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2007 Targeting Trends Review
Sensory experience determines enrichment-induced plasticity in rat auditory cortex.
Percaccio CR, Pruette AL, Mistry ST, Chen YH, Kilgard MP (2007) Sensory experience determines enrichment-induced plasticity in rat auditory cortex. Brain Res 1174:76-91. doi: 10.1016/j.brainres.2007.07.062
Summary: Animals housed in enriched environments display numerous signs of good neural health. In this work the authors examined the role acetylcholine plays in this plasticity. 2.6 µg of 192-IgG-SAP (Cat. #IT-01) was injected into the left lateral ventricle of rats. Auditory evoked responses were used to assess the effect of lesioning cholinergic neurons. Response strength was not reduced in lesioned animals, indicating that cholinergic deficits do not affect this system.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Neonatal basal forebrain cholinergic hypofunction affects ultrasonic vocalizations and fear conditioning responses in preweaning rats.
Ricceri L, Cutuli D, Venerosi A, Scattoni ML, Calamandrei G (2007) Neonatal basal forebrain cholinergic hypofunction affects ultrasonic vocalizations and fear conditioning responses in preweaning rats. Behav Brain Res 183:111-117. doi: 10.1016/j.bbr.2007.05.035
Summary: In order to expand on previous work investigating the effect of early cholinergic lesions on processing of aversive stimuli the authors administered 0.21 µg of 192-IgG-SAP (Cat. #IT-01) into the third ventricle of 7 day-old rat pups. One unexpected result in lesioned animals was the enhancement of fear-conditioned responses that are dependent on the hippocampus. The authors discuss several theories addressing the implications of these data. NOTE: material from Chemicon, CA
Related Products: 192-IgG-SAP (Cat. #IT-01)
Selective hippocampal cholinergic deafferentation impairs self-movement cue use during a food hoarding task.
Martin MM, Wallace DG (2007) Selective hippocampal cholinergic deafferentation impairs self-movement cue use during a food hoarding task. Behav Brain Res 183:78-86. doi: 10.1016/j.bbr.2007.05.026
Summary: There are conflicting data surrounding the role of the septohippocampal system in spatial orientation. The authors suggest that the presence of spatial clues during some of these tests may skew those results. Rats were injected with a total of 0.35 µg of 192-IgG-SAP (Cat. #IT-01) into the medial septum. Lesioned animals had more difficulty navigating by self-movement cues, but the ability to use of environmental cues was left intact. These experiments demonstrate that rats can use environmental information to compensate for loss of circuits that analyze self-movement.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Induction and survival of binucleated Purkinje neurons by selective damage and aging.
Magrassi L, Grimaldi P, Ibatici A, Corselli M, Ciardelli L, Castello S, Podesta M, Frassoni F, Rossi F (2007) Induction and survival of binucleated Purkinje neurons by selective damage and aging. J Neurosci 27:9885-9892. doi: 10.1523/JNEUROSCI.2539-07.2007
Summary: Donor bone marrow derived cells are thought to fuse with host Purkinje cells in small numbers to create binucleated cells. These fusions have been found to persist within the recipient for long periods of time. The authors injected 2.2 µg of 192-IgG-SAP (Cat. #IT-01) into the right lateral ventricle of rats; to examine whether the damage of host Purkinje cells is a method to increase the numbers of binucleated cells. The data suggest an alternate method is present for the creation of these cells. NOTE: material from Millipore, Billerica MA
Related Products: 192-IgG-SAP (Cat. #IT-01)
Raphe Magnus Nucleus is involved in ventilatory but not hypothermic response to CO2.
Dias MB, Nucci TB, Margatho LO, Antunes-Rodrigues J, Gargaglioni LH, Branco LG (2007) Raphe Magnus Nucleus is involved in ventilatory but not hypothermic response to CO2. J Appl Physiol 103(5):1780-1788. doi: 10.1152/japplphysiol.00424.2007
Summary: In this work the authors investigated the role that serotonergic neurons in the Raphe Magnus Nucleus (RMg) play in ventilatory and thermal responses to hypercapnia. 0.1 µl of 1 µM anti-SERT-SAP (Cat. #IT-23) was injected into the RMg of rats. Mouse IgG-SAP (Cat. #IT-18) was used as a control. Lesioned animals had a decreased ventilatory response to CO2, but hypercapnia-induced hypothermia was not affected. The data indicate that RMg serotonergic neurons contribute to CO2 ventilatory response but not to maintenance of ventilation.
Related Products: Anti-SERT-SAP (Cat. #IT-23), Mouse IgG-SAP (Cat. #IT-18)
Experimental dissociation of neural circuits underlying conditioned avoidance and hypophagic responses to lithium chloride.
