targeted-toxins

Gibbs RB, Chipman AM, Nelson D (2011) Donepezil plus estradiol treatment enhances learning and delay-dependent memory performance by young ovariectomized rats with partial loss of septal cholinergic neurons. Horm Behav 59(4):503-511. doi: 10.1016/j.yhbeh.2011.01.011

Summary: Among the beneficial effects of estrogen on the brain are improved cognitive performance and prevention of age-related cognitive decline. These positive effects diminish over time following loss of ovarian function. To investigate the role of cholinergic neurons in this process, rats received 96-250 ng of 192-IgG-SAP (Cat. #IT-01) into the medial septal nucleus followed by a cholinergic enhancer and estradiol therapy. The dual therapy had a positive effect on partially lesioned animals, but did not improve the performance of animals with severe lesions.

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

Leung LS, Petropoulos S, Shen B, Luo T, Herrick I, Rajakumar N, Ma J (2011) Lesion of cholinergic neurons in nucleus basalis enhances response to general anesthetics. Exp Neurol 228(2):259-269. doi: 10.1016/j.expneurol.2011.01.019

Summary: Consciousness and response to general anesthesia have been linked to acetylcholine in the brain. The authors treated rats with 150-ng bilateral injections of 192-IgG-SAP (Cat. #IT-01) into the nucleus basalis magnocellularis to examine this connection. Lesioned animals were more affected by propofol and phenobarbitol than control animals. Some effects of halothane were also increased. The data indicate a role for acetylcholine in the brain in the response to general anesthesia.

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

Q: Is there a saporin derivative available that selectively destroys all or some hippocampal neurons?

A: Assuming that you mean to eliminate cell bodies from the hippocampus, rather than just projections, a neat paper by Martin et al. describes the use of SSP-SAP (Cat #IT-11) to do this. NPY-SAP (Cat. #IT-28) could also be interesting.

Related: SSP-SAP (Cat. #IT-11), NPY-SAP (Cat. #IT-28)

References

1. Martin JL et al. Focal inhibitory interneuron loss and principal cell hyperexcitability in the rat hippocampus after microinjection of a neurotoxic conjugate of saporin and a peptidase-resistant analog of substance P. J Comp Neurol 436:127-152, 2001.

Q: I am interested in your product GAT1-SAP (Cat. #IT-32). Before ordering, I would like to know how long it takes until the toxin produces a lesion; Is seven days enough?

A: The usual time-course for saporin toxins is that behavioral effects start appearing at four days and usually plateau at seven days. However, keep in mind that it takes some time for dead cells to be cleared out, so histology on the animal should wait until at least two weeks after administration.

Related: Targeted Toxins

Goehler LE, Gaykema RPA (2011) Featured Article: Targeted lesion of caudal brainstem catecholamine neurons reveals their role in symptoms of fatigue. Targeting Trends 12(1)

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

Read the featured article in Targeting Trends.

Zhang L, Hadley GA (2010) Application of anti-CD103 immunotoxin for saving islet allograft in context of transplantation. Chin Med J (Engl) 123(24):3644-51.

Summary: This work investigates whether depletion of CD103-positive cells protects transplanted islets from host-immune cell attack. Diabetes was induced in mice, followed by an islet transplant. Anti-CD103-SAP (Cat. #IT-50) was administered via i.p. injection (1.0 mg/kg or 2.0 mg/kg). Rat IgG-SAP (Cat. #IT-17) was used as a control. Diabetic mice treated with anti-CD103-SAP after islet transplantation had an indefinite survival time as compared to untreated mice that survived fewer than 20 days.

Related Products: Anti-CD103-SAP (Cat. #IT-50), Rat IgG-SAP (Cat. #IT-17)

Cerminara NL (2010) Cerebellar modules: individual or composite entities?. J Neurosci 30(48):16065-16067. doi: 10.1523/JNEUROSCI.4823-10.2010

Summary: This short review discusses the compartmentalization of cerebellar modules. Much research has been done to associate particular motor control functions with particular modules. Chemical lesioning is an inadequate technique because the lesion is non-specific. The use of CTB-SAP (Cat. #IT-14) to affect the function of a single module is discussed.

