targeted-toxins

Vera-Portocarrero LP, Zhang ET, King T, Ossipov MH, Vanderah TW, Lai J, Porreca F (2007) Spinal NK-1 receptor expressing neurons mediate opioid-induced hyperalgesia and antinociceptive tolerance via activation of descending pathways. Pain 129:35-45. doi: 10.1016/j.pain.2006.09.033

Summary: Administration of opioids can induce hyperalgesia in humans and other mammals. In this work the authors examined the role of NK-1 receptor-expressing neurons in the spinal dorsal horn during a hyperalgesic condition not induced by tissue injury. 5 µl of 10 µM SP-SAP (Cat. #IT-07) was injected into the intrathecal space of rats. Saporin (Cat. #PR-01) was used as a control. Osmotic pumps then delivered morphine. Data from the lesioned animals indicate that NK-1 receptor-expressing neurons play a critical role in this hyperalgesic circuit.

Related Products: SP-SAP (Cat. #IT-07), Saporin (Cat. #PR-01)

Abdala AP, Schoorlemmer GH, Colombari E (2006) Ablation of NK(1) receptor bearing neurons in the nucleus of the solitary tract blunts cardiovascular reflexes in awake rats. Brain Res 1119(1):165-173. doi: 10.1016/j.brainres.2006.08.059

Summary: Cardiovascular function is largely controlled by the nucleus of the tractus solitarius (NTS). This work focuses on the baroreflex, cardiopulmonary chemoreflex, and arterial chemoreflex. Rats were injected with either 20 nl of 2 µM SP-SAP (Cat. #IT-07) into the subpostremal NTS, or 200 nl into the subpostremal and commissural NTS. Saporin (Cat. #PR-01) was used as a control. Using various testing methods it was established that NK-1 receptor-expressing neurons in the NTS are critical for these reflexes.

Related Products: SP-SAP (Cat. #IT-07), Saporin (Cat. #PR-01)

Milstein JA, Lehmann O, Theobald DE, Dalley JW, Robbins TW (2007) Selective depletion of cortical noradrenalin by anti-dopamine beta-hydroxylase-saporin impairs attentional function and enhances the effects of guanfacine in the rat. Psychopharmacology (Berl) 190(1):51-63. doi: 10.1007/s00213-006-0594-x

Summary: Building on previous work, the authors examined the effect of cortical noradrenalin depletion on a reaction time task. Rats received 0.2 µg-intracortical infusions of anti-DBH-SAP (Cat. #IT-03), then were trained in a reaction time task. The effect of guanfacine, a selective a-2 adrenergic agonist was also tested in these animals. Lesioned rats were not impaired on the baseline task, but were slower and less accurate during high rate conditions. Guanfacine only affected the lesioned animals.

Related Products: Anti-DBH-SAP (Cat. #IT-03)

Pedrino GR, Maurino I, de Almeida Colombari DS, Cravo SL (2006) Role of catecholaminergic neurons of the caudal ventrolateral medulla in cardiovascular responses induced by acute changes in circulating volume in rats. Exp Physiol 91(6):995-1005. doi: 10.1113/expphysiol.2006.034611

Summary: Catecholaminergic neurons in the caudal ventrolateral medulla (CVLM) are thought to help regulate body fluid homeostasis and cardiovascular response due to changes in circulating volume. The authors injected 6.3 ng of anti-DBH-SAP (Cat. #IT-03) into the CVLM of rats, and measured several physiological parameters following an injection of hypertonic or isotonic saline. Data from the lesioned rats indicate that catecholaminergic neurons mediate the cardiovascular response to volume expansion or increases in sodium levels.

Related Products: Anti-DBH-SAP (Cat. #IT-03)

Kalinchuk AV, Porkka-Heiskanen T, McCarley RW (2006) Basal forebrain and saporin cholinergic lesions: the devil dwells in delivery details. Sleep 29:1385-1389. doi: 10.1093/sleep/29.11.1385

Summary: The authors of this commentary discuss results presented by Blanco-Centurion et al. The topic is the role of adenosine in the basal forebrain in the control of sleep homeostasis. Discussion covers the potential differences found when 192-IgG-SAP (Cat. #IT-01) is administered locally as compared to an intracerebroventricular injection.

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

See Also:

• Blanco-Centurion C et al. Adenosine and sleep homeostasis in the basal forebrain. J Neurosci 26(31):8092-8100, 2006.

Garcia-Alloza M, Zaldua N, Diez-Ariza M, Marcos B, Lasheras B, Javier Gil-Bea F, Ramirez MJ (2006) Effect of selective cholinergic denervation on the serotonergic system: implications for learning and memory. J Neuropathol Exp Neurol 65(11):1074-1081. doi: 10.1097/01.jnen.0000240469.20167.89

Summary: The authors compared two lesioning methods using 192-Saporin (Cat. #IT-01) to examine the role of the serotonergic system in learning and memory. 0.067 µg of conjugate administered to each hemisphere of the nucleus basalis of Meynert reduced cholinergic markers in the frontal cortex. 1 µg of conjugate administered to the ventricle of each hemisphere reduced cholinergic markers in the frontal cortex and hippocampus. Both models reduced serotonin levels in the frontal cortex, but only the ICV injections modified learning.

