192 IgG—Saporin‐induced Loss of Cholinergic Neurons in the Septum Abolishes Cholinergic Sprouting After Unilateral Entorhinal Lesion in the Rat

Naumann, T.; Deller, Thomas; Bender, Roland A.; Frotscher, Michael

doi:10.1111/j.1460-9568.1997.tb01485.x

Cited by 20 publications

(11 citation statements)

References 77 publications

(78 reference statements)

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“…All these observations are in agreement with previous reports (eg Schliebs et al, 1996). We also confirmed the report by Naumann et al (1997) who showed, to our knowledge in the only yet published study that relied upon the combination of EC and 192 IgG-saporin lesions, that the destruction of septal cholinergic neurons abolished septohippocampal cholinergic sprouting in the dentate gyrus. In our present study, however, cholinergic sprouting was strongly reduced, not abolished, probably because of the few septal cholinergic neurons that were not affected by the toxin.…”

Section: Igg-saporin Lesions: Memory Vs Attentionsupporting

confidence: 83%

Combined Damage to Entorhinal Cortex and Cholinergic Basal Forebrain Neurons, Two Early Neurodegenerative Features Accompanying Alzheimer's Disease: Effects on Locomotor Activity and Memory Functions in Rats

Traissard

Herbeaux

Cosquer

et al. 2006

Neuropsychopharmacol

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In Alzheimer's disease (AD), cognitive decline is linked to cholinergic dysfunctions in the basal forebrain (BF), although the earliest neuronal damage is described in the entorhinal cortex (EC). In rats, selective cholinergic BF lesions or fiber-sparing EC lesions may induce memory deficits, but most often of weak magnitude. This study investigated, in adult rats, the effects on activity and memory of both lesions, alone or in combination, using 192 IgG-saporin (OX7-saporin as a control) and L-N-methyl-D-aspartate to destroy BF and EC neurons, respectively. Rats were tested for locomotor activity in their home cage and for working-and/or reference-memory in various tasks (water maze, Hebb-Williams maze, radial maze). Only rats with combined lesions showed diurnal and nocturnal hyperactivity. EC lesions impaired working memory and induced anterograde memory deficits in almost all tasks. Lesions of BF cholinergic neurons induced more limited deficits: reference memory was impaired in the probe trial of the water-maze task and in the radial maze. When both lesions were combined, performance never improved in the water maze and the number of errors in the Hebb-Williams and the radial mazes was always larger than in any other group. These results (i) indicate synergistic implications of BF and EC in memory function, (ii) suggest that combined BF cholinergic and fiber-sparing EC lesions may model aspects of anterograde memory deficits and restlessness as seen in AD, (iii) challenge the cholinergic hypothesis of cognitive dysfunctions in AD, and (iv) contribute to open theoretical views on AD-related memory dysfunctions going beyond the latter hypothesis.

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Section: Igg-saporin Lesions: Memory Vs Attentionsupporting

confidence: 83%

Combined Damage to Entorhinal Cortex and Cholinergic Basal Forebrain Neurons, Two Early Neurodegenerative Features Accompanying Alzheimer's Disease: Effects on Locomotor Activity and Memory Functions in Rats

Traissard

Herbeaux

Cosquer

et al. 2006

Neuropsychopharmacol

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“…This could result from sprouting of cholinergic axons and cholinergic neo-synaptogenesis on vacant synaptic sites on dendrites of granule cells after deafferentation. Indeed, previous studies suggest such axonal sprouting after deafferentation induced through both entorhinal cortex lesion (Forster et al, 1997; Naumann et al, 1997; Ramirez, 2001) and CA3 lesion in the opposite hippocampus (Nadler et al, 1980a,b). From these perspectives, it is possible that lack of DG neurogenesis plasticity in the aged hippocampus to partial deafferentation at least partially stems from the absence of cholinergic sprouting to deafferentation stimuli.…”

Section: Discussionmentioning

confidence: 93%

Deafferentation enhances neurogenesis in the young and middle aged hippocampus but not in the aged hippocampus

