targeted-toxins

Devoto P, Flore G, Saba P, Frau R, Gessa G (2015) Selective inhibition of dopamine-beta-hydroxylase enhances dopamine release from noradrenergic terminals in the medial prefrontal cortex. Brain Behav 5:e00393. doi: 10.1002/brb3.393

Summary: Dopamine-beta-hydroxylase (DBH) is a neuronal enzyme that is a potential target for the treatment of cocaine abuse, alcohol dependence, and eating disorders. Here the authors administered 5 μg of icv Anti-DBH-SAP (Cat. #IT-03) to rats, and assessed the effect of the dopaminergic lesion on levels of extracellular dopamine. Mouse IgG-SAP (Cat. #IT-18) and saporin (Cat. #PR-01) were used as controls. Extracellular levels of dopamine were significantly increased in both lesioned animals and those treated with the DBH inhibitor nepicastat. Clonadine could reverse the nepicastat effect, but not the effect of Anti-DBH-SAP treatement. The data demonstrate a mechanism for the synergistic effect of cocaine on nepicastat-induced dopamine release.

Related Products: Anti-DBH-SAP (Cat. #IT-03), Mouse IgG-SAP (Cat. #IT-18), Saporin (Cat. #PR-01)

Cao Q, Lu J, Li Q, Wang C, Wang X, Lee V, Wang C, Nguyen H, Zheng G, Zhao Y, Alexander S, Wang Y, Harris D (2016) CD103+ dendritic cells elicit CD8+ t cell responses to accelerate kidney injury in adriamycin nephropathy. J Am Soc Nephrol 27:1344-1360. doi: 10.1681/ASN.2015030229

Summary: Although it is known that dendritic cells (DCs) are involved in chronic kidney disease, it is not well understood how they either resolve or aggravate the condition. CD103+ dendritic cells in particular, are known to maintain tolerance through interaction with regulatory T cells, as well as protect against infection through interactions with CD8+ T cells. In this work the authors depleted CD103+ DCs by administering 1 mg/kg of anti-CD103-SAP (Cat. #IT-50) to the intraperitoneal space of mice subject to adriamycin nephropathy. Rat IgG-SAP (Cat. #IT-17) was used as a control. Elimination of the CD103+ DCs attenuated the kidney injury, indicating that in murine chronic kidney disease CD103+ DCs are pathogenic rather than therapeutic.

Related Products: Anti-CD103-SAP (Cat. #IT-50), Rat IgG-SAP (Cat. #IT-17)

Kras J, Weisshaar C, Pall P, Winkelstein B (2015) Pain from intra-articular NGF or joint injury in the rat requires contributions from peptidergic joint afferents. Neurosci Lett 604:193-198. doi: 10.1016/j.neulet.2015.07.043

Summary: Both peptidergic and non-peptidergic neurons innervate the facet joint, which is the source of pain in a majority of neck trauma. In this work the authors examined these subpopulations of neurons to determine the contribution of each in facet joint pain. 100 ng of SSP-SAP (Cat. #IT-11) was injected into bilateral C6/C7 facet joints of rats. Alternatively, rats received 5 μg of rIB4-SAP (Cat. #IT-10) via the same method. Saporin (Cat. #PR-01) was used as control. SSP-SAP, but not rIB4-SAP was able to prevent NGF-induced mechanical and thermal hypersensitivity. SSP-SAP administration also prevented behavioral hypersensitivity and NGF upregulation in the dorsal root ganglion after facet joint distraction. The data indicate that interference with peptidergic signaling within the facet joint may be a treatment for pain originating in that location.

Related Products: SSP-SAP (Cat. #IT-11), IB4-SAP (Cat. #IT-10), Saporin (Cat. #PR-01)

Saeed A, Pawlowski S, Ribeiro-da-Silva A (2015) Limited changes in spinal lamina I dorsal horn neurons following the cytotoxic ablation of non-peptidergic C-fibers. Mol Pain 11:54. doi: 10.1186/s12990-015-0060-z

Summary: For the most part nociceptive information is moved from the periphery to the spinal cord through small diameter primary afferents. One subclass of these afferents is further divided into peptidergic and non-peptidergic populations. The authors examined the role of the non-peptidergic afferents in normal nociception and pain, especially the aspect that in rat neuropathic and inflammatory pain models there is novel expression of neurokinin-1 receptors in some neurons normally devoid of this protein. Rats received 4.8-μg injections of rIB4-SAP (Cat. #IT-10) into the left sciatic nerve, over three injection sites. While the number of non-peptidergic neurons was significantly reduced, de novo expression of the neurokinin-1 receptor was not increased in lamina I pyramidal projection neurons.

