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Cholinergic lesions produce task-selective effects on delayed matching to position and configural association learning related to response pattern and strategy.
Gibbs RB, Johnson DA (2007) Cholinergic lesions produce task-selective effects on delayed matching to position and configural association learning related to response pattern and strategy. Neurobiol Learn Mem 88:19-32. doi: 10.1016/j.nlm.2007.03.007
Summary: It has been well established that the cholinergic system of the basal forebrain plays a critical role in many cognitive processes. This work utilized injections of 192-IgG-SAP (Cat. #IT-01) into the medial septum, the nucleus basalis magnocellularis, or both to examine the lesioning effect on two cognitive tasks in rats. The data indicate that cholinergic lesions of the basal forebrain produce learning deficits that are task specific, and that learning is affected without corresponding deficits in memory.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Extensive training in a maze task reduces neurogenesis in the adult rat dentate gyrus probably as a result of stress.
Aztiria E, Capodieci G, Arancio L, Leanza G (2007) Extensive training in a maze task reduces neurogenesis in the adult rat dentate gyrus probably as a result of stress. Neurosci Lett 416(2):133-137. doi: 10.1016/j.neulet.2007.01.069
Summary: Ascending cholinergic inputs from the basal forebrain modulate hippocampal neurogenesis, although it is not clear if the modulation is direct or indirect. In this study rats experienced extended training in a spatial navigation task following 192-IgG-SAP (Cat. #IT-01) lesions. 192-IgG-SAP was injected into the basal forebrain nuclei and the cerebellar cortex. Although the lesioned animals displayed an 80% reduction in neuron proliferation in the dentate gyrus, extended training and learning did not affect proliferation.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Agonist Effects
Q: Do conjugated toxins (dermorphin-saporin in particular) exhibit agonist effects? I’ve generated behavioral and tissue time course effects but have not established agonist effects for this conjugated toxin.
A: The peptide ligand toxins should exhibit agonist effects. They are constructed purposely to retain complete agonist activity, including for us the most important: internalization. So, for instance, SP-SAP (Cat. #IT-07) causes receptor internalization similar to SP, as reported in Mantyh et al.
As to dermorphin-SAP (Cat. #IT-12) specifically, it has agonist activity very much like dermorphin. This is reported in Porreca et al. in which it’s stated:
The bilateral microinjection of 3 pmol of dermorphin or of dermorphin-saporin directly into the RVM produced a robust antinociceptive effect in the 52°C hot-water tail-flick test. The peak antinociceptive effect of dermorphin, 78 ± 13.2% MPE, was not significantly different from that of the dermorphin-saporin conjugate, which was 59 ± 4.7% MPE (p > 0.5, Student’s t test).
Usually the amount needed to give a response is lower than the amount needed to kill a cell. Depending on what your system is; it may be a peculiarity of that system, but I would be a little concerned about not seeing an agonist effect. On the other hand, if you have demonstration of specific toxicity, it may not be all that crucial.
See: Targeted Toxins
Featured Article: Nucleus tractus solitarii injections of substance P-conjugated saporin selectively disrupts baroflex-dependent pathways
Potts JT (2007) Featured Article: Nucleus tractus solitarii injections of substance P-conjugated saporin selectively disrupts baroflex-dependent pathways. Targeting Trends 8(2)
Related Products: SP-SAP (Cat. #IT-07)
Read the featured article in Targeting Trends.
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Targeted deletion of neurokinin-1 receptor expressing nucleus tractus solitarii neurons precludes somatosensory depression of arterial baroreceptor-heart rate reflex.
Potts JT, Fong AY, Anguelov PI, Lee S, McGovern D, Grias I (2007) Targeted deletion of neurokinin-1 receptor expressing nucleus tractus solitarii neurons precludes somatosensory depression of arterial baroreceptor-heart rate reflex. Neuroscience 145(3):1168-1181. doi: 10.1016/j.neuroscience.2007.01.001
Summary: Previous work by these authors examined the role of substance P in arterial baroreflex. Here, 1.5 ng bilateral injections of SP-SAP (Cat. #IT-07) into the caudal nucleus tractus solitarii of rats were used to further elucidate the fundamental role of substance P in this system. The depressive effect of somatosensory input by neurokinin-1 receptor-expressing neurons on arterial baroreceptor-heart rate reflex was abolished in lesioned animals.
Related Products: SP-SAP (Cat. #IT-07)
Astrocytic reaction to a lesion, under hormonal deprivation.
