2018 Targeting Trends Review

Lee S, Shi XQ, Fan A, West B, Zhang J (2018) Targeting macrophage and microglia activation with colony stimulating factor 1 receptor inhibitor is an effective strategy to treat injury-triggered neuropathic pain. Mol Pain 14:1744806918764979. doi: 10.1177/1744806918764979

Summary: Depletion of spinal microglia with Mac-1-SAP was able to prevent and reverse neuropathic pain behavior.

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

Ing-Esteves S, Kostadinov D, Marocha J, Sing AD, Joseph KS, Laboulaye MA, Sanes JR, Lefebvre JL (2018) Combinatorial effects of alpha- and gamma-protocadherins on neuronal survival and dendritic self-avoidance. J Neurosci 38:2713-2729. doi: 10.1523/JNEUROSCI.3035-17.2018 PMID: 29439167

Objective: The clustered protocadherins (Pcdhs) comprise 58 cadherin-related proteins encoded by three tandemly arrayed gene clusters, Pcdh- , Pcdh- , and Pcdh- (Pcdha, Pcdhb, and Pcdhg, respectively). This study sought to determine roles of Pcdhas and Pcdhgs in the retina and cerebellum from mice (both sexes) lacking one or both clusters.

Summary: Study examined two regions of the CNS, the retina and cerebellum and showed that the 14 -Pcdhs and 22 -Pcdhs act synergistically to mediate neuronal survival and dendrite patterning. In retina, Pcdhgs are essential for survival of inner retinal neurons and dendritic self-avoidance of starburst amacrine cells, whereas Pcdhas are dispensable for both processes.

Usage: Anti-Melanopsin (1:5000) used to quantify two mutually exclusive RGC cell types, the Brn3a RGCs and the melanopsin-positive intrinsically photo- sensitive RGCs (Mel ipRGCs).

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

Jiao J, Tian W, Qiu P, Norton EL, Wang MM, Chen YE, Yang B (2018) Induced pluripotent stem cells with NOTCH1 gene mutation show impaired differentiation into smooth muscle and endothelial cells: Implications for bicuspid aortic valve-related aortopathy. J Thorac Cardiovasc Surg 156:515-522. doi: 10.1016/j.jtcvs.2018.02.087 PMID: 29653750

Objective: To develop an in vitro model with human-induced pluripotent stem cells (iPSCs) to evaluate the role of NOTCH1 in smooth muscle and endothelial cell differentiation.

Summary: NOTCH1 is critical in SMC and EC differentiation of iPSCs through neural crest stem cells and cardiovascular progenitor cells, respectively. NOTCH1gene mutations may potentially contribute to the development of thoracic aortic aneurysms by affecting SMC differentiation in some patients with bicuspid aortic valve-related aortopathy.

Usage: Immunofluorescence staining and flow cytometry was performed.

Related Products: NGFr (ME20.4, p75) Mouse Monoclonal (Cat. #AB-N07)

Kawakami Y, Kurihara Y, Saito Y, Fujita Y, Yamashita T, Takei K (2018) The soluble form of LOTUS inhibits Nogo receptor-mediated signaling by interfering with the interaction between Nogo receptor type 1 and p75 neurotrophin receptor. J Neurosci 38:2589-2604. doi: 10.1523/JNEUROSCI.0953-17.2018. PMID: 29440387

Objective: To investigate whether the soluble form of LOTUS (s-LOTUS) also has an inhibitory action on NgR1 function as a candidate for therapeutic agents

Summary: Findings suggest that s-LOTUS inhibits NgR1-mediated signaling possibly by interfering with the interaction between NgR1 and p75NTR. Thus, s-LOTUS may have potential as a therapeutic agent for neuronal regeneration in the damaged CNS

Usage: staining (1:1000)

Related Products: NGFr (mu p75) Rabbit Polyclonal, affinity-purified (Cat. #AB-N01AP)

Sparks NRL, Martinez IKC, Soto CH, Zur Nieden NA-O (2018) Low osteogenic yield in human pluripotent stem cells associates with differential neural crest promoter methylation. Stem Cells 36:349-362. doi: 10.1002/stem.2746 PMID: 29193426

Objective: To compare the osteogenic potential of two human induced pluripotent stem cell lines (RIV9 and RIV4) to human H9 embryonic stem cells.

