Targeting Topics 03q3

Intrathecal substance p-saporin attenuates operant escape from nociceptive thermal stimuli.

Vierck CJJ, Kline RH, Wiley RG.

Neuroscience 119(1):223-232, 2003.

Administration of SP-SAP (Cat. #IT-07) eliminates sensitization of nocifensive reflexes. The authors investigate whether SP-SAP elimination of neurokinin-1 receptor-expressing neurons in the lumbar spinal cord affects nociceptive sensitivity in general, or preferentially affects nociception dependent on spinal and brainstem, or cerebral processing. Rats treated with spinal intrathecal injections of 175 ng of SP-SAP showed attenuated thermal hyperalgesia, and no secondary hyperalgesia, while innate reflexes were unaffected by SP-SAP treatment.

Ablation of striatal interneurons influences activities of entopeduncular neurons.

Chiken S, Tokuno H.

Neuroreport 14(5):675-678, 2003.

To investigate the role of the basal ganglia in informational processing of voluntary movement, the authors used SP-SAP (Cat. #IT-07) to lesion SP receptor-expressing neurons in the striatum. A 0.5 µl injection of 40 ng/µl SP-SAP into the dorsolateral portion of the striatum decreased the spontaneous discharge of entopeduncular neurons. These data indicate that SP receptor-positive striatal interneurons indirectly regulate activity of basal ganglia output neurons.

Food- and light-entrained circadian rhythms in rats with hypocretin-2-saporin ablations of the lateral hypothalamus.

Mistlberger RE, Antle MC, Kilduff TS, Jones M.

Brain Res 980(2):161-168, 2003.

Food-anticipatory behaviors in mammals can follow circadian rhythms entrained by daily feeding schedules. Lateral hypothalamic (LH) neurons express hypocretin (also known as orexin) receptors, therefore rats were treated with four 500-ng injections of orexin-SAP (Cat. #IT-20) to eliminate these neurons. Lesioned animals displayed altered dietary behavior, but maintained anticipatory activity before the daily meal.

Neural stem cells and cholinergic neurons: regulation by immunolesion and treatment with mitogens, retinoic acid, and nerve growth factor.

Calza L, Giuliani A, Fernandez M, Pirondi S, D’Intino G, Aloe L, Giardino L.

Proc Natl Acad Sci U S A 100(12):7325-7330, 2003.

The authors explore the influence of exogenous administration of hormones, cytokines, and neurotrophins on stem cells following a lesion. Rats were treated with 2 or 3 µg of 192-Saporin (Cat. #IT-01) into the cerebral ventricles, which induced a lesion of the cholinergic system in the basal forebrain. The surgery was followed by infusion of EGF, bFGF, and NGF into the lesioned area, as well as addition of retinoic acid to the food pellets. This pharmacological control of endogenous neural stem cells increased the number of proliferating cells in both lesioned and non-lesioned animals, as well as improved performance in a water maze test.

Long-term effects of decreased noradrenergic central nervous system innervation on pain behavior and opioid antinociception.

Jasmin L, Boudah A, Ohara PT.

J Comp Neurol 460(1):38-55, 2003.

Noradrenaline (NA) is an essential element of the endogenous pain inhibitory system. The authors injected 5 µg of anti-DBH-SAP (Cat. #IT-03) into either the cerebral ventricles or lumbosacral cistern of rats to investigate whether a permanent reduction of noradrenergic innervation of the spinal cord leads to a chronic decreased nociceptive threshold. Although treated animals were less responsive to the antinociceptive effects of morphine, the results suggest that NA makes only a modest contribution to the nociceptive threshold.

Role of the medial septum diagonal band of Broca cholinergic neurons in oestrogen-induced spine synapse formation on hippocampal CA1 pyramidal cells of female rats.

Lam TT, Leranth C.

Eur J Neurosci 17(10):1997-2005, 2003.

Estrogen effects on the hippocampus are known to be mediated by subcortical structures. The authors examined the role that the medial septum diagonal band of Broca (MSDB) plays in this mediation. An injection of 0.5 µg of 192-Saporin (Cat. #IT-01) into the right lateral ventricle of rats was used to specifically investigate the role of cholinergic MSDB neuron projections to the hippocampus, since many of these neurons express estrogen receptors. The data suggest that septo-hippocampal cholinergic neurons are involved in mediating estrogen effects on the hippocampus.

