Effects of cholinergic-rich neural grafts on radial maze performance of rats after excitotoxic lesions of the forebrain cholinergic projection system—I. Amelioration of cognitive deficits by transplants into cortex and hippocampus but not into basal forebrain

Hodges, Helen; Allen, Y.S.; Kershaw, T. R.; Lantos, Peter L.; Gray, Jeffrey A.; Sinden, John D.

doi:10.1016/0306-4522(91)90273-q

Cited by 106 publications

(24 citation statements)

References 76 publications

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“…Whether this was due to active migration of the implanted fetal cells or to passive displacement, e.g., within the lateral ventricle of the growing brain, is unclear. Displacement or migration of grafted cholinergic neurons has been reported so far only in neonatal hosts (Lewis and Cotman, 1980) but not in adult hosts (see, e.g., Bjorklund and Stenevi, 1977;Bjorklund et al, 1983c;Nilsson et al, 1988;Hodges et al, 1991). The capacity of immature fetal neurons and neuroblasts to migrate over limited distances within the neonatal brain has been observed previously after transplantation into the developing neocortex (McConnell, 1985(McConnell, , 1988McConnell and Kaznowski, 1991).…”

Section: Growth Properties Of the Intraseptal Graftsmentioning

confidence: 80%

Extensive reinnervation of the hippocampus by embryonic basal forebrain cholinergic neurons grafted into the septum of neonatal rats with selective cholinergic lesions

et al. 1996

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Reconstruction of the septohippocampal pathways by axons extending from embryonic cholinergic neuroblasts grafted into the neuron-depleted septum has been explored in the neonatal rat by using a novel lesioning and grafting protocol. Neonatal ablation of the basal forebrain cholinergic projection neurons, accompanied by extensive bilateral cholinergic denervation of the hippocampus and neocortex, was produced at postnatal day (PD) 4 by 192 immunoglobulin (IgG)-saporin intraventricularly. Four days later, cholinergic neuroblasts (from embryonic day 14 rats) were implanted bilaterally into the neuron-depleted septum by using a microtransplantation approach. The results show that homotopically implanted septal neurons survive and integrate well into the developing septal area, extending axons caudally along the myelinated fimbria-fornix and supracallosal pathways that are able to reach the appropriate targets in the denervated hippocampus and cingulate cortex as early as 4 weeks postgrafting. Moreover, the laminar innervation patterns established by the graft-derived axons closely resembled the normal ones and remained essentially unchanged up to at least 6 months, which was the longest postoperative time studied. The reinnervating fibers restored tissue choline acetyltransferase activity (up to 50% of normal) in the dorsal hippocampus and the parietooccipital cortex. Retrograde labeling with Fluoro-Gold from the host hippocampus combined with immunocytochemistry confirmed that most of the projecting neurons, indeed, were cholinergic. The results suggest that the graft-host interactions that are necessary for target-directed axon growth are present in the septohippocampal system during early postnatal maturation. Thus, the present approach may contribute to overcome the functional limitations inherent in the use of ectopically placed intrahippocampal transplants.

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Section: Growth Properties Of the Intraseptal Graftsmentioning

confidence: 80%

Extensive reinnervation of the hippocampus by embryonic basal forebrain cholinergic neurons grafted into the septum of neonatal rats with selective cholinergic lesions

et al. 1996

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“…Consequently, rats showing impaired use of visuospatial cues may solve the task by alternative associative processes, involving associations with local cues, such as odours, for example [209]. However, a difference has emerged between the MWM and RAM tasks regarding the use of alternative strategies with some evidence suggesting that RAM allows more chance for the adoption of alternative strategies for spatial navigation [89,90,93]. This is because the RAM task involves a choice between discrete arms which make it more likely that the rat will associate each arm with local cues, like odour trails or textures, which is not possible in MWM [89] ( Table 2).…”

