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Comparison of growth and reinnervation properties of cholinergic neurons from different brain regions grafted to the hippocampus

Nilsson, O G LU ; Clarke, D J ; Brundin, P LU and Björklund, A LU orcid (1988) In Journal of Comparative Neurology 268(2). p.22-204
Abstract

Grafts of five different types of central cholinergic neurons, from the septal-diagonal band region, the nucleus basalis magnocellularis region (NBM), the striatum, the pontomesencephalic tegmentum of the brainstem, and the spinal cord, were compared with respect to their ability to grow and to reinnervate the cholinergically denervated hippocampal formation of adult rats. The areas were dissected from 14 to 15-day-old rat fetuses, and the same number of viable cells (35 X 10(4) from each of the different regions were stereotaxically injected as cell suspensions into the hippocampus of rats subjected to a transection of the intrinsic septo-hippocampal cholinergic pathways. At 17-19 weeks after transplantation, the various graft types... (More)

Grafts of five different types of central cholinergic neurons, from the septal-diagonal band region, the nucleus basalis magnocellularis region (NBM), the striatum, the pontomesencephalic tegmentum of the brainstem, and the spinal cord, were compared with respect to their ability to grow and to reinnervate the cholinergically denervated hippocampal formation of adult rats. The areas were dissected from 14 to 15-day-old rat fetuses, and the same number of viable cells (35 X 10(4) from each of the different regions were stereotaxically injected as cell suspensions into the hippocampus of rats subjected to a transection of the intrinsic septo-hippocampal cholinergic pathways. At 17-19 weeks after transplantation, the various graft types differed considerably in their volume, the total amount of acetylcholinesterase (AChE)-positive fiber outgrowth, and the innervation pattern and morphology of the AChE-positive fibers growing into the host hippocampus. On average the NBM and spinal cord grafts had grown to become three to four times larger than the septal and the brainstem grafts, and 15-20 times larger than the striatal grafts. By contrast, the total ingrowth score of AChE-positive fibers in the host hippocampus from the septal grafts was about twice that of the NBM and brainstem grafts, about five times greater than the striatal grafts, and about six times greater than that of the spinal cord grafts. The large NBM grafts thus exhibited similar fiber outgrowth to the much smaller brainstem grafts, and the AChE-positive neurons of the grafted spinal cord grew very poorly into the hippocampus despite the fact that they survived very well. The innervation pattern and morphological features of the ingrowing AChE-positive fibers in the host hippocampus proper and in the dentate gyrus resembled those of normal rats in animals with grafts from any of the three forebrain regions (i.e., septum, NBM, or striatum), whereas ingrowth from the brainstem and spinal cord grafts were markedly abnormal with respect to both innervation pattern and fiber morphology. These results provide further evidence that the overall survival, growth, and fiber outgrowth of intracerebral neural grafts depend on interactions with the surrounding host tissue. Since the ability to reinnervate the previously denervated host target was greatest for the neuron type normally innervating that area, i.e., the septal-diagonal band neurons, we conclude that neuronal properties beyond the transmitter type are essential for the optimal performance of implanted neurons in intracerebral grafting experiments.

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type
Contribution to journal
publication status
published
subject
keywords
Acetylcholinesterase/analysis, Animals, Cholinergic Fibers/growth & development, Female, Hippocampus/physiology, Nerve Regeneration, Neurons/physiology, Rats, Rats, Inbred Strains, Spinal Cord/transplantation
in
Journal of Comparative Neurology
volume
268
issue
2
pages
19 pages
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:3360985
  • scopus:0024281238
ISSN
0021-9967
DOI
10.1002/cne.902680206
language
English
LU publication?
yes
id
247bca35-fd82-4b89-af03-5290799b9a11
date added to LUP
2019-06-25 10:23:03
date last changed
2024-06-12 21:44:09
@article{247bca35-fd82-4b89-af03-5290799b9a11,
  abstract     = {{<p>Grafts of five different types of central cholinergic neurons, from the septal-diagonal band region, the nucleus basalis magnocellularis region (NBM), the striatum, the pontomesencephalic tegmentum of the brainstem, and the spinal cord, were compared with respect to their ability to grow and to reinnervate the cholinergically denervated hippocampal formation of adult rats. The areas were dissected from 14 to 15-day-old rat fetuses, and the same number of viable cells (35 X 10(4) from each of the different regions were stereotaxically injected as cell suspensions into the hippocampus of rats subjected to a transection of the intrinsic septo-hippocampal cholinergic pathways. At 17-19 weeks after transplantation, the various graft types differed considerably in their volume, the total amount of acetylcholinesterase (AChE)-positive fiber outgrowth, and the innervation pattern and morphology of the AChE-positive fibers growing into the host hippocampus. On average the NBM and spinal cord grafts had grown to become three to four times larger than the septal and the brainstem grafts, and 15-20 times larger than the striatal grafts. By contrast, the total ingrowth score of AChE-positive fibers in the host hippocampus from the septal grafts was about twice that of the NBM and brainstem grafts, about five times greater than the striatal grafts, and about six times greater than that of the spinal cord grafts. The large NBM grafts thus exhibited similar fiber outgrowth to the much smaller brainstem grafts, and the AChE-positive neurons of the grafted spinal cord grew very poorly into the hippocampus despite the fact that they survived very well. The innervation pattern and morphological features of the ingrowing AChE-positive fibers in the host hippocampus proper and in the dentate gyrus resembled those of normal rats in animals with grafts from any of the three forebrain regions (i.e., septum, NBM, or striatum), whereas ingrowth from the brainstem and spinal cord grafts were markedly abnormal with respect to both innervation pattern and fiber morphology. These results provide further evidence that the overall survival, growth, and fiber outgrowth of intracerebral neural grafts depend on interactions with the surrounding host tissue. Since the ability to reinnervate the previously denervated host target was greatest for the neuron type normally innervating that area, i.e., the septal-diagonal band neurons, we conclude that neuronal properties beyond the transmitter type are essential for the optimal performance of implanted neurons in intracerebral grafting experiments.</p>}},
  author       = {{Nilsson, O G and Clarke, D J and Brundin, P and Björklund, A}},
  issn         = {{0021-9967}},
  keywords     = {{Acetylcholinesterase/analysis; Animals; Cholinergic Fibers/growth & development; Female; Hippocampus/physiology; Nerve Regeneration; Neurons/physiology; Rats; Rats, Inbred Strains; Spinal Cord/transplantation}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{2}},
  pages        = {{22--204}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Journal of Comparative Neurology}},
  title        = {{Comparison of growth and reinnervation properties of cholinergic neurons from different brain regions grafted to the hippocampus}},
  url          = {{http://dx.doi.org/10.1002/cne.902680206}},
  doi          = {{10.1002/cne.902680206}},
  volume       = {{268}},
  year         = {{1988}},
}