Targeting Topics 04q3

Cognitive effects of neurotoxic lesions of the nucleus basalis magnocellularis in rats: differential roles for corticopetal versus amygdalopetal projections.

Beninger RJ, Dringenberg HC, Boegman RJ, Jhamandas K.

Neurotox Res 3(1):7-21, 2001.

The cholinergic hypothesis states that projections of cholinergic neurons from the nucleus basalis magnocellularis to cortical and amygdalar targets are important in memory. This review discusses the work done on the cholinergic hypothesis using non-specific lesioning agents such as ibotenate and quisqualate, and the specific targeted conjugate 192-Saporin (Cat. #IT-01). The authors conclude that cholinergic targets in both the cortex and amygdala are important for the control of memory.

Effects of hypocretin2-saporin and antidopamine-beta-hydroxylase-saporin neurotoxic lesions of the dorsolateral pons on sleep and muscle tone.

Blanco-Centurion C, Gerashchenko D, Salin-Pascual RJ, Shiromani PJ.

Eur J Neurosci 19(10):2741-2752, 2004.

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.

Impaired and spared cholinergic functions in the hippocampus after lesions of the medial septum/vertical limb of the diagonal band with 192 IgG-saporin.

Chang Q, Gold PE.

Hippocampus 14(2):170-179, 2004.

192-Saporin has been widely used to eliminate cholinergic neurons in the basal forebrain. These lesions can produce near-total loss of choline acetyltranferase (ChAT)-positive neurons in the medial septum/vertical limb of the diagonal band of Broca (MS/VDB). There is evidence that this ChAT deficit produces an upregulation of cholinergic mechanisms providing input to the hippocampus. Using either 0.2 or 0.3 µl of 0.5 µg/µl 192-Saporin (Cat. #IT-01) injected into the MS/DVB the authors examined the residual release of acetylcholine (Ach) in the hippocampus after lesioning.

Cortical cholinergic function and deficits in visual attentional performance in rats following 192 IgG-saporin-induced lesions of the medial prefrontal cortex.

Dalley JW, Theobald DE, Bouger P, Chudasama Y, Cardinal RN, Robbins TW.

Cereb Cortex 14(8):922-932, 2004.

Prior work has demonstrated that lesions of the cortical cholinergic system of the basal forebrain impair performance in attentional tasks. The authors examined the effects of selective depletion of acetylcholine from the prefrontal cortex (PFC) on these same attentional tasks. 50 or 100 ng of 192-Saporin (Cat. #IT-01) was infused into the PFC of rats. Treated animals displayed deficits in specific aspects of the attentional tasks, indicating a modulatory role in PFC function by basal forebrain cholinergic neurons.

[Interaction between sensory and cognitive processes in visual recognition: the role of the associative areas of the cerebral cortex].

Dudkin KN, Chueva IV, Makarov FN.

Ross Fiziol Zh Im I M Sechenova 89(10):1226-1239, 2003.

The authors used ME20.4-SAP (Cat. #IT-15).

Modulation of photic resetting in rats by lesions of projections to the suprachiasmatic nuclei expressing p75 neurotrophin receptor.

Erhardt C, Galani R, Jeltsch H, Cassel JC, Klosen P, Menet JS, Pevet P, Challet E.

Eur J Neurosci 19(7):1773-1788, 2004.

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 each 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.

Immunotoxins and neuropeptide-toxin conjugates experimental applications.

Lappi DA, Wiley RG.

Mini Rev Med Chem 4(5):585-595, 2004.

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.

Glucoprivation increases expression of neuropeptide Y mRNA in hindbrain neurons that innervate the hypothalamus.

Li AJ, Ritter S.

Eur J Neurosci 19(8):2147-2154, 2004.

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.

Effects of isolectin B4-conjugated saporin, a targeting cytotoxin, on bladder overactivity induced by bladder irritation.

Nishiguchi J, Sasaki K, Seki S, Chancellor MB, Erickson KA, de Groat WC, Kumon H, Yoshimura N.

Eur J Neurosci 20(2):474-482, 2004.

It has been demonstrated that IB4-binding non-peptidergic C-fiber neuronal populations are present in afferent pathways to the bladder. The authors used intrathecal administration of 8 µl of 2.5 µM IB4-SAP (Cat. #IT-10) to investigate what roles these neurons play in bladder function. Treated animals displayed a reduction of IB4 afferent nerve terminal staining, as well as a suppression of bladder overactivity due to bladder irritation, without a change in normal bladder function.

Altered neurotrophin receptor function in the developing prefrontal cortex leads to adult-onset dopaminergic hyperresponsivity and impaired prepulse inhibition of acoustic startle.

Rajakumar N, Leung LS, Ma J, Rajakumar B, Rushlow W.

Biol Psychiatry 55(8):797-803, 2004.

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.

Involvement of cholinergic neuronal systems in intravenous cocaine self-administration.

Smith JE, Co C, Yin X, Sizemore GM, Liguori A, Johnson WEr, Martin TJ.

Neurosci Biobehav Rev 27(8):841-850, 2004.

Recent studies have demonstrated that cholinergic neurons take part in the process of cocaine self-administration. In this study the authors used 0.25 µg-injections of 192-Saporin (Cat. #IT-01) into the posterior nucleus accumbens (Nacc)-ventral pallidum (VP) region of rats to identify specific subsets of cholinergic neurons that are involved. The results indicate that cholinergic innervations of the VP, the medial septum/diagonal band of Broca, and the Nacc are inhibitory to the underlying processes of cocaine self-administration.

Spinal neurons involved in the generation of at-level pain following spinal injury in the rat.

Yezierski RP, Yu CG, Mantyh PW, Vierck CJ, Lappi DA.

Neurosci Lett 361(1-3):232-236, 2004.

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.