Responses of young and aged rat CNS to partial cholinergic immunolesions and NGF treatment

Responses of young and aged rat CNS to partial cholinergic immunolesions and NGF treatment The cholinergic neurons of the basal forebrain (CNBF) are the major source of cholinergic innervation of the cortex and hippocampus. In Alzheimer's disease and aged brain, there are severe losses of cholinergic neurons in the nucleus basalis of Meynert, leading to a reduction of cortical cholinergic activity which correlates with the severity of cognitive deficits. While there is evidence that aged central nervous system (CNS) displays impaired stress response signaling, pharmacologic treatments with neurotrophic factors appear to ameliorate these age‐associated cholinergic deficits. To mimic these cholinergic deficits in experimental animals and study the acute effects of nerve growth factor (NGF), we induced a partial lesion of CBFNs by the intracerebroventricular (icv) injection of the cholinergic immunotoxin 192IgG‐saporin, in groups of 3‐ and 30‐month‐old rats. The lesion was followed 14 days later by icv administration of NGF, known to restore partial immunolesion‐induced cholinergic deficits in rat CNS, and all rats were killed 2 days after the NGF treatement. Here we report the effects of partial immunolesions on the levels of choline acetyltransferase (ChAT) activity and NGF receptor mRNA levels in the basal forebrain of 3‐ and 30‐month‐old rats. Because of their presence in the promoters of the NGF, NGF receptors, and ChAT genes, we also measured DNA‐binding activity of the transcription factors NFB and AP‐1 in the cortex and hippocampus. We discuss these findings in the context of endogenous NGF‐mediated signal transduction mechanisms and conclude that we have evidence for age‐associated decreases in endogenous NGF responses to partial deafferentation of the basal forebrain cholinergic projections. J. Neurosci. Res. 52:322–333, 1998. © 1998 Wiley‐Liss, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Neuroscience Research Wiley

Responses of young and aged rat CNS to partial cholinergic immunolesions and NGF treatment

Loading next page...
 
/lp/wiley/responses-of-young-and-aged-rat-cns-to-partial-cholinergic-rqY5E8nNH9
Publisher
Wiley
Copyright
Copyright © 1998 Wiley‐Liss, Inc.
ISSN
0360-4012
eISSN
1097-4547
D.O.I.
10.1002/(SICI)1097-4547(19980501)52:3<322::AID-JNR8>3.0.CO;2-F
Publisher site
See Article on Publisher Site

Abstract

The cholinergic neurons of the basal forebrain (CNBF) are the major source of cholinergic innervation of the cortex and hippocampus. In Alzheimer's disease and aged brain, there are severe losses of cholinergic neurons in the nucleus basalis of Meynert, leading to a reduction of cortical cholinergic activity which correlates with the severity of cognitive deficits. While there is evidence that aged central nervous system (CNS) displays impaired stress response signaling, pharmacologic treatments with neurotrophic factors appear to ameliorate these age‐associated cholinergic deficits. To mimic these cholinergic deficits in experimental animals and study the acute effects of nerve growth factor (NGF), we induced a partial lesion of CBFNs by the intracerebroventricular (icv) injection of the cholinergic immunotoxin 192IgG‐saporin, in groups of 3‐ and 30‐month‐old rats. The lesion was followed 14 days later by icv administration of NGF, known to restore partial immunolesion‐induced cholinergic deficits in rat CNS, and all rats were killed 2 days after the NGF treatement. Here we report the effects of partial immunolesions on the levels of choline acetyltransferase (ChAT) activity and NGF receptor mRNA levels in the basal forebrain of 3‐ and 30‐month‐old rats. Because of their presence in the promoters of the NGF, NGF receptors, and ChAT genes, we also measured DNA‐binding activity of the transcription factors NFB and AP‐1 in the cortex and hippocampus. We discuss these findings in the context of endogenous NGF‐mediated signal transduction mechanisms and conclude that we have evidence for age‐associated decreases in endogenous NGF responses to partial deafferentation of the basal forebrain cholinergic projections. J. Neurosci. Res. 52:322–333, 1998. © 1998 Wiley‐Liss, Inc.

Journal

Journal of Neuroscience ResearchWiley

Published: May 1, 1998

References

  • Involvement of nerve growth factor and its receptor in the regulation of the cholinergic function in aged rats
    Albrecht, Albrecht; Perez‐Navarro, Perez‐Navarro; Arenas, Arenas; Marsal, Marsal
  • Nerve growth factor binding in aged rat central nervous system: Effect of acetyl‐L‐carnitine
    Angelucci, Angelucci; Ramacci, Ramacci; Taglialatela, Taglialatela; Hulsebosch, Hulsebosch; Morgan, Morgan; Werrbach‐Perez, Werrbach‐Perez; Perez‐Polo, Perez‐Polo
  • Multiple signalling pathways interact in the regulation of nerve growth factor production in L929 fibroblasts
    D'Mello, D'Mello; Heinrich, Heinrich
  • A rapid radiochemical method for the determination of choline acetyltransferase
    Fonnum, Fonnum
  • Differential changes in cholinergic markers from selected brain regions after specific immunolesion of the rat cholinergic basal forebrain system
    Roßner, Roßner; Schliebs, Schliebs; Perez‐Polo, Perez‐Polo; Wiley, Wiley; Bigl, Bigl
  • Effects of intraventricular transplantation of NGF‐secreting cells on cholinergic basal forebrain neurons after partial immunolesion
    Roßner, Roßner; Yu, Yu; Pizzo, Pizzo; Werrbach‐Perez, Werrbach‐Perez; Schliebs, Schliebs; Bigl, Bigl; Perez‐Polo, Perez‐Polo
  • Glutamate receptor agonists increase the expression fo Fos, Fra, and AP‐1 DNA binding activity in the mammalian brain
    Sonnenberg, Sonnenberg; Mitchelmore, Mitchelmore; Macgregor‐Leon, Macgregor‐Leon; Hempstead, Hempstead; Morgan, Morgan; Curran, Curran
  • Nerve growth factor increases the intracellular content of acetylcholine in cultured septal neurons from developing rats
    Takei, Takei
  • Age‐associated alterations in hippocampal and basal forebrain nuclear factor Kappa B activity
    Toliver‐Kinsky, Toliver‐Kinsky; Papaconstantinou, Papaconstantinou; Perez‐Polo, Perez‐Polo
  • Transcription factor DNA binding activity in PC12 cells undergoing apoptosis after glucose deprivation
    Tong, Tong; Perez‐Polo, Perez‐Polo
  • Circadian variation in rat brain AP‐1 DNA binding activity after cholinergic stimulation: Modulation by lithium
    Williams, Williams; Jope, Jope
  • Role of the cholinergic system in the regulation of neurotrophin synthesis
    Yu, Yu; Pizzo, Pizzo; Hutton, Hutton; Perez‐Polo, Perez‐Polo
  • Altered NGF protein levels in different brain areas after immunolesion
    Yu, Yu; Wiley, Wiley; Perez‐Polo, Perez‐Polo

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create folders to
organize your research

Export folders, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off