Graft-induced behavioral recovery from subcallosal septohippocampal damage in rats depends on maturity stage of donor tissue (original) (raw)
Related papers
Experimental Brain Research, 1988
Fetal septal transplants have been shown to promote behavioral recovery in young adult rats with aspiration fimbria-fornix lesions, rats with septal lesions and in intact aged rats. The present study examined the behavioral impact of intrahippocampal septal cell suspension transplants (T) in young female rats that had received, l0 days earlier, either medial fimbria lesions (Group FI.T), dorsal (subcallosal) fornix lesions (Group FO.T) or these two lesions together (Group FIFO.T). Relative to rats with lesions only (groups FI, FO and FIFO), grafted rats, irrespective of lesion locus, displayed unexpected impairments in (i) a serial alternation learning task, 5 weeks and 6 months after transplantation, and (ii) in a radial maze, 7 months after transplantation. In the first alternation test, Group FIFO showed impaired performance relative to Groups FI, FO and the sham-operated controls (Group S). In the second alternation test, Groups FO.T and FO showed impaired performance relative to Groups FI.T and FI, and only the performance of Group FI did not differ from that of Group S. In the radial maze, Groups FI, FO and FIFO all showed impaired performance relative to Group S. By contrast, there were no deleterious effects of lesions or of grafts in the acquisition and retention of a step-through passive avoidance task, 10 weeks after transplantation. Our findings on the effects of selective fimbria-fornix lesions did not confirm the report that rats with FI lesions but not those with FO lesions are unable to learn a serial alternation task, nor the report that FO lesions impair passive avoidance retention. Acetylcholinesterase (ACHE) histochemistry revealed that grafts were present but graft-derived innervation of the host hippocampus varied from extensive to
Brain Research Bulletin, 1999
Three-month-old Long-Evans female rats sustained aspirative lesions of the dorsal septohippocampal pathways and, 2 weeks later, received intrahippocampal suspension grafts containing cells from the mesencephalic raphe, cells from the medial septum and the diagonal band of Broca, or a mixture of both. Lesion-only and sham-operated rats were used as controls. All rats were tested for locomotor activity 1 week, 3 and 5 months after lesion surgery, for spatial working memory in a radial maze from 5 to 9 months, and for reference and working memory in a water tank during the 9th month after lesioning. Determination of hippocampal concentration of acetylcholine, noradrenaline, and serotonin was made after completion of behavioral testing. Compared to sham-operated rats, all rats with lesions, whether grafted or not, exhibited increased levels of locomotor activity and made more errors in the radial maze. The lesioned rats were also impaired in the probe trial (30 first seconds) of the water-tank test made according to a protocol requiring intact reference memory capabilities. While rats with septal or raphe grafts were also impaired, the rats with co-grafts showed performances not significantly different from those of sham-operated rats. With a protocol requiring intact working memory capabilities, all lesioned rats, whether grafted or not, were impaired in the water-tank test. In the dorsal hippocampus of lesion-only rats, the concentration of acetylcholine and serotonin was significantly reduced. In rats with septal grafts or co-grafts, the concentration of acetylcholine was close to normal, as was that of serotonin in rats with raphe grafts or co-grafts. These results confirm previous findings showing that co-grafts enabled the neurochemical properties of single grafts to be combined. Data from the water-tank test suggest that cholinergic and serotonergic hippocampal reinnervations by fetal cell grafts may induce partial recovery of spatial reference, but not working memory capabilities in rats.
Neuroscience, 1998
Lesions of the septohippocampal pathway produce cognitive deficits that are partially attenuated by grafts of cholinergic-rich tissue into denervated target regions or by systemic administration of cholinomimetic drugs. In the present study, fibroblasts engineered to produce acetylcholine were used to test the hypothesis that restoration of hippocampal acetylcholine in rats with septohippocampal lesions is sufficient to improve cognitive processing post-damage. Rats received unilateral grafts of acetylcholineproducing or control fibroblasts into the hippocampus immediately prior to an aspirative lesion of the ipsilateral fimbria-fornix. Some rats with fimbria-fornix lesions were implanted with acetylcholineproducing or control fibroblasts into the neocortex, another major target of the basal forebrain cholinergic system, to determine if the site of acetylcholine delivery to the damaged brain is critical for functional recovery. Rats were tested in a hidden platform water maze task, a cued water maze task and activity chambers between one and three weeks post-grafting. Compared to unoperated controls, rats with fimbria-fornix lesions only were significantly impaired in hidden platform water maze performance. Hippocampal grafts of acetylcholine-producing cells reduced lesion-induced deficits in the water maze, whereas hippocampal control grafts and cortical grafts of either cell type were without effect. Locomotor activity and cued water maze performance were unaffected by the lesion or the implants.
