liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Galanin and NPY in the rodent brain: rapid effects of 17beta-estradiol and possible roles in hippocampal plasticity
Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The neuropeptides galanin and neuropeptide Y (NPY) play an important role in the reproduction of rodents, e.g. by modulating the release of gonadal hormones, the nutritional status by effects on feeding behavior and also by influencing mating behavior. There are age- and gender- differences in galanin- and NPY- like immunoreactivities (LIs) in brain areas important for higher functions including the hippocampal formation (HiFo) and cortex, that are related to the concentrations of 17β-estradiol.

Neuropeptides in general are currently not considered critical in normal integrative neuronal functions but are rather thought to act as slow modulators during periods of stress or injury. In the present thesis we attempted to investigate, if the normal cyclical changes in the female sex-hormone 17β-estradiol can affect neurotransmission in brain areas important for memory, cognition and mood. We studied not only ”long term” (days and weeks) but also ”short-term” (one hour) effects on galanin and NPY concentrations in 17β-estradiol-primed ovariectomized (ovx) rats and mice.

Radioimmunoassay (RIA) of galanin-LI in extracts of brain tissues from ”long-term” 17β-estradiol-treated ovx rats showed that its effects on galanin are dependent on boththe dose and on duration. Galanin - and NPY-LI in brain tissues of young ovx rats and mice increased in response to 17β-estradiol treatment in the HiFo, frontal cortex and striatum already within hours. This effect was not blocked by Tamoxifen® in rats. The mechanism of the 17β-estradiol effects on galanin levels in the rat HiFo may be related to decreased release of galanin into the extracellular fluid, since galanin-LI decreased in microdialysis samples two hours after a single injection of 17β-estradiol. Species differences were observed with regards to galanin, possibly due to tissue and species differences in the distribution of estrogen receptors.

In the HiFo and caudate nucleus of mice, we found an increase in NPY-transcript after two hours by means of insitu hybridization, perhaps a compensatory up-regulation of NPY mRNA after increased 17β-estradiol-induced release in these areas. Taken together with no effects of Tamoxifen® on the levels on galanin in the HiFo of rats, the short duration, and the fact that the density of classical estrogen receptors seems to be limited in the striatum, we suggest that these effects are mediated through a membrane-related mechanism perhaps not involving the classical ER route.

With an antiserum raised against the C-terminal end of the first 16 aminoacids of galanin- the sequence important for binding of intact galanin to its receptor - we found a novel compound which appears to be a homologue to galanin. Chromatographical analysis revealed that it was not galanin(1-29) or the galanin related peptide, galaninlike peptide (GALP), but appeared with immunohistochemistry in the galanin systems in the brain and was further influenced by 17β-estradiol in the HiFo and frontal cortex in a similar manner as galanin(1-29).

In conclusion, tissue concentrations of galanin, a putative galanin homologue and NPY can be altered already after one hour by 17β-estradiol treatment e.i. in the HiFo. These ”short-term” effects are most likely to be due to effects on estrogen-primed peptide release which might influence mechanisms important for memory, cognition and mood.

Place, publisher, year, edition, pages
Institutionen för biomedicin och kirurgi , 2005.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 911
Keyword [en]
Sex-hormones, Brain, Neuropeptides
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:liu:diva-4152ISBN: 91-85299-24-3 (print)OAI: oai:DiVA.org:liu-4152DiVA: diva2:20546
Public defence
2005-09-07, Berzeliussalen, Campus US, Ingång 65, Linköpings universitetssjukhus, Linköping, 09:00 (English)
Opponent
Supervisors
Available from: 2005-09-29 Created: 2005-09-29 Last updated: 2009-08-23
List of papers
1. Estrogen induces a rapid increase in galanin levels in female rat hippocampal formation: possibly a nongenomic/indirect effect
Open this publication in new window or tab >>Estrogen induces a rapid increase in galanin levels in female rat hippocampal formation: possibly a nongenomic/indirect effect
Show others...
2005 (English)In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 21, no 8, 2089-2099 p.Article in journal (Refereed) Published
Abstract [en]

Administration of 17β-estradiol to ovariectomized rats increased the concentrations of galanin-like immunoreactivity (LI) in the hippocampal formation by 215% (P < 0.001) within 1 h. An increase of 125% (P < 0.05) was observed in the same brain region in the proestrous phase of a normal estrous cycle. Tamoxifen® did not block the 17β-estradiol-induced increase in the concentration of galanin-LI but resulted in a 62% decrease in the hypothalamus within 1 h. In vivo microdialysis in the dorsal hippocampal formation showed a decrease of extracellular galanin-LI (P < 0.001) 1−2 h after treatment with 17β-estradiol, indicating a decreased release of galanin. For comparision, we studied the concentrations of neuropeptide Y, which were not influenced significantly in any of the regions studied. Taken together our results suggest that 17β-estradiol inhibits galanin release, presumably from noradrenergic nerve terminals, and primarily via a nongenomic/indirect action, not necessarily involving the classical nuclear receptors ER-α or ER-β. These rapid estrogen-induced changes in galanin release could influence transmitter signalling and plasticity in the hippocampal formation.

