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2009 Targeting Trends Review

54 entries

Efficacy of a murine-p75-saporin immunotoxin for selective lesions of basal forebrain cholinergic neurons in mice.

Nag N, Baxter MG, Berger-Sweeney JE (2009) Efficacy of a murine-p75-saporin immunotoxin for selective lesions of basal forebrain cholinergic neurons in mice. Neurosci Lett 452:247-251. doi: 10.1016/j.neulet.2009.01.006

Summary: The authors tested a new version of mu p75-SAP (Cat. #IT-16) in mice. Mice received bilateral injections of 0.65 or 1.3 µg of immunotoxin into each lateral ventricle. Both amounts produced a complete loss of cholinergic neurons in the medial septum, while a dose-dependent loss of cholinergic neurons was seen in the nucleus basalis magnocellularis.

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

Immunotoxic depletion of microglia in mouse hippocampal slice cultures enhances ischemia-like neurodegeneration.

Montero M, Gonzalez B, Zimmer J (2009) Immunotoxic depletion of microglia in mouse hippocampal slice cultures enhances ischemia-like neurodegeneration. Brain Res 1291:140-152. doi: 10.1016/j.brainres.2009.06.097

Summary: Data has shown microglia to be both neuroprotective and neurodegenerative in cerebral ischemia. This study presents a method for removing microglia from hippocampal slice cultures. Hippocampal slices from mouse were incubated with 13 nM Mac-1-SAP (Cat. #IT-06) for 3 to 7 days. The slices were then exposed to oxygen-glucose deprivation. Those cultures lacking microglia displayed significantly higher degeneration of CA1 pyramidal cells, indicating a neuroprotective role for microglia in this model.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)

Read the featured article in Targeting Trends.

Partial ablation of mu-opioid receptor rich striosomes produces deficits on a motor-skill learning task.

Lawhorn C, Smith DM, Brown LL (2009) Partial ablation of mu-opioid receptor rich striosomes produces deficits on a motor-skill learning task. Neuroscience 163(1):109-119. doi: 10.1016/j.neuroscience.2009.05.021

Summary: The functional role of basal ganglia striosomes is not well understood. In order to examine these cells in the context of motor behavior the authors injected 8.5 ng of dermorphin-SAP (Cat. #IT-12) into several areas of the striatum of mice (saporin, Cat. #PR-01, was used as a control). The animals were then evaluated in complex motor tasks involving the use of striatal circuitry. Animals receiving dermorphin-SAP showed deficits in specific motor tasks corresponding to the extent of the lesion.

Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12), Saporin (Cat. #PR-01)

T-cell reconstitution without T-cell immunopathology in two models of T-cell-mediated tissue destruction.

Penaloza-MacMaster P, Masopust D, Ahmed R (2009) T-cell reconstitution without T-cell immunopathology in two models of T-cell-mediated tissue destruction. Immunology 128:164-171. doi: 10.1111/j.1365-2567.2009.03080.x

Summary: Although antigen-specific T cells are vital to adaptive immune responses, they also contribute to a variety of diseases. In this work the authors examined the possibility of selectively removing epitope-specific T cells while preserving immune function. Biotinylated MHC class I tetramers were combined with streptavidin-ZAP (Cat. #IT-27) and used in a mouse transferable T-cell-dependent neurological disease model. This technique resulted in a dramatic reduction in targeted antigen specific T cells with no observable bystander toxicity.

Related Products: Streptavidin-ZAP (Cat. #IT-27)

NGF is essential for hippocampal plasticity and learning.

Conner JM, Franks KM, Titterness AK, Russell K, Merrill DA, Christie BR, Sejnowski TJ, Tuszynski MH (2009) NGF is essential for hippocampal plasticity and learning. J Neurosci 29:10883-10889. doi: 10.1523/JNEUROSCI.2594-09.2009

Summary: This work aimed to define NGF modulation of plasticity and function in adults. Rats received 50 ng injections of 192-IgG-SAP (Cat. #IT-01) into the medial septum. Lesioned animals exhibited impaired retention of spatial memory and significantly reduced hippocampal long term potentiation. These results indicate that NGF modulates neuronal plasticity and behavior by exerting effects on cholinergic projections to hippocampal and cortical targets.

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

The neurokinin-1 receptor modulates the methamphetamine-induced striatal apoptosis and nitric oxide formation in mice.

