Targeting Topics 07q3

Cholinergic modulation of spindle bursts in the neonatal rat visual cortex in vivo

Hanganu IL, Staiger JF, Ben-Ari Y, Khazipov R

J Neurosci 27(21):5694-5705, 2007.

The authors investigated the relationship between cholinergic drive and spindle burst oscillation driven by retinal waves. 0.5 µl of 0.2-µg/µl 192-IgG-SAP (Cat. #IT-01) was injected into both ventricles of rat pups. The lesioned animals displayed markedly decreased oscillatory activity. Since this activity may be used as a functional template for cortical networks and architecture, the results suggest a link between cholinergic activity and cortical development.

Anticonvulsant effects of damage to structures involved in seizure induction in rats exposed to soman

Myhrer T, Enger S, Aas P

Neurotoxicology 28(4):819-828, 2007.

Soman is a nerve agent that irreversibly inhibits acetylcholinesterase, resulting in respiratory dysfunction, seizures, convulsions, coma, and death. In this work the authors investigated whether elimination of cholinergic pathways in the medial septum (MS) or diagonal band nucleus (DBN) would affect the onset of convulsions. 0.3 µl of 0.5-µg/µl 192-IgG-SAP (Cat. #IT-01) was infused into the MS and/or DBN. Leisoned animals still experienced convulsions, suggesting that cholinergic MS systems are not the only ones involved.

Superficial NK1 expressing spinal dorsal horn neurones modulate inhibitory neurotransmission mediated by spinal GABA(A) receptors

Rahman W, Sikander S, Suzuki R, Hunt SP, Dickenson AH

Neurosci Lett 419(3):278-283, 2007.

It has been shown that elimination of lamina 1 NK1 receptor-expressing neurons affects pain behaviors. The authors investigated whether eliminating these neurons would alter GABAergic spinal inhibitory systems. Rats received 10-µl injections of 10-µM SP-SAP (Cat. #IT-07) into the L4-5 regions. Data generated by electrical and mechanical stimuli suggest that although GABAergic transmission is dependent on NK1 receptor-expressing neurons, loss of these cells results in a decrease in spinal cord excitability.

Cholinergic lesions produce task-selective effects on delayed matching to position and configural association learning related to response pattern and strategy

Gibbs RB, Johnson DA

Neurobiol Learn Mem 88(1):19-32, 2007.

It has been well established that the cholinergic system of the basal forebrain plays a critical role in many cognitive processes. This work utilized injections of 192-IgG-SAP (Cat. #IT-01) into the medial septum, the nucleus basalis magnocellularis, or both to examine the lesioning effect on two cognitive tasks in rats. The data indicate that cholinergic lesions of the basal forebrain produce learning deficits that are task specific, and that learning is affected without corresponding deficits in memory.

Anti-nociceptive effects of selectively destroying substance P receptor-expressing dorsal horn neurons using [Sar9,Met(O2)11]-substance P-saporin: Behavioral and anatomical analyses

Wiley RG, Kline RHt, Vierck CJ, Jr.

Neuroscience 146(3):1333-1345, 2007.

While lumbar injections of SP-SAP (Cat. #IT-07) produce specific lesions, use of this targeted conjugate in the forebrain has been problematic. The authors investigated the use of SSP-SAP (Cat. #IT-11), a conjugate of saporin with a stable analog of substance P. The greater stability of SSP-SAP resulted in increased potency as well as better specificity. SSP-SAP is shown to be a highly effective reagent for the removal of NK1 receptor-expressing neurons in the brain and spinal cord.

Olfactory neophobia and seizure susceptibility phenotypes in an animal model of epilepsy are normalized by impairment of brain corticotropin releasing factor

Pascual J, Heinrichs SC

Epilepsia 48(4):827-833, 2007.

Olfactory recognition has been linked to epilepsy in behavioral phenotype models. This work examines the role brain stress neuropeptides play in the manifestation of neurological perturbations. Mice were injected with 2 µg/5 µl of CRF-SAP (Cat. #IT-13) into the lateral ventricle. Saporin (Cat. #PR-01) was used as a control. The lesioned mice displayed a temporary reduction in seizure susceptibility, and the reversal of olfactory deficits towards the detection of food.

Specificity and generality of the involvement of catecholaminergic afferents in hypothalamic responses to immune insults

Schiltz JC, Sawchenko PE

J Comp Neurol 502(3):455-467, 2007.

Interleukin-1 (IL-1) is one of the cytokines that mediates interactions between the immune system and the central nervous system. 380-ng injections of anti-DBH-SAP (Cat. #IT-03) were made into the paraventricular nucleus (PVH) of rats. Saporin (Cat. #PR-01) and mouse IgG-SAP (Cat. #IT-18) were used as controls. Lesioned animals demonstrated reduced responses to administration of IL-1, but restraint stress responses were left intact. The data suggest that ascending catecholaminergic projections mediate PVH response to IL-1.

