Intraparenchymal infusions of 192 IgG-saporin: development of a method for selective and discrete lesioning of cholinergic basal forebrain nuclei

Pizzo, Donald; Waite, Jerene J.; Thal, Leon J.; Winkler, Jürgen

doi:10.1016/s0165-0270(99)00057-6

Cited by 56 publications

(45 citation statements)

References 35 publications

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“…The results of unilateral injections (n ϭ 17) (data not shown) were very similar to those of bilateral injections in terms of injection sites and the degrees of cell loss on the affected side. It has previously been reported that intraparenchymal injections of 192IgG-SAP did not destroy noncholinergic BF neurons containing neurotensin, galanin, somatostatin, NADPH-diaphorase, or neuropeptide Y (Wenk et al, 1994), nor did they affect cortical monoamine levels (Pizzo et al, 1999). Figure 3 shows representative microscopic images of the NBM/SI region depicting abundant PARV-positive (ϩ) and VAChTϩ neurons after ACSF injection ( A, B); a marked loss of PARVϩ neurons and a moderate loss of VAChTϩ neurons after IBO injection (C,D); and no apparent loss of PARVϩ neurons but a nearly complete loss of VAChTϩ neurons after SAP injection ( E, F ).…”

Section: Histological Analyses Of Ibo and 192igg-sap Lesionsmentioning

confidence: 92%

Effects of Ibotenate and 192IgG-Saporin Lesions of the Nucleus Basalis Magnocellularis/Substantia Innominata on Spontaneous Sleep and Wake States and on Recovery Sleep after Sleep Deprivation in Rats

Kaur¹,

Junek²,

Black³

et al. 2008

J. Neurosci.

115

110

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The basal forebrain (BF) is known for its role in cortical and behavioral activation, and has been postulated to have a role in compensatory mechanisms after sleep loss. However, specific neuronal phenotypes responsible for these roles are unclear. We investigated the effects of ibotenate (IBO) and 192IgG-saporin (SAP) lesions of the caudal BF on spontaneous sleep-waking and electroencephalogram (EEG), and recovery sleep and EEG after 6 h of sleep deprivation (SD). Relative to artificial CSF (ACSF) controls, IBO injections decreased parvalbumin and cholinergic neurons in the caudal BF by 43 and 21%, respectively, and cortical acetylcholinesterase staining by 41%. SAP injections nonsignificantly decreased parvalbumin neurons by 11%, but significantly decreased cholinergic neurons by 69% and cortical acetylcholinesterase by 84%. IBO lesions had no effect on sleep-wake states but increased baseline delta power in all states [up to 62% increase during non-rapid eye movement (NREM) sleep]. SAP lesions transiently increased NREM sleep by 13%, predominantly during the dark phase, with no effect on EEG. During the first 12 h after SD, animals with IBO and SAP lesions showed lesser rebound NREM sleep (32 and 77% less, respectively) and delta power (78 and 53% less) relative to ACSF controls. These results suggest that noncholinergic BF neurons promote cortical activation by inhibiting delta waves, whereas cholinergic BF neurons play a nonexclusive role in promoting wake. Intriguingly, these results also suggest that both types of BF neurons play important roles, probably through different mechanisms, in increased NREM sleep and EEG delta power after sleep loss.

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Section: Histological Analyses Of Ibo and 192igg-sap Lesionsmentioning

confidence: 92%

Effects of Ibotenate and 192IgG-Saporin Lesions of the Nucleus Basalis Magnocellularis/Substantia Innominata on Spontaneous Sleep and Wake States and on Recovery Sleep after Sleep Deprivation in Rats

Kaur¹,

Junek²,

Black³

et al. 2008

J. Neurosci.

115

110

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“…Tissue was homogenized by sonication in 100 l of a solution containing 0.1% Triton X-100 and 0.87 mM EDTA, pH 7.0, and was not further diluted because of the low activity present at this stage. ChAT activity was assayed in triplicate by the incorporation of 14 Cacetyl-coenzyme A into 14 C-acetylcholine as described previously and is expressed as nanomoles of ACh synthesized per hour per milligram of protein (Pizzo et al, 1999).…”