Section: Comparison Between the Radial Arm Maze And Morris Water Mazementioning

confidence: 99%

The impact of flavonoids on spatial memory in rodents: from behaviour to underlying hippocampal mechanisms

et al. 2009

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Emerging evidence suggests that a group of dietary-derived phytochemicals known as flavonoids are able to induce improvements in memory, learning and cognition. Flavonoids have been shown to modulate critical neuronal signalling pathways involved in processes of memory, and therefore are likely to affect synaptic plasticity and long-term potentiation mechanisms, widely considered to provide a basis for memory. Animal dietary supplementation studies have further shown that flavonoidrich foods are able to reverse age-related spatial memory and spatial learning impairments. A more accurate understanding of how a particular spatial memory task works and of which aspects of memory and learning can be assessed in each case, are necessary for a correct interpretation of data relating to diet-cognition experiments. Further understanding of how specific behavioural tasks relate to the functioning of hippocampal circuitry during learning processes might be also elucidative of the specific observed memory improvements. The overall goal of this review is to give an overview of how the hippocampal circuitry operates as a memory system during behavioural tasks, which we believe will provide a new insight into the underlying mechanisms of the action of flavonoids on cognition.

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“…After ibotenate lesions to the MS, at the source of the hippocampal branches of the forebrain cholinergic projection system, rats displayed long-lasting stable impairment in reference and working memory in both spatial (place) and associative (cue) radial maze tasks (12,13). Injections of ibotenic acid into the MS or the NBM in rats produced decreased activities of ChAT in the hippocampus and frontal cortex, respectively, followed by impairment in memory acquisition (37).…”

Section: Discussionmentioning

confidence: 99%

“…Lesion of the MS in animals has been widely accepted as animal model of memory loss (12,13). Cognitive dysfunctions after lesioning the MS are mainly considered to be due to deafferentiation of the hippocampus, which plays a pivotal role in learning and memory (14,15).…”

Section: Introductionmentioning

confidence: 99%

Effects of Methanol Extract of Uncariae Ramulus et Uncus on Ibotenic Acid-Induced Amnesia in the Rat

et al. 2004

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Abstract. In the present study, we investigated the effects of Uncariae Ramulus et Uncus (UR) on learning and memory in the Morris water maze task and the central cholinergic system of rats with excitotoxic medial septum (MS) lesion. In the water maze test, the animals were trained to find a platform in a fixed position during 6 days and then received a 60-s probe trial in which the platform was removed from the pool on the 7th day. Ibotenic lesion of the MS showed impaired performance of the maze test and severe cell losses in the septohippocampal cholinergic system (SHC), as indicated by decreased choline acetyltransferase-immunoreactivity and acetylcholinesterase-reactivity in the hippocampus. Daily administrations of UR (100 mg / kg, i.p.) for 21 consecutive days produced significant reversals of ibotenic acid-induced deficit in learning and memory. These treatments also reduced the loss of cholinergic immunoreactivity in the hippocampus induced by ibotenic acid. These results demonstrated that impairments of spatial learning and memory may be attributable to degeneration of SHC neurons and that UR ameliorated learning and memory deficits partly through neuroprotective effects on the central acetylcholine system. Our studies suggest that UR may be useful in the treatment of Alzheimer's disease.

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Effects of cholinergic-rich neural grafts on radial maze performance of rats after excitotoxic lesions of the forebrain cholinergic projection system—I. Amelioration of cognitive deficits by transplants into cortex and hippocampus but not into basal forebrain

Cited by 106 publications

References 76 publications

Extensive reinnervation of the hippocampus by embryonic basal forebrain cholinergic neurons grafted into the septum of neonatal rats with selective cholinergic lesions

Extensive reinnervation of the hippocampus by embryonic basal forebrain cholinergic neurons grafted into the septum of neonatal rats with selective cholinergic lesions

The impact of flavonoids on spatial memory in rodents: from behaviour to underlying hippocampal mechanisms

Effects of Methanol Extract of Uncariae Ramulus et Uncus on Ibotenic Acid-Induced Amnesia in the Rat

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