Clement MK, Pimentel CS, Swaine JA, Pimentel AJ, Hutchins D, McGaughy JA (2019) Dissociable attentional effects of dopaminergic and cholinergic lesions to the anterior cingulate cortex. Neuroscience 2019 Abstracts 418.11. Society for Neuroscience, Chicago, IL.

Summary: Prior work from our lab has shown that excitotoxic lesions to the anterior cingulate cortex (ACC) impairs the ability of rats to filter certain types of distracting stimuli (Newman and McGaughy 2011). Specifically, rats with lesions of the ACC cannot filter distractors that have been made salient through pairing with reinforcement. In contrast, these same subjects can filter distracting stimuli that have not been predictive of reward. The present study investigates the effects of neuromodulator specific lesions of the same region to determine how specific neuromodulators contribute to the attentional function of ACC. Cholinergic or dopaminergic deafferentation of the ACC was achieved using either 192 IgG saporin (n=10) or dopamine transporter saporin (n=10). Lesions were restricted to the rostral portion of the area and did not spread to nearby prefrontal sub-regions e.g prelimbic cortex. After lesioning, subjects were tested in an attentional set-shifting task (Birrell and Brown 2000). While both cholinergic and dopaminergic lesions increased distractibility, these deficits were not as severe as those produced after excitotoxic lesions (n= 8). In contrast to excitotoxic lesions, both cholinergic and dopaminergic lesions also impeded formation of an attentional set. Because dopaminergic lesions produced impairments in many stages of the tasks, we hypothesized that these subjects had a more general impairment in stimulus processing. In order to address these broader processing impairments, we analyzed the data to determine whether lesioned rats showed more sensitivity to novel stimuli, or made more perseverative errors. The implications of these data for understanding the unique contributions of acetylcholine and dopamine to attentional processing in the ACC will be discussed.

Related Products: 192-IgG-SAP (Cat. #IT-01), Anti-DAT-SAP (Cat. #IT-25)

Wang X, Ma S, Wu H, Shen X, Xu S, Guo X, Bolick ML, Wu S, Wang F (2018) Macrophage migration inhibitory factor mediates peripheral nerve injury-induced hypersensitivity by curbing dopaminergic descending inhibition. Exp Mol Med 50(2):e445. doi: 10.1038/emm.2017.271

Objective: To investigate whether the proinflammatory cytokine MIF participates in the regulation of neuropathic hypersensitivity by interacting with and suppressing the descending dopaminergic system.

Summary: MIF functions as a braking factor in curbing dopaminergic descending inhibition in peripheral nerve injury-induced hypersensitivity by mediating Th gene methylation through G9a/SUV39H1-associated H3K9 methylation.

Usage: Anti-DAT-SAP was injected i.t. or i.c.v. with ISO-1 alone or ISO-1 combined with one of the other regulators on Day 7 post-nerve injury for 14 days, and pain behaviors, including 50% withdrawal threshold, mechanical pressure and thermal withdrawal latency, were observed throughout the 70 days post nerve injury.

Related Products: Anti-DAT-SAP (Cat. #IT-25)

Foehr ED, Lorente G, Kuo J, Ram R, Nikolich K, Urfer R (2006) Targeting of the receptor protein tyrosine phosphatase beta with a monoclonal antibody delays tumor growth in a glioblastoma model. Cancer Res 66(4):2271-2278. doi: 10.1158/0008-5472.CAN-05-1221

Summary: The receptor protein tyrosine phosphatase ß (RPTPß) is overexpressed in astrocytomas, and is a potential target for tumor therapy. After testing antibodies against an extracellular domain of RPTPß in vitro with Mab-ZAP (Cat. #IT-04), two custom conjugates, 7E4B11-SAP and 7A9B5-SAP, were created by Advanced Targeting Systems. The authors tested the custom conjugates, using anti-DAT-SAP (Cat. #IT-25) as a positive control, and mouse IgG-SAP (Cat. #IT-18) as a negative control. The 7E4B11-SAP conjugate displayed significant antitumor activity in mice engrafted with U87 glioma cells.

Related Products: Mab-ZAP (Cat. #IT-04), Anti-DAT-SAP (Cat. #IT-25), Mouse IgG-SAP (Cat. #IT-18), Custom Conjugates

Saurer TB, Carrigan KA, Ijames SG, Lysle DT (2006) Suppression of natural killer cell activity by morphine is mediated by the nucleus accumbens shell. J Neuroimmunol 173(1-2):3-11. doi: 10.1016/j.jneuroim.2005.11.009

Summary: In this work the authors investigated the role of dopaminergic projections to the nucleus accumbens in modulation of immune parameters such as morphine-induced suppression of splenic natural killer (NK) cell activity. Studies have indicated that acute exposure to opioids decrease NK cell-mediated cytotoxicity. Rats received bilateral 0.5 µg-injections of anti-DAT-SAP (Cat. #IT-25) into the nucleus accumbens shell. Treated animals showed no immunosuppression upon administration of morphine, indicating that dopaminergic neurons in the nucleus accumbens play a major role in this pathway.

Related Products: Anti-DAT-SAP (Cat. #IT-25)

Stead S, Trottier N, Doering LC (2005) Characterization of an immunotoxin model of Parkinson’s disease in mice. Neuroscience 2005 Abstracts 664.9. Society for Neuroscience, Washington, DC.

