Time course of cholinergic and monoaminergic changes in rat brain after immunolesioning with 192 IgG-saporin

Waite, Jerene J.; Wardlow, M.L.; Chen, Andrew C.; Lappi, Douglas A.; Wiley, Ronald G.; Thal, Leon J.

doi:10.1016/0304-3940(94)90379-4

Cited by 105 publications

(47 citation statements)

References 23 publications

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“…Figure 1 illustrates the time line of surgery and behavioral testing. Although previous studies have conducted the context test up to 8 days after training (e.g., Anagnostaras et al, 1995Anagnostaras et al, , 1999Gale et al, 2001;Wallenstein and Vago, 2001), the interval between training and testing was longer in this study to allow enough time for the toxin to fully destroy BF cholinergic neurons (Waite et al, 1994). In addition, because all water maze testing occurred after surgery, the pre-and posttraining groups were combined and only two groups were analyzed: control (n ϭ 10) and lesion (n ϭ 20).…”

Section: Designmentioning

confidence: 99%

Effects of complete immunotoxin lesions of the cholinergic basal forebrain on fear conditioning and spatial learning

2004

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Administration of muscarinic cholinergic antagonists such as scopolamine impairs the acquisition of contextual fear conditioning, but the role of the basal forebrain (BF) cholinergic system in consolidation is unclear. To test the hypothesis that BF cholinergic neurons are critical for acquisition and consolidation of fear conditioning, male Sprague-Dawley rats with 192 IgG-saporin lesions of the entire cholinergic BF made either before or after fear conditioning were tested for conditioned fear to context and tone by assessing freezing and 22 kHz ultrasonic vocalization (USV) responses. Spatial learning in a 1-day water maze task provided a comparison for effects of the BF lesions on fear conditioning. In the test phase, neither pre-training nor posttraining BF lesions affected freezing to the context or tone. During both training and testing, pre-lesioned rats were impaired in production of USVs associated with fear. Postlesioned rats emitted fewer USVs only during testing. Acquisition of a spatial water maze task was mildly impaired in lesioned rats, although probe trial and cued performance was unimpaired. Nevertheless, these data suggest that conditioned fear-induced USVs are more sensitive to the loss of BF cholinergic neurons than is conditioned fear-induced freezing. The failure of BF cholinergic lesions to impair contextual fear conditioning indicates that scopolamine-induced impairments in fear conditioning may not be mediated by affecting cholinergic input to the hippocampus and neocortex.

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Section: Designmentioning

confidence: 99%

Effects of complete immunotoxin lesions of the cholinergic basal forebrain on fear conditioning and spatial learning

2004

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“…Intraventricular injection of 192 IgG-saporin produces a time and dose-dependent loss of ~7 5~"~-b e a r i n g cholinergic neurons in the rat basal forebrain and their neocortical and hippocampal afferents while sparing other neuronal systems in the region (Wiley et al, 1991;Heckers et al, 1994;Torres et al, 1994;Wenk et al, 1994;Leanza et al, 1995;RoBner et al, 1995a,b). In this study, we used 1.3 pg of 192 IgG-saporin to produce partial immunolesions to CBFNs and then started NGF treatments 2 weeks later, at a time when neuronal death is complete and a maximal decrease in cholinergic markers in the terminal fields has been reached (Nilsson et al, 1992;Waite et al, 1994;Yu et al, 1996b). Therefore, the effects of intraventricularly transplanted NGF-secreting cells on remaining CBFNs and their axons can be examined.…”

Section: Introductionmentioning

confidence: 98%

Effects of intraventricular transplantation of NGF-secreting cells on cholinergic basal forebrain neurons after partial immunolesion

