targeted-toxins

Coons KD, Wilson RE, Sengelaub DR (2007) Protection from dendritic atrophy with testosterone following partial motoneuron depletion: dose-dependence in males and efficacy in females. Neuroscience 2007 Abstracts 56.11/S5. Society for Neuroscience, San Diego, CA.

Summary: Partial depletion of motoneurons from the highly androgen-sensitive spinal nucleus of the bulbocavernosus (SNB), or the more typical somatic motoneuron population innervating the quadriceps muscles, induces dendritic atrophy in remaining motoneurons. Treatment with testosterone (T) is neuroprotective, and dendritic atrophy following partial motoneuron depletion is attenuated in both populations. In the present study, we examined the dose-dependency of T effects in male rats, as well as its potential efficacy in females. Motoneurons innervating the bulbocavernosus/levator ani (BC/LA) or vastus medialis muscles were selectively killed by intramuscular injection of cholera toxin-conjugated saporin. Simultaneously, saporin-injected rats were given T implants designed to produce plasma titers ranging from 0.75 to 5.0 ng/ml or left untreated. Four weeks later, motoneurons innervating the contralateral BC or the ipsilateral vastus lateralis muscles were labeled with cholera toxin-conjugated HRP, and dendritic arbors were reconstructed in 3 dimensions. Partial motoneuron depletion resulted in dendritic atrophy in remaining SNB and quadriceps motoneurons (40% and 36% of normal length, respectively). T treatment attenuated this atrophy in a dose-dependent manner, with maximum effectiveness at 2.0-2.5 ng/ml (the normal adult physiological level). This dosage of T resulted in SNB dendritic lengths that did not differ from those of intact control males. In contrast, although dendritic atrophy in quadriceps motoneurons was attenuated by the same dosage of T, resultant dendritic lengths were 60% of normal length, and did not improve further with higher levels of T. Neuroprotective effects of T treatment were also assessed in quadriceps motoneurons in female rats (adult female rats lack the SNB neuromuscular system). As described above, motoneurons innervating the vastus medialis muscles were selectively killed by saporin injection, and females were given T implants (resulting in plasma levels of 2.0-2.5 ng/ml) or left untreated. Four weeks later, motoneurons innervating the ipsilateral vastus lateralis muscles were labeled with cholera toxin-conjugated HRP, and dendritic arbors were reconstructed. As in males, partial motoneuron depletion in females resulted in dendritic atrophy (52% of normal length) in remaining quadriceps motoneurons, and this atrophy was attenuated (70% of normal length) with T treatment. Together, these findings suggest that the neuroprotective effects of T on dendrites are achieved with dosages within the normal physiological range, and furthermore can be observed in motoneurons of both male and female rats.

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

Ferguson AS, Sengelaub DR (2007) Dendritic atrophy following partial motoneuron depletion: time course of recovery and protection with testosterone. Neuroscience 2007 Abstracts 56.24/S18. Society for Neuroscience, San Diego, CA.