Summary: The primary event underlying the motor deficits of Parkinson’s disease (PD) is degeneration of neurons in the nigro-striatal system. The most widely employed laboratory rodent models of Parkinson’s are the neurotoxin 6-hydroxydopamine (6-OHDA) model that causes acute degeneration of the dopamine neurons in the substantia nigra (SN) and the MPTP mouse model. To date, there is no single model which accurately simulates the pathogenic, histological, biochemical and clinical features relevant for the investigation of PD. Toxins conveyed by axonal transport can be used to make selective lesions in the central nervous system. As previously shown in rats (Wiley et al., Cell. Mol. Biol., 2003), we have found that selective degeneration of the SN can be induced with an immunotoxin consisting of the highly active ribosome inactivating protein Saporin linked to an antibody to the dopamine transporter. A unilateral stereotaxic injection of anti-DAT-Saporin (0.25ug/2ul and 0.05ug/2ul) into the striatum of young (6-8 weeks old) female C57BL6 mice causes a progressive reduction in the number of DA neurons in the SN in comparison to the non-lesioned hemisphere and in various controls. Furthermore, in parallel to the immunohistochemical dopamine neuron death, the animals display a pronounced circling behaviour when challenged with apomorphine (3mg/kg). We are currently examining the affected brain sections for inclusion bodies and changes in astrocytes. This model exhibits the selective deterioration of the nigro-striatal system that occurs in Parkinson’s disease and provides a system to intervene at various stages of dopamine neuron loss and evaluate the effectiveness of stem cell therapy.

Related Products: Anti-DAT-SAP (Cat. #IT-25)

Stead S, Doering LC (2004) A novel mouse model for Parkinson’s disease using an immunotoxin directed at the dopamine transporter. Neuroscience 2004 Abstracts 563.1. Society for Neuroscience, San Diego, CA.

Summary: Current laboratory models of Parkinson’s disease utilize neurotoxins directed at midbrain dopamine neurons to mimic nigro-striatal dopaminergic neuron degeneration. To date, however, there is no single model that accurately simulates the pathogenic, histological, biochemical and clinical features relevant for the investigation of PD. The most common laboratory rodent model of Parkinson’s uses the neurotoxin 6-hydroxydopamine (6-OHDA) to cause relatively acute degeneration of the dopamine neurons in the substantia nigra (Schwarting RKW and Huston JP, 1996, Prog Neurobiol., 50:275-331). Axonally transported toxins can be used to make selective lesions in the central nervous system. We have found that a slower degeneration of the SN can be achieved with an immunotoxin directed against the dopamine transporter (DAT). This immunotoxin, consisting of the highly active ribosome inactivating protein Saporin linked to an antibody to the dopamine transporter, was recently reported to cause selective degeneration of the SN in rats (Wiley RG et al., 2003, Cell Mol Neurobiol., 23:839-850.). We have shown that unilateral stereotaxic injection of the Anti-DAT-Saporin into the striatum of female C57BL6 mice causes a progressive reduction in the numbers of DA neurons in the SN in comparison to the non-lesioned hemisphere, and sham controls. Furthermore, in parallel to the immunohistochemical dopamine neuron death, the animals display a pronounced circling behaviour when challenged with apomorphine (6mg/kg). This model is akin to the gradual deterioration of the nigro-striatal system that occurs in Parkinson’s Disease and provides a system to intervene at various stages of dopamine neuron loss and evaluate the effectiveness of stem cell therapy.

Related Products: Anti-DAT-SAP (Cat. #IT-25)

Wiley RG, Harrison MB, Levey A, Lappi DA (2003) Destruction of midbrain dopaminergic neurons by using an immunotoxin to the dopamine transporter. Cell Mol Neurobiol 23:839-850. doi: 10.1023/a:1025065306264

Summary: The authors demonstrate the effective and specific removal of neurons expressing the dopamine transporter in the substantia nigra pars compacta and the ventral tegmental area with anti-DAT-SAP (Cat. #IT-25). A 21-µg icv injection produced a highly significant loss of midbrain dopaminergic neurons, creating a useful model for Parkinson’s disease.

Related Products: Anti-DAT-SAP (Cat. #IT-25)

Wiley RG, Lappi DA (2003) Targeted toxins in pain. Adv Drug Deliv Rev 55(8):1043-1054. doi: 10.1016/s0169-409x(03)00102-9

Summary: The authors discuss the use of ‘molecular neurosurgery’ in the study of nociception. Applications using targeted toxins, which include immunotoxins, protein-toxin conjugates, or peptide-toxin conjugates, are illustrated. The authors describe the use of these molecules as research tools, as well as their potential for therapeutics. A helpful table is included that lists neuronal surface markers and class of cells targeted for each targeted toxin. Reagents discussed: CTB-SAP (Cat. #IT-14), IB4-SAP (Cat. #IT-10), OX7-SAP (Cat. #IT-02), 192-Saporin (Cat. #IT-01), ME20.4-SAP (Cat. #IT-15), Anti-DBH-SAP (Cat. #IT-03), Anti-DAT-SAP (Cat. #IT-25), SP-SAP (Cat. #IT-07), Dermorphin-SAP (Cat. #IT-12), Orexin-SAP (Cat. #IT-20), CRF-SAP (Cat. #IT-13), and acetylated LDL-SAP (Cat. #IT-08).

Related Products: CTB-SAP (Cat. #IT-14), IB4-SAP (Cat. #IT-10), OX7-SAP (Cat. #IT-02), 192-IgG-SAP (Cat. #IT-01), ME20.4-SAP (Cat. #IT-15), Anti-DBH-SAP (Cat. #IT-03), Anti-DAT-SAP (Cat. #IT-25), SP-SAP (Cat. #IT-07), Dermorphin-SAP / MOR-SAP (Cat. #IT-12), Orexin-B-SAP (Cat. #IT-20), CRF-SAP (Cat. #IT-13), Acetylated LDL-SAP (Cat. #IT-08)

Lappi DA (2003) Featured Article: A new immunotoxin for targeting dopaminergic neurons. Targeting Trends 4(3)

Related Products: Anti-DAT-SAP (Cat. #IT-25)

Read the featured article in Targeting Trends.