Rößner

Pizzo

et al. 1996

J. Neurosci. Res.

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The aim of the present study was to examine the effects of nerve growth factor on brain cholinergic function after a partial immunolesion to the rat cholinergic basal forebrain neurons (CBFNs) by 192 IgG‐saporin. Two weeks after intraventricular injections of 1.3 μg of 192 IgG‐saporin, about 50% of CBFNs were lost which was associated with 40–60% reductions of choline acetyltransferase (ChAT) and high‐affinity choline uptake (HACU) activities throughout the basal forebrain cholinergic system. Two groups of lesioned animals received intraventricular transplantations of mouse 3T3 fibroblasts retrovirally transfected with either the rat NGF gene (3T3NGF+) or the retrovirus alone (3T3NGF−) and were sacrificed eight weeks later. In vivo production of NGF by 3T3NGF+ cells was confirmed by NGF immunohistochemistry on the grafts and NGF immunoassay on cerebrospinal fluid (CSF) samples. Both ChAT and HACU activities returned to normal control levels in the basal forebrain and cortex after 3T3NGF+ transplants, whereas no recovery was observed in 3T3NGF− transplanted animals. There was a 25% increase in the size of remaining CBFNs and an increased staining intensity for NGF immunoreactivity in these cells after NGF treatments. Acetylcholinesterase (AChE) histochemistry revealed that the optical density of AChE‐positive fibers in the cerebral cortex and hippocampus were reduced by about 60% in immunolesioned rats which were completely restored by 3T3NGF+ grafts. In addition, decreases in growth‐associated protein (GAP)‐43 immunoreactivity after immunolesion and increases in synaptophysin immunoreactivity after 3T3NGF+ grafts were observed in the hippocampus. Our results further confirm the notion that transfected NGF‐secreting cells are useful in long‐term in vivo NGF treatment and NGF can upregulate CBFN function. They also highly suggest that NGF induces terminal sprouting from remaining CBFNs. © 1996 Wiley‐Liss, Inc.

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“…192 IgG-saporin, an immunotoxin linking an antibody to the low-affinity nerve growth factor receptor p75 to the ribosome inactivating protein saporin, has recently permitted specific lesioning of cholinergic neurons. When administered into the lateral ventricles, cholinergic neurons in the basal forebrain nuclei and some cerebellar Purkinje cells are destroyed (Heckers et al 1994;Waite et al 1994). The toxin spares GABAergic neurons in the basal forebrain and monoaminergic neurons because of its selectivity (Nilsson et al 1992;Heckers et al 1994;Waite et al 1994).…”

Section: Introductionmentioning

confidence: 99%

Changes in electrocortical power and coherence in response to the selective cholinergic immunotoxin 192 IgG-saporin

Holschneider

Waite

Leuchter

et al. 1999

Experimental Brain Research

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Changes in brain electrical activity in response to cholinergic agonists, antagonists, or excitotoxic lesions of the basal forebrain may not be reflective entirely of changes in cholinergic tone, in so far as these interventions also involve noncholinergic neurons. We examined electrocortical activity in rats following bilateral intracerebroventricular administration of 192 IgG-saporin (1.8 μg/ventricle), a selective cholinergic immunotoxin directed to the low-affinity nerve growth factor receptor p75. The immunotoxin resulted in extensive loss of choline acetyl transferase (ChAT) activity in neocortex (80%-84%) and hippocampus (93%), with relative sparing of entorhinalpiriform cortex (42%) and amygdala (28%). Electrocortical activity demonstrated modest increases in 1-to 4-Hz power, decreases in 20-to 44-Hz power, and decreases in 4-to 8-Hz intraand interhemispheric coherence. Rhythmic slow activity (RSA) occurred robustly in toxin-treated animals during voluntary movement and in response to physostigmine, with no significant differences seen in power and peak frequency in comparison with controls. Physostigmine significantly increased intrahemispheric coherence in lesioned and intact animals, with minor increases seen in interhemispheric coherence. Our study suggests that: (1) electrocortical changes in response to selective cholinergic deafferentation are more modest than those previously reported following excitotoxic lesions; (2) changes in cholinergic tone affect primarily brain electrical transmission within, in contrast to between hemispheres; and (3) a substantial

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Time course of cholinergic and monoaminergic changes in rat brain after immunolesioning with 192 IgG-saporin

Cited by 105 publications

References 23 publications

Effects of complete immunotoxin lesions of the cholinergic basal forebrain on fear conditioning and spatial learning

Effects of complete immunotoxin lesions of the cholinergic basal forebrain on fear conditioning and spatial learning

Effects of intraventricular transplantation of NGF-secreting cells on cholinergic basal forebrain neurons after partial immunolesion

Changes in electrocortical power and coherence in response to the selective cholinergic immunotoxin 192 IgG-saporin

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