targeted-toxins

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)

Wang B, Miao Y, Zhao Z, Zhong Y (2015) Inflammatory macrophages promotes development of diabetic encephalopathy. Cell Physiol Biochem 36:1142-1150. doi: 10.1159/000430285

Summary: Diabetes can cause neuroinflammation leading to dementia. Diabetes was induced in mice by injection of streptozotocin (STZ). In order to investigate the role of inflammatory macrophages in the development of diabetic encephalopathy, the authors used twice weekly 20-μg IP injections of Mac-1-SAP (Cat. #IT-06). Mice receiving Mac-1-SAP had significantly reduced numbers of inflammatory macrophages in the brain, and also reduced responses to STZ injection.

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

Aoki S, Liu A, Zucca A, Zucca S, Wickens J (2015) Role of striatal cholinergic interneurons in set-shifting in the rat. J Neurosci 35:9424-9431. doi: 10.1523/JNEUROSCI.0490-15.2015

Summary: The authors examined the role that cholinergic interneurons in the striatum play in a process called strategy set-shifting, where an attentional shift is required. Rats received bilateral injections of Anti-ChAT-SAP (Cat. #IT-42) into either the dorsomedial striatum or ventral striatum (500 ng total). Initial task learning was unaffected by either lesion. Lesioned animals displayed set-shifting deficits, and the deficit characteristics depended on the location of the lesion.

Related Products: Anti-ChAT-SAP (Cat. #IT-42)

Read the featured article in Targeting Trends.

Burke P, Kanbar R, Viar K, Stornetta R, Guyenet P (2015) Selective optogenetic stimulation of the retrotrapezoid nucleus in sleeping rats activates breathing without changing blood pressure or causing arousal or sighs. J Appl Physiol (1985) 118:1491-1501. doi: 10.1152/japplphysiol.00164.2015

Summary: Hypoxia and hypercapnia both play roles in the activation of normal breathing. If either one is severe enough, arousal will also occur. The authors looked to better define the CNS pathways utilized by hypoxia and hypercapnia, as well as the pathways responsible for activation of arousal due to these conditions. The authors used optogenetic activation of the retrotrapezoid nucleus and C1 and A5 catecholaminergic neurons, as well as selective C1 neuron stimulation in rats. Some rats also received bilateral injections of Anti-DBH-SAP (Cat. #IT-03) totaling 0.88 μg into the region of the lateral horn of the second thoracic segment.

Related Products: Anti-DBH-SAP (Cat. #IT-03)

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)

Gulino R, Parenti R, Gulisano M (2015) Novel mechanisms of spinal cord plasticity in a mouse model of motoneuron disease. Biomed Res Int 2015:654637. doi: 10.1155/2015/654637

Summary: Here the authors investigate spinal plasticity mechanisms involving a number of different proteins, including BDNF, Shh, Notch-1, Numb, and Noggin. The model used is a mouse motoneuron depletion strategy, where the animals receive 3 μg of CTB-SAP (Cat. #IT-14) into each of the medial and lateral gastrocnemius muscles. The results indicate that TDP-43, a nuclear DNA/RNA binding protein, may be an important regulator of synaptic plasticity.

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

Ono K, Ye Y, Viet C, Dang D, Schmidt B (2015) TRPV1 expression level in isolectin B₄-positive neurons contributes to mouse strain difference in cutaneous thermal nociceptive sensitivity. J Neurophysiol 113:3345-3355. doi: 10.1152/jn.00973.2014

Summary: In order to determine whether IB4-positive trigeminal sensory neurons affect pain sensitivity, the authors administered 2 μg of rIB4-SAP (Cat. #IT-10) to the right infraorbital foramen. Saporin (Cat. #PR-01) was used as a control.

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