2019 Targeting Trends Review

Nelson TS, Fu W, Donahue RR, Corder GF, Hökfelt T, Wiley RG, Taylor BK (2019) Facilitation of neuropathic pain by the NPY Y1 receptor-expressing subpopulation of excitatory interneurons in the dorsal horn. Sci Rep 9(1):7248. doi: 10.1038/s41598-019-43493-z PMID: 31076578

Objective: To test the relevance of the NPYY1 spinal population to the development and/or maintenance of acute and neuropathic pain.

Summary: This neuroanatomical and behavioral characterization of Y1R-expressing excitatory interneurons provides compelling evidence for the development of spinally-directed  Y1R agonists to reduce chronic neuropathic pain.

Usage: Selectively ablated Y1R-expressing interneurons while sparing the central terminals of primary afferents. Rats received intrathecal injections of either NPY-SAP or control Blank-SAP (1000 ng each).

Related Products: NPY-SAP (Cat. #IT-28), Blank-SAP (Cat. #IT-21)

Read More

Chun E, Bumanglag AV, Burke SN, Sloviter RS (2019) Targeted hippocampal GABA neuron ablation by stable substance P-saporin causes hippocampal sclerosis and chronic epilepsy in rats. Epilepsia 60(5):e52-e57. doi: 10.1111/epi.14723

Objective: Hippocampal GABA neurons were targeted for selective elimination to determine whether a focal hippocampal GABAergic defect in an otherwise normal brain can initiate cryptogenic temporal lobe epilepsy with hippocampal sclerosis.

Summary: Hippocampal GABAergic dysfunction is epileptogenic and can produce the defining features of cryptogenic temporal lobe epilepsy.

Usage: Intrahippocampal injections of SSP-SAP (0.4 ng/10 nL) were performed using a 0.5-μL Neuros Syringe lowered into four hippocampal sites along both the transverse and longitudinal hippocampal axes bilaterally.

Related Products: SSP-SAP (Cat. #IT-11)

Read the featured article in Targeting Trends.

Alarautalahti V, Ragauskas S, Hakkarainen JJ, Uusitalo-Järvinen H, Uusitalo H, Hyttinen J, Kalesnykas G, Nymark S (2019) Viability of mouse retinal explant cultures assessed by preservation of functionality and morphology. Invest Ophthalmol Vis Sci 60(6):1914-1927. doi: 10.1167/iovs.18-25156 PMID: 31042799

Summary: Organotypic retinal explant cultures have been used to study retinal development, retinal diseases and injuries, drug screening, and retinal stem cell therapies.

Usage: The amount of ganglion cells and melanopsin-expressing intrinsically photosensitive RGCs (ipRGCs) were detected by staining of RNA-binding protein. Melanopsin detection by immunostaining. 1:2500

Related Products: Melanopsin Rabbit Polyclonal (Cat. #AB-N38)

Porter D, Moore A, Goodman R, Hileman S, Coolen L, Lehman M (2019) Cell-specific ablation of GnRH neurons using kisspeptin-saporin in the preoptic area of sheep, but not mice. J Endocrine Society 3(1):SAT–421. ENDO 2019 – 101st Annual Meeting of the Endocrine Society, New Orleans, Louisiana doi: 10.1210/js.2019-SAT-421

Objective: To invesigate the potential of integrin α10β1 as a therapeutic target in glioblastomas (GBMs).

Summary: Integrin α10β1 has a crucial role in the migration, proliferation, and survival of GBM cells and that an integrin α10β1 antibody–drug conjugate induced cell death of GBM cells both in vitro and in vivo.

Usage: Infusions of anti-10-SAP or Anti-ctrl-SAP were made icv (1 µg/2 L per infusion).

Related Products: Custom Conjugates

Kim E, Hwang S-H, Kim H-K, Abdi S, Kim HK (2019) Losartan, an angiotensin II type 1 receptor antagonist, alleviates mechanical hyperalgesia in a rat model of chemotherapy-induced neuropathic pain by inhibiting inflammatory cytokines in the dorsal root ganglia. Mol Neurobiol 56(11):7408-7419. doi: 10.1007/s12035-019-1616-0 PMID: 31037647

Objective: To assess losartan’s analgesic effect on paclitaxel-induced neuropathic pain (PINP) in rats and its mechanism of action in dorsal root ganglion (DRG).

Summary: The mechanical thresholds, protein levels of inflammatory cytokines, and cellular location of AT1R and interleukin 1β (IL-1β) in the DRG were assessed with behavioral testing, Western blotting, and immunohistochemistry, respectively.

