targeted-toxins

Ramos-Rodriguez JJ, Pacheco-Herrero M, Thyssen D, Murillo-Carretero MI, Berrocoso E, Spires-Jones TL, Bacskai BJ, Garcia-Alloza M (2013) Rapid beta-amyloid deposition and cognitive impairment after cholinergic denervation in app/ps1 mice. J Neuropathol Exp Neurol 72(4):272-285. doi: 10.1097/NEN.0b013e318288a8dd

Summary: The authors investigated whether specific cholinergic neurodegeneration is responsible for the deposition of plaques. APPswe/PS1dE9 transgenic mice received bilateral icv injections of 1-1.2 μg of mu p75-SAP (Cat. #IT-16) into the basal forebrain. Although the transgenic mice show plaque deposition, they do not exhibit other signs of Alzheimer’s disease. Lesioned transgenic animals, however, displayed increased β-amyloid plaque deposition, increased Tau phosphorylation, and early memory impairment that worsened with age.

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

Matchynski JJ, Lowrance SA, Pappas C, Rossignol J, Puckett N, Sandstrom M, Dunbar GL (2013) Combinatorial treatment of tart cherry extract and essential fatty acids reduces cognitive impairments and inflammation in the mu-p75 saporin-induced mouse model of Alzheimer’s disease. J Med Food 16(4):288-295. doi: 10.1089/jmf.2012.0131 PMID: 23566055

Summary: The authors investigated the efficacy of a combinatorial therapy, Cerise Total-Body Rhythm (TBR) by treating mice with TBR prior to and following icv administration of 0.8 μg of mu p75-SAP (Cat. #IT-16).

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

Minces VH, Alexander AS, Datlow M, Alfonso SI, Chiba AA (2013) The role of visual cortex acetylcholine in learning to discriminate temporally modulated visual stimuli. Front Behav Neurosci 7:16. doi: 10.3389/fnbeh.2013.00016

Summary: In order to examine some of the minor differences in the temporal structure of stimuli, the authors bilaterally injected 37.5 ng of 192-IgG-SAP (Cat. #IT-01) between the lambda and bregma of rats. This injection reduced acetylcholine projections to the visual cortex. Loss of that cholinergic input impaired the ability of the lesioned animals to perform fine discriminations, but previously learned discriminations remained unimpaired.

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

Hernandez L, Flenker K, Hernandez F, Klingelhutz A, McNamara J, Giangrande P (2013) Methods for evaluating cell-specific, cell-internalizing RNA aptamers. Pharmaceuticals (Basel) 6:295-319. doi: 10.3390/ph6030295

Objective: Isolate aptamers that internalize upon binding to their cognate receptor on the cell surface

Summary: Among the methods used to characterize aptamers that internalize is a way to monitor for cytoplasmic delivery using the ribosome inactivating protein-based (RNA-RIP) assay. Biotin-labeled A9g was conjugated to streptavidin-modified saporin (streptavidin-ZAP).  First, it was verified that conjugation of biotinylated aptamer to Streptavidin-ZAP (A9g-SAP) did not affect the inhibitory effect of the aptamer. Next, the effect was examined of A9g-SAP on PC3(PSMA+) and PC3(PSMA-) cells.  Cells were treated with varying amounts of aptamer-saporin conjugate for 72 h at 37°C and then an assay was performed to determine potential cytotoxicity of the conjugate.  Results confirm that A9g is internalized preferentially into target cells and that A9g is efficiently accessing the cytoplasm of target cells possibly through a mechanism of endosomal escape, resulting in inhibition of protein synthesis and ultimate cell-death.  FGF-SAP was used as a control.

Related Products: Streptavidin-ZAP (Cat. #IT-27), FGF-SAP (Cat. #IT-38)

Laursen B, Mork A, Plath N, Kristiansen U, Bastlund JF (2013) Cholinergic degeneration is associated with increased plaque deposition and cognitive impairment in APPswe/PS1dE9 mice. Behav Brain Res 240:146-152. doi: 10.1016/j.bbr.2012.11.012

Summary: Extracellular plaques containing amyloid β-peptides (Aβ) and cholinergic dysfunction are two of the main hallmarks of Alzheimer’s disease. Using a transgenic mouse line that displays an age-related increase in plaque deposition, the authors examined the relationship between cholinergic degeneration and Aβ overexpresssion. Mice received 0.9-μg bilateral icv injections of mu p75-SAP (Cat. #IT-16). Working memory was significantly impaired in lesioned mice with plaques, and the plaque burden was increased as compared to wild-type mice that also received a lesion.

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

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)