Immunotoxic cholinergic lesions in the basal forebrain reverse the effects of entorhinal cortex lesions on conditioned odor aversion in the rat

Ferry B, Herbeaux K, Cosquer B, Traissard N, Galani R, Cassel JC

Neurobiol Learn Mem 88(1):114-126, 2007.

The entorhinal cortex (EC) is intimately involved in olfactory learning. Lesioning of this structure produces septo-cholinergic sprouting. Rats that had previously received EC lesions were treated with 5-µg intracerebroventricular injections of 192-IgG-SAP (Cat. #IT-01). The results point to a role for hippocampal cholinergic neurons in the modulation of memory processes involved with conditioned odor aversion.

Selective deletion of antigen-specific CD8+ T cells by MHC class I tetramers coupled to the type I ribosome-inactivating protein saporin

Hess PR, Barnes C, Woolard MD, Johnson MD, Cullen JM, Collins EJ, Frelinger JA

Blood 109(8):3300-3307, 2007.

Autoreactive T cells are involved in autoimmune diseases such as type 1 diabetes and multiple sclerosis. It is thought that selective depletion of pathogenic cytotoxic T lymphocytes would be an effective treatment. The authors coupled biotinylated major histocompatibility complex tetramers to streptavidin-ZAP (Cat. #IT-27) and were able to eliminate specific T-cells both in vitro and in vivo‚ while leaving control T-cells intact. This technique may prove to be a useful therapy for immune-mediated diseases.

Spinal NK-1 receptor expressing neurons mediate opioid-induced hyperalgesia and antinociceptive tolerance via activation of descending pathways

Vera-Portocarrero LP, Zhang ET, King T, Ossipov MH, Vanderah TW, Lai J, Porreca F

Pain 129(1-2):35-45, 2007.

Although used for treatment of pain, opioids can induce hyperalgesia. In this work the authors evaluated the role that NK-1 receptor-expressing neurons play in morphine-induced hyperalgesia and spinal antinociceptive tolerance. Rats received a 5-µl intrathecal injection of 10 µM SP-SAP (Cat. #IT-07). Saporin (Cat. #PR-01) was used as a control. The results indicate that NK-1 receptor-expressing neurons play a critical role in morphine-induced neuroplastic changes.

Scavenger receptor-A-targeted leukocyte depletion inhibits peritoneal ovarian tumor progression

Bak SP, Walters JJ, Takeya M, Conejo-Garcia JR, Berwin BL

Cancer Res 67(10):4783-4789, 2007.

Vascular leukocytes (VLC) are immunosuppressive cells that facilitate tumor progression in ovarian cancer. One potential tumor therapy is to eliminate these cells. The authors determined that scavenger receptor-A is specifically expressed on VLCs. Mice were injected with tumor cells, as well as an anti-scavenger receptor-A antibody combined with Rat-ZAP (Cat. #IT-26). This was followed by additional treatment with the antibody-Rat-ZAP complex. Treatment with the immunotoxin eliminated VLCs, inhibited peritoneal tumor burden, and reduced ascites accumulation.

Combined damage to entorhinal cortex and cholinergic basal forebrain neurons, two early neurodegenerative features accompanying Alzheimer’s disease: effects on locomotor activity and memory functions in rats

Traissard N, Herbeaux K, Cosquer B, Jeltsch H, Ferry B, Galani R, Pernon A, Majchrzak M, Cassel JC

Neuropsychopharmacology 32(4):851-871, 2007.

Cognitive decline in Alzheimer’s disease is linked with the cholinergic system of the basal forebrain (BF), but damage is also found in the entorhinal cortex (EC). This work describes the use of 192-IgG-SAP (Cat. #IT-01) and L-N-methyl-D-aspartate to eliminate neurons in the BF and EC. 5 µg of 192-IgG-SAP was injected into the ventricle of rats. OX7-SAP (Cat. #IT-02) was used as a control. The combination of BF and EC lesions resulted in larger permanent deficits in learning and memory than either lesion alone.

Effect of the destruction of cells containing the serotonin reuptake transporter on urethrogenital reflexes

Gravitt K, Marson L

J Sex Med 4(2):322-330, 2007.

Using the fact that the urethrogenital (UG) reflex is an autonomic and somatic response, the authors developed a model for ejaculatory-like reflexes. Anti-SERT-SAP (Cat. #IT-23) was bilaterally injected into the ventrolateral medulla of rats. 80 nl of a 1-µM solution removed inhibition of the UG reflex after acute spinal cord transection, while this reflex could not be evoked in control animals. The data suggest that SERT-expressing neurons in the ventral medulla are involved with the inhibition of UG reflex.