Section: Methodsmentioning

confidence: 99%

Aberrant Patterning of Neuromuscular Synapses in Choline Acetyltransferase-Deficient Mice

et al. 2003

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In this study we examined the developmental roles of acetylcholine (ACh) by establishing and analyzing mice lacking choline acetyltransferase (ChAT), the biosynthetic enzyme for ACh. As predicted, ChAT-deficient embryos lack both spontaneous and nerve-evoked postsynaptic potentials in muscle and die at birth. In mutant embryos, abnormally increased nerve branching occurs on contact with muscle, and hyperinnervation continues throughout subsequent prenatal development. Postsynaptically, ACh receptor clusters are markedly increased in number and occupy a broader muscle territory in the mutants. Concomitantly, the mutants have significantly more motor neurons than normal. At an ultrastructural level, nerve terminals are smaller in mutant neuromuscular junctions, and they make fewer synaptic contacts to the postsynaptic muscle membrane, although all of the typical synaptic components are present in the mutant. These results indicate that ChAT is uniquely essential for the patterning and formation of mammalian neuromuscular synapses.

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“…In these studies, 90 of 100 young adult female Long-Evans rats received bilateral injections of 192 IgG-saporin into the nucleus basalis magnocellularis and medial septum to deplete the cholinergic innervation of the cerebral cortex and hippocampus, respectively (Pizzo et al, 1999). Rats were anaesthetized with isoflurane and under stereotaxic guidance (coordinates: medial septum; AP + 0.6, L 1.2, D À7.5, À6.8 from bregma; nucleus basalis; AP À1, L73, D À7.5), 192 IgG-saporin (0.1 mg in 1.0 ml of phosphate-buffered saline, pH 7.4, over 15 s) was infused into each site.…”

Section: Behavioral Studiesmentioning

confidence: 99%

Cognitive Deficits in Rats after Forebrain Cholinergic Depletion are Reversed by a Novel NO Mimetic Nitrate Ester

Bennett

Reynolds

Prusky

et al. 2006

Neuropsychopharmacol

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Many conditions adversely affecting learning, memory, and cognition are associated with reductions in forebrain acetylcholine (ACh), most notably aging and Alzheimer's disease. In the current study, we demonstrate that bilateral depletion of neocortical and hippocampal ACh in rats produces deficits in a spatial learning task and in a recently described, delayed visual matching-to-sample task. Oral administration of the novel nitrate, GT1061 (4-methyl-5-(2-nitroxyethyl) thiazole HCl), and the acetylcholinesterase inhibitor, donepezil, reversed the cognitive deficits in both memory tasks in a dose-dependent manner. GT1061 was superior in the delayed matching-tosample task. GT1061 was absorbed rapidly after oral administration, crossed the blood brain barrier, and achieved brain concentrations that were slightly higher than those found in plasma. The activity of GT1061 was NO mimetic: soluble guanylyl cyclase (sGC) was activated, but selectivity was observed for sGC in the hippocampus relative to the vasculature; and hippocampal levels of phosphorylated ERK1/2, which is a postulated intermediary in the formation of long-term memory, were increased. The beneficial effect on visual and spatial memory task performance supports the concept that stimulating the NO/sGC/cGMP signal transduction system can provide new, effective treatments for cognitive disorders. This approach may be superior to that of current drugs that attempt only to salvage the residual function of damaged cholinergic neurons. Neuropsychopharmacology (2007) 32, 505-513.

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Intraparenchymal infusions of 192 IgG-saporin: development of a method for selective and discrete lesioning of cholinergic basal forebrain nuclei

Cited by 56 publications

References 35 publications

Effects of Ibotenate and 192IgG-Saporin Lesions of the Nucleus Basalis Magnocellularis/Substantia Innominata on Spontaneous Sleep and Wake States and on Recovery Sleep after Sleep Deprivation in Rats

Effects of Ibotenate and 192IgG-Saporin Lesions of the Nucleus Basalis Magnocellularis/Substantia Innominata on Spontaneous Sleep and Wake States and on Recovery Sleep after Sleep Deprivation in Rats

Aberrant Patterning of Neuromuscular Synapses in Choline Acetyltransferase-Deficient Mice

Cognitive Deficits in Rats after Forebrain Cholinergic Depletion are Reversed by a Novel NO Mimetic Nitrate Ester

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