Targeting Topics 04q1

Does the release of acetylcholine in septal slices originate from intrinsic cholinergic neurons bearing p75(NTR) receptors? A study using 192 IgG-saporin lesions in rats.

Birthelmer A, Lazaris A, Riegert C, Marques Pereira P, Koenig J, Jeltsch H, Jackisch R, Cassel JC.

Neuroscience 122(4):1059-1071, 2003.

The authors used 0.8 µg injections of 192-Saporin (Cat. #IT-01) into the medial septum and diagonal band of Broca to investigate whether release of acetylcholine was due to neurons expressing the p75 NTR.

Effects of hippocampal cholinergic deafferentation on learning strategy selection in a visible platform version of the water maze.

Bizon JL, Han JS, Hudon C, Gallagher M.

Hippocampus 13(6):676-684, 2003.

To investigate the effect of depleted acetylcholine (Ach) levels in the hippocampus on learning strategies that are thought to utilize the hippocampus, the authors lesioned the medial septum/vertical limb of the diagonal band of Broca in rats with two injections of 75 and 50 ng of 192-Saporin (Cat. #IT-01). The unexpected result was that a hippocampal place strategy was promoted in the absence of Ach.

Cytochrome oxidase activity in the monkey globus pallidus and subthalamic nucleus after ablation of striatal interneurons expressing substance P receptors.

Chiken S, Hatanaka N, Tokuno H.

Neurosci Lett 353(2):103-106, 2003.

1-6 µl of 15-20 ng/µl SP-SAP (Cat. #IT-07) was injected into the forelimb representation of the putamen. Animals were examined for the loss of interneurons as well as regional metabolic changes. The results indicate that substance P receptor-expressing neurons do not modulate inhibitory influences on the GP.

Early microglial activation following neonatal excitotoxic brain damage in mice: a potential target for neuroprotection.

Dommergues MA, Plaisant F, Verney C, Gressens P.

Neuroscience 121(3):619-628, 2003.

Brain lesions that mimic damage from cerebral palsy in mice are characterized by microglial activation within 24 hours of insult. Using intraperitoneal injections of Mac-1-SAP (90 µg/kg, Cat. #IT-06), a reduction in the density of resident microglial and blood-derived monocytes was obtained.

A combinatorial network of evolutionarily conserved myelin basic protein regulatory sequences confers distinct glial-specific phenotypes.

Farhadi HF, Lepage P, Forghani R, Friedman HC, Orfali W, Jasmin L, Miller W, Hudson TJ, Peterson AC.

J Neurosci 23(32):10214-10223, 2003.

The authors used intrathecal injections of 0.3 µg CTB-SAP (Cat. #IT-14) to induce spinal cord demyelination for the purpose of defining the regulatory network controlling myelin basic protein transcription in mice.

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.

Previous work has demonstrated that mice lacking the neurokinin-1 receptor do not show some of the behaviors associated with morphine reward. Bilateral 1.0-µl injections of 1.0 µM SP-SAP (Cat. #IT-07) were made into either the nucleus accumbens or the amygdala of mice. Animals with lesions of the amygdala displayed a reduction of morphine reward behavior and an increase in anxiety-like behavior in an elevated maze test.

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 investigate whether the effects of nerve injury-induced afferent discharge and central changes associated with experimental neuropathic pain might intersect at the spinal level. 1.5 pmol of dermorphin-SAP (Cat. #IT-12) was injected into each side of the rostral ventromedial medulla of rats. The data indicate that increased afferent input is a driving force of neuropathic pain, and that some aspects of nerve injury-induced hyperesthesias may occur through the convergence of descending modulation, spinal plasticity, and afferent drive.

Differential effects of cholinergic lesions on dendritic spines in frontal cortex of young adult and aging rats.

Harmon KM, Wellman CL.

Brain Res 992(1):60-68, 2003.

The authors used 0.15 µg of 192-Saporin (Cat. #IT-01) injected into the nucleus basalis magnocellularis of rats to study whether dendritic spine density is altered by cholinergic deafferentation. While the spine density decreased in young rats, middle-aged and aged animals did not display a density significantly different than controls.

