targeted-toxins

St Peters M, Sarter M (2012) Featured Article: Motivation’s modulation of attention through the mesolimbic-corticopetal cholinergic circuitry. Targeting Trends 13(1)

Related Products: 192-IgG-SAP (Cat. #IT-01), Mouse IgG-SAP (Cat. #IT-18)

Read the featured article in Targeting Trends.

See Also:

• St Peters M et al. Enhanced control of attention by stimulating mesolimbic-corticopetal cholinergic circuitry. J Neurosci 31(26):9760-9771, 2011.

Taxini CL, Takakura AC, Gargaglioni LH, Moreira TS (2011) Control of the central chemoreflex by A5 noradrenergic neurons in rats. Neuroscience 199:177-186. doi: 10.1016/j.neuroscience.2011.09.068

Summary: The A5 group of noradrenergic neurons in the ventrolateral pons is involved in the control of sympathetic and respiratory networks. Using anti-DBH-SAP (Cat. #IT-03) the authors eliminated TH+ neurons in order to clarify which aspects of respiration are modulated by A5 neurons. Rats received bilateral 4.2-ng injections of the toxin into the A5 region. The results suggest that A5 noradrenergic neurons are involved in control of mean arterial pressure, splanchnic sympathetic nerve activity, and phrenic nerve activity.

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

Alvarez P, Gear RW, Green PG, Levine JD (2012) IB4-saporin attenuates acute and eliminates chronic muscle pain in the rat. Exp Neurol 233(2):859-865. doi: 10.1016/j.expneurol.2011.12.019

Summary: In order to clarify the roles of isolectin B4-positive and IB4-negative nociceptors in inflammatory and ergonomic muscle pain, the authors administered 3.2 µg of IB4-SAP (Cat. #IT-10) into the intrathecal space of rats. Although the baseline mechanical nociceptive threshold was not affected in the lesioned animals, mechanical hyperalgesia had a shorter duration. In the ergonomic models peak hyperalgesia was attenuated, and prolongation of PGE2-induced mechanical hyperalgesia was completely prevented.

Related Products: IB4-SAP (Cat. #IT-10)

Staudt MD, Truitt WA, McKenna KE, de Oliveira CV, Lehman MN, Coolen LM (2012) A pivotal role of lumbar spinothalamic cells in the regulation of ejaculation via intraspinal connections. J Sex Med 9(9):2256-2265. doi: 10.1111/j.1743-6109.2011.02574.x

Summary: The authors examined the hypothesis that specific lumbar spinothalamic (LSt) cells control ejaculation through intraspinal connections. Rats received six bilateral injections of SSP-SAP (Cat. #IT-11) into the spinal cord, 48 ng in total. Saporin (Cat. #PR-01) was used as a control. It was found that while erectile function and emission were not affected, the usual rhythmic contractions of the bulbocaveronosus muscle during ejaculation were prevented.

Related Products: SSP-SAP (Cat. #IT-11), Saporin (Cat. #PR-01)

Read the featured article in Targeting Trends.

Khan AM KKL, Sanchez-Watts, Ponzio TA, Kuzmiski JB, Bains JS, Watts AG (2011) MAP kinases couple hindbrain-derived catecholamine signals to hypothalamic adrenocortical control mechanisms during glycemia-related challenges. J Neurosci 31(50):18479-18491. doi: 10.1523/JNEUROSCI.4785-11.2011

Summary: This work uses in vivo and ex vivo techniques to clarify how hypothalamic afferent pathways use intracellular mechanisms to modulate glycemia related adrenocortical responses. Rats received 42 ng injections of anti-DBH-SAP (Cat. #IT-03) into the paraventricular nucleus of the hypothalamus. Mouse IgG-SAP (Cat. #IT-18) was used as a control. The results establish a relationship between neurons from nutrient-sensing regions and intracellular mechanisms in hypothalamic corticotropin-releasing hormone neuroendocrine neurons.

Related Products: Anti-DBH-SAP (Cat. #IT-03), Mouse IgG-SAP (Cat. #IT-18)

Hayashida K, Peters CM, Gutierrez S, Eisenach JC (2012) Depletion of endogenous noradrenaline does not prevent spinal cord plasticity following peripheral nerve injury. J Pain 13(1):49-57. doi: 10.1016/j.jpain.2011.09.009

Summary: The authors examined what involvement noradrenergic fibers in the spinal cord have in neuronal and glial plasticity associated with neuropathic pain states. Rats received 5 μg intrathecal injections of anti-DBH-SAP (Cat. #IT-03). Lesioned animals did not display altered mechanical withdrawal thresholds, but L5-L6 spinal nerve ligation in these animals caused enhanced mechanical hypersensitivity and analgesia induced by intrathecal clonidine. The data suggest that endogenous noradrenaline may play an inhibitory role on glial activation.

