2018 Targeting Trends Review

Mousseau M, Burma NE, Lee KY, Leduc-Pessah H, Kwok CHT, Reid AR, O’Brien M, Sagalajev B, Stratton JA, Patrick N, Stemkowski PL, Biernaskie J, Zamponi GW, Salo P, McDougall JJ, Prescott SA, Matyas JR, Trang T (2018) Microglial pannexin-1 channel activation is a spinal determinant of joint pain. Sci Adv 4:1-12. doi: 10.1126/sciadv.aas9846

Objective: To identify therapeutic targets for alleviating mechnical allodynia, a sign/symptom of arthritis.

Summary: The pannexin-1 (Panx1) channel is validated as a target; blockade of P2X7 receptors or ablation of spinal microglia prevented and reversed mechanical allodynia.

Usage: Mac-1-SAP and unconjugated Saporin (15 mg per intrathecal injection on days 0, 1, and 2). The specific depletion of spinal lumbar microglia attenuated the development of MIA-induced hypersensitivity indicating that spinal microglia causally contribute to the development of mechanical allodynia. By contrast, intrathecal injection of Control (unconjugated Saporin) did not alter the development of MIA-induced mechanical allodynia.

Related Products: Mac-1-SAP rat (Cat. #IT-33), Saporin (Cat. #PR-01)

Xiong L, Liu Y, Zhou M, Wang G, Quan D, Shuai W, Shen C, Kong B, Huang C, Huang H (2018) Targeted ablation of cardiac sympathetic neurons attenuates adverse post-infarction remodeling and left ventricle dysfunction. Exp Physiol 103:1221-1229. doi: 10.1113/EP086928

Objective: To determine whether targeted ablation of cardiac sympathetic neurons (TACSN) could suppress myocardial infarction-induced adverse cardiac remodeling and left ventricle dysfunction.

Summary: TACSN significantly alleviated sympathetic remodeling and neuroendocrine activation, attenuated cardiac hypertrophy and fibrosis, and improved the left ventricular function. Thus, TACSN may have a beneficial effect on adverse post-infarction remodeling and left ventricle dysfunction.

Usage: 20 μl of CTB-SAP (1.2 mg/ml) was mixed with 4 μl of 3% Evans blue dye to make it visible (CTB-SAP is colorless), ensuring localization within the ganglia. The CTB-SAP/Evans blue dye solution was slowly and intermittently injected into the left stellate ganglia using a glass micropipette.

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

Bhat SA, Sood A, Shukla R, Hanif K (2019) AT2R activation prevents microglia pro-inflammatory activation in a nox-dependent manner: Inhibition of PKC activation and p47(PHOX) phosphorylation by PP2A. Mol Neurobiol 56(4):3005-3023. doi: 10.1007/s12035-018-1272-9 PMID: 30076526

Objective: To investigate the involvement of AT2R in NADPH oxidase (NOX)-mediated microglia activation.

Summary: AT2R, via PP2A-mediated inhibition of PKC, prevents the NOX activation, ROS generation, and subsequent pro-inflammatory activation of microglia.

Usage: Immunoblotting: membranes were incubated with respective primary antibodies AT1R (1:1000), AT2R (1:500). Immunocytochemistry: AT1R (1:100), AT2R (1:100).

Related Products: Angiotensin II receptor (AT-1R) Rabbit Polyclonal, affinity-purified (Cat. #AB-N27AP), Angiotensin II receptor (AT-2R) Rabbit Polyclonal, affinity-purified (Cat. #AB-N28AP)

Tan HL, Yong C, Tan BZ, Fong WJ, Padmanabhan J, Chin A, Ding V, Lau A, Zheng L, Bi X, Yang Y, Choo A (2018) Conservation of oncofetal antigens on human embryonic stem cells enables discovery of monoclonal antibodies against cancer. Sci Rep 8:11608. doi: 10.1038/s41598-018-30070-z

Objective: To identify and characterize an antibody raised using human embryonic stem cells with potential as a cancer therapeutic.

Summary: Antibody A19 not only binds to undifferentiated hESCs by flow cytometry, it also reacts with ovarian and breast cancer cell lines with low or no binding to normal cells.

Usage: in vitro – Number of viable cells treated showed a decrease in cell number (Hum-ZAP mixed with A19; Streptavidin-ZAP mixed with biotinylated A19). To determine if there were off-target effects, Hum-ZAP and chA19 were incubated with a non-binding cell line OVCAR10; no apparent cytotoxicity was observed. invivo – 5 x 106 SKOV3 cells were implanted s.c. in NUDE mice and Biotinylated A19-Streptavidin-ZAP (ADC), administered ip. The controls were free Saporin and naked A19. By the end of 10 weeks, mice administered with the ADC saw a 60% reduction in tumor size compared to control groups.