Usage: western blot (1:100)

Related Products: Angiotensin II receptor (AT-1R) Rabbit Polyclonal, affinity-purified (Cat. #AB-N27AP)

Thorén MM, Chmielarska Masoumi K, Krona C, Huang X, Kundu S, Schmidt L, Forsberg-Nilsson K, Floyd Keep M, Englund E, Nelander S, Holmqvist B, Lundgren-Åkerlund E (2019) Integrin α10, a novel therapeutic target in glioblastoma, regulates cell migration, proliferation, and survival. Cancers (Basel) 11(4):587. doi: 10.3390/cancers11040587 PMID: 31027305

Objective: To investigate the potential of integrin alpha10beta1 as a therapeutic target in glioblastomas (GBMs).

Summary: Integrin alpha10beta1 has a crucial role in the migration, proliferation, and survival of GBM cells and that an integrin alpha10beta1 antibody–drug conjugate induced cell death of GBM cells both in vitro and in vivo.

Usage: Infusions of anti- 10-SAP or Anti-ctrl-SAP were made icv (1 mcg/2 L per infusion).

Related Products: Custom Conjugates

Pang HW, Linares A, Couling L, Santollo J, Ancheta L, Daniels D, Speth RC (2019) Novel high molecular weight albumin-conjugated angiotensin II activates β-arrestin and G-protein pathways. Endocrine 66(2):349-359. doi: 10.1007/s12020-019-01930-z

Objective: To study the ability of a novel bovine serum albumin-angiotensin II (BSA-Ang II) conjugate to effect responses of the AT1 angiotensin II receptor subtype mediated by the G-protein-coupled and the beta-arrestin pathways.

Summary: BSA-Ang II and Ang II stimulated water appetite equivalently but BSA-Ang II stimulated saline appetite more than Ang II. Both BSA-Ang II and Ang II were considerably more potent at causing calcium mobilization than β-arrestin binding.

Usage: Angiotensin II (Ang II) was conjugated with bovine serum albumin and compared with Ang II for competition binding to AT1 receptors, to stimulate aldosterone release from adrenocortical cells, to promote beta-arrestin binding to AT1 receptors, to promote calcium mobilization, and stimulate drinking of water and saline by rats.

Related Products: Custom Conjugates

Deura C, Minabe S, Ikegami K, Inoue N, Uenoyama Y, Maeda KI, Tsukamura H (2019) Morphological analysis for neuronal pathway from the hindbrain ependymocytes to the hypothalamic kisspeptin neurons. J Reprod Dev 65(2):129-137. doi: 10.1262/jrd.2018-122

Objective: To examine the existence of a neuronal pathway from the hindbrain ependymocytes to kisspeptin neurons in the arcuate nucleus (ARC) and anteroventral periventricular nucleus (AVPV).

Summary: The hindbrain ependymocytes have neuronal connections with the kisspeptin neurons, most probably via hindbrain noradrenergic and CRH neurons to relay low energetic signals for regulation of reproduction.

See: I’Anson H et al. Immunotoxic destruction of distinct catecholaminergic neuron populations disrupts the reproductive response to glucoprivation in female rats. Endocrinology 144(10):4325-4331, 2003.

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

Benade V, Daripelli S, Tirumalasetty C, Subramanian R, Petlu S, Badange R, Nirogi R (2019) 0054 SUVN-G3031, a histamine H3 receptor inverse agonist produces wake promoting effect in orexin-2-saporin lesioned rats. Sleep 42(Supplement_1):A22-A23. doi: 10.1093/sleep/zsz067.053

Summary: Rats lesioned with Orexin-SAP in lateral hypothalamus produced narcoleptic-like behavior.

Related Products: Orexin-B-SAP (Cat. #IT-20)

Souza G, Stornetta R, Stornetta D, Abbott S, Guyenet P (2019) Contribution of retrotrapezoid nucleus and carotid bodies to asphyxia‐induced arousal in rats. FASEB J 33(1):733.6. Experimental Biology 2019 Meeting Abstracts doi: 10.1096/fasebj.2019.33.1_supplement.733.6

Objective: To determine whether the retrotrapezoid nucleus (RTN) is implicated in CO2-induced arousal.

Summary: The authors confirm the importance of the CBs to hypoxia-induced arousal and demonstrate that arousal to hypercapnia is selectively reduced after RTN lesion.

Usage: RTN was nearly completely destroyed with microinjections of SSP-SAP (2.4 ng).

Related Products: SSP-SAP (Cat. #IT-11)