Martinez L, de Lacalle S (2007) Astrocytic reaction to a lesion, under hormonal deprivation. Neurosci Lett 415(2):190-193. doi: 10.1016/j.neulet.2007.01.020
Summary: One effect of estradiol on astrocytes is the mediation of neuronal sprouting. Astrocytes express glial fibrillary acidic protein (GFAP) in response to injury, but estradiol has been shown to repress GFAP expression. Ovariectomized female rats received 15 ng of 192-IgG-SAP (Cat. #IT-01) into the horizontal limb of the diagonal band of Broca, followed by long-term estrogen treatment. The results suggest that estradiol deprivation may exacerbate the effects of a cholinergic lesion, and administration of estradiol may aid the recovery of lesioned cholinergic neurons by blocking GFAP expression.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Decreased vesicular acetylcholine transporter and alpha(4)beta(2) nicotinic receptor density in the rat brain following 192 IgG-saporin immunolesioning.
Quinlivan M, Chalon S, Vergote J, Henderson J, Katsifis A, Kassiou M, Guilloteau D (2007) Decreased vesicular acetylcholine transporter and alpha(4)beta(2) nicotinic receptor density in the rat brain following 192 IgG-saporin immunolesioning. Neurosci Lett 415(2):97-101. doi: 10.1016/j.neulet.2006.08.065
Summary: The vesicular acetylcholine transporter (VAChT) is a useful imaging target to assess Alzheimer’s disease, since this transporter is expressed on cholinergic cells that are lost as the disease progresses. Through the use of 192-IgG-SAP (Cat. #IT-01) the authors demonstrate the use of two radioligands, one that binds VAChTs, the other which binds nicotinic acetylcholine receptors (nAChRs). The results show the efficacy of each radioligand, as well as the loss of nAChRs on cholinergic neurons after treatment with 192-IgG-SAP.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Olfactory neophobia and seizure susceptibility phenotypes in an animal model of epilepsy are normalized by impairment of brain corticotropin releasing factor.
Pascual J, Heinrichs SC (2007) Olfactory neophobia and seizure susceptibility phenotypes in an animal model of epilepsy are normalized by impairment of brain corticotropin releasing factor. Epilepsia 48:827-833. doi: 10.1111/j.1528-1167.2007.01024.x
Summary: Olfactory recognition has been linked to epilepsy in behavioral phenotype models. This work examines the role brain stress neuropeptides play in the manifestation of neurological perturbations. Mice were injected with 2 µg/5 µl of CRF-SAP (Cat. #IT-13) into the lateral ventricle. Saporin (Cat. #PR-01) was used as a control. The lesioned mice displayed a temporary reduction in seizure susceptibility, and the reversal of olfactory deficits towards the detection of food.
Related Products: CRF-SAP (Cat. #IT-13), Saporin (Cat. #PR-01)
Immunotoxic cholinergic lesions in the basal forebrain reverse the effects of entorhinal cortex lesions on conditioned odor aversion in the rat.
Ferry B, Herbeaux K, Cosquer B, Traissard N, Galani R, Cassel JC (2007) Immunotoxic cholinergic lesions in the basal forebrain reverse the effects of entorhinal cortex lesions on conditioned odor aversion in the rat. Neurobiol Learn Mem 88:114-126. doi: 10.1016/j.nlm.2007.01.007
Summary: The entorhinal cortex (EC) is intimately involved in olfactory learning. Lesioning of this structure produces septo-cholinergic sprouting. Rats that had previously received EC lesions were treated with 5-µg intracerebroventricular injections of 192-IgG-SAP (Cat. #IT-01). The results point to a role for hippocampal cholinergic neurons in the modulation of memory processes involved with conditioned odor aversion.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Lesions to the nucleus basalis magnocellularis lower performance but do not block the retention of a previously acquired learning set.
Bailey AM, Lee JM (2007) Lesions to the nucleus basalis magnocellularis lower performance but do not block the retention of a previously acquired learning set. Brain Res 1136:110-121. doi: 10.1016/j.brainres.2006.12.028
Summary: A major source of cholinergic innervation to several cortices is the nucleus basalis magnocellularis (NBM). Rats were trained to acquire an olfactory discrimination learning set, then were lesioned with 192-IgG-SAP (Cat. #IT-01) or quisqualic acid. 0.075 µg of 192-IgG-SAP was administered in 2 sets of bilateral infusions. While treated animals performed poorly following the surgery, performance improved to better than expected by chance during the second trial. The authors discuss the role of the NBM in cognitive flexibility.
Related Products: 192-IgG-SAP (Cat. #IT-01)