Summary: The study demonstrates that different hPSC lines, including individual hiPSC clones, could have inherently different abilities to produce functional osteoblasts potentially based on the methylation marks placed on promotor regions important for lineage decisions

Usage: immunohistochemistry

Related Products: NGFr (mu p75) Rabbit Polyclonal, affinity-purified (Cat. #AB-N01AP)

Strichartz G, Khasabov S, Barr T, Wang J, Simone D (2018) Modulation of chronic post-thoracotomy pain by NK-1 neurons in the rostral ventromedial medulla is not paralleled by changes spinal MAPKinase activation. J Pain 19:S14. doi: 10.1016/j.jpain.2017.12.065

Objective: To evaluate SSP-SAP in treatment of tactile hypersensitivity for Chronic Post-Thoractotomy Pain (CPTP).

Summary: SSP-SAP 3 weeks before thoracotomy and rib retraction (TRR) was able to completely prevent CPTP, assayed by tactile hypersensitivity.

Usage: Ablation of Neurokinin-1 receptor (NK-1R)- expressing neurons in the rat rostral ventromedial medulla (RVM), by micro-injection of the specific neurotoxin SSP-SAP.  No effect with treatment of control, Blank-SAP (IT-21).

Related Products: SSP-SAP (Cat. #IT-11), Blank-SAP (Cat. #IT-21)

Ermine CM, Wright JL, Frausin S, Kauhausen JA, Parish CL, Stanic D, Thompson LH (2018) Modelling the dopamine and noradrenergic cell loss that occurs in Parkinson’s disease and the impact on hippocampal neurogenesis. Hippocampus 28(5):327-337. doi: 10.1002/hipo.22835

Objective: The mechanisms underlying reduced neurogenesis in Parkinson’s Disease (PD) are not well established. The authors tested the hypothesis that noradrenergic and dopaminergic depletion, as occurs in PD, impairs hippocampal neurogenesis.

Summary: Mechanisms of neurotransmitter-based regulation of cognition and hippocampal neurogenesis may well overlap under certain conditions but the present results do not suggest a simple relationship associated with the degeneration of the two most prominently affected transmitter systems in PD.

Usage: Rats received 1 mcg Anti-DBH-SAP icv.

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

Maxwell GK, Szunyogova E, Shorrock HK, Gillingwater TH (2018) Developmental and degenerative cardiac defects in the Taiwanese mouse model of severe spinal muscular atrophy. J Anat 232:965-978. doi: 10.1111/joa.12793 PMID: 29473159

Objective: To investigate changes occurring in the heart, predominantly at pre- and early symptomatic ages, in the Taiwanese mouse model of severe Spinal muscular atrophy (SMA).

Summary: The findings support the requirement to develop systemic therapies for SMA capable of treating non-neuromuscular pathologies.

Usage: Immunohistochemistry, Western blot

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

Turnbull MT, Boskovic Z, Coulson EJ (2018) Acute down-regulation of BDNF signaling does not replicate exacerbated amyloid-β levels and cognitive impairment induced by cholinergic basal forebrain lesion. Front Mol Neurosci 11:51. doi: 10.3389/fnmol.2018.00051

Objective: To determine if degeneration of BFCNs causes a decrease in neurotrophin levels in innervated brain areas, which in turn promotes the development of Amyloid beta  pathology and cognitive impairment.

Summary: Lesion of septo-hippocampal BFCNs in a pre-symptomatic transgenic amyloid AD mouse model (APP/PS1 mice) increases soluble Ab levels in the hippocampus, and induces cognitive deficits in a spatial memory task that are not seen in either unlesioned APP/PS1 or non-transgenic littermate control mice. Cognitive decline and Amyloid-beta pathology induced by cholinergic basal forebrain neuron loss occur independent of dysfunctional neuronal BDNF signaling, and may therefore be directly underpinned by reduced cholinergic neurotransmission.

Usage: To lesion BFCNs, a single infusion of murine p75-SAP or control rabbit IgG-SAP (0.4 mg/ml) was stereotaxically injected into the basal forebrain.

Related Products: mu p75-SAP (Cat. #IT-16), Rabbit IgG-SAP (Cat. #IT-35)

May Z, Kumar R, Fuehrmann T, Tam R, Vulic K, Forero J, Lucas Osma A, Fenrich K, Assinck P, Lee M, Moulson A, Shoichet M, Tetzlaff W, Biernaskie J, Fouad K (2018) Adult skin-derived precursor Schwann cell grafts form growths in the injured spinal cord of Fischer rats. Biomed Mater 13:034101. doi: 10.1088/1748-605X/aa95f8 PMID: 29068322

Objective: To improve grafted cell survival in the injured spinal cord, which is typically low.

Summary: It is of utmost importance to define the precise culture/transplantation parameters for maintenance of normal cell function and safe and effective use of cell therapy.

Usage: Immunohistochemistry (1:500)

Related Products: NGFr (192-IgG, p75) Mouse Monoclonal (Cat. #AB-N43)