2014 Targeting Trends Review

Laursen B, Mork A, Plath N, Kristiansen U, Frank Bastlund J (2014) Impaired hippocampal acetylcholine release parallels spatial memory deficits in Tg2576 mice subjected to basal forebrain cholinergic degeneration. Brain Res 1543:253-262. doi: 10.1016/j.brainres.2013.10.055

Summary: The Tg2576 mouse strain provides a limited model for Alzheimer’s disease because they do not display degeneration of cholinergic neurons in the basal forebrain – the other main hallmark of Alzheimer’s disease in humans. Using 0.9 μg icv injections of mu p75-SAP (Cat. #IT-16) the authors evaluated mice that had both Aβ deposition and cholinergic depletion. The data show that these mice display cognitive decline and compromised cholinergic levels, creating a viable model for Alzheimer’s disease.

Related Products: mu p75-SAP (Cat. #IT-16)

Roland JJ, Stewart AL, Janke KL, Gielow MR, Kostek JA, Savage LM, Servatius RJ, Pang KC (2014) Medial septum-diagonal band of Broca (MSDB) GABAergic regulation of hippocampal acetylcholine efflux is dependent on cognitive demands. J Neurosci 34(2):506-514. doi: 10.1523/JNEUROSCI.2352-13.2014

Summary: GABAergic and cholinergic neurons in the medial septum-diagonal band of Broca (MSDB) are both involved with spatial memory. In order to better understand the relationship between these two neuronal populations the authors administered 552.5 ng of GAT-1-SAP (Cat. #IT-32) to the MSDB of rats in several injections. Using a combination of behavioral assays and in vivo microdialysis it was shown that GAT-1-SAP lesions impaired hippocampal acetylcholine efflux as well as performance in the non-matching to position with delay test. The data indicate that GABAergic MSDB neurons are important during high memory load conditions.

Related Products: GAT1-SAP (Cat. #IT-32)

Weisshaar CL, Winkelstein BA (2014) Ablating spinal NK1-bearing neurons eliminates the development of pain and reduces spinal neuronal hyperexcitability and inflammation from mechanical joint injury in the rat. J Pain 15(4):378-386. doi: 10.1016/j.jpain.2013.12.003

Summary: A high percentage of chronic neck pain involves the facet joint. Although the facet joint is innvervated by peptide-responsive nociceptive afferents, the role of these cells in the development and modulation of nociceptive signaling remains unclear. Using a previously developed rat model of facet joint injury, the authors examined the role of neurokinin-1 receptor-expressing spinal cells in this pathway. Rats received 100 ng SSP-SAP (Cat. #IT-11) via lumbar puncture. Blank-SAP (Cat. #IT-21) was used as a control. The results demonstrate that spinal NK1r-expressing cells are essential for nociception and inflammation due to a mechanical joint injury.

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

Douglas AD, Williams AR, Knuepfer E, Illingworth JJ, Furze JM, Crosnier C, Choudhary P, Bustamante LY, Zakutansky SE, Awuah DK, Alanine DG, Theron M, Worth A, Shimkets R, Rayner JC, Holder AA, Wright GJ, Draper SJ (2014) Neutralization of Plasmodium falciparum merozoites by antibodies against PfRH5. J Immunol 192(1):245-258. doi: 10.4049/jimmunol.1302045 PMID: 24293631

Summary: Plasmodium falciparum is a protozoan parasite that can cause malaria in humans. The human malaria parasite reticulocyte –binding protein homolog 5 (PfRH5) is a potential target for neutralizing antibodies. PfRH5 binds basigin on erythrocytes, and through the use of anti-basigin (Cat. #AB-42), among other antibodies, the authors better characterized aspects of this binding that may be useful in preventing malaria.

Related Products: Antibody to Basigin (Cat. #AB-42)

Yin S, Noetzel MJ, Johnson KA, Zamorano R, Jalan-Sakrikar N, Gregory KJ, Conn PJ, Niswender CM (2014) Selective actions of novel allosteric modulators reveal functional heteromers of metabotropic glutamate receptors in the CNS. J Neurosci 34(1):79-94. doi: 10.1523/JNEUROSCI.1129-13.2014 PMID: 24381270

Summary: The eight mGlu receptor subtypes that have been discovered have been thought to function only as homodimers. Although recent studies have suggested that these receptors can form heterodimers in vitro, this has not been demonstrated in vivo. Using a variety of methods, including western blots, coimmunoprecipitation, thallium flux assays, transient transfections, and whole cell patch recordings the authors show that mGlu2 and mGlu4 form a hetero-complex in both rat and mouse tissues. An anti-mGluR2 (Cat. #AB-N32) was used in coimmunoprecipitation.