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

Joseph EK, Levine JD (2010) Mu and delta opioid receptors on nociceptors attenuate mechanical hyperalgesia in rat. Neuroscience 171(1):344-350. doi: 10.1016/j.neuroscience.2010.08.035

Summary: In this work the authors analyzed nociceptor populations mediating mechanical hyperalgesia in the rat. Rats received 3.2 µg of IB4-SAP (Cat. #IT-10) into the subarachnoid space between the L4 and L5 vertebrae. Hyperalgesia due to the administration of NGF was inhibited by DAMGO and SNC even in lesioned animals. These data indicate that most nociceptor populations are involved in mechanical hyperalgesia, and that the mu opioid and delta opioid receptors are co-expressed on some TrkA-positive nociceptors.

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

Koppen JR, Winter SS, Cheatwood JL, Wallace DG (2010) Role of the septohippocampal GABAergic system in spatial orientation. Neuroscience 2010 Abstracts 806.16/KKK21. Society for Neuroscience, San Diego, CA.

Summary: Spatial orientation depends on the integrity of multiple neural systems. For example, during the progression of Alzheimer’s Disease, degeneration of the basal forebrain is associated with cognitive impairments including episodes of wandering. The medial septum projects both cholinergic and GABAergic fibers into the hippocampus. Research and therapies have typically focused on enhancing function of the cholinergic component; however, the GABAergic component has also been shown to contribute to hippocampal function. Previous attempts to characterize the role of the GABAergic system in spatial orientation involved non-selective lesion techniques in combination with the water maze task have failed to characterize the nature of the deficit mediating the impaired performance. Development of GAT1-Saporin immunotoxin provides a novel tool to selectively destroy GABAergic neurons in the medial septum. The current study examined the effects of injecting GAT1-Saporin or saline (sham lesion) into the medial septum on spatial orientation using the food-hoarding paradigm. The food-hoarding paradigm involves training rats to search for food pellets on a large circular table and carrying the food pellet directly to a visible refuge. Three probes dissociate the use of environmental and self-movement cues: 1) Hidden probe involved placing the refuge below the surface of the table, limiting rats to use distal environmental or self-movement cues to locate the refuge; 2) Dark Probe involved using the hidden refuge with the room lights off, limiting rats to use self-movement cues to locate the refuge; 3) New probe involved placing the hidden refuge on the opposite side of table, placing environmental and self-movement cues in conflict. Both sham and GAT1-Saporin rats were accurate in returning to the refuge during the Hidden probe. Only sham rats were accurate in carrying food to the refuge during the Dark probe. During the New probe, both groups initially carried the food pellet to the former refuge location. Although sham rats consistently carried the food pellet to the new refuge location after their initial error, GAT1-Saporin rats continued to perseverate to the former refuge location. The current study demonstrates a role for the septohippocampal GABAergic system in spatial orientation related to processing self-movement cues.

Related Products: GAT1-SAP (Cat. #IT-32)

Rossi CA, Lehmkhule MJ, Kesner RP, Dudek FE (2010) Evidence that focal hippocampal interneuron loss disrupts theta-rhythm activity in dorsal CA1. Neuroscience 2010 Abstracts 811.1/LLL64. Society for Neuroscience, San Diego, CA.

Summary: Hippocampal theta activity (6-12 Hz) is an oscillatory local field potential that is thought to play a critical role in the encoding and storage of new information. As a hypothetical mechanism for theta rhythm generation, interneurons have been proposed to appropriately time the GABAergic inhibition of principal cells, as a means of organizing the theta pattern; however, little experimental work has been done to test this hypothesis directly. The current study aims to test in a relatively direct manner the hypothesis that interneurons synchronize the activity of pyramidal cells into theta-band oscillations. In the current study, SSP-saporin (a selective interneuron-targeting neurotoxic lesioning agent) was infused into six sites located in dorsal CA1 in order to create an interneuron-only lesion confined to that area. Animals were also implanted with chronic field potential recording electrodes aimed at areas CA1, CA3, and dentate gyrus. All animals were then monitored, using video and EEG recordings, 24 h per day for the next 7 to 10 days. In addition, EEG was recorded while animals were allowed to explore a novel open field for 30 min in order to create a situation where theta rhythm activity is highly likely to occur. Local field potentials from animals that received SSP-Saporin injections into the dorsal CA1 area revealed attenuation of theta rhythm activity in the lesioned area. Recordings from controls, however, showed a robust peak of activity in the theta frequency band, similar to what has been traditionally described in the hippocampus of naive rats. Together, these results suggest that local elimination of interneurons disrupts local theta rhythm without induction of seizure activity. These experiments provide evidence concerning the possible organizational role of GABAergic interneurons in theta rhythm, an important component of normal hippocampal function.

Related Products: SSP-SAP (Cat. #IT-11)