saporin

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)

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)

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 PMID: 26100338

Objective: Investigate the impact of neuron ablation in the striatum on stereotypy, a form of repetitive and uncontrollable behavior, in rats following cocaine administration.

Summary: Stereotypy, characterized by rigid, repetitive behaviors after psychostimulant exposure, is linked to the activation of the patch compartment within the striatum. To clarify the role of these neurons, they were selectively ablated, resulting in a noticeable reduction in the intensity of stereotypy behaviors.

Usage: 2 microliters of Dermorphin-SAP (IT-12) at a concentration of 17 ng/μl were administered bilaterally into the patch compartment of the striatum. Saporin (Cat. #PR-01) was used as a control.

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

See Also:

• Saporin (Cat. #PR-01) was used as a control.

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)

Rust A, Hassan HH, Sedelnikova S, Niranjan D, Hautbergue G, Abbas SA, Partridge L, Rice D, Binz T, Davletov B (2015) Two complementary approaches for intracellular delivery of exogenous enzymes. Sci Rep 5:12444. doi: 10.1038/srep12444 PMID: 26207613

Summary: Botulinum-derived proteases can be easily delivered into neuroendocrine cells using certain DNA lipofection reagents, revealing a novel action of botulinum enzyme type C in neuroendocrine tumor cells. Other uses were studied that could be applied to other bio-medically relevant proteins such as translation-inhibiting enzymes. Different cancer cell lines show that lipofectamine 3000 efficiently delivers enzymes into the cytosol. A macrophage cell line, J774.2, exhibited high sensitivity to extracellular proteins even without lipofection, enabling future high-throughput screening of bioactive enzymes.

Sorge R, Mapplebeck J, Rosen S, Beggs S, Taves S, Alexander J, Martin L, Austin J, Sotocinal S, Chen D, Yang M, Shi X, Huang H, Pillon N, Bilan P, Tu Y, Klip A, Ji R, Zhang J, Salter M, Mogil J (2015) Different immune cells mediate mechanical pain hypersensitivity in male and female mice. Nat Neurosci 18:1081-1083. doi: 10.1038/nn.4053

Summary: A large and rapidly increasing body of evidence indicates that microglia-to-neuron signaling is essential for chronic pain hypersensitivity. Using multiple approaches, the authors found that microglia are not required for mechanical pain hypersensitivity in female mice; female mice achieved similar levels of pain hypersensitivity using adaptive immune cells, likely T lymphocytes. This sexual dimorphism suggests that male mice cannot be used as proxies for females in pain research. Mac-1-SAP mouse/human toxin (Cat. #IT-06, 15 μg in 8.8 μl) and Saporin control (Cat. #PR-01, 8.8 μg in 8.8 μl) were administered via i.t. injection. The topic of immune system involvement in chronic pain pathophysiology is one of the most active in the pain field; that this sex difference has not been observed until now is very surprising indeed. An important implication of the current findings is that distinct strategies targeting neuroimmune signaling might be required for the treatment of chronic pain in men versus women.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06), Saporin (Cat. #PR-01)

Bostad M, Olsen C, Peng Q, Berg K, Høgset A, Selbo P (2015) Light-controlled endosomal escape of the novel CD133-targeting immunotoxin AC133-saporin by photochemical internalization – A minimally invasive cancer stem cell-targeting strategy. J Control Release 206:37-48. doi: 10.1016/j.jconrel.2015.03.008

Summary: Previously the authors demonstrated the use of photochemical internalization of a custom conjugate consisting of a CD133 antibody coupled to saporin (ATS Custom conjugation). Several cancer cell lines were plated, and incubated in the presence of a photosensitizer with either CD133-SAP at 8.6 pM or Saporin (Cat. #PR-01) at 24 pM. The different concentrations equalized the number of saporin molecules in each sample. A light source was used to initiate the internalization of the molecules. The results indicate that this is a viable strategy for the targeted treatment of cancer stem cells.

Related Products: Anti-CD133-SAP (Cat. #IT-82), Saporin (Cat. #PR-01), Custom Conjugates

Li A, Wang Q, Elsarelli M, Brown R, Ritter S (2015) Hindbrain catecholamine neurons activate orexin neurons during systemic glucoprivation in male rats. Endocrinology 156:2807-2820. doi: 10.1210/en.2015-1138

Summary: Norepinephrine and epinephrine-secreting catecholamine neurons are strong stimulators of food intake. The authors investigated the interaction between these catecholamine neurons and orexin neurons in the perifornical lateral hypothalamus (PeFLH), which are known to be involved with the stimulation of food intake, increased arousal, and behavioral activation. Rats received 82-ng injections of Anti-DBH-SAP (Cat. #IT-03) into the PeFLH terminal field in order to lesion catecholamine neurons. Saporin (Cat. #PR-01) was used as a control. Assessment of food intake in response to 2-deoxy-D-glucose, as well as selective catecholamine activation, indicated that orexin neuron activation may be involved in glucoprivic appetite responses.

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

Navratilova E, Xie J, Meske D, Qu C, Morimura K, Okun A, Arakawa N, Ossipov M, Fields H, Porreca F (2015) Endogenous opioid activity in the anterior cingulate cortex is required for relief of pain. J Neurosci 35:7264-7271. doi: 10.1523/JNEUROSCI.3862-14.2015

Summary: There are a number of neuronal circuits involved in the processing of pain, including those that control somatosensory, affective, and cognitive aspects of pain perception. Opioid signaling in the anterior cingulate cortex (ACC) plays a part in pain modulation – this area has also been implicated in the encoding of pain aversiveness. In order to examine the neuronal mechanisms of pain relief and the following reward, the authors of this paper administered 48 ng of Dermorphin-SAP (Cat. #IT-12) into the rostral ACC of rats. Saporin (Cat. #PR-01) was used as a control. The results illuminate the opioid pathway during pain treatment, and the dependence of nucleus accumbens dopaminergic transmission on upstream ACC opioid circuits during pain processing.

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

Nichols N, Vinit S, Bauernschmidt L, Mitchell G (2015) Respiratory function after selective respiratory motor neuron death from intrapleural CTB-saporin injections. Exp Neurol 267:18-29. doi: 10.1016/j.expneurol.2014.11.011

Summary: Amyotrophic lateral sclerosis (ALS) ultimately causes death from ventilator failure. Genetic models of ALS suffer from high variability of the rate, timing, and extent of respiratory motor neuron death. The authors created a novel model of induced respiratory motor neuron death using CTB-SAP (Cat. #IT-14). Rats received 25 μg or 50 μg intrapleural injections of CTB-SAP; Saporin (Cat. #PR-01) was used as a control. After 7 days, motor neuron survival approximated what is seen in end-stage ALS rats, while there was minimal cell death in other brainstem or spinal cord regions. CTB-SAP also caused microglial activation, decreased breathing during chemoreceptor stimulation, and diminished phrenic motor output in anesthetized rats – all hallmarks of ALS.

Related Products: CTB-SAP (Cat. #IT-14), Saporin (Cat. #PR-01)