Immunotoxic destruction of distinct catecholaminergic neuron populations disrupts the reproductive response to glucoprivation in female rats.

I’Anson H, Sundling LA, Roland SM, Ritter S.

Endocrinology 144(10):4325-4331, 2003.

The authors hypothesized that hindbrain catcholamine neurons suppressed estrous cycles during chronic glucoprivation as an extension of their role in glucoprivic feeding. 42-ng bilateral injections of anti-DBH-SAP (Cat. #IT-03) were made into the paraventricular nucleus of female rats. Lesioned rats demonstrated inhibition of reproductive function during chronic glucose deficit, but not when a normal amount of glucose was available.

Macrophage-derived IL-18 targeting for the treatment of Crohn’s disease.

Kanai T, Uraushihara K, Totsuka T, Okazawa A, Hibi T, Oshima S, Miyata T, Nakamura T, Watanabe M.

Curr Drug Targets Inflamm Allergy 2(2):131-136, 2003.

A single intravenous injection of Mac-1-SAP (Cat. #IT-06) significantly reduced the amount of intestinal inflammation in a 2, 4, 6-trinitrobenzene sulfonic acid-induced colitis model.

Cholinergic activity enhances hippocampal long-term potentiation in CA1 during walking in rats.

Leung LS, Shen B, Rajakumar N, Ma J.

J Neurosci 23(28):9297-9304, 2003.

To investigate the role of the cholinergic system in long term potentiation (LTP) the authors lesioned the left and right medial septum of rats with 0.14 µg of 192-Saporin (Cat. #IT-01). LTP induced in lesioned walking animals is less robust than in control animals.

Rostral ventrolateral medulla C1 neurons and cardiovascular regulation.

Madden CJ, Sved AF.

Cell Mol Neurobiol 23(4-5):739-749, 2003.

The authors review the use of anti-DBH-SAP (Cat. #IT-03) to study the role of C1 neurons within the rostral ventromedial medulla in cardiovascular regulation. This immunotoxin specifically removes C1 neurons containing dopamine beta-hydroxylase.

Hindbrain noradrenergic lesions attenuate anorexia and alter central cFos expression in rats after gastric viscerosensory stimulation.

Rinaman L.

J Neurosci 23(31):10084-10092, 2003.

Using 5-ng injections of anti-DBH-SAP (Cat. #IT-03) into hindbrain nucleus of the solitary tract in rats, the author investigated the role of DBH-positive neurons in the mediation of anorexigenic and central nervous system activation effects due to exogenous CCK.

Neonatal cholinergic lesions and development of exploration upon administration of the GABAa receptor agonist muscimol in preweaning rats.

Scattoni ML, Calamandrei G, Ricceri L.

Pharmacol Biochem Behav 76(2):213-221, 2003.

The authors investigated GABAergic development in young rats lesioned with two 0.42-ng injections of 192-Saporin (Cat. #IT-01) into the third ventricle. The rats were then treated with the GABA agonist muscimol chloride and observed during locomotor and exploration tests. No change was noted in GABAergic agonist reactivity in lesioned animals.

Changes in cortical acetyl-CoA metabolism after selective basal forebrain cholinergic degeneration by 192IgG-saporin.

Tomaszewicz M, Rossner S, Schliebs R, Cwikowska J, Szutowicz A.

J Neurochem 87(2):318-324, 2003.

Alzheimer’s disease subjects often show deficits in cerebral glucose metabolism. To investigate whether cortical cholinergic input affects acetyl-CoA metabolism in cholinoceptive cortical target regions, rats received 4 µg 192-Saporin (Cat. #IT-01) into the left lateral ventricle. The data show evidence of differential distribution of acetyl-CoA in subcellular compartments of cholinergic and non-cholinergic nerve terminals.

Destruction of midbrain dopaminergic neurons by using immunotoxin to dopamine transporter.

Wiley RG, Harrison MB, Levey AI, Lappi DA.

Cell Mol Neurobiol 23(4-5):839-850, 2003.

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.