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

Araldi D, Ferrari L, Levine J (2015) Repeated mu-opioid exposure induces a novel form of the hyperalgesic priming model for transition to chronic pain. J Neurosci 35:12502-12517. doi: 10.1523/JNEUROSCI.1673-15.2015

Summary: Repeated administration of mu-opioid receptor agonists can lead to persistent mechanical hyperalgesia. One current hypothesis is that a form of hyperalgesic priming is triggered by the repeated activation of these receptors. Classic hyperalgesic priming is associated with signaling via protein kinase Cε (PKε), which is mediated by isolectin-B4+ (IB4) nociceptors. In this work the authors eliminated the IB4+ nociceptors with a 3.2 μg intrathecal injection of recombinant IB4-SAP (Cat. #IT-10). The authors found that hyperalgesic priming induced through the use of DAMGO was dependent on protein kinase A activation rather than activation of PKε. This work demonstrates a novel model for hyperalgesic priming transitioning to chronic pain.

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

Murray R, Logan M, Horner K (2015) Striatal patch compartment lesions reduce stereotypy following repeated cocaine administration. Brain Res 1618:286-298. doi: 10.1016/j.brainres.2015.06.012

Summary: Stereotypy is defined as abnormally repetitive motor movements accompanied by an inability to initiate normal adaptive responses. Psychostimulants such as cocaine will often produce these movements. It is thought that stereotypy is related to activation of the patch compartment of the striatum. In order to better understand the function of the patch compartment in stereotypy due to repeated exposure to cocaine, the authors administered bilateral injections of Dermorphin-SAP (Cat. #IT-12) into the rostral striatum. Saporin (Cat. #PR-01) was used as a control.

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

Li A, Wang Q, Davis H, Wang R, Ritter S (2015) Orexin-A enhances feeding in male rats by activating hindbrain catecholamine neurons. Am J Physiol Regul Integr Comp Physiol 309:R358-367. doi: 10.1152/ajpregu.00065.2015

Summary: Although administration of orexin, norepinephrine, and epinephrine all induce significantly increased food intake, the potential interaction between the networks affected by these molecules has not been studied. In this work, the authors investigate the hypothesis that orexin neurons may stimulate feeding through the activation of catecholamine neurons. Rats received 82-ng injections of Anti-DBH-SAP (Cat. #IT-03) into the hypothalamus in order to lesion hypothalamically-projecting catecholamine neurons. Saporin (Cat. #PR-01) was used as a control. While the normal response to orexin A is increased food intake, lesioned animals did not display this response, indicating that catecholamine neurons are necessary for orexin modulation of food intake.

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

Li J, Pan Y, Zhang B, Chen Q (2015) Macrophages are needed in the progression of tuberculosis into lung cancer. Tumour Biol 36:6063-6066. doi: 10.1007/s13277-015-3283-8

Summary: Approximately 30% of lung carcinomas also have tuberculosis lesions. The authors investigated the potential link between inflammatory processes and cancer in the lung. Mice with established tuberculosis infections received weekly 20 μg tail vein injections of Mac-1-SAP (Cat. #IT-06) in order to eliminate macrophages. Six months later the mice receiving Mac-1-SAP had a significantly lower incidence of lung carcinoma than control animals.

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

McHugh S, Francis A, McAuley J, Stewart A, Baxter M, Bannerman D (2015) Hippocampal acetylcholine depletion has no effect on anxiety, spatial novelty preference, or differential reward for low rates of responding (DRL) performance in rats. Behav Neurosci 129:491-501. doi: 10.1037/bne0000072

Summary: It is unclear whether cholinergic lesions in the hippocampus affect both learning and behavior, or learning only. In this study the authors lesioned cholinergic neurons in the medial septum/vertical limb of the diagonal band of Broca of rats with bilateral 30-ng injections of 192-IgG-SAP (Cat. #IT-01). Although hippocampal cholinergic innervations were significantly reduced, with a concomitant reduction in choline acetyltransferase activity, the lesioned animals did not perform differently in several behavioral tests. The data do not provide evidence that the septo-hippocampal cholingeric projections play a role in anxiety, spatial novelty preference, or differential reward for low rates of responding tests.

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

Xing D, Wu Y, Li G, Song S, Liu Y, Liu H, Wang X, Fei Y, Zhang C, Li Y, Zhang L (2015) Role of cerebrospinal fluid-contacting nucleus in sodium sensing and sodium appetite. Physiol Behav 147:291-299. doi: 10.1016/j.physbeh.2015.04.034

Summary: Sodium concentration in the cerebrospinal fluid (CSF) is tightly regulated, and this regulation requires numerous sensors spread throughout the brain. Here the authors injected 900 ng CTB-SAP (Cat. #IT-14) into the lateral ventricles. Investigation of spontaneous and induced sodium intake indicates the CSF-contacting nucleus is an important link in the sodium sensing network, and interacts with the lateral parabrachial nucleus.

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