Targeting Topics 02q4

Unilateral lesions of the cholinergic basal forebrain and fornix in one hemisphere and inferior temporal cortex in the opposite hemisphere produce severe learning impairments in rhesus monkeys.

Easton A, Ridley RM, Baker HF, Gaffan D.

Cereb Cortex 12(7):729-736, 2002. PMID: 12050084

The authors used a combination of basal forebrain lesioning using ME20.4-SAP (Cat. #IT-15) and surgery to isolate the inferior temporal cortex and medial temporal cortex from cholinergic afferents in rhesus monkeys. Testing of the treated animals demonstrated severe impairments in learning visual scenes and object-reward associations.

Selective lesion of cholinergic neurons in the medial septum by 192 IgG-saporin impairs learning in a delayed matching to position T-maze paradigm.

Johnson DA, Zambon NJ, Gibbs RB.

Brain Res 943(1):132-141, 2002. PMID: 12088847

The authors investigated the effects of selective cholinergic depletion in the medial septum on a spatial memory (DMP) task. Direct infusion of 0.22 or 1.0 μg 192-Saporin (Cat. #IT-01) produced a near complete depletion of cholinesterase-positive neurons for either dose. The DMP task provides a sensitive behavioral assay for deficits in cholinergic projections.

Hippocampal brain-derived neurotrophic factor gene regulation by exercise and the medial septum.

Berchtold NC, Kesslak JP, Cotman CW.

J Neurosci Res 68(5):511-521, 2002. PMID: 12111841

Brain-derived neurotrophic factor (BDNF) enhances neuron function and plasticity. The authors lesioned rats with medial septal injections of 192-Saporin (Cat. #IT-01, 375 ng in 0.5 μl PBS) or OX7-SAP (Cat #IT- 02, 12.5 or 25 ng in 0.5 μl PBS). 192-Saporin affected the sedentary, but not exercise-induced levels of BDNF. OX7-SAP reduced levels in both groups in a dose-dependent manner.

Grafts of fetal septal cells after cholinergic immunotoxic denervation of the hippocampus: a functional dissociation between dorsal and ventral implantation sites.

Cassel JC, Gaurivaud M, Lazarus C, Bertrand F, Galani R, Jeltsch H.

Neuroscience 113(4):871-882, 2002. PMID: 12182893

The authors lesioned rats with intraseptal infusions of 0.8 μg 192- Saporin (Cat. #IT-01), then implanted fetal cells in either the dorsal or ventral hippocampus. Only grafts into the dorsal hippocampus counteracted the effect of cholinergic lesions on spatial working memory performance.

Inhibition of neuropathic pain by selective ablation of brainstem medullary cells expressing the mu-opioid receptor.

Porreca F, Burgess SE, Gardell LR, Vanderah TW, Malan TPJ, Ossipov MH, Lappi DA, Lai J.

J Neurosci 21(14):5281-5288, 2001. PMID: 11438603

The presence of descending projections in the pain pathway raises the possibility that abnormal sustained activity may perpetuate chronic pain. Using 3-pmol injections of dermorphin-SAP (Cat. #IT-12) on either side of the RVM in rats the authors both prevented and reversed neuropathic pain caused by spinal nerve ligation.

Identification of a potential ejaculation generator in the spinal cord.

Truitt WA, Coolen LM.

Science 297(5586):1566-1569, 2002. PMID: 12202834

The authors lesioned a specific population of rat spinothalamic neurons using 6-8 injections of 4 ng SSP-SAP (Cat. #IT-11). Whereas the treated rats exhibited no change in sexual behavior such as mounts and intromissions, ejaculatory behavior was completely abolished. The data suggest that this population of neurons may function as an ejaculation generator in the spinal cord.

Immunotoxic catecholamine lesions attenuate 2DG-induced increase of AGRP mRNA.

Fraley GS, Dinh TT, Ritter S.

Peptides 23(6):1093-1099, 2002. PMID: 12126736

The authors investigated mRNA levels of both agouti gene-related protein (AGRP) and neuropeptide Y (NPY) in rats after lesioning the PVH with (Anti-DBH-SAP (42 ng in 200 nl, Cat. #IT-03). The results show that the increase in AGRP mRNA levels due to 2DG administration was completely blocked.

Cholinergic depletion by IgG192-saporin retards development of rat barrel cortex.

Zhu XO, de Permentier PJ, Waite PM.

Brain Res Dev Brain Res 136(1):1-16, 2002. PMID: 12036512

It has been shown that cholinergic afferents from the basal forebrain are necessary for normal cortical morphogenesis. However, the role of these projections in the development of the thalamocortical topographical map has not been investigated. Using the facial whisker barrel field in the rat somatosensory cortex as a development model, the authors administered 192-Saporin to newborn pups (0.1 μg, Cat. #IT-01). The data show a transient delay in the development of the barrel pattern over the first postnatal week.

Reduced aversion to oral capsaicin following neurotoxic destruction of superficial medullary neurons expressing NK-1 receptors.

Simons CT, Gogineni AG, Iodi Carstens M, Carstens E.

Brain Res 945(1):139-143, 2002. PMID: 12113962

Capsaicin-induced irritation of the dorsal anterior tongue is mediated by nociceptors expressing VR-1 receptors. The role of NK-1 receptor- expressing neurons during the ingestion of capsaicin was examined by injecting 20 μl of 2.27 μM SP- SAP (Cat. #IT-07) into the cisterna magna of rats. Lesioned rats consumed significantly more water containing high concentrations of capsaicin than control animals.

Spinal noradrenergic activation mediates allodynia reduction from an allosteric adenosine modulator in a rat model of neuropathic pain.

Li X, Conklin D, Ma W, Zhu X, Eisenach JC.

Pain 97(1-2):117-125, 2002. PMID: 12031785

T62 is a thiobene compound that enhances adenosine agonist binding to the A1 receptor. Activation of the adenosine receptor has been effective in several different pain models. The authors used a spinal nerve ligation model for mechanical allodynia to assess T62 efficacy and mode of action. Rats treated with anti-DBH- SAP (4 μg in 5 μl, Cat. #IT-03) experienced no anti-allodynia effects from T62 administration, indicating that modulation of mechanical allodynia by T62 utilizes the spinal noradrenergic system.

Effects of 192 IgG-saporin on acetylcholinesterase histochemistry in male and female rats.

Galani R, Jeltsch H, Lehmann O, Bertrand F, Cassel JC.

Brain Res Bull 58(2):179-186, 2002. PMID: 12127015

Male rats were treated with estradiol, and during the treatment performed 2μg i.c.v. injections of 192-Saporin (Cat. #IT-01).

Selective immunolesions of CH4 cholinergic neurons do not disrupt spatial memory in rats.

Galani R, Lehmann O, Bolmont T, Aloy E, Bertrand F, Lazarus C, Jeltsch H, Cassel JC.

Physiol Behav 76(1):75-90, 2002. PMID: 12175591

Rat NBM was lesioned using 0.2 or 0.4 μg of 192-Saporin (Cat. #IT-01).

Combined 192 IgG-saporin and 5,7-dihydroxytryptamine lesions in the male rat brain: a neurochemical and behavioral study.

Lehmann O, Jeltsch H, Lazarus C, Tritschler L, Bertrand F, Cassel JC.

Pharmacol Biochem Behav 72(4):899-912, 2002. PMID: 12062580

Injections of 1 μg per ventricle of 192-Saporin (Cat. #IT-01).