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

Banihashemi L, Rinaman L (2006) Noradrenergic inputs to the bed nucleus of the stria terminalis and paraventricular nucleus of the hypothalamus underlie hypothalamic-pituitary-adrenal axis but not hypophagic or conditioned avoidance responses to systemic yohimbine. J Neurosci 26(44):11442-11453. doi: 10.1523/JNEUROSCI.3561-06.2006

Summary: Yohimbine (YO) is an a2 adrenoceptor antagonist that increases transmitter release from adrenergic/noradrenergic (NA) neurons. The authors investigated whether NA inputs to the bed nucleus of the stria terminalis (BNST) were required for YO effects. After receiving 11 ng of anti-DBH-SAP (Cat. #IT-03) in the left and right BNST, rats displayed a marked decrease in the hypothalamic-pituitary-adrenal axis in response to YO administration.

Related Products: Anti-DBH-SAP (Cat. #IT-03)

Willis CL, Ray DE, Marshall H, Elliot G, Evans JG, Kind CN (2006) Basal forebrain cholinergic lesions reduce heat shock protein 72 response but not pathology induced by the NMDA antagonist MK-801 in the rat cingulate cortex. Neurosci Lett 407(2):112-117. doi: 10.1016/j.neulet.2006.08.020

Summary: The NMDA receptor antagonist MK-801 may have use in establishing a model for schizophrenia. The mechanism by which cortical neurons are damaged by these antagonists is unknown. The authors tested the theory that cholinergic hyperstimulation of cingulate neurons is involved by administering 80 ng of 192-Saporin (Cat. #IT-01) unilaterally to rats. The results indicate that although cholinergic neurons are involved in the heat shock response to MK-801, the pathological effects follow a different pathway.

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

Failor SW, Evans MM, Cang J, Stryker MP, McQuillen PS (2006) Impaired cortical plasticity after early hypoxia–ischemia. Neuroscience 2006 Abstracts 717.14. Society for Neuroscience, Atlanta, GA.

Summary: Background: Unique forms of structural plasticity occur in sensory cortex during critical periods in the developing brain. Recovery from neonatal hypoxic-ischemic brain injury may involve plasticity mechanisms. Objective: To investigate the effect of hypoxic-ischemic injury on plasticity, we examined quantifiable forms of use-dependent structural thalamocortical plasticity in somatosensory and visual cortex following early cerebral hypoxia-ischemia (HI) within a rodent model. Methods: Plasticity in primary somatosensory cortex (S1) was induced by lesion of whisker pad row C on selective days during the first postnatal week with or without preceding hypoxia-ischemia (HI, Vannucci model). The whisker barrel map was visualized with cytochrome oxidase staining and 5-HT immunohistochemistry and quantified by measuring the ratio of D-row to C-row areas in tangential sections. Plasticity in primary visual cortex (V1) was induced by 4-day monocular deprivation (MD) beginning at postnatal day (PND) 28. Ocular dominance was quantified using intrinsic signal optical imaging and expressed as an index of the response to right or left eye stimulation, with or without MD and/or preceding early HI. Changes in markers of inhibitory neurons, extracellular matrix and myelin-associated molecules following HI are correlated with plasticity measurements. Results: S1 plasticity following neonatal HI is attenuated throughout the critical period (PND 1-3). S1 plasticity is significantly decreased (P<0.01, all ages) by an average of 66%. HI does not affect timing of the critical period for S1 plasticity. Following MD, the ocular dominance index (ODI) decreases from 0.14 +/- 0.12 (mean +/- SD, n=9) to -0.16 +/- 0.18 (n=5). Following neonatal HI, this ODI shift is attenuated (n=2). Similar respective effects following MD are observed using a selective immunotoxin (192-saporin) to destroy subplate neurons underlying visual cortex (n=6). Conclusions: Neonatal cerebral hypoxia-ischemia impairs structural plasticity in primary somatosensory and visual cortex. Similar results following selective immunoablation of subplate neurons, taken together with prior observations of selective subplate neuron death following neonatal HI, suggests a role for subplate neurons in structural plasticity during critical periods in sensory cortex.

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

Hernandez-Martinez H, Arias-Carrion O, Drucker-Colin R, Murillo-Rodriguez E (2006) Transplant of hypocretin neurons into the lateral hypothalamus of rats with lesions of the hypocretin neurons. Neuroscience 2006 Abstracts 719.2. Society for Neuroscience, Atlanta, GA.

Summary: Narcolepsy, a disabling neurological disorder is characterized by excessive daytime sleepiness, sleeps attacks, sleep fragmentation, and cataplexy. This sleep disorder has been linked to a loss of neurons containing the neuropeptide hypocretin (HCRT). Our group has developed an experimental model to induce narcolepsy in rats. The bilateral administration of the neurotoxin hypocretin-2-saporin (HCRT2-SAP) into the lateral hypothalamus (LH) of rats destroys the HCRT neurons. Therefore, the loss of HCRT neurons leads to developing narcolepsy. In order to replace the HCRT lost neurons by HCRT2-SAP, a suspension of cells from the posterior hypothalamus of 3-5 days old rat pups were stained with GFP and injected into the LH of lesioned rats. Animals were sacrificed 21 days after transplant, and cryostat-cut coronal sections of the LH sections were examined for presence of HCRT-immunofluorescence neurons. Preliminary data shows that HCRT transplanted neurons into the LH of lesioned rats were present at the target area 21 days after implant. These somata were similar in size and appearance to adult rat HCRT-immunoreactive neurons. Our results indicate that HCRT neurons obtained from rat pups can be grafted into a host brain and graft survives during 21 days. Importantly, our study addresses the possibility to replace HCRT neurons in narcolepsy in order to reverse this disease.

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