References

Dinh TT, Huston N, Ritter S (2014) Lesions of hindbrain catecholaminergic projections to nucleus accumbens, bed nucleus of the stria terminalis, lateral parabrachial nucleus or locus coeruleus do not impair glucoprivic feeding. Neuroscience 2014 Abstracts 256.05. Society for Neuroscience, Washington, DC.

Summary: We have shown previously that injection of the retrogradely transported immunotoxin, anti-dopamine beta-hydroxylase (DBH) saporin (DSAP), into the paraventricular nucleus of the hypothalamus (PVH) or arcuate nucleus, abolishes feeding in response to central or systemic glucoprivation. Since DSAP injection destroys DBH-expressing neurons with projections to the injection site, these results strongly implicate hindbrain catecholamine neurons as major mediators of glucoprivic feeding. In order to further define the essential circuitry underlying glucoprivic feeding, we injected DSAP into these additional sites: locus coeruleus (LC), accumbens shell (AcbSh), ventrolatersal bed nucleus of the stria terminalis (vlBNST) and lateral parabrachial nucleus (LPBN). These sites are innervated by hindbrain catecholamine neurons and some sites receive collateral innervation from PVH-projecting catecholamine neurons. Appropriate placement and volume for DSAP administration was determined by co-labeling of DBH-ir neurons with retrograde tracer injected into target sites. Lesions were confirmed by postmortem evaluation of DSAP injection site and by hindbrain catecholamine cell and terminal loss. We found that the feeding response to systemic glucoprivation was not significantly or permanently impaired by injection of DSAP into any of these sites. Based on our results to date, we tentatively conclude that direct projections from hindbrain catecholamine neurons to the LC, AcbSh, vlBNST and LPBN are not required for glucoprivic feeding. The hypothalamus appears to be the major recipient of direct innervation from catecholamine neurons required for glucoprivic feeding

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

Fu R, Chen X, Zho W, Li J, Ye J-H (2014) Selective ablation of mu opioid receptor expressing gaba neurons in the rostromedial tegmental nucleus promotes ethanol intake. Neuroscience 2014 Abstracts 267.30. Society for Neuroscience, Washington, DC.

Summary: BACKGROUND AND PURPOSE The cellular mechanisms underlying the aversive effect of ethanol that limits its intake are not well understood, although recent evidence has linked aversion with synaptic inhibition of dopamine neurons in the ventral tegmental area. Emerging evidence indicates that the rostromedial tegmental nucleus (RMTg), a newly defined midbrain structure exerts a major GABAergic inhibitory control over midbrain dopamine neurons and encodes aversive stimuli. The RMTg contains mostly GABAergic neurons and with dense μ-opioid receptor (MOR) immunoreactivity. However, the role of RMTg in the regulation of ethanol intake has not been well investigated. EXPERIMENTAL APPROACH We compared voluntary ethanol intake and locomotion in rats with intra-RMTg infusion of dermorphin-saporin or blank saporin. Dermorphin-saporin is a neurotoxin, which could selectively lesion MOR-expressing neurons. We measured ethanol intake in rats given intermittent access to ethanol (20% vol/vol) using a two bottle choice paradigm. We euthanized the rats, dissected their brains and analyzed the glutamic acid decarboxylase67 (GAD67) and MOR protein expression and immunoreactivity immediately following the behavioral test. KEY RESULTS In rats that received intra-RMTg injection of dermorphin-saporin, we observed a robust increase in the intake of and the preference to ethanol, and in the locomotor activity; but a significantly reduced GAD67 and MOR protein expression, as well as a massive loss of neurons with GAD67 and MOR immunoreactivity within the RMTg. We observed no such changes in rats that received injection of blank saporin or saline. Together, These findings indicate that MOR-expressing GABA neurons in the RMTg play a crucial role in the regulation of ethanol consumption, implicating the dysfunction of these neurons likely play a critical role in the pathogenesis of alcoholism, and that these neurons should represent an appropriate target for the development of therapeutic strategies against alcohol use disorders.

Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12)

Mang Y, Zhao Z, Zeng Z, Wu X, Li Z, Zhang L (2015) Efficient elimination of CD103-expressing cells by anti-CD103 antibody drug conjugates in immunocompetent mice. Int Immunopharmacol 24:119-127. doi: 10.1016/j.intimp.2014.11.004

Summary: Previous work has demonstrated that an M290-SAP custom conjugate promoted the long-term survival of pancreatic islet allografts by reducing the number of CD103+ cells. M290 is an antibody that targets CD103. Systemic use of the saporin conjugate can result in toxicity and bystander effects to the animal. In this work the authors used M290 conjugated to three different cytotoxic agents in order to avoid these bystander effects. The various reagents were compared in several assays, including internalization studies, flow cytometry, and cytotoxicity studies. The results indicate that the alternative cytotoxic drugs can be used systemically with M290 to eliminate CD103+ cells.

Related Products: Custom Conjugates

Speer C, Sun C, Liets L, Stafford B, Chapman B, Cheng H (2014) Eye-specific retinogeniculate segregation proceeds normally following disruption of patterned spontaneous retinal activity. Neural Dev 9:25. doi: 10.1186/1749-8104-9-25

Summary: The authors administered 0.88-1.66 μg of an Anti-VaChT-SAP custom conjugate to ferrets with an intraocular injection. Although the lesioned animals demonstrated normal eye-specific retinogeniculate development, there were significant abnormalities in spontaneous retinal activity. These differences in activity manifested themselves as eye-specific segregation defects.

