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Highly selective effects of nerve growth factor, brain‐derived neurotrophic factor, and neurotrophin‐3 on intact and injured basal forebrain magnocellular neurons

Koliatsos, Vassilis E. ; Price, Donald L. ; Gouras, Gunnar K. LU ; Cayouette, Michelle H. ; Burton, Louis E. and Winslow, John W. (1994) In Journal of Comparative Neurology 343(2). p.247-262
Abstract

Cholinergic neurons of the basal nucleus complex (BNC) respond to nerve growth factor (NCF), the first member of a polypeptide gene family that also includes brain‐derived neurotrophic factor (BDNF), neurotrophin‐3 (NT‐3), and neurotrophin‐4/5 (NT‐4/5), NGF, BDNF, and NT‐3 are enriched in hippocampus. In addition, NGF and, more recently, BDNF have been shown to stimulate the cholinergic differentiation and enhance the survival of BNC cells in vitro. The present investigation was designed to test, in a comparative fashion, the in vivo effects of human recombinant NGF, BDNF, and NT‐3 with confirmed activities in vitro on cholinergic and γ‐aminobutyric acid (GABA)‐ergic BNC neurons. The specific questions asked were whether and, to what... (More)

Cholinergic neurons of the basal nucleus complex (BNC) respond to nerve growth factor (NCF), the first member of a polypeptide gene family that also includes brain‐derived neurotrophic factor (BDNF), neurotrophin‐3 (NT‐3), and neurotrophin‐4/5 (NT‐4/5), NGF, BDNF, and NT‐3 are enriched in hippocampus. In addition, NGF and, more recently, BDNF have been shown to stimulate the cholinergic differentiation and enhance the survival of BNC cells in vitro. The present investigation was designed to test, in a comparative fashion, the in vivo effects of human recombinant NGF, BDNF, and NT‐3 with confirmed activities in vitro on cholinergic and γ‐aminobutyric acid (GABA)‐ergic BNC neurons. The specific questions asked were whether and, to what extent, biologically active recombinant neurotrophins stimulate the transmitter phenotypes of intact cholinergic and GABAergic neurons of the BNC, and whether, and to what extent, recombinant neurotrophins protect the transmitter phenotypes of axotomized cholinergic and GABAergic neurons of the BNC following complete transections of the fimbria‐fornix (measured by ChAT mRNA hybridization). Our results confirm the profound stimulatory and p75NGFR expression in both intact and axotomized cholinergic neurons and to exert minor effects on some cholinergic markers (e.g., ChAT immunoreactivity). NT‐3 had no influence on GABAergic neurons. Taken together, these results indicate that, despite their significant sequence homologies and their shared abundance in target fields of BNC neurons, NGF, BDNF, and NT‐3 show striking differences in their efficacies as cholinergic trophic factors. GABAergic neurons of the BNC are resistant to neurotrophins. The result of the present investigation establish that NGF excels among neurotrophins as a trophic factor for intact and injured basal forebrain cholinergic neurons. © 1994 Wiley‐Liss, Inc.

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author
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type
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publication status
published
subject
keywords
Alzheimer's disease, choline acetyltransferase, cholinergic neurons, medial septum, trophic factors
in
Journal of Comparative Neurology
volume
343
issue
2
pages
247 - 262
publisher
John Wiley and Sons Inc.
external identifiers
  • pmid:8027442
  • scopus:0028334932
ISSN
0021-9967
DOI
10.1002/cne.903430206
language
English
LU publication?
no
id
3562d329-b140-4949-b347-25e1fe69089d
date added to LUP
2020-02-20 14:36:06
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2020-05-24 06:30:06
@article{3562d329-b140-4949-b347-25e1fe69089d,
  abstract     = {<p>Cholinergic neurons of the basal nucleus complex (BNC) respond to nerve growth factor (NCF), the first member of a polypeptide gene family that also includes brain‐derived neurotrophic factor (BDNF), neurotrophin‐3 (NT‐3), and neurotrophin‐4/5 (NT‐4/5), NGF, BDNF, and NT‐3 are enriched in hippocampus. In addition, NGF and, more recently, BDNF have been shown to stimulate the cholinergic differentiation and enhance the survival of BNC cells in vitro. The present investigation was designed to test, in a comparative fashion, the in vivo effects of human recombinant NGF, BDNF, and NT‐3 with confirmed activities in vitro on cholinergic and γ‐aminobutyric acid (GABA)‐ergic BNC neurons. The specific questions asked were whether and, to what extent, biologically active recombinant neurotrophins stimulate the transmitter phenotypes of intact cholinergic and GABAergic neurons of the BNC, and whether, and to what extent, recombinant neurotrophins protect the transmitter phenotypes of axotomized cholinergic and GABAergic neurons of the BNC following complete transections of the fimbria‐fornix (measured by ChAT mRNA hybridization). Our results confirm the profound stimulatory and p<sup>75NGFR</sup> expression in both intact and axotomized cholinergic neurons and to exert minor effects on some cholinergic markers (e.g., ChAT immunoreactivity). NT‐3 had no influence on GABAergic neurons. Taken together, these results indicate that, despite their significant sequence homologies and their shared abundance in target fields of BNC neurons, NGF, BDNF, and NT‐3 show striking differences in their efficacies as cholinergic trophic factors. GABAergic neurons of the BNC are resistant to neurotrophins. The result of the present investigation establish that NGF excels among neurotrophins as a trophic factor for intact and injured basal forebrain cholinergic neurons. © 1994 Wiley‐Liss, Inc.</p>},
  author       = {Koliatsos, Vassilis E. and Price, Donald L. and Gouras, Gunnar K. and Cayouette, Michelle H. and Burton, Louis E. and Winslow, John W.},
  issn         = {0021-9967},
  language     = {eng},
  month        = {05},
  number       = {2},
  pages        = {247--262},
  publisher    = {John Wiley and Sons Inc.},
  series       = {Journal of Comparative Neurology},
  title        = {Highly selective effects of nerve growth factor, brain‐derived neurotrophic factor, and neurotrophin‐3 on intact and injured basal forebrain magnocellular neurons},
  url          = {http://dx.doi.org/10.1002/cne.903430206},
  doi          = {10.1002/cne.903430206},
  volume       = {343},
  year         = {1994},
}