Summary: In male rats, motoneurons of the spinal nucleus of the bulbocavernosus (SNB) project to the bulbocavernosus and levator ani (BC/LA) muscles, and both the motoneurons and their target muscles are highly androgen-sensitive. We have previously demonstrated that partial depletion of motoneurons from the SNB induces dendritic atrophy in remaining motoneurons, and that treatment with testosterone (T) is neuroprotective against this atrophy. In the present study, we assessed dendritic atrophy after partial motoneuron depletion in SNB motoneurons at a variety of time points, to determine its time course and pattern with and without T treatment. Motoneurons innervating the BC/LA muscles in gonadally intact males were selectively killed by intramuscular injection of cholera toxin-conjugated saporin. Simultaneously, saporin-injected males were given T implants (45mm) or left untreated. At 2, 4, 6, or 10 weeks after motoneuron depletion, motoneurons innervating the contralateral BC were labeled with cholera toxin-conjugated HRP, and dendritic arbors were reconstructed in 3 dimensions. As previously reported, partial motoneuron depletion resulted in dendritic atrophy in remaining SNB motoneurons. While motoneuron depletion occurs within 7 days after saporin injection, dendritic atrophy in remaining SNB motoneurons progresses linearly over several weeks, with a decrease of 32% present at 2 weeks after motoneuron depletion, and a decrease to 66% at 4 weeks. Evidence of recovery in dendritic lengths was observed at 6 weeks post depletion (only 43% decreased), and by 10 weeks SNB dendritic lengths had returned to those of normal, intact males. Treatment with T altered the pattern of dendritic atrophy. While initial dendritic atrophy was similar to that of untreated saporin-injected males (29% decreased at 2 weeks post motoneuron depletion), T treatment attenuated dendritic atrophy. Four weeks after motoneuron depletion, SNB dendritic lengths had not declined further in T-treated males (32% decreased), and were now 102% longer than those of untreated, saporin-injected males. These findings suggest that SNB dendrites undergo a protracted atrophy and subsequent recovery following partial motoneuron depletion, and that the neuroprotective effects of T attenuate the magnitude of the induced atrophy.

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

Cai L, Johnson DA (2007) Poster: Recognition of novel objects and their location in rats with selective cholinergic lesion of the medial septum. Neuroscience 2007 Abstracts 92.21/TT2. Society for Neuroscience, San Diego, CA.

Summary: The goal of this project was to determine whether cholinergic neurons projecting from the medial septum (MS) to the hippocampus play a role in novel object recognition or location. The specific aim was to determine whether lesion of cholinergic neurons in MS by the selective cholinergic neurotoxin 192IgG-saporin (SAP) would induce retrograde amnesia and/or anterograde amnesia for a novel object and/or its location. Male SD rats were tested in an object recognition paradigm. The time the rats spent examining old and novel objects was measured. Infusion of SAP into medial septum was performed 2 days after a one week pre-surgery training. Fourteen days after surgery post-surgery retention testing for retrograde object memory was carried out. Then 3 days later, a new acquisition training and retention testing for anterograde memory was started. One-way ANOVA and Fisher’s exact test were used for statistical analysis. There were no significant differences in the exploration ratios between the control group without surgery and the CSF surgical group. The mean exploration ratios for both groups demonstrated retention of memory for the novel object and its placement. SAP infusion into the MS failed to induce a deficit in retrograde amnesia 2 days after training, but did show a strong trend for anterograde amnesia for novel object recognition and a significant association with anterograde amnesia for object location. Conclusions were that cholinergic neurons of MS were not involved in retrograde object memory 2 days before the infusion of SAP and may or may not be necessary for anterograde object memory formation, but cholinergic neurons of the MS were involved in anterograde spatial memory formation for novel objects.

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

Khan IM, Wart CV, Singletary EA, Stanislaus S, Deerinck T, Yaksh TL, Printz MP (2008) Elimination of rat spinal substance P receptor bearing neurons dissociates cardiovascular and nocifensive responses to nicotinic agonists. Neuropharmacology 54(2):269-279. doi: 10.1016/j.neuropharm.2007.09.014

Summary: Nocifensive behavior and cardiovascular responses due to nicotinic agonists may be sustained by substance P-positive primary afferents. Rats received 10-µl intrathecal injections of 10 µM SP-SAP (Cat. #IT-07); unconjugated saporin (Cat. #PR-01) was used as a control. Lesioned animals displayed reduced nocifensive response to nicotinic agonists. Tachycardia and pressor responses were enhanced upon administration of cytisine and epibatidine.

Related Products: Saporin (Cat. #PR-01), SP-SAP (Cat. #IT-07)

Percaccio CR, Pruette AL, Mistry ST, Chen YH, Kilgard MP (2007) Sensory experience determines enrichment-induced plasticity in rat auditory cortex. Brain Res 1174:76-91. doi: 10.1016/j.brainres.2007.07.062

Summary: Animals housed in enriched environments display numerous signs of good neural health. In this work the authors examined the role acetylcholine plays in this plasticity. 2.6 µg of 192-IgG-SAP (Cat. #IT-01) was injected into the left lateral ventricle of rats. Auditory evoked responses were used to assess the effect of lesioning cholinergic neurons. Response strength was not reduced in lesioned animals, indicating that cholinergic deficits do not affect this system.