Related Products: Hum-ZAP (Cat. #IT-22), Streptavidin-ZAP (Cat. #IT-27), Saporin (Cat. #PR-01)

Holschbach MA, Vitale EM, Lonstein JS (2018) Serotonin-specific lesions of the dorsal raphe disrupt maternal aggression and caregiving in postpartum rats. Behav Brain Res 348:53-64. doi: 10.1016/j.bbr.2018.04.008

Objective: To determine the effects of behavioral modifications associated with early motherhood by permanently disrupting serotonin signaling at one of its primary sources, the dorsal raphe (DR).

Summary: Prepartum serotonin-specific lesions of the DRdm impaired maternal aggression. Larger postpartum DR serotonin lesions affected both aggression and caregiving. DR serotonin lesions did not affect postpartum anxiety.

Usage: 1 μL of 0.1M anti-SERT-SAP or control Mouse IgG-SAP was slowly infused into the DR.

Related Products: Anti-SERT-SAP (Cat. #IT-23), Mouse IgG-SAP (Cat. #IT-18)

Li J, Rao D, Gibbs RB (2018) Effects of cholinergic lesions and cholinesterase inhibitors on aromatase and estrogen receptor expression in different regions of the rat brain. Neurosci 384:203-213. doi: 10.1016/j.neuroscience.2018.05.033

Objective: To determine if effects of cholinergic inputs on synaptic plasticity and neuronal function are mediated by effects on local estrogen production or ER expression. 

Summary: Selectively destroying cholinergic projections to the hippocampus had little effect on ARO and ER expression in many regions of the rat brain.

Usage: Rats received intraseptal injections of 2.0 ml (0.2 mg/ml) or icv injections of 0.4 mcg.  Lesions resulted in loss of ChAT-positive cells in the septum, and ChAT activity in the hippocampus.  Septal infusions eliminated most of the ChAT-IR cells in MS; ChAT activity in hippocampus also significantly decreased.  ChAT activity in the frontal cortex was not significantly affected.

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

Ueki Y, Shchepetkina V, Lefcort F (2018) Retina-specific loss of Ikbkap/Elp1 causes mitochondrial dysfunction that leads to selective retinal ganglion cell degeneration in a mouse model of familial dysautonomia. Dis Model Mech 11(7):dmm033746. doi: 10.1242/dmm.033746 PMID: 29929962

Objective: To determine the pathophysiological mechanisms that are triggered by the absence of IKAP (inhibitor of kappa B kinase complex-associated protein) in the retina.

Summary: The loss of IKAP caused progressive degeneration of retinal ganglion cells (RGCs) by 1 month of age. There was no loss of melanopsin+ intrinsically photosensitive RGCs at 18 months. RGCs were the only cell type that degenerated, with the survival of other retinal neurons unaffected.

Usage: Immunohistochemistry (IHC), RGC Counts, and H&E staining – Anti-melanopsin (1:5000).

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

Leanza G, Gulino R, Zorec R (2018) Noradrenergic hypothesis linking neurodegeneration-based cognitive decline and astroglia. Front Mol Neurosci 11:254. doi: 10.3389/fnmol.2018.00254

Objective: To examine noradrenergic dysfunction in AD-related cognitive decline in humans and its potential involvement in AD pathology and disease progression.

Summary: The authors discuss noradrenergic dysfunction in AD-related cognitive decline. The research focuses on animal models to allow the validation of the noradrenergic hypothesis of AD, including those based upon the Anti-DBH-SAP-mediated ablation of LC. The article also addresses how astrocytes may participate in the regulation of neurogenesis, a new strategy for preventing LC neuron loss.

Usage: DBH (–/–) knockout mice do not seem to offer the possibility to obtain partial or graded neurotransmitter depletions. In light of these limitations, the authors used Anti-DBH-SAP which is able to target noradrenergic neurons in the LC with unprecedented selectivity and efficiency. Anti-DBH-SAP was injected bilaterally into the LC.

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

Naves LM, Marques SM, Mourão AA, Fajemiroye JO, Xavier CH, de Castro CH, Rebelo ACS, Rosa DA, Gomes RM, Colombari E, Pedrino GR (2018) Involvement of median preoptic nucleus and medullary noradrenergic neurons in cardiovascular and sympathetic responses of hemorrhagic rats. Sci Rep 8:11276. doi: 10.1038/s41598-018-29310-z

Objective: To evaluate the involvement of median preoptic nucleus (MnPO) and medullary noradrenergic neurons (A1 and A2) in HSS-induced cardiovascular and sympathetic responses in hemorrhagic rats.

Summary: The recovery of MAP and HSS-induced sympathoinhibition in hemorrhaged rats depend on intact neural projections from A1 and A2 to MnPO.

Usage: In order to achieve A1 and/or A2 neuronal lesions, Anti-DBH-SAP (100 nL, 0.105 ng·nL−1 ) was nanoinjected into the CVLM and NTS region, respectively. In sham groups, the equimolar of Saporin (100 nL, 0.022 ng·nL−1 ) was nanoinjected into the same site.

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

Káradóttir RT, Kuo CT (2018) Neuronal activity-dependent control of postnatal neurogenesis and gliogenesis. Annu Rev Neurosci 41:139-161. doi: 10.1146/annurev-neuro-072116-031054

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