Shetty¹,

Hattiangady

Rao

et al. 2011

Hippocampus

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Increased neurogenesis in the dentate gyrus (DG) after brain insults such as excitotoxic lesions, seizures or stroke is a well known phenomenon in the young hippocampus. This plasticity reflects an innate compensatory response of neural stem cells (NSCs) in the young hippocampus to preserve function or minimize damage after injury. However, injuries to the middle-aged and aged hippocampi elicit either no or dampened neurogenesis response, which could be due to an altered plasticity of NSCs and/or the hippocampus with age. We examined whether the plasticity of NSCs to increase neurogenesis in response to a milder injury such as partial deafferentation is preserved during aging. We quantified DG neurogenesis in the hippocampus of young, middle-aged and aged F344 rats after partial deafferentation. A partial deafferentation of the left hippocampus without any apparent cell loss was induced via administration of Kainic acid (0.5 μg in 1.0 μl) into the right lateral ventricle of the brain. In this model, degeneration of CA3 pyramidal neurons and dentate hilar neurons in the right hippocampus results in loss of commissural axons which leads to partial deafferentation of the dendrites of dentate granule cells and CA1-CA3 pyramidal neurons in the left hippocampus. Quantification of newly born cells that are added to the dentate granule cell layer at post-deafferentation days 4-15 using 5′-bromodeoxyuridine (BrdU) labeling revealed greatly increased addition of newly born cells (~3 fold increase) in the deafferented young and middle-aged hippocampi but not in the deafferented aged hippocampus. Measurement of newly born neurons using doublecortin (DCX) immunostaining also revealed similar findings. Analyses using BrdU-DCX dual immunofluorescence demonstrated no changes in neuronal fate-choice decision of newly born cells after deafferentation, in comparison to the age-matched naive hippocampus in all age groups. Thus, the plasticity of hippocampal NSCs to increase DG neurogenesis in response to a milder injury such as partial hippocampal deafferentation is preserved until middle age but lost at old age.

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“…One might also reasonably question whether the AChE label is a valid marker for the cholinergic nature of the septodentate pathway (Aubert et al, 1994). Naumann et al (1997) recently demonstrated that the selective destruction of cholinergic septal neurons with 192 IgGsaporin (a neurotoxin that selectively destroys cholinergic neurons in the basal forebrain) (Heckers et al, 1994) eliminated the AChE-containing septodentate pathway that normally sprouts after an entorhinal lesion. Finally, the possibility exists that increases in OML density may be an artifact of shrinkage, because there is such a massive denervation after a unilateral entorhinal lesion.…”

Section: Discussionmentioning

confidence: 99%

Adeno-Associated Virus Vector Expressing Nerve Growth Factor Enhances Cholinergic Axonal Sprouting after Cortical Injury in Rats

et al. 2003

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Nerve growth factor (NGF) is known to promote both the survival of cholinergic neurons after injury and the regeneration of damaged cholinergic axons. Recent evidence has implicated NGF in the regulation of cholinergic axonal sprouting by intact neurons projecting to the hippocampus of rats, sustaining a lesion of the entorhinal cortex. We explored the possibility that NGF may regulate this lesioninduced cholinergic sprouting by injecting recombinant adeno-associated virus (rAAV) vector expressing NGF and green fluorescent protein (GFP) into the dentate gyrus of rats that were subsequently given unilateral entorhinal lesions. Sprague Dawley rats were unilaterally injected with (1) rAAV vector expressing NGF and GFP or (2) rAAV vector expressing GFP. Fourteen days after injection, the animals received lesions of the entorhinal area ipsilateral to the virus injection. Four days after lesion, GFP expression and the septodentate sprouting response in the dentate gyrus were assessed. Optical densitometric analyses revealed a significant increase in acetylcholinesterase label (a marker for cholinergic septodentate sprouting) in the ipsilateral outer molecular layer of the dentate gyrus in rats injected with rAAV vector expressing NGF. Thus, NGF-expressing rAAV vector enhanced the sprouting response of intact cholinergic neurons after unilateral entorhinal lesions in rats.

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192 IgG—Saporin‐induced Loss of Cholinergic Neurons in the Septum Abolishes Cholinergic Sprouting After Unilateral Entorhinal Lesion in the Rat

Cited by 20 publications

References 77 publications

Combined Damage to Entorhinal Cortex and Cholinergic Basal Forebrain Neurons, Two Early Neurodegenerative Features Accompanying Alzheimer's Disease: Effects on Locomotor Activity and Memory Functions in Rats

Combined Damage to Entorhinal Cortex and Cholinergic Basal Forebrain Neurons, Two Early Neurodegenerative Features Accompanying Alzheimer's Disease: Effects on Locomotor Activity and Memory Functions in Rats

Deafferentation enhances neurogenesis in the young and middle aged hippocampus but not in the aged hippocampus

Adeno-Associated Virus Vector Expressing Nerve Growth Factor Enhances Cholinergic Axonal Sprouting after Cortical Injury in Rats

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