References

Kanju PM, Sims CM, Parameshwaran K, Huggins K, Josephson EM, Suppiramaniam V (2005) Medial-septal cholinergic denervation leads to synaptic glutamatergic dysfunction in hippocampus. Neuroscience 2005 Abstracts 157.2. Society for Neuroscience, Washington, DC.

Summary: Accumulating evidences support the role of septohippocampal cholinergic projections in learning and memory mechanisms. Hence, a complete and selective destruction of the septal cholinergic neurons projecting to the hippocampus by immunotoxin 192 IgG-saporin results in memory impairment. Alterations in glutamate receptor (NMDA & AMPA receptors) binding properties have also been reported following septohippocampal cholinergic denervation. A decrease in NMDA binding and an increase or no change in AMPA binding was observed seven days after lesioning. Therefore, it is important to study the effects of cholinergic lesioning on functional properties of glutamate receptors. This study investigated the electrophysiological properties of AMPA and NMDA receptors 4 to 6 days after medial septal lesioning. Selective medial-septal lesioning was performed in rats with the immunotoxin 192-IgG saporin. Whole cell recording of mEPSC and sEPSC were performed in CA1 hippocampal region in slices from lesioned and sham lesioned animals. The single channel recordings of synaptosomes isolated from hippocampi of these animal groups incorporated into lipid bilayer were also performed. Our results indicate a reduction in the frequency and amplitude of AMPA and NMDA mediated mEPSCs and sEPSCs of animals lesioned with 192-IgG saporin. Furthermore, single channel recording of isolated synaptosomes demonstrate a reduction in channel open probability (30-50% for AMPA & 20-32% for NMDA receptors), and conductance (35-46% AMPA & 28-39% for NMDA receptors). Collectively, our results indicate that synaptic AMPA and NMDA receptor functions are altered 4-6 days following medial septal lesioning.

Related Products: 192-IgG-SAP (Cat. #IT-01)

Gerashchenko D, Murillo-Rodriguez E, Blanco-Centurion C, Lin L, Nishino S, Mignot E, Shiromani PJ (2005) Adenosine levels do not increase with 6 h waking in rats with lesions of the lateral hypothalamus. Neuroscience 2005 Abstracts 63.9. Society for Neuroscience, Washington, DC.

Summary: The hypocretin neurons in the lateral hypothalamus (LH) have been implicated in wakefulness, but it is not clear which projection is responsible for the arousal. One possibility is that the LH neurons induce wakefulness by driving the basal forebrain (BF) wake-active neurons (Gerashchenko and Shiromani, Cellular & Molec Neurosci, 29: 41, 2004). Here we measure adenosine (AD) levels in the BF as a marker of arousal and test the LH-BF circuit in Sprague-Dawley rats with lesions of the LH induced by hypocretin-2-saporin. 64 days after lesions the rats were kept awake (gentle handling) for six hours (ZT 3-9) and microdialysis samples (5ul) were collected hourly for 9 hours (24h after probe stabilization). AD levels were assessed using HPLC. Hypocretin-saporin ablated 95% of the hypocretin neurons and reduced CSF hypocretin levels (-75% versus control). AD levels increased with 6h waking in saline control rats (n=9), consistent with previous studies in cats (Strecker et al., Behav Brain Res 115: 183, 2000) and rats (Murillo-Rodriguez et al., Neuroscience 123: 361, 2004). However, in rats with LH lesions (n=5) such an increase with waking did not occur. Sleep drive was measured by conducting a rodent version of a multiple sleep latency test (MSLT). In this test, conducted over 10h (from ZT2-ZT12) the rats were kept awake for 20min and then allowed 20min to sleep. The lesioned rats had more sleep during the 20min sleep periods indicating a higher sleep drive. These results suggest that in narcolepsy when the HCRT LH neurons die, there is a loss of stimulation of the wake-active BF neurons and the decline in this pathway may be the cause of the increased sleep attacks. Supported by VA Medical Research and NIH

Related Products: Orexin-B-SAP (Cat. #IT-20)

Gerashchenko D, Blanco-Centurion CA, Miller JD, Shiromani PJ (2006) Insomnia following hypocretin2-saporin lesions of the substantia nigra. Neuroscience 137(1):29-36. doi: 10.1016/j.neuroscience.2005.08.088

Objective: To investigate which regions of major arousal areas might be responsible for the changes in sleep-wake architecture

Summary: It is known that orexin (also known as hypocretin) is involved in waking. The results suggest that motor activity is under inhibitory control of the substantia nigra.

Usage: Bilateral injection of Orexin-SAP (92 and 184 ng/ml, 0.25 ml in the ventral tegmental area and 0.5 ml in the substantia nigra) of rats induced insomnia, as well as hyperactivity and stereotypic movements.