Zhu J, Xu W, Wang J, Ali SF, Angulo JA (2009) The neurokinin-1 receptor modulates the methamphetamine-induced striatal apoptosis and nitric oxide formation in mice. J Neurochem 111(3):656-668. doi: 10.1111/j.1471-4159.2009.06330.x

Summary: This study examined the role of neurokinin-1 receptors (NK1R) on the methamphetamine-induced apoptosis of striatal neurons. 4 ng of SSP-SAP (Cat. #IT-11) or the control, saporin (Cat. #PR-01), was administered to the striatum of mice. Ablation of NK1R-expressing striatal neurons resulted in a significant reduction of methamphetamine-induced apoptosis. The data suggests that the NK1R circuitry in the striatum may be a target for treatment of methamphetamine abuse.

Related Products: SSP-SAP (Cat. #IT-11), Saporin (Cat. #PR-01)

Cellular basis of itch sensation.

Sun YG, Zhao ZQ, Meng XL, Yin J, Liu XY, Chen ZF (2009) Cellular basis of itch sensation. Science 325:1531-1534. doi: 10.1126/science.1174868

Summary: Whether itch and pain use separate neuronal pathways has long been a subject of debate. The authors injected 400 ng of bombesin-SAP (Cat. #IT-40) into the intrathecal space of mice and examined itch and pain behavior. Lesioned mice had dramatic deficits in all itch behavior tested regardless of the histamine dependence of the itch. All pain behaviors, however, were left intact. These data indicate that the gastrin-releasing peptide receptor-expressing neurons are essential for itch transmission.

Related Products: Bombesin-SAP (Cat. #IT-40)

Read the featured article in Targeting Trends.

Ketamine-induced deficit of auditory gating in the hippocampus of rats is alleviated by medial septal inactivation and antipsychotic drugs.

Ma J, Tai SK, Leung LS (2009) Ketamine-induced deficit of auditory gating in the hippocampus of rats is alleviated by medial septal inactivation and antipsychotic drugs. Psychopharmacology (Berl) 206:457-467. doi: 10.1007/s00213-009-1623-3

Summary: Schizophrenic patients do not experience the usual diminished response to repeated stimuli, otherwise known as gating. Gating loss can be caused by the administration of some psychotomimetic drugs. This study used 170 ng injections of 192-IgG-SAP (Cat. #IT-01) to examine the effect of ketamine on sensory gating loss. Elimination of septohippocampal cholinergic neurons alleviated the disruption of auditory gating caused by ketamine.

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

Neuroprotective effect of testosterone treatment on motoneuron recruitment following the death of nearby motoneurons.

Fargo KN, Foster AM, Sengelaub DR (2009) Neuroprotective effect of testosterone treatment on motoneuron recruitment following the death of nearby motoneurons. Dev Neurobiol 69:825-835. doi: 10.1002/dneu.20743

Summary: Previous work has demonstrated that testosterone treatment can prevent dendritic atrophy due to death of nearby motoneurons. This experiment examined whether this protection extends to motor activation. Rats received a 1 µg injection of CTB-SAP (Cat. #IT-14) into each of the right bulbocavernosus and levator ani muscles. Animals treated with testosterone preserved more of the activity duration than untreated animals, as well as no decrease in motoneuron recruitment.

Related Products: CTB-SAP (Cat. #IT-14)

An anti-CD103 immunotoxin promotes long-term survival of pancreatic islet allografts.

Zhang L, Moffatt-Bruce SD, Gaughan AA, Wang JJ, Rajab A, Hadley GA (2009) An anti-CD103 immunotoxin promotes long-term survival of pancreatic islet allografts. Am J Transplant 9:2012-2023. doi: 10.1111/j.1600-6143.2009.02735.x

Summary: The integrin CD103 is suspected of promoting organ allograft rejection and graft-versus-host disease. A custom conjugation was done between the non-depleting aCD103 antibody M290 and saporin. The conjugate was administered at 2.0 mg/kg to mice as an intraperitoneal injection (mouse IgG-SAP, Cat. #IT-18) was used as a control). The mice had previously received an islet transplant into a kidney capsule. Mice treated with M290-SAP were effectively depleted of CD103+ cells and had long term acceptance of the allografts.

Related Products: Mouse IgG-SAP (Cat. #IT-18), Custom Conjugates

Medullary circuitry regulating rapid eye movement sleep and motor atonia.

