targeted-toxins

Rahimi O, Tatham D, Juliano SL (2000) Sensory training improves the ability to process stimuli in barrel cortex after basal forebrain lesion. Neuroscience 2000 Abstracts 51.22. Society for Neuroscience, New Orleans, LA.

Summary: Lesions of the basal forebrain deplete the cerebral cortex of acetylcholine and result in decreased ability to process stimuli. Using a model of unilateral basal forebrain lesion (BFL), we previously determined that the ability to perceive simple touch to the whiskers is impaired after BFL, but improves over time. Functional responses in barrel cortex, however, as measured by 2-deoxyglucose uptake (2DG) or electrophysiological recordings, remain reduced even after long survival times. We questioned whether the impaired cortical responses could be improved with behavioral training involving sensory discrimination using the whiskers. To do this, one group of rats was trained to discriminate between different textures using the whiskers on one side of the face, which projected to the lesioned hemisphere. After learning the task, this group of rats received a BFL using the immunotoxin, 192-IgG Saporin. They then continued the sensory discrimination task for at least 2 months. The second group of rats received a BFL, but no sensory training. They survived after the lesion for comparable periods of time; each rat of both groups then underwent a 2DG experiment. During the 2DG study, 1-4 matched sets of whiskers on both sides of the face were stimulated using an electromagnetic device. The magnitude of the response was measured in barrel cortex by preparing 2-dimensional maps of the label evoked by whisker stimulation. The area of barrel cortex activated in each hemisphere by whisker stimulation was measured and expressed as a ratio of the lesioned to normal hemisphere. We found that the evoked response in the lesioned hemisphere remained diminished compared to the normal side regardless of training. When the magnitude of response was compared between the trained and untrained group, however, the area of 2DG uptake in each barrel in response to stimulation was significantly increased in the animals receiving sensory discrimination training. These findings suggest that sensory training plays a role in improving cortical responses to stimulation after lesion of the basal forebrain.

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

Daniels D, Miselis RR, Flanagan-Cato LM (2000) Local immunotoxin treatment prevents transneuronal labeling of the intermediolateral column; but not the ventral horn; of the spinal cord after tracer injection into lumbar epaxial muscle. Neuroscience 2000 Abstracts 77.13. Society for Neuroscience, New Orleans, LA.

Summary: Pseudorabies virus (PRV) has been used as a transneuronal tracer to study central neural circuits that control various peripheral targets. Our laboratory has injected PRV into the lumbar epaxial muscles that produce the lordosis posture to label sequentially specific brain regions along the neuraxis. However, concomitant uptake of PRV through sympathetic innervation of nearby vasculature has made the interpretation of higher-order labeling problematic. To avoid this confound, we have designed a procedure for focal sympathetic denervation using dopamine-β-hydroxylase immunotoxin (DHIT). Five days after injecting DHIT (5 μg) into the medial portion of lateral longissimus, the Bartha strain of PRV was injected into the pre-treated area. After survival times of 72 or 96 h, animals were sacrificed and the spinal cords were immunostained for PRV. In preliminary studies, DHIT treatment was not effective in all animals, as determined by PRV labeling in the sympathetic preganglionic neurons that reside in IML. However, at each survival time, in 50% of the animals DHIT virtually eliminated PRV-labeling in cells within IML of the thoracic and lumbar spinal cord, whereas robust labeling of motoneurons in the ventral horn was retained. These preliminary results suggest that this procedure for local sympathectomy may allow for selective transneuronal labeling of somatic motor pathways.

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

Grindstaff RJ, Grindstaff RR, Cunningham JT (2000) Baroreceptor sensitivity of rat supraoptic vasopressin neurons involves noncholinergic neurons in the DBB. Am J Physiol Reul Integr Comp Physiol 279:R1934-R1943. doi: 10.1152/ajpregu.2000.279.5.R1934

Summary: Baroreceptors are one component of the system that buffers acute changes in blood pressure. Part of this control stems from the baroreceptor ability to regulate vasopressin release from the neurohypophysis. Using 192-Saporin (Cat. #IT-01) to specifically eliminate cholinergic neurons in the diagonal band of Broca, Grindstaff et al. demonstrated that these neurons are not utilized in the pathway that relays baroreceptor information to the brain.

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

Schreihofer AM, Guyenet PG (2000) Role of presympathetic C1 neurons in the sympatholytic and hypotensive effects of clonidine in rats. Am J Physiol Regul Integr Comp Physiol 279:R1753-R1762. doi: 10.1152/ajpregu.2000.279.5.R1753

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

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Schreihofer AM, Stornetta RL, Guyenet PG (2000) Regulation of sympathetic tone and arterial pressure by rostral ventrolateral medulla after depletion of C1 cells in rat. J Physiol 529(1):221-236. doi: 10.1111/j.1469-7793.2000.00221.x

Summary: The rostral ventrolateral medulla (RVLM) controls and maintains basal sympathetic vasomotor tone, and is also vital to many sympathetic reflexes. Sympathetic nerve activity and arterial pressure correlate with the C1 adrenergic neurons in the RVLM, but there are also non-catecholaminergic neurons present. Schreihofer et al. used anti-DBH-SAP (Cat. #IT-03) to eliminate the C1 cells of the RVLM to investigate the non-catecholaminergic neuron contribution to vasomotor tone. Their data indicate C1 cells are necessary for full expression of sympathoexitatory responses generated by the RVLM.

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

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Gu Z, Wortwein G, Yu J, Perez-Polo JR (2000) Model for aging in the basal forebrain cholinergic system. Antiox Redox Signal 2(3):437-447. doi: 10.1089/15230860050192215

Summary: A wide range of evidence indicates that cholinergic neurons play a role in memory and learning. Loss of these neurons is seen both in aged subjects and Alzheimer’s Disease patients. The authors discuss the use of 192-Saporin (Cat. #IT-01) to model this phenomenon. Many lesioning methods have been developed, including fimbria-fornix transections, mechanical lesions with radiofrequency or electrolysis, and intracerebral injections of excitotoxins. Information obtained through these methods suffers because non-cholinergic neurons are depleted as well as the desired cholinergic neurons. 192-Saporin provides a solution by specifically targeting and eliminating cholinergic neurons expressing p75 in the basal forebrain, closely mimicking a key component of aging.

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

Beach T (2000) Featured Article: CBF lesioning in rabbits. Targeting Trends 1(1)

Related Products: ME20.4-SAP (Cat. #IT-15)

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See Also:

• Beach TG et al. Cholinergic deafferentation of the rabbit cortex: a new animal model of Abeta deposition. Neurosci Lett 283:9-12, 2000.

Lappi DA, Wiley RG (2000) Entering through the doors of perception: characterization of a highly selective Substance P receptor-targeted toxin. Neuropeptides 34(5):323-328. doi: 10.1054/npep.2000.0827

Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12)

Silveira DC, Holmes GL, Schachter SC, Geula C, Schomer DL (2000) Increased susceptibility to generalized seizures after immunolesions of the basal forebrain cholinergic neurons in rats. Brain Res 878:223-227. doi: 10.1016/s0006-8993(00)02703-7

Usage: 192-SAP (Cat. #IT-01), 4 µg intracerebroventricular injection

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

Taylor BK, Roderick RE, Basbaum AI (2000) Brainstem noradrenergic control of nociception is abnormal in the spontaneously hypertensive rat. Neurosci Lett 291:139-142. doi: 10.1016/s0304-3940(00)01389-6

Usage: anti-DBH-SAP (Cat. #IT-03), 5 µg

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