Related Products: Orexin-B-SAP (Cat. #IT-20)

Mattsson A, Lindqvist E, Ogren SO, Olson L (2005) Increased phencyclidine-induced hyperactivity following cortical cholinergic denervation. Neuroreport 16(16):1815-1819. doi: 10.1097/01.wnr.0000185018.29316.87

Summary: A potential contribution to schizophrenia is altered cholinergic function. The authors investigated how lesioning cholinergic corticopetal projections might affect glutaminergic activity. Rats were injected with 0.134 µg of 192-IgG-SAP (Cat. #IT-01) into the nucleus basalis magnocellularis. The authors found that cholinergic lesioning of the neocortex led to enhanced sensitivity to phencyclidine, which has been shown to induce clinical symptoms similar to those of schizophrenia. These data suggest that glutaminergic dysfunction may be relevant to schizophrenia pathophysiology.

Related Products: 192-IgG-SAP (Cat. #IT-01)

Kim DM, Ahn CW, Kim KR, Hong SW, Nam MS, Cha BS, Lim SK, Lee HC, Lee EJ (2005) Duodenal somatostatinoma associated with diabetic ketoacidosis presumably caused by somatostatin-28 hypersecretion. J Clin Endocrinol Metab 90(11):6310-6315. doi: 10.1210/jc.2004-1904 PMID: 16105971

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Pang K, Smith H (2005) Featured Article: Effects of intraseptal orexin-saporin on spatial memory. Targeting Trends 6(4)

Related Products: Orexin-B-SAP (Cat. #IT-20)

Read the featured article in Targeting Trends.

See Also:

• Smith HR et al. Orexin-saporin lesions of the medial septum impair spatial memory. Neuroscience 132(2):261-271, 2005.

Thinschmidt JS, Frazier CJ, King MA, Meyer EM, Papke RL (2005) Septal innervation regulates the function of alpha7 nicotinic receptors in CA1 hippocampal interneurons. Exp Neurol 195(2):342-352. doi: 10.1016/j.expneurol.2005.05.006

Summary: The authors examined whether hippocampal innervation by medial septum/diagonal band of Broca projections is necessary for normal a7 receptor function. 1 µg of 192-Saporin (Cat. #IT-01) was injected into the medial septum of rats. Various methods, including whole-cell patch clamping and immunohistochemistry, were used to evaluate the effects of these lesions. Lesioning with 192-Saporin did not affect a7 receptor currents, indicating that cholinergic neurons are not linked to a7 function.

Related Products: 192-IgG-SAP (Cat. #IT-01)

Kremer BE, Haystead T, Macara IG (2005) Mammalian septins regulate microtubule stability through interaction with the microtubule-binding protein MAP4. Mol Biol Cell 16(10):4648-4659. doi: 10.1091/mbc.e05-03-0267 PMID: 16093351

Related Products: Antibody to Septin-6 (9E7) (Cat. #AB-V87)

Suzuki R, Rahman W, Rygh LJ, Webber M, Hunt SP, Dickenson AH (2005) Spinal-supraspinal serotonergic circuits regulating neuropathic pain and its treatment with gabapentin. Pain 117(3):292-303. doi: 10.1016/j.pain.2005.06.015

Summary: The anticonvulsant, gabapentin, is thought to modulate calcium channel function. In animals, it also affects abnormal pain function. 10 µl of 1 µM SP-SAP (Cat. #IT-07) was injected into the subarachnoid space of rats. It was found that the effects of gabapentin were blocked when NK-1r expressing neurons in the dorsal horn were eliminated. The results suggest that not only is the NK-1r pathway a determinant of neuronal and behavioral manifestations of neuropathy, it is also involved in the action of gabapentin.

Related Products: SP-SAP (Cat. #IT-07)

Vago R, Marsden CJ, Lord JM, Ippoliti R, Flavell DJ, Flavell SU, Ceriotti A, Fabbrini MS (2005) Saporin and ricin A chain follow different intracellular routes to enter the cytosol of intoxicated cells. FEBS J 272(19):4983-4995. doi: 10.1111/j.1742-4658.2005.04908.x

Summary: Some bacterial toxins such as Pseudomonas aeruginosa exotoxin A carry a KDEL-like C-terminal peptide sequence, which targets the protein to the endoplasmic reticulum. Saporin (Cat. #PR-01) is a plant ribosome-inactivating protein, which does not contain a KDEL-like sequence. Here the authors examined the intracellular pathways utilized by saporin. Although ricin, another plant ribosome-inactivating protein, could be visualized in the Golgi complex, saporin was not. The data suggest that saporin may utilize endosomes during its journey through the cell.

Related Products: Saporin (Cat. #PR-01)