Related Products: Metabotropic Glutamate Receptor 2 (mGluR2) Mouse Monoclonal (Cat. #AB-N32)

Takakura AC, Barna BF, Cruz JC, Colombari E, Moreira TS (2014) Phox2b-expressing retrotrapezoid neurons and the integration of central and peripheral chemosensory control of breathing in conscious rats. Exp Physiol 99(3):571-585. doi: 10.1113/expphysiol.2013.076752

Summary: Previous work has shown that lesions to the retrotrapezoid nucleus (RTN) have at least a modest effect on breathing, but it is unclear whether those lesions affected the entire nucleus or were incomplete. The authors used bilateral lesions of the RTN with 0.3 to 1.2 ng total of SSP-SAP (Cat. #IT-11) to eliminate neurokinin-1 receptor-expressing neurons; these are also Phox2b+TH- neurons. The results indicate that loss of Phox2b(+)TH(-) neurons may cause deficits seen after RTN lesion, and help define the ways in which these cells are involved in controlling central and peripheral chemoreflexes.

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

Freiria-Oliveira AH, Blanch GT, De Paula PM, Menani JV, Colombari DS (2013) Lesion of the commissural nucleus of the solitary tract/A2 noradrenergic neurons facilitates the activation of angiotensinergic mechanisms in response to hemorrhage. Neuroscience 254:196-204. doi: 10.1016/j.neuroscience.2013.09.017

Summary: Previous work has generated conflicting data on the role of catecholaminergic A2 neurons in the nucleus of the solitary tract (NTS) in control of arterial pressure lability. The authors used Anti-DBH-SAP (Cat. #IT-03) to lesion these neurons in a hypotensive hemorrhage model. Rats received two injections of 12.6 ng into the commissural NTS. Mouse IgG-SAP (Cat. #IT-18) was used as a control. The lesioned animals quickly recovered from hypotension, but were impaired by the icv administration of losartan.

Related Products: Anti-DBH-SAP (Cat. #IT-03), Mouse IgG-SAP (Cat. #IT-18)

Kinikoglu B, Kong Y, Liao EC (2014) Characterization of cultured multipotent zebrafish neural crest cells. Exp Biol Med (Maywood) 239(2):159-168. doi: 10.1177/1535370213513997 PMID: 24326414

Summary: This work details the isolation of neural crest cells (NCCs) from transgenic zebrafish embryos expressing GFP and flow cytometry; the authors analyzed lineage markers and differentiation of the NCCs. Anti-mu p75 (Cat. #AB-N01AP) was used in immunocytochemistry at a 1:20 dilution on fixed cells.

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

Burke RM, Norman TA, Haydar TF, Slack BE, Leeman SE, Blusztajn JK, Mellott TJ (2013) BMP9 ameliorates amyloidosis and the cholinergic defect in a mouse model of Alzheimer’s disease. Proc Natl Acad Sci U S A 110(48):19567-19572. doi: 10.1073/pnas.1319297110 PMID: 24218590

Summary: During development bone morphogenetic protein 9 (BMP9) induces the cholinergic phenotype in the basal forebrain. The authors investigated the use of BMP9 as a treatment of basal forebrain cholinergic degeneration, such as is seen in Alzheimer’s disease (AD). Transgenic mice displaying AD phenotypes and expressing GFP in cholinergic neurons received icv infusions of BMP9, and several cholinergic markers were assessed. Anti-p75NTR (Cat. #AB-N01) was used in immunoblotting at a 1:3000 dilution to measure p75 levels. The results demonstrate the protective and therapeutic activity of BMP9 on AD symptoms.

Related Products: NGFr (mu p75) Rabbit Polyclonal (Cat. #AB-N01)

Leoni G, Rattray M, Fulton D, Rivera A, Butt AM (2014) Immunoablation of cells expressing the NG2 chondroitin sulphate proteoglycan. J Anat 224(2):216-227. doi: 10.1111/joa.12141

Summary: In this work the authors use an antibody against the NG2-glia marker chondroitin sulphate proteoglycan (CSPG) along with Mab-ZAP (Cat. #IT-04) on cell lines and brain slices to eliminate cells expressing CSPG. The results demonstrate selective and effective killing, providing a method to study the function of these cells.

Related Products: Mab-ZAP (Cat. #IT-04)