Targeting Topics 01q4

Focal inhibitory interneuron loss and principal cell hyperexcitability in the rat hippocampus after microinjection of a neurotoxic conjugate of saporin and a peptidase-resistant analog of Substance P.

Martin JL, Sloviter RS.

J Comp Neurol 436(2):127-152, 2001. PMID: 11438920

The authors used SSP-SAP (0.4 ng/10 nl; Cat. #IT-11). See Cover Story.

Selective cholinergic denervation inhibits expression of long-term potentiation in the adult but not infant rat hippocampus.

Motooka Y, Kondoh T, Nomura T, Tamaki N, Tozaki H, Kanno T, Nishizaki T.

Brain Res Dev Brain Res 129(1):119-123, 2001. PMID: 11454420

The authors studied the possible role of cholinergic systems in long-term potentiation (LTP), which is one of the most intensively studied models of learning and memory. 192-Saporin (4.2 μg/5 μl, Cat. #IT-01) injections were made in both infant and adult rats and the probability of LTP development was studied in hippocampal slices from animals treated 2 weeks or 2 months before. Cholinergic denervation by 192- Saporin did not affect LTP expression in the infant brain, however, the results strongly suggest that cholinergic systems in the adult brain participate in an LTP pathway.

Effects of hypocretin-saporin injections into the medial septum on sleep and hippocampal theta.

Gerashchenko D, Salin-Pascual R, Shiromani PJ.

Brain Res 913(1):106-115, 2001. PMID: 11532254

Hypocretin, also known as orexin, neurons are located only in the lateral hypothalamus. Recently, the loss of these neurons was shown to be associated with narcolepsy. The authors used orexin- SAP (100 ng/0.5 μl; Cat. #IT-20) to eliminate parvalbumin and cholinergic neurons (orexin B receptor-expressing) in the rat medial septum. They used 192- Saporin (1 μg/ 1 μl; Cat. #IT-01) to contrast the effect and eliminate only cholinergic neurons (NGF/p75 receptor- expressing). Hippocampal theta activity was completely eliminated in orexin- SAP treated rats by day 12, suggesting that orexin neurons influence cognitive processes critical for survival.

Transneuronal tracing from sympathectomized lumbar epaxial muscle in female rats.

Daniels D, Miselis RR, Flanagan-Cato LM.

J Neurobiol 48(4):278-290, 2001. PMID: 11500841

The authors use pseudorabies virus (PRV) to study central neural networks such as the one controlling the lordosis reflex (increased curvature of the spine). To aid in the separation of the sympathetic nervous system and higher order systems, rats were treated with lumbar injections of anti-DBH-SAP (156 ng to 5 μg; Cat. #IT-03), then labeled with PRV. PRV labeling in the brain was absent in areas associated with vasomotor tone, but persisted in areas implicated in control of the lordosis response.

Hippocampal sympathetic ingrowth occurs following 192-IgG-Saporin administration.

Harrell LE, Parsons D, Kolasa K.

Brain Res 911(2):158-162, 2001. PMID: 11511384

Electrolytic lesions of the medial septal region in rats cause peripheral sympathetic fibers from the superior cervical ganglia to grow into the cholinergically-denervated areas of the hippocampus. This lesioning method is non-specific and disrupts several other cell types in the area of the lesion. The authors infused 192-Saporin (1 μg/10 μl saline into medial septum; Cat. #IT-01) to eliminate only the cholinergic neurons, leaving other cell types intact. Hippocampal sympathetic ingrowth still occurs when only the cholinergic neurons are eliminated, indicating that this occurrence is in response to the loss of cholinergic projections from the medial septum.

Selective antibody-induced cholinergic cell and synapse loss produce sustained hippocampal and cortical hypometabolism with correlated cognitive deficits.

Browne SE, Lin L, Mattsson A, Georgievska B, Isacson O.

Exp Neurol 170(1):36-47, 2001. PMID: 11421582

The authors used 192-Saporin (two 2.5- μg bilateral injections of 1 μg/μl; Cat. #IT-01) to eliminate cholinergic neurons in the rat, then measured cerebral rates of glucose utilization. The findings show sustained reduction in glucose utilization in the brain regions showing loss of cholinergic neurons, specifically the frontal cortical and hippocampal regions. These same animals demonstrated impaired performance in a Morris water maze. The results reinforce the theory that cholinergic systems influence metabolism and cognition in the cortex and hippocampus.