Keyword
estrogen receptors, immunohistochemistry, in situ hybridization, microdialysis, radioimmunoassay
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13379 (URN)10.1111/j.1460-9568.2005.04050.x (DOI)
Available from: 2005-09-29 Created: 2005-09-29 Last updated: 2017-12-13
2. Galanin in the hippocampal formation of female rats: effects of 17beta estradiol
Open this publication in new window or tab >>Galanin in the hippocampal formation of female rats: effects of 17beta estradiol
Show others...
2005 (English)In: Neuropeptides, ISSN 0143-4179, Vol. 39, no 3, 253-257 p.Article in journal (Refereed) Published
Abstract [en]

17β-Estradiol induced an increase in tissue concentrations of galanin in the hippocampal formation of ovariectomized rats. This increase was dose- and time dependent, and occurred already 60 min after steroid administration and was not blocked by Tamoxifen®. There was also an increase in galanin in the pro-estrous phase in regularly cycling rats. The estrogen-induced rapid increase may at least in part be due to decreased release of galanin as demonstrated by in vivo microdialysis studies. Thus, sex steroid hormones may influence signalling molecules in brain areas of importance for cognitive functions.

Keyword
Estrogen receptors; Radioimmunoassay; Microdialysis; Immunohistochemistry; In situ hybridization
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13380 (URN)10.1016/j.npep.2005.01.002 (DOI)
Available from: 2005-09-29 Created: 2005-09-29
3. Rapid versus prolonged treatment with 17beta estradiol induces different effects on galanin and neuropeptide Y concentrations in the brain of ovariectomized mice
Open this publication in new window or tab >>Rapid versus prolonged treatment with 17beta estradiol induces different effects on galanin and neuropeptide Y concentrations in the brain of ovariectomized mice
Show others...
Manuscript (Other academic)
Identifiers
urn:nbn:se:liu:diva-13381 (URN)
Available from: 2005-09-29 Created: 2005-09-29 Last updated: 2010-01-13
4. A short estrogen-responsive N-terminal galanin homologue found in rat brain and gut with antiserum raised against rat galanin(1-16)
Open this publication in new window or tab >>A short estrogen-responsive N-terminal galanin homologue found in rat brain and gut with antiserum raised against rat galanin(1-16)
2007 (English)In: Neurochemical Research, ISSN 0364-3190, Vol. 31, no 2, 177-188 p.Article in journal (Refereed) Published
Abstract [en]

Galanin-like peptide (GALP) is currently the only known galanin(1-29) homologue. However, three different galanin receptors, of which GalR3 exhibits comparatively low affinity for galanin(1-29), and molecular heterogeneity of immunoreactive galanin are arguments for presence of other endogenous galanin homologues. Since antibodies recognize three-dimensional structures of 3–5 amino acids in a peptide, we raised antibodies in rabbits against galanin(1-16) conjugated to bovine serum albumin, looking for the presence of endogenous N-terminal galanin homologues in rat tissues. The antiserum selected had 7,830 times higher avidity for galanin(1-16) compared to galanin(1-29). A single immunoreactive component with a Stokes radius of about 8 amino acids was found. Immunohistochemistry strongly suggested that this immunoreactivity is localised in the same neurons as galanin(1-29). Furthermore, its concentration was increased in response to estrogen treatment in the same brain regions as galanin(1-29), although not as rapidly. The present results indicate the presence of a novel endogenous N-terminal galanin homologue.

Keyword
Hippocampus, HPLC, Hypothalamus, Immunohistochemistry, Radioimmunoassay
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13382 (URN)10.1007/s11064-005-9007-5 (DOI)
Available from: 2005-09-29 Created: 2005-09-29 Last updated: 2009-08-18

Open Access in DiVA

fulltext(703 kB)1072 downloads
File information
File name FULLTEXT01.pdfFile size 703 kBChecksum MD5
c4bee2ec7e4f6903d821252f1e02fbc29c552484eef1c568ed2335444a3ba58d5030ca56
Type fulltextMimetype application/pdf

Authority records BETA

Hilke, Susanne

Search in DiVA

By author/editor
Hilke, Susanne
By organisation
Clinical ChemistryFaculty of Health Sciences
Neurosciences

Search outside of DiVA

GoogleGoogle Scholar
Total: 1072 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 1573 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf