of mice to examine the hypothesis that the cholinergic medial septo-hippocampal circuit is important for idiothetic navigation. Rabbit IgG-SAP (Cat. #IT-35) was used as a control. Lesioned animals were similar to controls in contextual fear conditioning, spatial working memory, as well as several other parameters. But exploratory behavior requiring idiothetic signals was very disorganized, indicating that cholinergic cells are vital to idiothetic navigation.

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

LaPlante F (2013) Featured Article: Role of cholinergic neurons in the nucleus accumbens and their involvement in schizophrenic pathology. Targeting Trends 14(1)

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

Read the featured article in Targeting Trends.

See Also:

• Laplante F et al. Reduction in cholinergic interneuron density in the nucleus accumbens attenuates local extracellular dopamine release in response to stress or amphetamine. Synapse 67(1):21-29, 2013.

Kaminski KL, Watts AG (2012) Intact catecholamine inputs to the forebrain are required for appropriate regulation of corticotrophin-releasing hormone and vasopressin gene expression by corticosterone in the rat paraventricular nucleus. J Neuroendocrinol 24(12):1517-1526. doi: 10.1111/j.1365-2826.2012.02363.x

Summary: Corticosterone releasing hormone (CRH) neurons in the paraventricular nucleus of the hypothalamus (PVH) control release of adrenocorticotropic hormone and glucocorticoids. In order to determine the contribution of these neurons to CRH and vasopressin expression in the PVH the authors administered bilateral 42 ng injections of anti-DBH-SAP (Cat. #IT-03) into the PVH of both normal and adrenalectomized rats. Mouse IgG-SAP (Cat. #IT-18) was used as a control. The data demonstrate that under certain conditions CRH and vasopressin gene expression is modulated by interactions between corticosterone and catecholaminergic projections to the hypothalamus.

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

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