Vetrivelan R, Fuller PM, Tong Q, Lu J (2009) Medullary circuitry regulating rapid eye movement sleep and motor atonia. J Neurosci 29:9361-9369. doi: 10.1523/JNEUROSCI.0737-09.2009

Summary: Data concerning rapid-eye movement (REM) motor atonia in rats has not agreed with results seen in large amount of data from cats. Here the authors traced the medullary networks in rats involved with this REM function. 120-300 ng injections of orexin-SAP (Cat. #IT-20) were administered to 6 different sites in the medulla. Ablation of orexin receptor-expressing neurons in one site in the ventromedial medulla resulted in intermittent loss of muscle atonia, indicating that glutaminergic neurons in this area are key components of the REM atonia circuit.

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

Hypocretin-2 saporin lesions of the ventrolateral periaquaductal gray (vlPAG) increase REM sleep in hypocretin knockout mice.

Kaur S, Thankachan S, Begum S, Liu M, Blanco-Centurion C, Shiromani PJ (2009) Hypocretin-2 saporin lesions of the ventrolateral periaquaductal gray (vlPAG) increase REM sleep in hypocretin knockout mice. PLoS One 4:e6346. doi: 10.1371/journal.pone.0006346

Summary: Not all connections between narcolepsy and orexin are understood, since orexin neurons are located in the lateral hypothalamus and some sleep functions are controlled by the brainstem. This experiment used 16.5 ng injections of orexin-SAP (Cat. #IT-20) into each side of the ventrolateral periaqueductal gray (v/PAG to) examine these connections. The results indicate that loss of orexin neurons in the v/PAG results in loss of inhibitory control over REM sleep, but does not cause cataplexy.

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

Role of layer 6 of V2 visual cortex in object-recognition memory.

Lopez-Aranda MF, Lopez-Tellez JF, Navarro-Lobato I, Masmudi-Martin M, Gutierrez A, Khan ZU (2009) Role of layer 6 of V2 visual cortex in object-recognition memory. Science 325:87-89. doi: 10.1126/science.1170869

Summary: The authors examined the role of the V2 visual cortex in visual memory. Working with the prediction that object-recognition memory (ORM) control is centered in the V2 visual cortex, rats received 0.9 µg injections of OX7-SAP (Cat. #IT-02) into this area. Treatment with OX7-SAP eliminated virtually all neurons in layer 6 of area V2 of the visual cortex without damaging the hippocampus. The results indicate that this area of the visual cortex is important for ORM formation, but not storage.

Related Products: OX7-SAP (Cat. #IT-02)

Evaluation of side effects through selective ablation of the mu opioid receptor expressing descending nociceptive facilitatory neurons in the rostral ventromedial medulla with dermorphin-saporin.

Cao F, Chen SS, Yan XF, Xiao XP, Liu XJ, Yang SB, Xu AJ, Gao F, Yang H, Chen ZJ, Tian YK (2009) Evaluation of side effects through selective ablation of the mu opioid receptor expressing descending nociceptive facilitatory neurons in the rostral ventromedial medulla with dermorphin-saporin. Neurotoxicology 30(6):1096-1106. doi: 10.1016/j.neuro.2009.06.004

Summary: Selective ablation of rostral ventromedial (RVM) neurons expressing mu opioid receptors has been suggested as a treatment for pathological pain. This work investigated the side effects of a 0.5 µg injection of dermorphin-SAP (Cat. #IT-12) into the RVM. Saporin (Cat. #PR-01) was used as a control. Lesioned animals experienced a temporary increase in heart rate and systolic blood pressure, and mild microglial responses, but even these soon returned to normal. The data suggest this system has potential as a target for pain therapeutics.

Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12), Saporin (Cat. #PR-01)

A cholinergic-dependent role for the entorhinal cortex in trace fear conditioning.

Esclassan F, Coutureau E, Di Scala G, Marchand AR (2009) A cholinergic-dependent role for the entorhinal cortex in trace fear conditioning. J Neurosci 29:8087-8093. doi: 10.1523/JNEUROSCI.0543-09.2009

Summary: Higher cognitive involvement can be modeled through the use of trace conditioning in simple associative tasks. Rats received several 20-80 ng injections of 192-IgG-SAP (Cat. #IT-01) into the entorhinal cortex (EC) in order to clarify the mechanisms that allow learning through the association of events that occur at different times. Cholinergic depletion of the EC did not result in a training deficit, indicating that these cells are not necessary for trace conditioning.

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

Neuropeptide Y receptor-expressing dorsal horn neurons: role in nocifensive reflex responses to heat and formalin.

