targeted-toxins

Sato M, Miyoshi K, Nagao Y, Nishi Y, Ohtsuka M, Nakamura S, Sakurai T, Watanabe S (2014) The combinational use of CRISPR/Cas9-based gene editing and targeted toxin technology enables efficient biallelic knockout of the α-1,3-galactosyltransferase gene in porcine embryonic fibroblasts. Xenotransplantation 21:291-300. doi: 10.1111/xen.12089

Summary: Results indicate that a combination of the CRISPR/Cas9 system and targeted toxin technology using IB4-SAP allows efficient enrichment of genome-edited clones, particularly bi-allelic KO clones.

Usage: Cells were trypsinized 3 days after transfection and approximately 80% were incubated for 30 min at 37°C in a solution (25 mcL) containing 0.5–1.0 mcg IB4-SAP.

Related Products: IB4-SAP (Cat. #IT-10)

Li AJ, Wang Q, Dinh TT, Powers BR, Ritter S (2014) Stimulation of feeding by three different glucose-sensing mechanisms requires hindbrain catecholamine neurons. Am J Physiol Regul Integr Comp Physiol 306(4):R257-R264. doi: 10.1152/ajpregu.00451.2013

Summary: The glucoregulatory system of the brain requires catecholamine neurons in the hindbrain. he sensory mechanisms and connected circuitry controlling the response to glucose deficit are not well understood. In order to investigate different drugs that stimulate food intake but interfere with cellular glucose metabolism and transport the authors administered 82 ng of anti-DBH-SAP (Cat. #IT-03) into the paraventricular nucleus as bilateral injections. Saporin (Cat. #PR-01) was used as a control. Lesioned animals did not increase food intake in response to any of the drugs, indicating that stimulation of food intake is activated through a catecholamine-dependent pathway.

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

Ye Y, Bae S, Viet CT, Troob S, Bernabe D, Schmidt BL (2014) IB4(+) and TRPV1(+) sensory neurons mediate pain but not proliferation in a mouse model of squamous cell carcinoma. Behav Brain Funct 10(1):5. doi: 10.1186/1744-9081-10-5

Objective: To evaluate subtypes of sensory neurons involved in cancer pain and proliferation.

Summary: IB4(+) neurons play an important role in cancer-induced mechanical allodynia, while TRPV1 mediates cancer-induced thermal hyperalgesia. Characterization of the sensory fiber subtypes responsible for cancer pain could lead to the development of targeted therapeutics.

Usage: IB4(+) neurons play an important role in cancer-induced mechanical allodynia, while TRPV1 mediates cancer-induced thermal hyperalgesia. Characterization of the sensory fiber subtypes responsible for cancer pain could lead to the development of targeted therapeutics.

Related Products: IB4-SAP (Cat. #IT-10), Saporin (Cat. #PR-01)

Ljubojevic V, Luu P, De Rosa E (2014) Cholinergic contributions to supramodal attentional processes in rats. J Neurosci 34(6):2264-2275. doi: 10.1523/JNEUROSCI.1024-13.2014

Summary: Previous work has shown that cholinergic transmission is important for attentional processing of visual stimuli. It is not known whether the role of the cholinergic system is specifically in visual processing, or if it is involved in all types of attentional processing. The authors administrated bilateral 40 ng injections of 192-IgG-SAP (Cat. #IT-01) to the nucleus basalis magnocellularis of rats. Animals had been previously trained on both visual and olfactory 5-choice serial reaction time tasks. Lesioned animals displayed deficits on both the visual and olfactory tasks when the attentional demand of the task was increased. The data suggest a modular cortical network that services both visual and olfactory attentional processes.

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

Hartig W, Saul A, Kacza J, Grosche J, Goldhammer S, Michalski D, Wirths O (2014) Immunolesion-induced loss of cholinergic projection neurones promotes beta-amyloidosis and tau hyperphosphorylation in the hippocampus of triple-transgenic mice. Neuropathol Appl Neurobiol 40(2):106-120. doi: 10.1111/nan.12050

Summary: 3xTg transgenic mice were treated with 2 μg of mu p75-SAP (Cat. #IT-16) into the right lateral ventricle to eliminate cholinergic neurons in the basal forebrain. These mice already have age-dependent β-amyloidosis and tau hyperphosphorylation. This new model supplies a potential framework in which to study the entire pathology of Alzheimer’s disease.