Brain Research, 1988
The septal/diagonal band (SDB) area, obtained from a 9-to 10-week-old aborted human fetus, was grafted to the hippocampal formation of adult, immunosuppressed rats subjected to an aspirative lesion of the fimbria-fornix. Nineteen weeks after transplantation, microscopical analysis revealed large, partly acetylcholinesterase (AChE)-positive grafts in the hippocampus in 3 of the 5 recipients. The AChE-positive grafts gave rise to a reinnervation of the host hippocampus and an AChE-positive lamination of the different hippocampal subfields with the same characteristics as the normal septum-derived innervation. Immunological evaluation of host sera revealed that all rats were immunized by the graft. This indicates that grafted human cholinergic SDB neurons can respond to or interact with factors that regulate and guide the innervation of the rat hippocampus.
Neural Plasticity, 1997
Two groups of Sprague-Dawley male rats received bilateral aspirative lesions of the fimbriafornix under chloral hydrate anesthesia. One group (n=9) received no further treatment (lesioned). In the second group (n=8), a piece of septal fetal tissue, obtained at day E15-16, was implanted into each lesion cavity (transplanted). A third group consisted of shamlesioned rats (controls, n=14). Two months after the operations, a recording electrode was implanted in the hilar region of the dentate gyrus of each animal, and a bipolar stimulating electrode was implanted in the perforant path.
Brain Research Bulletin, 1992
Transplantarion offetal cholinergic neurons into the hippocampus attenuates the cognitive and neurochemical deficits induced by AF64A. BRAIN RES BULL 28(2) 219-226, 1992.-The present experiments examined whether transplanted fetal cholinergic neurons would attenuate the behavioral and nemochemical deficits induced by the cholinotoxin AF64A (ethylcholine aziridinium ion). Bilateral injections of AF64A (3 nmol) into the laterai ventricles produced significant learning and memory impairments together with decreases in hippocampal hi~-~~ni~ choline uptake (HAChU). AF64A-treated rats were impaired on both a standard radial arm maze (RAM) task and a working memory version in which a one-hour delay was imposed between tbe fourth and fifth arm choices. Transplan~tion of embryonic day E-17 septapdiagonal band tissue into the hippocampus (HPC) promoted recovery of performance on the standard version of the RAM task. However, this recovery was not observed when tbe animals were tested on the more difficult delay version of the task. Neurochemical analysis indicated that AF64A produced a significant (31%) decrease in hippocampal HAChU that was attenuated (14%) by transplantation of fetal cholinergic neurons. Histological analysis revealed that the transplants survived and innervated the HFC. There was no apparent relationship between fiber ingrowth into the HFC and behavioral recovery. These data indicate that transplant-induced behaviorai recovery may be related to and hmited by the cognitive demands of the testing si~ation. Generalized increases in cholinergic activity, ~~splant-mediated release of trophic factors, or a combination of both may underlie the behavioral recovery observed in the present studies. Hippocampus Septum Neural transplantation AF64A Radial arm maze
Brain Research, 1989
Three groups of rats showing disrupted taste aversion due to gustatory neocortex lesions, were studied. One group received a transplant of homotopic conical tissue, another of heterotopic tectal tissue, obtained from 17-day-old fetuses. The third group remained without transplant as a lesioned control group. Comparisons of the taste aversion scores before and after graft, revealed that cortical grafted animals significantly improved the taste aversion, whereas those which received tectal grafts, and the cortical-lesioned controis did not. Moreover, results with horseradish peroxidase (HRP) histochemistry revealed that the homotopic, but not the heterotopic, brain transplants we~ able to re-establish connections with amygdala and with the ventromedial nucleus of the thalamus areas who normally kept connectivity with the gustatory neocortex. These results support the hypothesis that fetal brain transplants can reestablish cognitive functions, as well as connectivity with its host tissue.
Neocortical Grafting to Newborn and Adult Rats: Developmental, Anatomical and Functional Aspects
Advances in Anatomy Embryology and Cell Biology, 1998
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Neuroscience, 1992
Ah&met--Monkeys with bilateral transection of the fomix were severely but selectively impaired on learning and retention of visuospatial conditional discriminations, visual conditional discriminations and non-conditional spatial-response tasks. Bilateral transplantation of cholinergic-rich fetal basal forebrain tissue into the hippocampus abolished significant learning impairments on all those tasks impaired by fomix lesions when tested three to nine months after transplantation whereas bilateral transplants of non-cholinergic fetal hippocampal tissue into hippocampus showed no such beneficial effect. Acetylcholinesterase staining was severely depleted throughout the dentate gyms and hippocampus in fomixtransected monkeys compared with animals with control corpus callosum ablations. Staining was largely restored to normal in the host hippocampus and dentate gyms in monkeys with cholinergic transplants, whereas acetylcholinesterase staining was abnormal in those with non-choline@ grafts. These experiments suggest that where a 'higher order" cognitive function, in this case the acquisition of specific types of information into long-term memory, is disturbed by a neuropharmacologically simple lesion, cognitive function can be restored by transplantation of neurons containing appropriate neurotransmitters.