192 IgG-saporin : I. Specific Lethality for Cholinergic Neurons in the Basal Forebrain of the Rat

Book, Adam A.; Wiley, Ronald G.; Schweitzer, John B.

doi:10.1097/00005072-199401000-00012

Cited by 107 publications

(49 citation statements)

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“…The 192-IgG-Sap kills BF cholinergic neurons by binding to the p75 NGF receptor found on these neurons (Book et al, 1994). The preferred method of delivery of the toxin is intracerebroventricularly, and the lesion is complete by 7 d after injection (Waite, 2005).…”

Section: Discussionmentioning

confidence: 99%

Adenosine and Sleep Homeostasis in the Basal Forebrain

et al. 2006

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It is currently hypothesized that the drive to sleep is determined by the activity of the basal forebrain (BF) cholinergic neurons, which release adenosine (AD), perhaps because of increased metabolic activity associated with the neuronal discharge during waking, and the accumulating AD begins to inhibit these neurons so that sleep-active neurons can become active. This hypothesis grew from the observation that AD induces sleep and AD levels increase with wake in the basal forebrain, but surprisingly it still remains untested. Here we directly test whether the basal forebrain cholinergic neurons are central to the AD regulation of sleep drive by administering 192-IgGsaporin to lesion the BF cholinergic neurons and then measuring AD levels in the BF. In rats with 95% lesion of the BF cholinergic neurons, AD levels in the BF did not increase with 6 h of prolonged waking. However, the lesioned rats had intact sleep drive after 6 and 12 h of prolonged waking, indicating that the AD accumulation in the BF is not necessary for sleep drive. Next we determined that, in the absence of the BF cholinergic neurons, the selective adenosine A 1 receptor agonist N6-cyclohexyladenosine, administered to the BF, continued to be effective in inducing sleep, indicating that the BF cholinergic neurons are not essential to sleep induction. Thus, neither the activity of the BF cholinergic neurons nor the accumulation of AD in the BF during wake is necessary for sleep drive.

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Section: Discussionmentioning

confidence: 99%

Adenosine and Sleep Homeostasis in the Basal Forebrain

et al. 2006

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“…A strong microglial reaction accompanying neuronal death was observed in the MS after intraventricular injection of 192 IgG-saporin. It is remarkable that there was a much heavier microglial reaction after immunotoxin application than after ff-t, although the former approach affects only the cholinergic component of the septohippocampal projection and leaves GABAergic septohippocampal neurons unaltered (Wiley et al, 1991;Book et al, 1994;Heckers et al, 1994). This massive microglial activation accompanying the degeneration of the cholinergic MS neurons (Roβner et al, 1995;present observations) still persists 3 weeks after injection of the immunotoxin, again contrasting with the mild, shortlasting changes observed after ff-t.…”

Section: Postlesional Microglial Activation Varies With the Lesion Pamentioning

confidence: 97%

“…To monitor the extent of phagocytotic activity associated with neuronal death following ff-t, septohippocampal projection neurons were prelabeled with the retrograde fluorescent tracer Fluoro-Gold (FG) prior to axotomy, and microglial cells were then studied for the uptake of FG-labeled debris. In addition, the microglial reaction after irreversible degeneration of cholinergic neurons in the MS induced by immunolesioning with 192 IgG-saporin was investigated (Wiley, 1992;Book et al, 1994;Heckers et al, 1994;Hä ge et al, 1996).…”

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confidence: 99%

Region-specific activation of microglial cells in the rat septal complex following fimbria-fornix transection

et al. 1998

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Studies of postlesional microglial activation may gain insight into microglia/neuronal interactions in processes of neurodegeneration. We compared the microglial response after axotomy of septohippocampal projection neurons with that seen after selective immunolesioning of cholinergic septohippocampal neurons with the immunotoxin 192 IgG-saporin. Using the microglial marker isolectin B4 from Griffonia simplicifolia (GSA I-B4), we found striking differences in the microglial response between these two lesion paradigms. Following axotomy of septohippocampal neurons by fimbria-fornix transection (ff-t), there was only a moderate and short-lasting microglial reaction in the medial septum (MS) in the early postlesion period. Prelabeling of septohippocampal neurons with Fluoro-Gold (FG) prior to axotomy revealed the survival of most neurons, and only very rarely were microglial cells observed that had phagocytosed FG-labeled debris. In the lateral septum (LS) containing the degenerating terminals of hippocamposeptal fibers transected by ff-t, a heavy reaction of lectin-labeled activated microglial cells associated with high phagocytotic activity was noticed. Unexpectedly, after a long survival time (6 months) following ff-t, we observed an increase in microglial GSA I-B4 labeling in the MS. In contrast, an inverse pattern of the microglial response, i.e., a strong initial reaction in the MS and very little microglial activation in the LS, was observed after immunolesioning. Our results indicate that the microglial reaction in the MS following ff-t differs substantially from that seen in other models of axotomy.

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“…Numerous experimental animal model studies have attempted to clarify this cognitive impairment using basal forebrain lesions. Selective lesioning of cholinergic basal forebrain neurons became possible by the development of 192 IgG-saporin [5,6,7,8]. 192 IgG-saporin, composed of a monoclonal antibody, has a low affinity for the rat nerve growth factor receptor p75 located on cholinergic cell bodies in the basal forebrain, and contains a ribosomal inactivating protein called saporin.…”

Section: Introductionmentioning

confidence: 99%

Decrease of GABAergic Markers and Arc Protein Expression in the Frontal Cortex by Intraventricular 192 IgG-Saporin

Jeong¹,

Chang²,

Hwang³

et al. 2011

Dement Geriatr Cogn Disord

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Background/Aims: Previous studies used 192 IgG-saporin to study cholinergic function because of its facility for selective lesioning; however, results varied due to differences in the methods of administration and behavioral tests used. We examined an animal model of dementia using 192 IgG-saporin to confirm its features before applying this model to research of therapeutic drugs or electrical stimulation techniques. Methods: Features were verified by the Morris water maze test, immunochemistry, and Western blotting. Animals were examined after intraventricular injection of 192 IgG-saporin (0.63 µg/µl; 6, 8, and 10 µl) or phosphate-buffered saline. Results: In the acquisition phase of the Morris water maze test, the latencies of the injection groups were significantly delayed, but recovered within 1 week. In the probe test, 2 of 4 indices (time in the platform zone and the number of crossings) were significantly different in the 8-µl injection group. Immunohistochemistry revealed the extent of cholinergic destruction. Activity-regulated cytoskeleton-associated protein and glutamate decarboxylase expression significantly decreased in the frontal cortex (8- and 10-µl groups), but not in the hippocampus. Conclusion: Spatial memory impairment was associated with cholinergic basal forebrain injury as well as frontocortical GABAergic hypofunction and synaptic plasticity deceleration.

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192 IgG-saporin : I. Specific Lethality for Cholinergic Neurons in the Basal Forebrain of the Rat

Cited by 107 publications

References 0 publications

Adenosine and Sleep Homeostasis in the Basal Forebrain

Adenosine and Sleep Homeostasis in the Basal Forebrain

Region-specific activation of microglial cells in the rat septal complex following fimbria-fornix transection

Decrease of GABAergic Markers and Arc Protein Expression in the Frontal Cortex by Intraventricular 192 IgG-Saporin

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