References

Chauhan NB (2006) Cholinergic immunolesioning produced tangle-like inclusions in TgCRND8 brain. Neuroscience 2006 Abstracts 271.8. Society for Neuroscience, Atlanta, GA.

Summary: Today’s Alzheimer’s disease (AD) research lacks a “complete” model that would represent both plaque and tangle pathology together with correlative memory deficits. Although currently developed transgenic model including APP/PS1/tau mutations do not “truly” represent AD because tangles observed in AD brain are independent of tau mutations. Subtly increased β-amyloid (Aβ) levels either due to familial mutations or sporadic causes, primarily targets pre-tangle cytopathology and degeneration of basal forebrain cholinergic neurons (BFCN) via deranged signaling of glygogen synthase kinase 3-beta (GSK3β)-, protein kinase A (PKA)-, and extracellular signal-regulated kinase (ERK2) of ERK-mitogen-activated protein kinase (MAPK) cascade, leading to reduced phosphorylation of cAMP responsive element binding protein (CREB) that results in synaptic and memory deficits much earlier than the emergence of classic AD-pathology. Thus, subtly elevated Aβ, together with BFCN deficits resulting from Aβ-induced deranged signaling, set up a vicious feedback loop to produce characteristic plaque- and tangle-pathology observed in AD. Based on these facts, we wished to test if selective lesioning of basal fore brain cholinergic neurons during the early stages of amyloid build-up will exacerbate tau phosphorylation and produce tangle-like inclusions in transgenic mice with APP mutations. We produced selective immunotoxic lesions of BFCN by injecting the BFCN-specific cholinergic immunotoxin, which is known to specifically target p75-expressing BFCN and spare p75-expressing cerebellar neurons (Mu-p75-Saporin, Advanced Targeting Systems, #IT-16), intracerebroventricularly (ICV) in TgCRND8 mice harboring Swedish (KM670/671NL) and Indiana (V717F) mutations. This model exhibited tangle-like inclusions, provoked already existing plaque pathology, and worsened already impaired behavioral deficits.

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

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Keener WK, Rivera VR, Young CC, Poli MA (2006) An activity-dependent assay for ricin and related RNA N-glycosidases based on electrochemiluminescence. Anal Biochem 357(2):200-207. doi: 10.1016/j.ab.2006.07.005

Summary: The authors use synthetic biotinylated RNA substrates to assay adenine-specific RNA N-glycosidases, one of which is saporin (Cat. #PR-01). The RNA substrates are annealed to a ruthenylated oligodeoxynucleotide, allowing the capture of ruthenium chelate on magnetic beads. The N-glycosidase activity can then be detected by enzyme-linked chemiluminescence. The developed assay provides a robust method for assessing threats involving N-glycosidases.

Related Products: Saporin (Cat. #PR-01)

Masawaki A, Sugiyo S, Shimoda T, Sakai Y, Watanabe M, Moritani M, Yoshida A, Niwa H, Takemura M (2006) Formalin-induced pain-related responses in rat lacking neurokinin-1 receptor neurons in the trigeminal nucleus caudalis. Neuroscience 2006 Abstracts 50.8. Society for Neuroscience, Atlanta, GA.

Summary: This study examines the effect of intra cisterna magna injection of substance P (SP) conjugated to saporin (SP-Sap; 5µM, 5µl) on formalin-induced pain-related behavior (PRB; face scrubbing behavior ) and c-Fos expression in the trigeminal nucleus caudalis (SpVc). In SP-Sap-treated rats, the numbers of NK-1-immunoreactive neurons in lamina I of the SpVc decreased compared with those in saline- or blank Sap-treated rats. The mean numbers ±SEM of PRB /5 min at the first phase (0-5 min after For injection) were 58.2±19.2 in the SP-Sap-treated rats, 115.6±14.0 in the saline treated rats and 86.9±45.7 in the blank-Sap-treated rats. The numbers at the quiescent period (5-10 min) were 45.2±26.3 in the SP-Sap- treated rats, 93.6±26.5 in the saline treated rats and 69.4±16.3 in the blank-Sap-treated rats. These at the former second phase (10-50 min) were 58.1±22.3 in the SP-Sap-treated rats, 133.6±26.1 in the saline treated rats and 95.8±29.6in the blank-Sap-treated rats. These at the latter second phase (55-90 min) were 7.0±5.6 in the SP-Sap-treated rats,13.7±12.4 in the saline treated rats and 10.4±22.5 in the blank-Sap-treated rats. These results indicate that formalin-induced nociceptive responses in the SP-Sap-treated rats are reduced.

Related Products: SP-SAP (Cat. #IT-07), Blank-SAP (Cat. #IT-21)

Martin MM, Schultz MD, Winter SS, Wallace DG (2006) Selective cholinergic lesions of the medial septum disrupt dead reckoning-based navigation. Neuroscience 2006 Abstracts 66.10. Society for Neuroscience, Atlanta, GA.