Immunotoxin lesion of hypothalamically projecting norepinephrine and epinephrine neurons differentially affects circadian and stressor-stimulated corticosterone secretion.

Ritter S, Watts AG, Dinh TT, Sanchez-Watts G, Pedrow C.

Endocrinology 144(4):1357-1367, 2003.

Hindbrain norepinephrine (NE) and epinephrine (E) neurons are important in the distribution of internal sensory signals. Injecting 42 ng of anti-DBH-SAP (Cat. #IT-03) into the paraventricular nucleus of rat hypothalamus, the authors were able to specifically destroy NE and E neurons. This study revealed the contribution of NE/E afferents to hypothalamo-pituitary-adrenal activation during stress and confirmed that NE and E neurons are required for specific stress responses.

A role for the basal forebrain cholinergic system in estrogen-induced disinhibition of hippocampal pyramidal cells.

Rudick CN, Gibbs RB, Woolley CS.

J Neurosci 23(11):4479-4490, 2003.

Estrogen plays a strong regulatory role in control of synaptic input to the hippocampus of female rats. Injection of 0.22 µg of 192-Saporin (Cat. #IT-01) directly into the medial septum eliminated NGFr-positive cholinergic neurons of the basal forebrain, producing evidence that estrogen-induced disinhibition is partially dependent on these neurons. GABAergic synapses were also found to be involved in this system.

Breathing: Rhythmicity, Plasticity, Chemosensitivity.

Feldman JL, Mitchell GS, Nattie EE.

Annu Rev Neurosci 26:239-266, 2003.

Recent research has indicated that specific areas of the brain exert control over several aspects of breathing, such as rhythm generation, reaction to hypoxia, and regulation of carbon dioxide levels and pH. This review covers many of the latest advances, some of which utilize SP-SAP (Cat. #IT-07) and anti-SERT-SAP (Cat. #IT-23). The use of these targeted toxins allows altered breathing behavior through elimination of very specific cell populations.

192 IgG-saporin lesions to the nucleus basalis magnocellularis (nBM) disrupt acquisition of learning set formation.

Bailey AM, Rudisill ML, Hoof EJ, Loving ML.

Brain Res 969(1-2):147-159, 2003.

Previous studies by Bailey and others have used quisqualic acid to lesion the nucleus basalis (nBM) in order to understand Alzheimer’s disease. Injections of 75 ng of 192-Saporin (Cat. #IT-01) were made into each of four sites in the rat nBM. Behavioral tests showed initial learning set deficits followed by recovery, whereas with quisqualic acid lesions, the deficits were profound. The authors conclude noncholinergic neurons are involved in learning set formation.

Distinct roles of P2X receptors in modulating glutamate release at different primary sensory synapses in rat spinal cord.

Nakatsuka T, Tsuzuki K, Ling JX, Sonobe H, Gu JG.

J Neurophysiol 89(6):3243-3252, 2003.

P2X receptors are important modulating neurons in the spinal cord. These authors used IB4-SAP (Cat. #IT-10) to target a neuronal subset, those neurons expressing P2X3 receptors. 2 µg of IB4-SAP were injected directly into the sciatic nerve on one side. Histological examination showed efficient removal of IB4 and P2X3-staining ipsilaterally in the dorsal horn outer laminae. Behavioral experiments showed intact modulation of glutamate release in the absence of P2X3-positive neurons, indicating involvement by other P2X neurons.

Effects of septal grafts on acetylcholine release from rat hippocampus after 192 IgG-saporin lesion.

Hilgert M, Hartmann J, Loffelholz K, Jeltsch H, Cassel JC, Klein J.

Neurochem Res 28(3-4):467-472, 2003.

A model for transplantation efficacy was created using injections of 400 ng each into the vertical limb of the rat diagonal band of Broca and the medial septum for the specific removal of cholinergic neurons. Thirteen months after lesioning, sham-operated animals had measured acetylcholine release at 20% of control. 192-Saporin (Cat. #IT-01)-lesioned animals were transplanted with fetal septal cells 15 days after lesioning. Thirteen months later, their septal level of acetylcholine release was near normal (71%) of controls. A serotonin uptake inhibitor briefly stimulated acetylcholine release similar to sham control animals.