Targeting Topics 03q4

Hilar neuropeptide Y interneuron loss in the aged rat hippocampal formation.

Cadacio CL, Milner TA, Gallagher M, Pierce JP.

Exp Neurol 183(1):147-158, 2003.

The authors investigate the loss of neuropeptide Y-immunoreactive (NPY-I) interneurons in the dentate gyrus of aged rats. Their results show a loss of a select group of interneurons in these animals. The behavioral as well as structural changes correlated with the results of previous studies on young rats treated with 192-Saporin (Cat. #IT-01). NPY-I neurons may therefore be affected by age-related losses of cholinergic neurons in the basal forebrain.

Lesions of the Basal forebrain cholinergic system impair task acquisition and abolish cortical plasticity associated with motor skill learning.

Conner JM, Culberson A, Packowski C, Chiba AA, Tuszynski MH.

Neuron 38(5):819-829, 2003.

Neuronal plasticity has been associated with normal learning. The authors wished to investigate the role of the cholinergic basal forebrain (CBF) system in learning motor skills. Rats received bilateral 95-ng injections of 192-Saporin (Cat. #IT-01) in either the medial septum, the nucleus basalis magnocellularis, or both. The results indicate that lesioned animals, with many aspects of attention still preserved, are unable to adapt attention to meet the demands of a particular task. The authors conclude that the CBF system may be implicated in learning forms that require plasticity of cortical representations.

Neurokinin-1 receptor-expressing neurons in the amygdala modulate morphine reward and anxiety behaviors in the mouse.

Gadd CA, Murtra P, De Felipe C, Hunt SP.

J Neurosci 23(23):8271-8280, 2003.

Mice lacking the neurokinin-1
(NK-1) receptor are insensitive to opiates in models of drug abuse. To assess what areas of the brain may be involved in this process, the authors used 1.0-µl injections of 1.0 µM SP-SAP (Cat. #IT-07) to eliminate NK-1 receptor-positive neurons in the nucleus accumbens, dorsomedial caudate putamen or amygdala of mice. Only mice with amygdala lesions displayed behavior comparable to NK-1 receptor knockout mice–increase in anxiety-like behavior, reduction in stimulant effect of morphine. These data suggest that the amygdala plays an important role in anxiety behaviors and the response to opiates.

Enhanced evoked excitatory transmitter release in experimental neuropathy requires descending facilitation.

Gardell LR, Vanderah TW, Gardell SE, Wang R, Ossipov MH, Lai J, Porreca F.

J Neurosci 23(23):8370-8379, 2003.

The authors examine whether afferent discharge produced by nerve injury and central changes in experimental neuropathic pain might interact at the spinal level. Rats were treated with 48 ng of dermorphin-SAP (Cat. #IT-12) and various markers for neuropathic pain were evaluated. The results link several consequences of the post-injury state, including support for increased afferent input as a driving force for neuropathic pain.

Role of subplate neurons in functional maturation of visual cortical columns.

Kanold PO, Kara P, Reid RC, Shatz CJ.

Science 301(5632):521-525, 2003.

Subplate neurons play a role in the development of connections between the thalamus and cerebral cortex. The authors used 0.5-µl injections of 0.25-1.0 mg/ml of ME20.4-SAP (Cat. #IT-15) to eliminate p75 receptor-positive neurons in the subplate of cats to investigate whether these neurons are involved in the organization and maturation of the visual cortex. This study also uses mouse IgG-saporin (Cat. #IT-18) as a control. (see cover article “Subplate Neurons and Functional Maturation of Thalamocortical Synapses.”)

The role of the septo-hippocampal cholinergic projection in T-maze rewarded alternation.

Kirby BP, Rawlins JN.

Behav Brain Res 143(1):41-48, 2003.

192-Saporin (Cat. #IT-01) has been used extensively to lesion cholinergic projections to the medial septum from the hippocampal region. It is not yet clear how post-lesion neural regeneration may affect the results. The authors used four 50-ng injections of 192-Saporin to investigate effects prior to any suspected neural regeneration. Significant microglia activation, loss of hippocampal acetylcholinesterase, and a clear inflammatory response were observed; but there was no impairment of spatial working memory.

A double dissociation between serial reaction time and radial maze performance in rats subjected to 192 IgG-saporin lesions of the nucleus basalis and/or the septal region.

Lehmann O, Grottick AJ, Cassel JC, Higgins GA.

Eur J Neurosci 18(3):651-666, 2003.

Using 0.4-µl injections containing 0.4 µg of 192-Saporin (Cat. #IT-01) into either the nucleus basalis magnocellularis, the medial septum/vertical limb of the diagonal band of Broca, or both, the authors examined the contributions of the p75 receptor-positive neurons on cognitive function in rats. Data indicate there is a functional dissociation between the two pathways in attention and memory.

Subtypes of substance P receptor immunoreactive interneurons in the rat basolateral amygdala.

Levita L, Mania I, Rainnie DG.

Brain Res 981(1-2):41-51, 2003.

SP-SAP (Cat. #IT-07) has been used to lesion substance P receptor (SPr)-expressing neurons in the basolateral amygdala (BLA), but the interneuron subgroups targeted by SP-SAP in the BLA have not yet been defined. The authors used dual-labeling immunofluorescence to examine SPr colocalization with calbindin-D28K, parvalbumin, calretinin, somatostatin, and neuropeptide Y (NPY). All neurons in the BLA that express NPY also express the SPr and therefore SP-SAP, which specifically eliminates SP receptor-positive neurons is a useful tool to study the role of NPY in the BLA.

Neonatal 192 IgG-saporin lesion of forebrain cholinergic neurons: focus on the life span?

Pappas BA, Sherren N.

Neurosci Biobehav Rev 27(4):365-376, 2003.

In this review, the authors discuss the use of 192-Saporin (Cat. #IT-01) in the investigation of neurodevelopmental disorders, and propose that the effects of these lesions are amplified as the animal ages and experiences normal age-related synapse loss.

Behavioral patterns under cholinergic control during development: lessons learned from the selective immunotoxin 192 IgG saporin.

Ricceri L.

Neurosci Biobehav Rev 27(4):377-384, 2003.

The author reviews the effects of 192-Saporin (Cat. #IT-01) neonatal lesions (0.42 μg in each hemisphere) on the cholinergic basal forebrain system in rats. Short-term effects are seen in pups in learning tasks, as well as ultrasound vocalizations. Longer term effects are seen in task-specific behaviors. Data suggest that the extent of these effects are linked to the attentional load of the task. The age of the animal when lesioned may also play a role in the extent of the deficits caused by 192-Saporin; studies show that early in the first week of life is a particularly vulnerable period.

Targeted toxins in pain.

Wiley RG, Lappi DA.

Adv Drug Deliv Rev 55(8):1043-1054, 2003.

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).