Summary: Recent investigations using selective lesion techniques have suggested that the septohippocampal cholinergic system may not be critical for spatial orientation. These studies employ spatial tasks that provide the animal with access to both allothetic and idiothetic cues; therefore, the spared performance may reflect intact spatial orientation or compensatory mechanisms associated with one class of spatial cues. The present study examined the contribution of the septohippocampal cholinergic system to spatial behavior by examining performance in foraging tasks in which cue availability was manipulated. Female Long-Evans rats were either given a sham surgery or a selective medial septum/ vertical limb of the diagonal band cholinergic lesion using the neurotoxin 192 IgG-saporin. Rats were then trained to find food pellets randomly located on an open field which they then carried back to a visible home base (“cued”) to eat. Once they became proficient at returning to their home base location, cued training was alternated with probes. The three probes included 1) replacing the visible home base with a hidden home base to measure ability to use cues not associated with the home base (“uncued”); 2) moving the hidden home base to a new location to pit use of allothetic cues against idiothetic cues (“reversal”); and 3) testing under completely dark conditions thereby limiting access only to idiothetic cues (“dark”). Although both groups could use allothetic cues as evidenced by intact performance on cued and uncued probes, rats with compromised septohippocampal cholinergic systems were impaired during the reversal and dark probes. These observations are consistent with a selective role for the septohippocampal cholinergic system in idiothetic cue processing necessary for dead reckoning based navigation.

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

Bugarith K, Dinh TT, Li AJ, Speth RC, Ritter S (2006) Featured Article: Basomedial hypothalamic injections of neuropeptide Y conjugated to saporin selectively disrupt hypothalamic controls of food intake. Targeting Trends 7(4)

Related Products: Anti-DBH-SAP (Cat. #IT-03), NPY-SAP (Cat. #IT-28), Saporin (Cat. #PR-01), Blank-SAP (Cat. #IT-21)

Read the featured article in Targeting Trends.

See Also:

• Bugarith K et al. Basomedial hypothalamic injections of neuropeptide Y conjugated to saporin selectively disrupt hypothalamic controls of food intake. Endocrinology 146(3):1179-1191, 2005.

Turner LH, Lim CE, Heinrichs SC (2007) Antisocial and seizure susceptibility phenotypes in an animal model of epilepsy are normalized by impairment of brain corticotropin-releasing factor. Epilepsy Behav 10(1):8-15. doi: 10.1016/j.yebeh.2006.08.013

Summary: There appears to be an inverse relationship between seizure susceptibility and social interaction. This work examines the role that CRF may play in this system. 2.5 µg of CRF-SAP (Cat. #IT-13) was administered to the lateral ventricle of rats, and the lesioned animals were assessed in terms of social investigation times as well as handling-induced seizures. The results support the involvement of CRF systems in facilitating evoked seizures and suppression of social activity.

Related Products: CRF-SAP (Cat. #IT-13)

van der Staay FJ, Bouger P, Lehmann O, Lazarus C, Cosquer B, Koenig J, Stump V, Cassel JC (2006) Long-term effects of immunotoxic cholinergic lesions in the septum on acquisition of the cone-field task and noncognitive measures in rats. Hippocampus 16(12):1061-1079. doi: 10.1002/hipo.20229

Summary: 192-Saporin (Cat. #IT-01) has been used to make extremely specific lesions in the septohippocampal cholinergic system of the brain. The specificity of these lesions is allowing researchers to more accurately map the involvement of the septohippocampal cholinergic system in spatial learning and memory. Here, rats received 0.8 µg of 192-Saporin in the medial septum and the vertical limb of diagonal band of Broca. Lesioned animals only exhibited deficits in attentional learning.

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

Hawkes C, Kabogo D, Amritraj A, Kar S (2006) Up-regulation of cation-independent mannose 6-phosphate receptor and endosomal-lysosomal markers in surviving neurons after 192-IgG-saporin administrations into the adult rat brain. Am J Pathol 169(4):1140-1154. doi: 10.2353/ajpath.2006.051208

Summary: The cation-independent mannose 6-phosphate receptor (CI-MPR) plays a major role in the endosomal-lysosomal (EL) system. One of the tasks carried out by the EL system is clearance of abnormal proteins after injury. By administering 2.0 µg bilateral injections of 192-Saporin (Cat. #IT-01) to rats, the researchers were able to increase CI-MPR expression levels, as well as other EL markers in response to the lesion. The upregulation of EL components suggests that the EL system may be able to repair neuronal abnormalities induced by injury.

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

Muller HK, Wiborg O, Haase J (2006) Subcellular redistribution of the serotonin transporter by secretory carrier membrane protein 2. J Biol Chem 281(39):28901-28909. doi: 10.1074/jbc.M602848200 PMID: 16870614

Related Products: Antibody to Serotonin Transporter (SERT, Cat. #AB-N09)

Marcos B, Gil-Bea FJ, Hirst WD, Garcia-Alloza M, Ramirez MJ (2006) Lack of localization of 5-HT6 receptors on cholinergic neurons: implication of multiple neurotransmitter systems in 5-HT6 receptor-mediated acetylcholine release. Eur J Neurosci 24(5):1299-1306. doi: 10.1111/j.1460-9568.2006.05003.x

Summary: The authors investigated a potential link between 5-HT6 receptors, cholinergic activity, and learning. After 0.067 µg of 192-Saporin (Cat. #IT-01) was injected into each hemisphere of the nucleus basalis magnocellularis in the basal forebrain of rats, 5-HT6 receptor mRNA and protein expression were measured. Results demonstrate the involvement of multiple neurotransmitter systems in neurochemical actions following 5-HT6 receptor blockade.

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