Targeting Topics 08q3

Noradrenergic innervation of the dorsal medial prefrontal cortex modulates hypothalamo-pituitary-adrenal responses to acute emotional stress.

Radley JJ, Williams B, Sawchenko PE

J Neurosci 28:5806-5816, 2008.

Rats were injected with 90-120 nl of 0.475-µg/µl anti-DBH-SAP (Cat. #IT-03) into the cortical field containing noradrenergic neurons that project to the dorsal medial prefrontal cortex. The results indicate that the locus ceruleus functions as an upstream component in medial prefrontal cortex modulation of hypothalamo-pituitary-adrenal activation due to emotional stress.

Vascular smooth cell proliferation in perfusion culture of porcine carotid arteries.

Liao D, Lin PH, Yao Q, Chen C

Biochem Biophys Res Commun 372(4):668-673, 2008.

The authors used FGF-SAP (Cat. #IT-38) to help characterize a model of vascular smooth muscle cell proliferation with porcine carotid arteries. Arteries isolated from pigs were cultured under several different conditions, one of which included FGF-SAP at a concentration of 0.4 nM. In all cases the arteries maintained viability for up to 96 hours.

Neuromodulatory role of acetylcholine in visually-induced cortical activation: Behavioral and neuroanatomical correlates.

Dotigny F, Ben Amor AY, Burke M, Vaucher E

Neuroscience 154(4):1607-1618, 2008.

After rats were treated with 192-IgG-SAP (Cat. #IT-01, 2 µl of 2.4 µg/µl into the lateral ventricle) visual acuity and performance in a visual water maze task were analyzed. Lesioned animals displayed no loss in acuity, but were less able to learn a new orientation discrimination task.

Selective ablation of GABA neurons in the ventral tegmental area increases spontaneous locomotor activity.

Shank EJ, Seitz PK, Bubar MJ, Stutz SJ, Cunningham KA

Behav Neurosci 121:1224-1233, 2007.

To further examine the importance of the ventral tegmental area (VTA) γ-aminobutyric acid (GABA) neurons in behavioral function, the authors lesioned the VTA of rats. Animals received 1 or 2 pmol/200 nl bilateral injections of dermorphin-SAP (Cat. #IT-12); blank-SAP (Cat. #IT-21) was used as a control. Rats treated with dermorphin-SAP displayed significantly elevated motility as compared to control animals.

Oxytocin deficiency mediates hyperphagic obesity of Sim1 haploinsufficient mice.

Kublaoui BM, Gemelli T, Tolson KP, Wang Y, Zinn AR

Mol Endocrinol 22(7):1723-1734, 2008.

Central administration of neuropeptides in the paraventricular nucleus (PVN) is known to inhibit feeding. Hypothalamic expression of several neuropeptides, including corticotrophin releasing hormone (CRH) was measured. To do so, anti-CRH (Cat. #AB-02, 1:800) was used in immunohistochemistry.

Environmental enrichment mitigates the effects of basal forebrain lesions on cognitive flexibility.

De Bartolo P, Leggio MG, Mandolesi L, Foti F, Gelfo F, Ferlazzo F, Petrosini L

Neuroscience 154(2):444-453, 2008.

This work examines whether environmental enrichment can reduce the effect of cholinergic lesions on learning and memory tasks. Rats received 0.4-µg bilateral injections of 192-IgG-SAP (Cat. #IT-01) into the cholinergic projection to the neocortex. Deficits caused by the lesion were attenuated in rats experiencing an enriched environment.

Targeting CUB domain-containing protein 1 with a monoclonal antibody inhibits metastasis in a prostate cancer model.

Siva AC, Wild MA, Kirkland RE, Nolan MJ, Lin B, Maruyama T, Yantiri-Wernimont F, Frederickson S, Bowdish KS, Xin H

Cancer Res 68:3759-3766, 2008.

After demonstrating in vitro activity of the monoclonal antibody 25A11 with Mab-ZAP (Cat. #IT-04) and Hum-ZAP (Cat. #IT-22) the authors had ATS do a direct conjugation of 25A11 and saporin. Goat-IgG-SAP (Cat. #IT-19) was used as a control for in vivo experiments, and saporin (Cat. #PR-01) was the control in vitro. In treated mice, the direct conjugate significantly inhibited tumor growth as well as metastasis in vivo.

