2013 Targeting Trends Review

Brayda-Bruno L, Mons N, Yee BK, Micheau J, Abrous DN, Nogues X, Marighetto A (2013) Partial loss in septo-hippocampal cholinergic neurons alters memory-dependent measures of brain connectivity without overt memory deficits. Neurobiol Dis 54:372-381. doi: 10.1016/j.nbd.2013.01.010

Summary: The authors examined whether partial degeneration of septo-hippocampal neurons alters brain activity patterns even without overt memory loss. Mice received 45 ng of mu p75-SAP (Cat. #IT-16) into the medial septal area. Lesioned animals had significantly altered functional activities in the brain, despite lack of an overt behavioral deficit. Some changes observed are also altered with the initial signs of Alzheimer’s disease.

Related Products: mu p75-SAP (Cat. #IT-16)

Szigeti C, Bencsik N, Simonka AJ, Legradi A, Kasa P, Gulya K (2013) Long-term effects of selective immunolesions of cholinergic neurons of the nucleus basalis magnocellularis on the ascending cholinergic pathways in the rat: A model for Alzheimer’s disease. Brain Res Bull 94C:9-16. doi: 10.1016/j.brainresbull.2013.01.007

Summary: 192-IgG-SAP (Cat. #IT-01) has been used extensively to generate models of Alzheimer’s disease in rats. In this work, the authors detailed the time course of neuronal loss with an eye on potential recovery from the lesion. The nucleus basalis magnocellularis of rats was injected with 75 ng of 192-IgG-SAP (Cat. #IT-01) and long-term changes were tracked by immunohistochemistry. While some acetylcholinesterase neurons, considered cholinoceptive, were lost, choline acetyltransferase (cholinergic) neurons sustained a massive irreversible reduction in number.

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

Shia WW, Bailey RC (2013) Single domain antibodies for the detection of ricin using silicon photonic microring resonator arrays. Anal Chem 85(2):805-810. doi: 10.1021/ac3030416 PMID: 23268548

Summary: A major hurdle to clear in the fight against bioterrorism is the ability to identify various biowarfare agents. One of the more difficult substances to identify is ricin. This work describes the use of single domain antibodies to identify ricin in a microring resonator array assay. Saporin (Cat. #PR-01) along with affinity purified chicken anti-saporin (Cat. #AB-17AP) were used as controls when constructing the assay. The results demonstrate the feasibility of using microring resonator arrays for the detection of biowarfare agents.

Related Products: Saporin Chicken Polyclonal, affinity-purified (Cat. #AB-17AP), Saporin (Cat. #PR-01)

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)

Ferrini F, Trang T, Mattioli TA, Laffray S, Del’Guidice T, Lorenzo LE, Castonguay A, Doyon N, Zhang W, Godin AG, Mohr D, Beggs S, Vandal K, Beaulieu JM, Cahill CM, Salter MW, De Koninck Y (2013) Morphine hyperalgesia gated through microglia-mediated disruption of neuronal Cl(-) homeostasis. Nat Neurosci 16(2):183-192. doi: 10.1038/nn.3295

Summary: Although morphine is the drug of choice in dealing with chronic pain, it paradoxically can produce a hyperalgesic state. The authors examined the issue from several different angles. One method was to eliminate spinal microglia of rats through the intrathecal application of 16-32 μg of Mac-1-SAP (Cat. #IT-33). 20 μg of saporin (Cat. #PR-01) was used as a control. It was found that P2X4 receptors expressed by microglia were necessary for the development of morphine hyperalgesia, but not morphine tolerance.

Related Products: Mac-1-SAP rat (Cat. #IT-33), Saporin (Cat. #PR-01)

Read the featured article in Targeting Trends.

Kukkonen JP (2013) Physiology of the orexinergic/hypocretinergic system: a revisit in 2012. Am J Physiol Cell Physiol 304(1):C2-32 . doi: 10.1152/ajpcell.00227.2012

Summary: This review updates an original review from a decade ago on the subject of orexins. These neuropeptides have been shown to be involved in sleep, wakefulness, appetite, metabolism, stress response, reward/addiction, and analgesia. This broad spectrum of action affects many processes including neuronal excitation, synaptic plasticity, and cell death. The use of orexin-SAP (Cat. #IT-20) in some of this work is discussed.

Related Products: Orexin-B-SAP (Cat. #IT-20)

Anaclet C, Lin JS, Vetrivelan R, Krenzer M, Vong L, Fuller PM, Lu J (2012) Identification and characterization of a sleep-active cell group in the rostral medullary brainstem. J Neurosci 32(50):17970-17976. doi: 10.1523/JNEUROSCI.0620-12.2012

Summary: The authors attempt to locate and identify specific neuronal populations that promote sleep. One method utilized was 130-330 pg injections of orexin-SAP (Cat. #IT-20) into the parafacial zone. These results establish the parafacial zone as a delimited node of sleep-active neurons.

Related Products: Orexin-B-SAP (Cat. #IT-20)

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)