Rinaman L, Dzmura V (2007) Experimental dissociation of neural circuits underlying conditioned avoidance and hypophagic responses to lithium chloride. Am J Physiol Regul Integr Comp Physiol 293(4):R1495-1503. doi: 10.1152/ajpregu.00393.2007
Summary: Lithium chloride (LiCl) is frequently used to study neural attributes of “sickness behavior.” Previous work by these authors showed that noradrenergic neurons (NA) in the nucleus of the solitary tract (NST) are involved in the inhibition of food uptake by cholecystokinin. Here, 20 ng total of anti-DBH-SAP (Cat. #IT-03) was injected into the NST of rats. Lesioned animals demonstrated significantly reduced inhibition of food intake in response to LiCl, but conditioned flavor avoidance was left intact.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Behavioral and immunohistological effects of cholinergic damage in immunolesioned rats: Alteration of c-Fos and polysialylated neural cell adhesion molecule expression.
Chambon C, Paban V, Manrique C, Alescio-Lautier B (2007) Behavioral and immunohistological effects of cholinergic damage in immunolesioned rats: Alteration of c-Fos and polysialylated neural cell adhesion molecule expression. Neuroscience 147:893-905. doi: 10.1016/j.neuroscience.2007.05.022
Summary: In this work the authors looked to expand the knowledge of molecular events and brain structure changes following cholinergic immunolesion. Rats were treated with bilateral injections of 192-IgG-SAP (Cat. #IT-01); 37.5 ng per side into the medial septum, and 75 ng per side into the nucleus basalis magnocellularis. 1 month after treatment behavioral deficits were drastic and cholinergic neurons had completely disappeared. Elevated levels of polysialylated neural cell adhesion molecule were temporarily able to compensate for the loss of cholinergic neurons. NOTE: material from Chemicon, Paris.
Related Products: 192-IgG-SAP (Cat. #IT-01)
A limited role for microglia in antibody mediated plaque clearance in APP mice.
Garcia-Alloza M, Ferrara BJ, Dodwell SA, Hickey GA, Hyman BT, Bacskai BJ (2007) A limited role for microglia in antibody mediated plaque clearance in APP mice. Neurobiol Dis 28(3):286-292. doi: 10.1016/j.nbd.2007.07.019
Summary: Microglia are thought to play a key role in the clearance of amyloid-b (Ab) in Alzheimer’s disease. To examine this role the authors applied 30 µl of 0.5 mg/ml Mac-1-SAP (Cat. #IT-06) to the brain surface of mice for 20 minutes. The number of microglia and plaques was determined by counting of immunohistochemical samples. Results indicate that microglia play a minor role in clearing Ab plaques, although the interaction of microglia-mediated inflammation and anti-Ab antibodies appears to be vital in this process.
Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)
Cortical cholinergic deficiency enhances amphetamine-induced dopamine release in the accumbens but not in the striatum.
Mattsson A, Olson L, Svensson TH, Schilstrom B (2007) Cortical cholinergic deficiency enhances amphetamine-induced dopamine release in the accumbens but not in the striatum. Exp Neurol 208(1):73-79. doi: 10.1016/j.expneurol.2007.07.012
Summary: Previous data has implicated cholinergic dysfunction in the pathogenesis of schizophrenia. Here the authors investigated whether increased amphetamine-induced release of dopamine was a response to cortical cholinergic denervation. Rats received bilateral 0.067 µg injections of 192-IgG-SAP (Cat. #IT-01) into the nucleus basalis magnocellularis, and dopamine release was monitored in the nucleus accumbens and striatum. Surprisingly, the increased dopamine release was not linked to loss of cholinergic neurons, but to blocking of muscarinic receptors.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Ketanserin-induced baroreflex enhancement in spontaneously hypertensive rats depends on central 5-HT(2A) receptors.
Shen FM, Wang J, Ni CR, Yu JG, Wang WZ, Su DF (2007) Ketanserin-induced baroreflex enhancement in spontaneously hypertensive rats depends on central 5-HT(2A) receptors. Clin Exp Pharmacol Physiol 34:702-707. doi: 10.1111/j.1440-1681.2007.04626.x
Summary: Ketanserin is an anytihypertensive drug that effectively lowers blood pressure, decreases blood pressure variability, and enhances blood pressure response in spontaneously hypertensive rats. Using the fact that ketanserin is a selective 5-HT2A antagonist the authors investigated which of these effects utilized the 5-HT2A receptor. Following a 5 nmol ventricular injection of anti-SERT-SAP (Cat. #IT-23) the blood pressure parameters modified by ketanserin were monitored. The data suggest that the baroreflex sensitivity-enhancing effects of ketanserin use the 5-HT2A pathway, but antihypertensive effects follow a different route.
Related Products: Anti-SERT-SAP (Cat. #IT-23)
Superficial NK1 expressing spinal dorsal horn neurones modulate inhibitory neurotransmission mediated by spinal GABA(A) receptors.
