Targeting Topics 11q3

BDNF concentrations are decreased in serum and parietal cortex in immunotoxin 192 IgG-Saporin rat model of cholinergic degeneration.

Angelucci F, Gelfo F, Bartolo PD, Caltagirone C, Petrosini L.

Neurochem Int 59(1):1-4, 2011.

Brain-derived neurotrophic factor (BDNF) plays a role in neuronal function during the degeneration of neurons caused by pathological conditions such as Alzheimer’s disease. In order to investigate the relationship between brain and serum BDNF levels the authors administered 2 µg of 192-IgG-SAP (Cat. #IT-01) into each lateral ventricle of rats and measured brain and serum BDNF levels by ELISA. It was found that BDNF levels dropped in lesioned animals, but not until 15 days post surgery.

Enhanced control of attention by stimulating mesolimbic-corticopetal cholinergic circuitry.

St Peters M, Demeter E, Lustig C, Bruno JP, Sarter M.

J Neurosci 31(26):9760-9771, 2011.

Motivation and attention interact to preserve cognitive performance under challenging conditions. In order to better define the circuitry connecting these two processes, the authors lesioned the prefrontal cortex (200 ng of 192-IgG-SAP, Cat. #IT-01) and the posterior parietal cortex (280 ng of 192-IgG-SAP). Mouse IgG-SAP (Cat. #IT-18) was used as a control. The data indicate that cholinergic projections to the cortex modulate detection of clues and filtering of distractors during attentional tasks, accentuating cognitive control.

Selective formation of covalent protein heterodimers with an unnatural amino acid.

Hutchins BM, Kazane SA, Staflin K, Forsyth JS, Felding-Habermann B, Smider VV, Schultz PG.

Chem Biol 18(3):299-303, 2011.

This work demonstrates the creation of a variety of constructs containing specific defined conjugation sites. One use for these molecules is to create homogenous antibody conjugates – meaning the properties of these conjugates can be quantitatively evaluated. Having greater control of such conjugations is essential if these types of constructs are to move toward use as therapeutics. The authors created an anti-Her2 Fab-saporin molecule and tested it in vitro. Analysis by western used anti-SAP-HRP (Cat. #AB-15HRP) to detect the conjugated molecule.

A common substrate for prefrontal and hippocampal inhibition of the neuroendocrine stress response.

Radley JJ, Sawchenko PE.

J Neurosci 31(26):9683-9695, 2011.

In order to better understand how response to emotional stress is regulated, the authors injected 114 ng of GAT-1-SAP (Cat. #IT-32) into each side of the anterior bed nucleus of the stria terminalis. Mouse IgG-SAP (Cat. #IT-18) was used as a control. The results suggest that medial prefrontal cortex and hippocampal formation influences on stress regulation use the same access to modulate emotional stress rather than having parallel networks.

Contribution of afferent pathways to nerve injury-induced spontaneous pain and evoked hypersensitivity.

King T, Qu C, Okun A, Mercado R, Ren J, Brion T, Lai J, Porreca F.

Pain 152(9):1997-2005, 2011.

Whether exaggerated pain response to a normally innocuous tactile stimulus should be defined as allodynia has been debated. Through the use of several techniques, one of which was intrathecal injection of SSP-SAP (Cat. #IT-11, 16.5 pg), the authors examined which pathways were utilized in this type of pain. Blank-SAP (Cat. #IT-21) was used as a control. The data indicate that tactile stimulation may reflect a different pain state than allodynia.

Synaptic plasticity and pain: role of ionotropic glutamate receptors.

Larsson M, Broman J.

Neuroscientist 17(3):256-273, 2011.

This review discusses the role of glutaminergic sensory synapses in pain hypersensitivity caused by tissue or nerve injury. The focus is on the roles of ionotrophic glutamate receptors, and how they are involved in dorsal horn synaptic plasticity. The role of substance P in such mechanisms is briefly discussed, as elucidated by the use of SP-SAP (alternative: SSP-SAP; Cat. #IT-11).

Involvement of Tuberomamillary Histaminergic Neurons in Isoflurane Anesthesia.

Luo T, Leung LS.

Anesthesiology 115(1):36-43, 2011.

Although previous studies indicate that histaminergic neurotransmission may mediate reaction to general anesthesia, it is not clear whether the histominergic tuberomammilary nucleus (TMN) is involved. Rats received 250-ng infusions of orexin-SAP (Cat. #IT-20, discontinued) into the TMN after which the righting reflex was assessed for several anesthetics. Loss of histaminergic neurons in the TMN only altered the effect of isoflurane – suggesting that the neural circuits involved in isoflurane anesthesia are different than circuits affected by propofol, pentobarbital, and ketamine.

Signal peptide-regulated toxicity of a plant ribosome-inactivating protein during cell stress.

Marshall RS, D’Avila F, Di Cola A, Traini R, Spano L, Fabbrini MS, Ceriotti A.

Plant J 65(2):218-229, 2011.

Type I ribosome inactivating proteins (RIPs) are thought to have a role in defending plants against viral or fungal infections. Most type I RIPs have signal peptides for insertion into the endoplasmic reticulum, followed by transportation to a vacuole or the cell wall. The authors examined signal peptide regulation under stress in tobacco plants transfected with saporin. One method of analysis was western blots using anti-saporin (Cat. #AB-15).

Activation of immobility-related hippocampal theta by cholinergic septohippocampal neurons during vestibular stimulation.

Tai SK, Ma J, Ossenkopp KP, Leung LS.

Hippocampus Epub, 2011.

The vestibular system is highly involved with spatial navigation and memory. It is thought that modulation of hippocampal function by the vestibular system is mediated by a hippocampal theta rhythm. Rats received 140 ng of 192-IgG-SAP (Cat. #IT-01) infused into the medial septum, followed by measurement of hippocampal EEG’s and evoked potentials. Theta was attenuated in rats receiving the lesion, as well as other changes that suggest the importance of septohippocampal cholinergic activity in sensorimotor processing and spatial memory.

Ventilatory Effects of Substance P-Saporin Lesions in the Nucleus Tractus Solitarii of Chronically Hypoxic Rats.

Wilkinson KA, Fu Z, Powell FL.

Am J Physiol Regul Integr Comp Physiol 301(2):R343-50, 2011.

Interaction of the multiple brainstem areas that have been established as CO2-sensitive is not well understood. In order to investigate chemoreceptor roles in the nucleus tractus solitarii (NTS) the authors injected 2.6 ng of SP-SAP (alternative: SSP-SAP; Cat. #IT-11) into the caudal NTS of rats. Blank-SAP (Cat. #IT-21) was used as a control. The results indicate that neurokinin-1 receptor-expressing cells in the NTS contribute to plasticity during chronic hypoxia.

SIGLEC12: A human-specific segregating (PSEUDO) gene encodes a signaling molecule expressed in prostate carcinomas.

Mitra N, Banda K, Altheide T, Schaffer L, Johnson-Pais TL, Beuten J, Leach RJ, Angata T, Varki N, Varki A.

J Biol Chem 286(26):23003-23011, 2011.

Siglec 12 (sialic acid-binding immunoglobulin-like lectin 12) is a sugar molecule that has mutated in humans to be inactive, but is active in other primates. The human version is found on some macrophages, various epithelial cell surfaces, and some human carcinoma cell lines. Using Mab-ZAP (Cat. #IT-04) and monoclonal antibodies against Siglec 12, the researchers demonstrated binding and internalization in a prostate cancer cell line, indicating that Siglec 12 may be a target for some cancer therapies.