Related Products: Custom Conjugates

Kalinchuk A, Porkka-Heiskanen T, McCarley R, Basheer R (2015) Cholinergic neurons of the basal forebrain mediate biochemical and electrophysiological mechanisms underlying sleep homeostasis. Eur J Neurosci 41:182-195. doi: 10.1111/ejn.12766

Summary: Previous work has indicated that non-rapid eye movement during recovery sleep after sleep deprivation requires cholinergic neurons in the BF. The authors examined how BF cholinergic neurons affect the levels of HSP markers during sleep deprivation. Rats received 230-ng injections of 192-IgG-SAP (Cat. #IT-01) into the horizontal limb of the diagonal band/substantia innominata/ magnocellular preoptic area. The results indicate that cholinergic neurons in the BF are important for regulating the biochemical and EEG mechanisms that contribute to HSP.

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

Frankel AE, Nymeyer H, Lappi DA, Higgins D, Ahn C, Noe C (2014) Preliminary results from a phase I study of substance P-saporin in terminal cancer patients with intractable pain. Journal of Clinical Oncology 32:191. doi: 10.1200/jco.2014.32.31_suppl.191

Summary: Existing pain therapies are insufficient to control cancer pain in 10-15% of patients. Substance P (SP) and its receptor, neurokinin-1 (NK-1r) have been determined to play a major role in spinal transmission of chronic pain. Animal studies have demonstrated that disruption of the NK-1r pathway alleviates chronic pain caused by a variety of stimuli. The authors are conducting a Phase I clinical trial in humans (NCT02036281) assessing the ability of SP-SAP (Cat. #IT-07) to treat intractable chronic pain due to cancer. Patients have received intrathecal injections of 1, 2, or 4 µg of SP-SAP with no evidence of toxicity or neurological or cardiac abnormalities. Doses will escalate up to 90 µg.

Related Products: SP-SAP (Cat. #IT-07)

Akiyama T, Tominaga M, Takamori K, Carstens M, Carstens E (2014) Role of spinal bombesin-responsive neurons in nonhistaminergic itch. J Neurophysiol 112:2283-2289. doi: 10.1152/jn.00409.2014

Summary: Recent papers have demonstrated that pruritogen-evoked scratching behavior is reduced or eliminated by intrathecal injection of Bombesin-SAP (Cat. #IT-40). In this work the authors build on those data by investigating if spinal neurons that are responsive to pruritogens administered intradermally are also responsive to a spinal infusion of bombesin. Through the use of intradermal chloroquine injections, spinal superfusion of bombesin, and noxious pinch, the overlap of neurons processing itch and nociception was examined. The results demonstrate that chloroquine- and bombesin-sensitive neurons are involved in the transmission of itch, and that these are a separate neuronal population from those involved in nociception.

Related Products: Bombesin-SAP (Cat. #IT-40)

Thakkar JP, Dolecek TA, Horbinski C, Ostrom QT, Lightner DD, Barnholtz-Sloan JS, Villano JL (2014) Epidemiologic and molecular prognostic review of glioblastoma. Cancer Epidemiol Biomarkers Prev 23(10):1985-1996. doi: 10.1158/1055-9965.EPI-14-0275 PMID: 25053711

Objective: The authors report on the current epidemiology of glioblastomas (GBM) with data from the Central Brain Tumor Registry of the United Stated (CBTRUS) as well as discuss the trends in incidence and survival. They provide a review on molecular markers in GBM that helped distinguish the similar subtypes of GBM and have prognostic and predictive value.

Summary: GBM is the most common brain and CNS malignancy, accounting for 45.2% of malignant primary brain and CNS tumors, 54% of all gliomas, and 16% of all primary brain and CNS tumors. GBMs comprise of primary and secondary subtypes which evolve through different genetic pathways, affect patients at different ages and have differences in outcomes. While many studies have investigated the basis of incidence differences by gender, age, race, and risk factors for GBM, many of these studies had inconclusive findings. The field has invested significant resources on the characterization for the various subclassifications of GBM and is in position to advance therapies specific to the genetic abnormalities of each. The success of m-TOR pathway inhibition for subependymal giant-cell astrocytomas and the possibility of identifying a subtype of GBM sensitive to up-front treatment with bevacizumab are examples. The complex molecular changes associated with GBM will likely make personalized therapy challenging. Although clinical advances in GBM are rare, the authors look to the new era in cancer biology we are in for meaningful advances.

Mao C, Li H, Zhang Z, Kiyama T, Panda S, Hattar S, Ribelayga C, Mills S, Wang S (2014) T-box transcription regulator Tbr2 is essential for the formation and maintenance of Opn4/melanopsin-expressing intrinsically photosensitive retinal ganglion cells. J Neurosci 34:13083-13095. doi: 10.1523/JNEUROSCI.1027-14.2014 PMID: 25253855

Summary: Opsin 4/melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) are responsible for controlling non-image-forming visual functions in the retina. The findings show that opsin 4 is only expressed in Tbr2-positive ipRGCs, no ipRGCs are found if Tbr2 is deleted before RGC specialization, and most ipRGCs are eliminated when Tbr2 is deleted from established ipRGCs. An antibody against melanopsin (Cat. #AB-N39) was used at a 1:1000 dilution for immunohistochemical analyses.

Related Products: Melanopsin Rabbit Polyclonal, affinity-purified (Cat. #AB-N39)

Luo W, Lin B, Wang Y, Zhong J, O’Meally R, Cole R, Pandey A, Levchenko A, Semenza G (2014) PHD3-mediated prolyl hydroxylation of nonmuscle actin impairs polymerization and cell motility. Mol Biol Cell 25:2788-2796. doi: 10.1091/mbc.E14-02-0775 PMID: 25079693

Usage: Western blot

Related Products: Trans-4-Hydroxy-L-Proline Rabbit Polyclonal, Conjugated (Cat. #AB-T044)