Rahman W, Sikander S, Suzuki R, Hunt SP, Dickenson AH (2007) Superficial NK1 expressing spinal dorsal horn neurones modulate inhibitory neurotransmission mediated by spinal GABA(A) receptors. Neurosci Lett 419:278-283. doi: 10.1016/j.neulet.2007.04.039
Summary: It has been shown that elimination of lamina 1 NK1 receptor-expressing neurons affects pain behaviors. The authors investigated whether eliminating these neurons would alter GABAergic spinal inhibitory systems. Rats received 10-µl injections of 10-µM SP-SAP (Cat. #IT-07) into the L4-5 regions. Data generated by electrical and mechanical stimuli suggest that although GABAergic transmission is dependent on NK1 receptor-expressing neurons, loss of these cells results in a decrease in spinal cord excitability.
Related Products: SP-SAP (Cat. #IT-07)
Estradiol enhances DMP acquisition via a mechanism not mediated by turning strategy but which requires intact basal forebrain cholinergic projections.
Gibbs RB (2007) Estradiol enhances DMP acquisition via a mechanism not mediated by turning strategy but which requires intact basal forebrain cholinergic projections. Horm Behav 52:352-359. doi: 10.1016/j.yhbeh.2007.05.011
Summary: Estradiol appears to enhance cholinergic projections to the hippocampus and frontal cortex as shown by tests of response patterns and strategy in rats. The author tested whether this affect was involved with turning strategy, defined as which arm was chosen first in a T-maze. 0.22 µg injections of 192-IgG-SAP (Cat. #IT-01) were made into the medial septum of rats. Lesioned animals utilized a persistent turning strategy; they always chose the same arm of the maze first, even after the administration of estradiol. These data suggest that although the effects of estradiol are not linked to turning strategy, estradiol does interact with the cholinergic system.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Anti-nociceptive effects of selectively destroying substance P receptor-expressing dorsal horn neurons using [Sar(9),Met(O(2))(11)]-substance P-saporin: Behavioral and anatomical analyses.
Wiley RG, Kline IV RH, Vierck Jr CJ (2007) Anti-nociceptive effects of selectively destroying substance P receptor-expressing dorsal horn neurons using [Sar(9),Met(O(2))(11)]-substance P-saporin: Behavioral and anatomical analyses. Neuroscience 146:1333-1345. doi: 10.1016/j.neuroscience.2007.01.066
Summary: While lumbar injections of SP-SAP (Cat. #IT-07) produce specific lesions, use of this targeted conjugate in the forebrain has been problematic. The authors investigated the use of SSP-SAP (Cat. #IT-11), a conjugate of saporin with a stable analog of substance P. The greater stability of SSP-SAP resulted in increased potency as well as better specificity. SSP-SAP is shown to be a highly effective reagent for the removal of NK1 receptor-expressing neurons in the brain and spinal cord.
Related Products: SP-SAP (Cat. #IT-07), SSP-SAP (Cat. #IT-11)
Cholinergic modulation of spindle bursts in the neonatal rat visual cortex in vivo.
Hanganu IL, Staiger JF, Ben-Ari Y, Khazipov R (2007) Cholinergic modulation of spindle bursts in the neonatal rat visual cortex in vivo. J Neurosci 27:5694-5705. doi: 10.1523/JNEUROSCI.5233-06.2007
Summary: The authors investigated the relationship between cholinergic drive and spindle burst oscillation driven by retinal waves. 0.5 µl of 0.2-µg/µl 192-IgG-SAP (Cat. #IT-01) was injected into both ventricles of rat pups. The lesioned animals displayed markedly decreased oscillatory activity. Since this activity may be used as a functional template for cortical networks and architecture, the results suggest a link between cholinergic activity and cortical development.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Specificity and generality of the involvement of catecholaminergic afferents in hypothalamic responses to immune insults.
Schiltz JC, Sawchenko PE (2007) Specificity and generality of the involvement of catecholaminergic afferents in hypothalamic responses to immune insults. J Comp Neurol 502:455-467. doi: 10.1002/cne.21329
Summary: Interleukin-1 (IL-1) is one of the cytokines that mediates interactions between the immune system and the central nervous system. 380-ng injections of anti-DBH-SAP (Cat. #IT-03) were made into the paraventricular nucleus (PVH) of rats. Saporin (Cat. #PR-01) and mouse IgG-SAP (Cat. #IT-18) were used as controls. Lesioned animals demonstrated reduced responses to administration of IL-1, but restraint stress responses were left intact. The data suggest that ascending catecholaminergic projections mediate PVH response to IL-1.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Saporin (Cat. #PR-01), Mouse IgG-SAP (Cat. #IT-18)
Scavenger receptor-A-targeted leukocyte depletion inhibits peritoneal ovarian tumor progression.
