targeted-toxins

Murray RC, Gilbert YE, Logan AS, Hebbard JC, Horner KA (2014) Striatal patch compartment lesions alter methamphetamine-induced behavior and immediate early gene expression in the striatum, substantia nigra and frontal cortex. Brain Struct Funct 219:1213-1229. doi: 10.1007/s00429-013-0559-x

Summary: In this work, the authors investigated the function of the patch compartment in abnormally repetitive motor actions (stereotypy) in response to a psychostimulant such as methampheta-mine (meth). Rats received bilateral injections of Dermorphin-SAP (Cat. #IT-12; 17 ng) into the rostral striatum. When treated with meth, lesioned animals displayed reduced stereotypy, increased motor activity, and enhanced c-Fos expression.

Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12)

Liu Y, Weick JP, Liu H, Krencik R, Zhang X, Ma L, Zhou GM, Ayala M, Zhang SC (2013) Medial ganglionic eminence-like cells derived from human embryonic stem cells correct learning and memory deficits. Nat Biotechnol 31(5):440-447. doi: 10.1038/nbt.2565

Summary: Progenitor cells were transplanted into mice that had received 1.5 μg of mu p75-SAP (Cat. #IT-16) into the medial septum.

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

Read the featured article in Targeting Trends.

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)

Leach ND, Nodal FR, Cordery PM, King AJ, Bajo VM (2013) Cortical cholinergic input is required for normal auditory perception and experience-dependent plasticity in adult ferrets. J Neurosci 33(15):6659-6671. doi: 10.1523/JNEUROSCI.5039-12.2013

Summary: In order to study how cholinergic input from the nucleus basalis affects auditory perception and learning, the authors injected a total of 35.2 ng of ME20.4-SAP (Cat. #IT-15) into the nucleus basalis in each hemisphere of ferrets. Based on several learning tasks, the data suggest that these cholinergic inputs aid in the perception of sound source location and aid in the adaptation of the auditory system to changes in spatial cues.

Related Products: ME20.4-SAP (Cat. #IT-15)

Talman WT, Lin LH (2013) Sudden death following selective neuronal lesions in the rat nucleus tractus solitarii. Auton Neurosci 175(1-2):9-16. doi: 10.1016/j.autneu.2012.11.008

Summary: The nucleus tracts solitarii (NTS) is the terminus of cardiovascular reflex nerves. Early work in this area sought to identify transmitters involved in the control of this region. The authors used SSP-SAP (Cat. #IT-11) and anti-DBH-SAP (Cat. #IT-03) to examine the role of NK-1r-expressing neurons and catecholaminergic neurons in baroreflex control in the NTS. Either 3 ng of SSP-SAP or 42 ng of anti-DBH-SAP was injected into the NTS of rats and baroreflex function was compared 7 days later. Although each toxin had a specific effect in terms of the types of cells eliminated, both toxins initiated a disturbance of the central baroreflex control that led to the death of some animals.

Related Products: SSP-SAP (Cat. #IT-11), Anti-DBH-SAP (Cat. #IT-03)

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)