2004 Targeting Trends Review

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.

Winters BD, Dunnett SB (2004) Selective lesioning of the cholinergic septo-hippocampal pathway does not disrupt spatial short-term memory: a comparison with the effects of fimbria-fornix lesions. Behav Neurosci 118(3):546-562. doi: 10.1037/0735-7044.118.3.546

Summary: The authors wished to investigate the role of the cholinergic system of the basal forebrain in delayed matching (DMTP)- and nonmatching (DNMTP)-to-position tasks after bilateral injections of 0.035 µg of 192-Saporin (Cat. #IT-01) into the dorsal and ventral hippocampus. The treated animals were compared to rats given fimbria-fornix (FF) lesions. Only the FF-lesioned animals showed impairment on DMTP and DNMTP tasks, demonstrating that the cholinergic septohippocampal system is not required for successful DMTP or DNMTP performance.

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

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)

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)

Nattie EE, Li A, Richerson GB, Lappi DA (2004) Medullary serotonergic neurons and adjacent neurons that express neurokinin-1 receptors are both involved in chemoreception in vivo. J Physiol 556(1):235-253. doi: 10.1113/jphysiol.2003.059766 PMID: 14724193

Summary: The retrotrapezoid nucleus contains neurokinin-1 receptor (NK-1r)-expressing neurons that are involved in chemoreception. NK-1r-expressing neurons are also present in areas that contain medullary serotonergic neurons. These serotonergic neurons have been shown to be chemosensitive in vitro. With two 100-nl injections of 1 µM SP-SAP (Cat. #IT-07), anti-SERT-SAP (Cat. #IT-23), or both, the authors examined whether both cell populations are involved in chemoreception in vivo in rats. The results support that separate populations of serotonergic and NK-1r-expressing neurons are each involved in chemoreception in vivo.

Related Products: SP-SAP (Cat. #IT-07), Anti-SERT-SAP (Cat. #IT-23), Antibody to Serotonin Transporter (SERT, Cat. #AB-N09)