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

Janiesch PC, Kruger HS, Poschel B, Hanganu-Opatz IL (2011) Cholinergic control in developing prefrontal-hippocampal networks. J Neurosci 31(49):17955-17970. doi: 10.1523/JNEUROSCI.2644-11.2011

Summary: In this work the authors examined the role of acetylcholine in the maturation of cognitive processing due to oscillatory rhythms entraining neuronal networks. Rats received 50 ng of 192-IgG-SAP (Cat. #IT-01) into each lateral ventricle, or 25 ng directly into the medial septum. Among other results, cholinergic input was shown to reach the prefrontal cortex toward the end of the first postnatal week, initially targeting GABAergic neurons. Reduction of this activity by lesioning cholinergic neurons may cause global diminishment of neocortical activity.

Related Products: 192-IgG-SAP (Cat. #IT-01), Mouse IgG-SAP (Cat. #IT-18)

Huckstepp RT, Dale N (2011) Redefining the components of central CO2 chemosensitivity – towards a better understanding of mechanism. J Physiol 589(Pt 23):5561-5579. doi: 10.1113/jphysiol.2011.214759

Summary: This review discusses advances in the field of CO2 chemosensitivity over the past few years. Discussion of the role that locus coeruleus (LC) neurons play in this process describe the use of anti-DBH-SAP (Cat. #IT-03) to reduce the hypercapnic ventilatory response. Data from these and other experiments support a role of the LC in modulation of the ventilatory response to hypercapnia.

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

Botly LC, De Rosa E (2012) Impaired visual search in rats reveals cholinergic contributions to feature binding in visuospatial attention. Cereb Cortex 22(10):2441-2453. doi: 10.1093/cercor/bhr331

Summary: Previous work established the role of acetylcholine from the nucleus basalis magnocellularis in attentional processing and visuospatial attention. In order to investigate the necessity of cortical cholinergic input for support of feature binding in visuospatial attention the authors administered bilateral intraparenchymal injections of 192-IgG-SAP (Cat. #IT-01, 4 injections, 40 ng per injection). Lesioned animals took longer to locate targets during type-specific search trials, demonstrating that cholinergic input influences feature binding during visuospatial attention tasks.

Related Products: 192-IgG-SAP (Cat. #IT-01), Mouse IgG-SAP (Cat. #IT-18)

Savage ST, Olson L, Mattsson A (2011) Alterations in gene expression following cortical cholinergic denervation in rats. Neuroscience 2011 Abstracts 790.01. Society for Neuroscience, Washington, DC.

Summary: Alterations in cholinergic signaling in the brain have been implicated as a contributing factor in the pathogenesis of schizophrenia. Altered function and expression of both nicotinic and muscarinic acetylcholine receptors have been reported in cortical and subcortical regions in post-mortem schizophrenic brains. Pharmacologically, dopamine-releasing compounds, such as amphetamine, can induce the psychotic symptoms in healthy volunteers and exacerbate the symptoms in schizophrenics. Furthermore, the NMDA receptor antagonist phencyclidine (PCP) induces both negative symptoms (such as social withdrawal) and cognitive deficits similar to those exhibited in schizophrenics. We have previously shown that cholinergic denervation of cortex cerebri by stereotaxic infusion of the immunotoxin 192 IgG-saporin in the nucleus basalis magnocellularis (nbm) in adult rats leads to an enhanced sensitivity to both amphetamine and PCP. The enhanced sensitivity to amphetamine, shown by a potentiated dopamine release in nucleus accumbens, along with a marked increase in locomotor activity in response to both amphetamine and PCP, suggested that the disruption of cortical cholinergic activity can lead to disturbances of glutamatergic and dopaminergic transmission. Furthermore, bilateral lesioning of nbm led to a decrease in active social interaction, as well as, impairment after an acute PCP challenge in a cognitive task (novel object recognition). To further evaluate the consequences of cortical cholinergic denervation, we are analyzing the possible changes in mRNA expression levels of selected genes in rats with unilateral removal of the cortical cholinergic innervation by 192 IgG-saporin injections into nbm following acute PCP administration. Our data indicate that the induction of c-fos mRNA expression in cortex in response to PCP administration is markedly reduced in cholinergically denervated animals as compared to controls. Other genes are under investigation to elucidate the interplay between the cholinergic, dopaminergic, and glutamatergic systems.

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