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

Tai SK, Ma J, Leung LS (2014) Medial septal cholinergic neurons modulate isoflurane anesthesia. Anesthesiology 120(2):392-402. doi: 10.1097/ALN.0b013e3182a7cab6

Summary: General anesthesia is associated with a decrease in cholinergic function. This work examines the effect of volatile anesthetics such as isoflurane or ketamine in the context of cholinergic depletion. Rats received 105-ng bilateral injections of 192-IgG-SAP (Cat. #IT-01) into the medial septum. Anesthetic effects were evaluated using a loss of righting reflex test. There was no difference between lesioned and control groups in the response to ketamine. When treated with isoflurane, lesioned animals were affected for longer periods of time, and hippocampal response was reduced. The results suggest a role for septal cholinergic neurons in the sensitivity to isoflurane.

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

Suto T, Severino AL, Eisenach JC, Hayashida KI (2014) Gabapentin increases extracellular glutamatergic level in the locus coeruleus via astroglial glutamate transporter-dependent mechanisms. Neuropharmacology 81C:95-100. doi: 10.1016/j.neuropharm.2014.01.040

Summary: Gabapentin is effective in reducing acute and chronic pain, but the mechanisms by which it works are not well understood. The authors assessed extracellular glutamate levels and glutamate interaction with several different cellular membrane proteins. Rats received a 0.25 μg injection of anti-DBH-SAP (Cat. #IT-03) into the locus coeruleus (LC) in order to deplete noradreline levels. Mouse IgG-SAP (Cat. #IT-18) was used as a control. The gabapentin-induced glutamate increase in the LC was not affected by the lesion, supporting data indicating that gabapentin induces glutamate release from astrocytes to stimulate descending inhibition.

Related Products: Anti-DBH-SAP (Cat. #IT-03), Mouse IgG-SAP (Cat. #IT-18)

Laursen B, Mork A, Plath N, Kristiansen U, Frank Bastlund J (2014) Impaired hippocampal acetylcholine release parallels spatial memory deficits in Tg2576 mice subjected to basal forebrain cholinergic degeneration. Brain Res 1543:253-262. doi: 10.1016/j.brainres.2013.10.055

Summary: The Tg2576 mouse strain provides a limited model for Alzheimer’s disease because they do not display degeneration of cholinergic neurons in the basal forebrain – the other main hallmark of Alzheimer’s disease in humans. Using 0.9 μg icv injections of mu p75-SAP (Cat. #IT-16) the authors evaluated mice that had both Aβ deposition and cholinergic depletion. The data show that these mice display cognitive decline and compromised cholinergic levels, creating a viable model for Alzheimer’s disease.

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

Lee LC, Rajkumar R, Dawe GS (2014) Selective lesioning of nucleus incertus with corticotropin releasing factor-saporin conjugate. Brain Res 1543:179-190. doi: 10.1016/j.brainres.2013.11.021 PMID: 24287211

Objective: To investigate the role of Nucleus Incertus (NI) neurons in behavior by lesioning these neurons in rats using CRF-SAP (IT-13).

Summary: NI neurons are integral to CRF1, Relaxin-3, and GABA signaling pathways. By targeting the NI region with CRF-SAP, these neurons are selectively eliminated, allowing for the study of Relaxin-3’s influence on mood and behavior. Given the NI neurons’ involvement in emotional regulation, this approach sheds light on their contribution to mental illness and psychiatric disorders.

Usage: Infusion of 172 ng of CRF–SAP (IT-13) into the NI of rats. Blank-SAP (Cat. #IT-21) was used as a control.

Related Products: CRF-SAP (Cat. #IT-13), Blank-SAP (Cat. #IT-21)

Read the featured article in Targeting Trends.

Roland JJ, Stewart AL, Janke KL, Gielow MR, Kostek JA, Savage LM, Servatius RJ, Pang KC (2014) Medial septum-diagonal band of Broca (MSDB) GABAergic regulation of hippocampal acetylcholine efflux is dependent on cognitive demands. J Neurosci 34(2):506-514. doi: 10.1523/JNEUROSCI.2352-13.2014

Summary: GABAergic and cholinergic neurons in the medial septum-diagonal band of Broca (MSDB) are both involved with spatial memory. In order to better understand the relationship between these two neuronal populations the authors administered 552.5 ng of GAT-1-SAP (Cat. #IT-32) to the MSDB of rats in several injections. Using a combination of behavioral assays and in vivo microdialysis it was shown that GAT-1-SAP lesions impaired hippocampal acetylcholine efflux as well as performance in the non-matching to position with delay test. The data indicate that GABAergic MSDB neurons are important during high memory load conditions.

Related Products: GAT1-SAP (Cat. #IT-32)