Bak SP, Walters JJ, Takeya M, Conejo-Garcia JR, Berwin BL (2007) Scavenger receptor-A-targeted leukocyte depletion inhibits peritoneal ovarian tumor progression. Cancer Res 67:4783-4789. doi: 10.1158/0008-5472.CAN-06-4410
Summary: Vascular leukocytes (VLC) are immunosuppressive cells that facilitate tumor progression in ovarian cancer. One potential tumor therapy is to eliminate these cells. The authors determined that scavenger receptor-A is specifically expressed on VLCs. Mice were injected with tumor cells, as well as an anti-scavenger receptor-A antibody combined with Rat-ZAP (Cat. #IT-26). This was followed by additional treatment with the antibody-Rat-ZAP complex. Treatment with the immunotoxin eliminated VLCs, inhibited peritoneal tumor burden, and reduced ascites accumulation.
Related Products: Rat-ZAP (Cat. #IT-26)
Guanidinylated-Neomycin delivers large, bioactive cargo into cells through a heparan sulfate dependent pathway.
Elson-Schwab L, Garner OB, Schuksz M, Esko JD, Tor Y (2007) Guanidinylated-Neomycin delivers large, bioactive cargo into cells through a heparan sulfate dependent pathway. J Biol Chem 282(18):13585-13591. doi: 10.1074/jbc.M700463200
Summary: The uptake of high molecular weight drugs into cells is a stumbling block for some potential therapeutics. Using a neomycin derivative in which guanidinium groups have replaced the ammonium groups, the authors show heparan sulfate-dependent uptake of large molecules. The guanidine-neomycin was biotinylated, and incubated with streptavidin-ZAP (Cat #IT-27). This complex was effective in killing CHO cells in vitro, but was no more effective than streptavidin-ZAP alone on cells lacking heparan sulfate expression, demonstrating specificity.
Related Products: Streptavidin-ZAP (Cat. #IT-27)
Anticonvulsant effects of damage to structures involved in seizure induction in rats exposed to soman.
Myhrer T, Enger S, Aas P (2007) Anticonvulsant effects of damage to structures involved in seizure induction in rats exposed to soman. Neurotoxicology 28(4):819-828. doi: 10.1016/j.neuro.2007.03.010
Summary: Soman is a nerve agent that irreversibly inhibits acetylcholinesterase, resulting in respiratory dysfunction, seizures, convulsions, coma, and death. In this work the authors investigated whether elimination of cholinergic pathways in the medial septum (MS) or diagonal band nucleus (DBN) would affect the onset of convulsions. 0.3 µl of 0.5-µg/µl 192-IgG-SAP (Cat. #IT-01) was infused into the MS and/or DBN. Lesioned animals still experienced convulsions, suggesting that cholinergic MS systems are not the only ones involved.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Cholinergic lesions produce task-selective effects on delayed matching to position and configural association learning related to response pattern and strategy.
Gibbs RB, Johnson DA (2007) Cholinergic lesions produce task-selective effects on delayed matching to position and configural association learning related to response pattern and strategy. Neurobiol Learn Mem 88:19-32. doi: 10.1016/j.nlm.2007.03.007
Summary: It has been well established that the cholinergic system of the basal forebrain plays a critical role in many cognitive processes. This work utilized injections of 192-IgG-SAP (Cat. #IT-01) into the medial septum, the nucleus basalis magnocellularis, or both to examine the lesioning effect on two cognitive tasks in rats. The data indicate that cholinergic lesions of the basal forebrain produce learning deficits that are task specific, and that learning is affected without corresponding deficits in memory.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Selective deletion of antigen-specific CD8+ T cells by MHC class I tetramers coupled to the type I ribosome-inactivating protein saporin.
Hess PR, Barnes C, Woolard MD, Johnson MD, Cullen JM, Collins EJ, Frelinger JA (2007) Selective deletion of antigen-specific CD8+ T cells by MHC class I tetramers coupled to the type I ribosome-inactivating protein saporin. Blood 109:3300-3307. doi: 10.1182/blood-2006-06-028001
Objective: To discover if pathogenic T cells could be selectively deleted.
Summary: A single injection of the SAP-coupled tetramer eliminated more than 75% of cognate, but not control, T cells. This work demonstrates the therapeutic potential of cytotoxic tetramers to selectively eradicate pathogenic clonotypes while leaving overall T-cell immunity intact.
Usage: Streptavidin-SAP-coupled biotinylated tetramers were administered at low (22.2 pM) or high (66.6 pM) dose. Following the addition of Saporin Goat Polyclonal, affinity-purified FITC-labeled, T cells were subsequently incubated at either 37°C or 4°C, which permitted or prohibited endocytosis, respectively.
Related Products: Streptavidin-ZAP (Cat. #IT-27)