targeted-toxins

Sato M, Akasaka E, Saitoh I, Ohtsuka M, Nakamura S, Sakurai T, Watanabe S (2013) Targeted toxin-based selectable drug-free enrichment of Mammalian cells with high transgene expression. Biology (Basel) 2:341-355. doi: 10.3390/biology2010341

Summary: Cell transfection is a powerful tool for evaluation of function and expression of newly discovered genes as well as for both small and large scale eukaryotic expression of proteins. Most transfection strategies require a selection agent to eliminate cells that do not internalize the plasmid containing the gene of interest. Subsequent maintenance of the tranfected cells requires the presence of the selection agent, and the expression levels of the gene of interest have to be evaluated on a cell by cell basis. In this work the authors designed a system utilizing 50 μg/ml rIB4-SAP (Cat. #IT-10) to eliminate non-transfected cells and select for strong expression of the gene of interest. The data demonstrate that this technique will generate stable transfected cells that express the gene of interest at high levels.

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

Gritton HJ, Stasiak AM, Sarter M, Lee TM (2013) Cognitive performance as a zeitgeber: cognitive oscillators and cholinergic modulation of the SCN entrain circadian rhythms. PLoS One 8(2):e56206. doi: 10.1371/journal.pone.0056206 PMID: 23441168

Objective: To examine how attention-demanding task performance interacts with circadian mechanisms in the SCN.

Summary: The authors used site-specific injections of the 192 IgG-SAP to selectively eliminate cholinergic projections to the SCN originating from the basal forebrain, thereby testing the necessity of forebrain cholinergic neurotransmission in mediating entrainment to cognitive tasks. The findings provide a basis for the hypothesis that in vivo cholinergic signaling, modulated by cognitive demand, entrains non-SCN oscillators and promotes diurnal activity through cholinergic-SCN interactions.

Usage: Rats received 0.4 µL per hemisphere of a 200 ng/µL of 192 IgG-SAP (IT-01) suspended in artificial cerebro-spinal fluid (ACSF).

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

Zheng H, Rinaman L (2013) Yohimbine anxiogenesis in the elevated plus maze requires hindbrain noradrenergic neurons that target the anterior ventrolateral bed nucleus of the stria terminalis. Eur J Neurosci 37(8):1340-1349. doi: 10.1111/ejn.12123

Summary: The anterior ventrolateral bed nucleus of the stria terminalis (vIBST) appears to be important for increased noradrenergic signaling to trigger anxiety-like behavior. 42.8 ng of anti-DBH-SAP (Cat. #IT-03) was administered to the vIBST of rats in bilateral injections. Elimination of noradrenergic neurons in the vIBST abolished yohimbine-induced anxiogenesis in an elevated plus maze, indicating that hindbrain noradrenergic neurons targeting the vIBST are involved in this mechanism.

Related Products: Anti-DBH-SAP (Cat. #IT-03)

Ren C, Luan L, Wui-Man Lau B, Huang X, Yang J, Zhou Y, Wu X, Gao J, Pickard GE, So KF, Pu M (2013) Direct retino-raphe projection alters serotonergic tone and affective behavior. Neuropsychopharmacology 38(7):1163-1175. doi: 10.1038/npp.2013.35

Summary: Although recent work has shown that some intrinsically photosensitive retinal ganglion cells (ipRGCs) are responsible for processing nonimage-forming visual functions, it is unclear whether the ipRGCs or conventional RGCs modulate affective behavior. The authors injected 2 μg of melanopsin-SAP (Cat. #IT-44) into each eye of gerbils, or biotinylated CTB monoclonal antibody coupled to Streptavidin-ZAP (Cat. #IT-27). The data suggest that retino-raphe signals modulate dorsal raphe nucleus serotonergic tone and affective behavior.

Related Products: Melanopsin-SAP (Cat. #IT-44), Streptavidin-ZAP (Cat. #IT-27)

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)

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.

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.

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)