Selective loss of cholinergic neurons projecting to the olfactory system increases perceptual generalization between similar, but not dissimilar, odorants.

Linster C, Garcia PA, Hasselmo ME, Baxter MG.

Behav Neurosci 115(4):826-833, 2001. PMID: 11508721

Selective cholinergic lesioning of the basal forebrain has been linked to attentional and cognitive deficits. 192-Saporin (Cat. #IT-01) was administered to the horizontal limb of the diagonal band of Broca (0.3 μl at 0.175 μg/μl in each hemisphere) destroying projections to the olfactory bulb and cortex. The results demonstrate cholinergic lesions affect the perceptual qualities of odors, and may possibly represent a general mechanism for cholinergic effects on information processing.

Contribution of the cholinergic basal forebrain to proactive interference from stored odor memories during associative learning in rats.

De Rosa E, Hasselmo ME, Baxter MG.

Behav Neurosci 115(2):314-327, 2001. PMID: 11345957

Proactive interference (PI) is the damaging effect of previously learned information on the acquisition of new, related information. Human patients with basal forebrain (BF) damage due to aneurysms are sensitive to PI. The authors administered 192-Saporin (Cat. #IT-01) to the horizontal limb of the diagonal band of Broca (two 0.2-μl injections of 0.175 μg/μl in each hemisphere) in rats and evaluated performance in an olfactory discrimination task. The treated rats had more difficulty acquiring an overlapping odor pair when muscarinic receptors were blocked by scopalomine. These results indicate that cholinergic neurons have a role in the modulation of PI in associative learning.

It’s enough to raise your blood pressure!

Deuchars J, Deuchars S.

Trends Neurosci 24(4):200, 2001. PMID: 11249993

The authors review studies completed by Schreihofer and Guyenet using anti- DBH-SAP (Cat. #IT-03) to eliminate C1 adrenergic neurons. The results show that, although C1 neurons play a role in some sympathoexcitatory responses, they are probably not responsible for maintaining sympathetic tone.

Effects of selective immunotoxic lesions on learning and memory.

Baxter MG.

Methods Mol Biol 166:249-265, 2001. PMID: 11217371

Dr. Baxter presents a brief review of studies using immunotoxins to study learning and memory. In particular, this chapter (from the book entitled “Immunotoxin Methods and Protocols”) focuses on the use of 192-Saporin (Cat. #IT-01) for elimination of basal forebrain cholinergic neurons and cerebellar Purkinje cells.

Distribution and co-localization of choline acetyltransferase and p75 neurotrophin receptors in the sheep basal forebrain: implications for the use of a specific cholinergic immunotoxin.

Ferreira G, Meurisse M, Tillet Y, Levy F.

Neuroscience 104(2):419-439, 2001. PMID: 11377845

ME20.4 is a monoclonal antibody (Cat. #AB-N07) that has been shown to bind the p75 receptor in rabbit, sheep, dog, cat, raccoon, pig, and several primate species. Ferreira et al. investigate ME20.4-SAP (bilateral, 150 μl per ventricle, 50-150 μg total; Cat. #IT-15) use in sheep to assess distribution and localization of p75. The authors demonstrate 80-95% loss of basal forebrain cholinergic neurons and acetylcholinesterase-positive fibers in the hippocampus, olfactory bulb, and entorhinal cortex.

Hypocretin-2-saporin lesions of the lateral hypothalamus produce narcoleptic-like sleep behavior in the rat.

Gerashchenko D, Kohls MD, Greco M, Waleh NS, Salin-Pascual R, Kilduff TS, Lappi DA, Shiromani PJ.

J Neurosci 21(18):7273-7283, 2001. PMID: 11549737

Orexin (also knows as hypocretin) peptides are produced exclusively by neurons in the lateral hypothalamus, however non-specific lesioning in this region has not produced narcoleptic-like sleep. Gerashchenko et al. use orexin- SAP (490 ng/0.5 μl; Cat. # IT-20) to specifically eliminate orexin neurons in rats. The treated rats displayed several sleep disturbances found in narcolepsy, including increased slow-wave sleep, and sleep-onset REM sleep periods. The data suggest that orexin-SAP can be used to create a model for narcolepsy in rats (see page 7, Featured Products).