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

Caudle RM (2007) Featured Article: Inducing central sensitization with a substance P/ cholera toxin conjugate. Targeting Trends 8(4)

Related Products: SP-SAP (Cat. #IT-07), SP-CTA (Cat. #IT-39)

Read the featured article in Targeting Trends.

See Also:

• Caudle RM Sensitization of spinal cord nociceptive neurons with a conjugate of substance P and cholera toxin. BMC Neuroscience 8:30, 2007.

Ricceri L, Cutuli D, Venerosi A, Scattoni ML, Calamandrei G (2007) Neonatal basal forebrain cholinergic hypofunction affects ultrasonic vocalizations and fear conditioning responses in preweaning rats. Behav Brain Res 183:111-117. doi: 10.1016/j.bbr.2007.05.035

Summary: In order to expand on previous work investigating the effect of early cholinergic lesions on processing of aversive stimuli the authors administered 0.21 µg of 192-IgG-SAP (Cat. #IT-01) into the third ventricle of 7 day-old rat pups. One unexpected result in lesioned animals was the enhancement of fear-conditioned responses that are dependent on the hippocampus. The authors discuss several theories addressing the implications of these data. NOTE: material from Chemicon, CA

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

Martin MM, Wallace DG (2007) Selective hippocampal cholinergic deafferentation impairs self-movement cue use during a food hoarding task. Behav Brain Res 183:78-86. doi: 10.1016/j.bbr.2007.05.026

Summary: There are conflicting data surrounding the role of the septohippocampal system in spatial orientation. The authors suggest that the presence of spatial clues during some of these tests may skew those results. Rats were injected with a total of 0.35 µg of 192-IgG-SAP (Cat. #IT-01) into the medial septum. Lesioned animals had more difficulty navigating by self-movement cues, but the ability to use of environmental cues was left intact. These experiments demonstrate that rats can use environmental information to compensate for loss of circuits that analyze self-movement.

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

Severino M, Pedersen AF, Trajkovska V, Christensen E, Lohals R, Veng LM, Knudsen GM, Aznar S (2007) Selective immunolesion of cholinergic neurons leads to long-term changes in 5-HT2A receptor levels in hippocampus and frontal cortex. Neurosci Lett 428:47-51. doi: 10.1016/j.neulet.2007.09.026

Summary: Changes in several neurotransmitter systems, including serotonin and 5HT2A receptors, are associated with early Alzheimer’s disease (AD). The authors gave rats intracerebroventricular injections of either 2.5 or 5 µg of 192-IgG-SAP (Cat. #IT-01) then examined both of these systems. 5HT2A receptor levels were markedly decreased in the frontal cortex and markedly increased in the hippocampus of animals lesioned with 5 µg of 192-IgG-SAP. The change in 5HT2A receptor number suggests that the AD effect stems from interaction with the cholinergic system.

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

Magrassi L, Grimaldi P, Ibatici A, Corselli M, Ciardelli L, Castello S, Podesta M, Frassoni F, Rossi F (2007) Induction and survival of binucleated Purkinje neurons by selective damage and aging. J Neurosci 27:9885-9892. doi: 10.1523/JNEUROSCI.2539-07.2007

Summary: Donor bone marrow derived cells are thought to fuse with host Purkinje cells in small numbers to create binucleated cells. These fusions have been found to persist within the recipient for long periods of time. The authors injected 2.2 µg of 192-IgG-SAP (Cat. #IT-01) into the right lateral ventricle of rats; to examine whether the damage of host Purkinje cells is a method to increase the numbers of binucleated cells. The data suggest an alternate method is present for the creation of these cells. NOTE: material from Millipore, Billerica MA

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