targeted-toxins

Lappi DA, Wiley RG (2004) Immunotoxins and neuropeptide-toxin conjugates experimental applications. Mini Rev Med Chem 4(5):585-595. doi: 10.2174/1389557043403882

Summary: The use of targeted toxins in research is rich and varied; here the authors describe some of the exciting results that researchers have made in the neurosciences.

Blanco-Centurion C, Gerashchenko D, Salin-Pascual RJ, Shiromani PJ (2004) Effects of hypocretin2-saporin and antidopamine-beta-hydroxylase-saporin neurotoxic lesions of the dorsolateral pons on sleep and muscle tone. Eur J Neurosci 19(10):2741-2752. doi: 10.1111/j.0953-816X.2004.03366.x

Summary: Narcolepsy is linked to the loss of orexin (or hypocretin)-containing neurons in the brain. These neurons are located in the perifornical region of the posterior hypothalamus and innervate the locus coeruleus (LC). To investigate the role of the LC in sleep the authors injected 0.3 µl of 192-Saporin (Cat. IT-01) or anti-DBH-SAP (Cat. #IT-03) at 1 µg/µl. They also used 0.3 µl of orexin-SAP (Cat. #IT-20) at either 90 ng/µl or 60 ng/µl in a separate group of animals. The results indicate that orexin innervation to the pons plays a role in arousal from sleep.

Related Products: 192-IgG-SAP (Cat. #IT-01), Anti-DBH-SAP (Cat. #IT-03), Orexin-B-SAP (Cat. #IT-20)

Li AJ, Ritter S (2004) Glucoprivation increases expression of neuropeptide Y mRNA in hindbrain neurons that innervate the hypothalamus. Eur J Neurosci 19(8):2147-2154. doi: 10.1111/j.1460-9568.2004.03287.x

Summary: It is suspected that hypothalamic neuropeptide Y (NPY) innvervation of the hypothalamus contributes to glucoregulatory feeding. Along with mRNA studies, the authors injected 42 ng of anti-DBH-SAP (Cat. #IT-03) into the paraventricular nucleus. Elimination of the hindbrain catecholamine/NPY neurons abolished increases in NPY expression due to glucoprivic conditions. This response suggests that NPY hindbrain neurons play a role in glucoprivic feeding and other glucoregulatory responses.

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

Yezierski RP, Yu CG, Mantyh PW, Vierck CJ, Lappi DA (2004) Spinal neurons involved in the generation of at-level pain following spinal injury in the rat. Neurosci Lett 361(1-3):232-236. doi: 10.1016/j.neulet.2003.12.035

Summary: The elimination of substance P receptor-expressing neurons in lamina I of the spinal cord using SP-SAP (Cat. #IT-07) has been shown to reduce behavior associated with chronic pain. The authors investigated the effects of 150 or 300 ng SP-SAP treatment during or after intraspinal administration of quisqualic acid in rats. Both treatments resulted in a reduction of pain-associated behavior. These results demonstrate that pain following spinal cord injury involves a population of spinal neurons expressing the substance P receptor.

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

Jasmin L, Ohara PT (2004) Recurrent paraplegia after remyelination of the spinal cord. J Neurosci Res 77(2):277-284. doi: 10.1002/jnr.20143

Summary: Previously, the authors demonstrated that a 3 µg-injection of CTB-SAP (Cat. #IT-14) into the lumbosacral intrathecal space caused a loss of motor function due to spinal demyelination. The motor function was recovered and stable for up to 9 months, after which the rats exhibited a slow deterioration of motor function, loss of spinal white matter, and the appearance of calcium deposits. The results indicate that the CTB-SAP-induced demyelination model is useful for investigating long term effects of axon and motoneuron loss.

Related Products: CTB-SAP (Cat. #IT-14)

Mattsson A, Pernold K, Ogren SO, Olson L (2004) Loss of cortical acetylcholine enhances amphetamine-induced locomotor activity. Neuroscience 127(3):579-591. doi: 10.1016/j.neuroscience.2004.05.038

Summary: The authors have recently shown that cholinergic denervation of the basal forebrain in rats leads to an increased motor response to d-amphetamine, a hallmark of schizophrenia. In the present study 192-Saporin (Cat. #IT-01) was injected into the nucleus basalis magnocellularis or the medial septum/diagonal band of Broca, and OX7-SAP (Cat. #IT-02) was injected intracerebroventricularly. The dopaminergic hyper-reactivity was induced by lesions to the cortex cerebri, but not by damage to the cerebellum or hippocampus.

Related Products: 192-IgG-SAP (Cat. #IT-01), OX7-SAP (Cat. #IT-02)

Margeta M, Ohara PT, Bollen AW, Jasmin L (2004) Intrathecal application of saporin conjugates leads to development of pituitary adenomas in rats. J Neuropathol Exp Neurology 63(5):518.

Objective: To study the recovery from spinal cord demyelination or the effects of decreased central noradrenergic tone on pain behavior.

Summary: The spectrum of findings varied from small, sometimes multifocal nodules to large neoplasms that entirely replaced the normal gland and showed a significant degree of mitotic activity and nuclear pleomorphism. Development of this novel animal model will enable investigation of non-hormonal factors important in the pathogenesis of pituitary adenomas

Usage: Rats were injected intrathecally with CTB-SAP (IT-14) or to the anti-DBH-SAP (IT-03)

Related Products: CTB-SAP (Cat. #IT-14), Anti-DBH-SAP (Cat. #IT-03)

Rajakumar N, Leung LS, Ma J, Rajakumar B, Rushlow W (2004) Altered neurotrophin receptor function in the developing prefrontal cortex leads to adult-onset dopaminergic hyperresponsivity and impaired prepulse inhibition of acoustic startle. Biol Psychiatry 55(8):797-803. doi: 10.1016/j.biopsych.2003.12.015

Summary: Neurodevelopmental abnormalities are suspected to play a role in the pathogenesis of schizophrenia. The authors injected 0.75 µl of 192-Saporin (Cat. #IT-01) bilaterally into the prefrontal cortex of postnatal day 1 rats. The rats were then evaluated in tests designed to measure behavioral abnormalities relevant to schizophrenia. The behavior of the treated animals indicated that damage to p75-receptor-expressing neurons in the prefrontal cortex may be involved in the manifestation of schizophrenia.

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

Erhardt C, Galani R, Jeltsch H, Cassel JC, Klosen P, Menet JS, Pevet P, Challet E (2004) Modulation of photic resetting in rats by lesions of projections to the suprachiasmatic nuclei expressing p75 neurotrophin receptor. Eur J Neurosci 19(7):1773-1788. doi: 10.1111/j.1460-9568.2004.03281.x

Summary: The circadian clock in mammals is located within suprachiasmatic nuclei of the hypothalamus (SCN). The authors investigated how cholinergic afferents from the basal forebrain may be involved in control of the circadian clock. 3 µg of 192-Saporin (Cat. #IT-01) was injected intracerebroventricularly, or 1 µg was injected in SCN of rats, and various aspects of the circadian system were investigated. The data suggest that the forebrain cholinergic system is involved in the phase resetting properties of light.

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

Smith J (2004) Featured Article: 192 IgG-saporin-induced lesions identify an inhibitory role in cocaine reward for cholinergic neuronal systems in the diagonal band and ventral pallidum. Targeting Trends 5(2)

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

Read the featured article in Targeting Trends.

See Also:

• Smith JE et al. Involvement of cholinergic neuronal systems in intravenous cocaine self-administration. Neurosci Biobehav Rev 27(8):841-850, 2004.