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  • Selective neuronal death  (2)
  • 2-deoxyglucose autoradiography  (1)
  • 1
    ISSN: 1432-1106
    Keywords: 5-Hydroxytryptamine ; Substance P ; Thyrotropin releasing hormone ; Transplantation ; Medullary and mesencephalic raphé ; Fibre outgrowth ; Selective neuronal death
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Suspensions of cells taken from the mesencephalic or medullary raphé regions of the 13–14 day old embryonic rat brain were injected into the hippocampus of adult rats which had previously been denervated of its serotoninergic input by 5,7-dihydroxytryptamine. At periods of up to 14 months after implantation, the brains were taken for immunohistochemical analysis of 5-hydroxytryptamine (5HT)-, substance P (SP)- and thyrotropin releasing hormone (TRH)-like immunoreactivity. Surviving grafts were found in all animals. The implants derived from mesencephalic raphé contained neurones immunoreactive to 5HT, SP or both substances together. On average 19% of the potential number of mesencephalic 5HT neurones were found in the grafts. Outgrowth of 5HT-immunoreactive fibres was extensive, and displayed the typical pattern of 5HT innervation in the normal hippocampus — the densest plexuses were found in the dentate gyrus, with sparser networks in the CA1 and CA2 regions. SP-positive processes were principally found only in the graft itself. Transplants of medullary raphé cells contained 5HT-immunoreactive neurones, some of which also contained SP- and/or TRH-like immunoreactivity, thereby mirroring the situation found in the caudal raphé complex in situ. An average of 18% of the total available medullary serotoninergic neurones were found at each graft site. A rich outgrowth of 5HT-immunoreactive varicose processes was evident, with the same pattern as the 5HT innervation by the mesencephalic raphé grafts, and as in the normal hippocampus. SP- and TRH-positive fibres were essentially detectable only in the graft, but not in the host hippocampus. The present studies indicate that the milieu of the hippocampus does not preferentially attenuate the survival of the serotoninergic cells which do not normally project to it. Nor is the fibre outgrowth of these medullary raphé 5HT neurones significantly different from that of the mesencephalic raphé. However, the hippocampal environment may be responsible for the appearance of SP-LI in the otherwise apparently solely 5HT-containing mesencephalic raphé neurones, and for repressing the outgrowth of fibres containing TRH-, or SP-like immunoreactivity, regardless of their origin.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1106
    Keywords: Septal transplants ; Septo-hippocampal pathway ; 2-deoxyglucose autoradiography ; Acetylcholine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Transection of the septo-hippocampal connections through fimbria-fornix damage in the rat results in profound hippocampal cholinergic deafferentation, and, when applied bilaterally, leads to severe and long-lasting impairments in learning and memory. Previous studies have shown that intrahippocampal septal grafts can reestablish a new cholinergic innervation in the inititally denervated hippocampal formation and at least partly compensate for the lesion-induced learning impairments in fimbria-fornix lesioned rats. The purpose of the present study was to determine the magnitude of lesion-induced alterations in cerebral function as reflected in local glucose use measured by (14C)-2-deoxyglucose (2-DG) autoradiography, and the degree to which this index of functional activity could be normalized following reinnervation from transplants of fetal cerebral tissue from the primordial septal region. Six months after unilateral fimbriafornix transection the rate of glucose utilization was reduced markedly throughout the ipsilateral hippocampus when compared to the intact contralateral side, while in the neocortex only the cingulate cortex showed long-lasting reductions in glucose use. Rats that received a transplant of fetal septal-diagonal band tissue at the time of fimbria-fornix transection, and were sacrificed 6 months later, displayed significantly greater glucose utilization in the ipsilateral hippocampus and cingulate cortex than was measured in these areas in rats with lesion alone. The recovery in glucose use was paralleled by a significant increase in acetylcholinesterase (AChE) staining in several areas of the ipsilateral hippocampal formation and cingulate cortex. This index of graft-induced cholinergic reinnervation was, moreover, significantly correlated with the rate of glucose use. Thus, in the fimbria-fornix transected animals the magnitude of glucose depression correlated with the extent of reduction in AChE staining, and in the grafted animals the degree of normalization of glucose use was correlated with the graft-induced increase in AChE-staining density. These results thus indicate that the 2-DG autoradiographic technique can provide a unique opportunity to map both altered functional activity in localized areas of the brain following specific lesions and the extent to which transplant-derived reinnervation of the host may induce a return to normal functional levels in the target site.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1106
    Keywords: Transplantation ; Medullary and mesencephalic raphé ; Host spinal cord ; Transmitter phenotypy ; Fibre outgrowth ; Selective neuronal death
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Suspensions of cells derived from the mesencephalic raphé or medullary raphé regions of the 13–14 day old embryonic rat brain were injected into the spinal cord of adult rats which had been previously denervated with 5,7-dihydroxytryptamine. At periods of up to 12 months after grafting, the spinal cords were taken for immunohistochemical analysis of 5-hydroxytryptamine (5HT), substance P (SP) and thyrotropin releasing hormone (TRH). In nearly all cases, surviving transplants were found. The grafts derived from mesencephalic raphé cells contained neurones which were immunoreactive to 5HT, or SP, but not both together. On average 4% of the total possible number of the available embryonic mesencephalic serotoninergic cells were found. A very dense outgrowth of 5HT positive fibres from the transplant was observed, extending up to 1.5 cm in both the caudal and rostral directions from the graft locus. Some SP immunoreactive fibres were also apparent near the implant. The grafts derived from the medullary transplant also contained 5HT-immunoreactive cells, comprising on average 25% of the total 5HT neurones available from the embryonic medullary primordium. In addition, neurones colocalizing 5HT together with SP and TRH were visible, closely reflecting the situation found in the medullary raphé in situ. Dense plexi of fibres containing 5HT-LI extended both caudally and rostrally up to 12–15 mm from the transplant. Outgrowth of SP and TRH varicose fibres was also demonstrable, although to a lesser degree than for 5HT. It was also possible to find many motoneurones surrounded by varicose fibres containing both 5HT and SP, in contrast to the situation with the mesencephalic grafts, where no such patterns of innervation were seen. The experiments indicate that the milieu of the spinal cord may compromise the survival of mesencephalic raphé 5HT neurones far more than of medullary serotonin cells. However, despite this effect on cell survival, the outgrowth of fibres from the remaining mesencephalic 5HT neurones was apparently unaffected by their ectopic position. Similarly, the transmitter content of both classes of raphé cells was largely unaltered, either by the transplantation process or by the environment into which they were placed. It is concluded that although the adult denervated spinal cord can selectively affect neuronal survival, it is incapable either of inducing in other serotoninergic cells placed within it the transmitter phenotype typical of medullary raphé neurones, or of causing those ectopically located 5HT cells to form connections appropriate to the descending serotonin fibres.
    Type of Medium: Electronic Resource
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