Wiley RG, Lemons LL, Kline IV RH (2009) Neuropeptide Y receptor-expressing dorsal horn neurons: role in nocifensive reflex responses to heat and formalin. Neuroscience 161:139-147. doi: 10.1016/j.neuroscience.2008.12.017

Summary: This work examines the effect of lumbar intrathecal administration of NPY-SAP (Cat. #IT-28), and the role of Y1 NPY receptor-expressing neurons (Y1R) in response to thermal and chemical stimulation. Rats received 500 ng or 750 ng intrathecal injections of NPY-SAP. Blank-SAP (Cat. #IT-21) was used as a control. Lesioned animals displayed a specific loss of Y1R in the dorsal horn, as well as reduced nocifensive reflex responses.

Related Products: NPY-SAP (Cat. #IT-28), Blank-SAP (Cat. #IT-21)

Neonatal stress affects vulnerability of cholinergic neurons and cognition in the rat: Involvement of the HPA axis.

Aisa B, Gil-Bea FJ, Marcos B, Tordera R, Lasheras B, Del Rio J, Ramirez MJ (2009) Neonatal stress affects vulnerability of cholinergic neurons and cognition in the rat: Involvement of the HPA axis. Psychoneuroendocrinology 34(10):1495-1505. doi: 10.1016/j.psyneuen.2009.05.003

Summary: Early adverse life events such as maternal separation (MS) can increase vulnerability to psychopathology as an adult. The authors administered bilateral intracerebroventricular 1 µg injections of 192-IgG-SAP (Cat. #IT-01) to MS rats then analyzed choline acetyltransferase and acetylcholinesterase activity. Lesioned animals displayed reduced activity of both of these enzymes, as well as decreased glucocorticoid receptor density. The results suggest that vulnerability of basal forebrain cholinergic cells may be affected by the hypothalamic-pituitary-adrenal axis.

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

Ablation of least shrew central neurokinin NK1 receptors reduces GR73632-induced vomiting.

Ray AP, Chebolu S, Ramirez J, Darmani NA (2009) Ablation of least shrew central neurokinin NK1 receptors reduces GR73632-induced vomiting. Behav Neurosci 123:701-706. doi: 10.1037/a0015733

Summary: In this work the authors investigated the role of central and peripheral nervous systems components that mediate the emetic reflex. Least shrews received an 600-ng injection of SSP-SAP (Cat. #IT-11) into the lateral ventricle. Some animals also received a 4.8-µg intraperitoneal injection of SSP-SAP. Blank-SAP (Cat. #IT-21) and unconjugated saporin (Cat. #PR-01) were used as controls. Lesioned animals displayed reduced emesis, but the data indicate that a minor peripheral nervous system component is also present.

Related Products: SSP-SAP (Cat. #IT-11), Blank-SAP (Cat. #IT-21), Saporin (Cat. #PR-01)

Effect of voluntary running on adult hippocampal neurogenesis in cholinergic lesioned mice.

Ho NF, Han SP, Dawe GS (2009) Effect of voluntary running on adult hippocampal neurogenesis in cholinergic lesioned mice. BMC Neurosci 10:57. doi: 10.1186/1471-2202-10-57

Summary: The act of running can induce hippocampal neurogenesis. In this work the authors investigated whether running can offset the loss of septohippocamal cholinergic neurons caused by a lesion using mu p75-SAP (Cat. #IT-16). Mice received 3.6 µg of the toxin into each lateral ventricle. Although the number of surviving neurons was similar in both lesioned and control animals, most of the progenitor cells in the lesioned animals could not survive without cholinergic input.

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

A discrete GABAergic relay mediates medial prefrontal cortical inhibition of the neuroendocrine stress response.

Radley JJ, Gosselink KL, Sawchenko PE (2009) A discrete GABAergic relay mediates medial prefrontal cortical inhibition of the neuroendocrine stress response. J Neurosci 29:7330-7340. doi: 10.1523/JNEUROSCI.5924-08.2009

Summary: GABAergic neurons have been implicated in the negative regulation of the hypothalamic-pituitary-adrenal axis (HPA). In order to clarify GABAergic input to the paraventricular hypothalamic nucleus the authors injected 0.23 µg of GAT1-SAP (Cat. #IT-32) into the anterior bed nucleus of the stria terminalis. Both unilateral and bilateral injections were used. Rabbit IgG-SAP (Cat. #IT-35) was used as a control. The data indicate that the GABAergic neuronal population functions as proximate mediator of HPA-inhibitory limbic influences.

Related Products: GAT1-SAP (Cat. #IT-32), Rabbit IgG-SAP (Cat. #IT-35)

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