Selective ablation of dorsal horn NK1 expressing cells reveals a modulation of spinal alpha2-adrenergic inhibition of dorsal horn neurones.

Rahman W, Suzuki R, Hunt SP, Dickenson AH

Neuropharmacology 54:1208-1214, 2008.

In this work the spinal origin of the major descending noradrenergic inhibitory pathway is examined with the help of SP-SAP (Cat. #IT-07). Rats received a 10-µl infusion of 1 mM SP-SAP (Saporin, Cat. #PR-01, was used as a control) into the sub-arachnoid space terminating in the L4-5 region. Results suggest that NK1r-expressing cells are involved with activity in noradrenergic pathways and descending facilitation.

Emergence of spatial impairment in rats following specific cholinergic depletion of the medial septum combined with chronic stress.

Craig LA, Hong NS, Kopp J, McDonald RJ

Eur J Neurosci 27:2262-2271, 2008.

Rats received bilateral injections of 192-IgG-SAP (Cat. #IT-01) into the medial septum and vertical limb of the diagonal band of Broca totaling 0.075 µg. Animals were not impaired in a water maze task, but lesioning combined with stress caused significant reduction in performance.

Substance P receptor-expressing dorsal horn neurons: Lessons from the targeted cytotoxin, substance P-saporin.

Wiley RG

Pain 136:7-10, 2008.

This review covers some of the more recent work utilizing SP-SAP (Cat. #IT-07) and SSP-SAP (Cat. #IT-11) in the dorsal horn. The potential of these conjugates as pain therapeutics is explored.

Involvement of the basal cholinergic forebrain in the mediation of general (propofol) anesthesia.

Laalou FZ, de Vasconcelos AP, Oberling P, Jeltsch H, Cassel JC, Pain L

Anesthesiology 108:888-896, 2008.

192-IgG-SAP (Cat. #IT-01) was injected three ways: icv injection of 2 µg, 0.4 µg into the nucleus basalis magnocellularis, and 0.8 µg into the medial septum/ vertical diagonal band of Broca. The results suggest that loss of cholinergic neurons in the cortex and hippocampus leads to potentiation of the anesthetic effects of Propofol.

Unilateral Ablation of preBötzinger Complex Disrupts Breathing During Sleep but not Wakefulness.

McKay LC, Feldman JL

Am J Respir Crit Care Med 178(1):89-95, 2008.

Here rats received a unilateral injection of SP-SAP (Cat. #IT-07, 6.7 ng) into the left preBötC. SP plus unconjugated saporin (Cat. #PR-01) was used as control. Unilaterally-treated rats did not develop disrupted breathing patterns during wakefulness.

Selective cholinergic lesions in the rat nucleus basalis magnocellularis with limited damage in the medial septum specifically alter attention performance in the five-choice serial reaction time task.

Harati H, Barbelivien A, Cosquer B, Majchrzak M, Cassel JC

Neuroscience 153:72-83, 2008.

Here the authors examined the effect of lesions in the nucleus basalis magnocellularis (NBM) when septal damage was kept to a minimum. The NBM received bilateral 0.2-µg injections of 192-IgG-SAP (Cat. #IT-01), and the animals were then tested in a 5-choice serial reaction time task. The disruption of sustained visual attention remained, but other variables were close to normal.

Oxaliplatin Acts on IB4-Positive Nociceptors to Induce an Oxidative Stress-Dependent Acute Painful Peripheral Neuropathy.

Joseph EK, Chen X, Bogen O, Levine JD

J Pain 9:463-472, 2008.

The authors administered 3.2-µg intrathecal injections of IB4-SAP (Cat. #IT-10), using saporin (Cat. #PR-01) as a control. Lesioning IB4-binding neurons in the dorsal horn completely prevented oxaliplatin-induced hyperalgesia.

Selective lesion of retrotrapezoid Phox2b-expressing neurons raises the apnoeic threshold in rats.

Takakura AC, Moreira TS, Stornetta RL, West GH, Gwilt JM, Guyenet PG

J Physiol 586.12: 2975-2991, 2008

Injections of SSP-SAP (Cat. #IT-11) into the retrotrapezoid nucleus eliminated Phox2b+TH- neurons but spared other neuron classes. Several different amounts of the conjugate were used (0.15, 0.3, or 0.6 ng in 1 or 2 injections). Elimination of ≥70% of Phox2b+TH- neurons markedly attenuated the central chemoreflex.