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Hilke, Susanne
Publications (10 of 14) Show all publications
Holm, L., Liang, W., Thorsell, A. & Hilke, S. (2014). Acute effects on brain cholecystokinin-like concentration and anxiety-like behaviour in the female rat upon a single injection of 17β-estradiol. Pharmacology, Biochemistry and Behavior, 122, 222-227
Open this publication in new window or tab >>Acute effects on brain cholecystokinin-like concentration and anxiety-like behaviour in the female rat upon a single injection of 17β-estradiol
2014 (English)In: Pharmacology, Biochemistry and Behavior, ISSN 0091-3057, E-ISSN 1873-5177, Vol. 122, p. 222-227Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The neuropeptide cholecystokinin (CCK) has been implicated in the neurobiology of anxiety and panic disorders, as well as in dopamine-related behaviours. Anxiety and panic-disorders are twice as common in females compared to males, but studies of females are rare, although increasing in number. Limited studies have found that CCK fluctuates in limbic regions during the estrous cycle, and that CCK and its receptors are sensitive to estrogen.

AIM/PURPOSE: The aim of the present work was to study the acute effects of 17β-estradiol on anxiety-like behaviour and on CCK-like immunoreactivity (LI) in the female rat brain (amygdala, hippocampus, nucleus accumbens, and cingulate cortex).

METHODS: Four groups of female Sprague-Dawley rats were used: ovariectomized, ovariectomized+17β-estradiol-replacement, sham, and sham+17β-estradiol-replacement. The effect of 17β-estradiol-replacement on anxiety-related behaviour was measured in all animals on the elevated plus maze 2-24h after injection. CCK-LI concentration was measured in punch biopsies by means of radioimmunoassay.

RESULTS: 17β-estradiol decreased anxiety-like behaviour 2h after administration in ovariectomized and sham-operated animals, as demonstrated by increased exploration of the open arms compared to respective sesame oil-treated controls. This effect was not present when testing occurred 24h post-treatment. The rapid behavioural effect of 17β-estradiol was accompanied by changes in CCK-LI concentrations in regions of the limbic system including cingulate cortex, hippocampus, amygdala and nucleus accumbens.

CONCLUSION: Although the interpretation of these data requires caution since the data were collected from two different experiments, our results suggest that estrogen-induced anxiolytic effects may be associated with changes of the CCK-system in brain regions controlling anxiety-like behaviour.

Place, publisher, year, edition, pages
Elsevier, 2014
Keywords
Anxiety, Cholecystokinin, Estrogen
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-106089 (URN)10.1016/j.pbb.2014.04.004 (DOI)000338597000025 ()24732637 (PubMedID)
Available from: 2014-04-24 Created: 2014-04-24 Last updated: 2017-12-05Bibliographically approved
Holm, L., Hilke, S., Theodorsson, E., Hokfelt, T. & Theodorsson, A. (2012). Changes in galanin and GalR1 gene expression in discrete brain regions after transient occlusion of the middle cerebral artery in female rats. Neuropeptides, 46(1), 19-27
Open this publication in new window or tab >>Changes in galanin and GalR1 gene expression in discrete brain regions after transient occlusion of the middle cerebral artery in female rats
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2012 (English)In: Neuropeptides, ISSN 0143-4179, E-ISSN 1532-2785, Vol. 46, no 1, p. 19-27Article in journal (Refereed) Published
Abstract [en]

Injury to neurons results in upregulation of galanin in some central and peripheral systems, and it has been suggested that this neuropeptide may play a protective and trophic role, primarily mediated by galanin receptor 2 (GalR2). The objective of the present study was to investigate galanin, GalR1, GalR2 and GalR3 gene expression in the female rat brain seven days after a 60-min unilateral occlusion of the middle cerebral artery followed by reperfusion. Quantitative real-time PCR was employed in punch-biopsies from the locus coeruleus, somatosensory cortex and dorsal hippocampal formation including sham-operated rats as controls. Galanin gene expression showed a ~2.5-fold increase and GalR1 a ~1.5-fold increase in the locus coeruleus of the ischemic hemisphere compared to the control side. Furthermore, the GalR1 mRNA levels decreased by 35% in the cortex of the ischemic hemisphere. The present results indicate that a stroke-induced forebrain lesion upregulates synthesis of galanin and GalR1 in the locus coeruleus, a noradrenergic cell group projecting to many forebrain areas, including cortex and the hippocampal formation. These results support the notion that galanin may play a role in the response of the central nervous system to injury and have trophic eff ects.

Place, publisher, year, edition, pages
Elsevier, 2012
Keywords
cerebral ischemia, galanin receptor, RT-PCR
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-68085 (URN)10.1016/j.npep.2011.11.001 (DOI)000300268800003 ()
Note

On the day of the defence day the status of this article was Manuscript funding agencies|County Council of Ostergotland, Sweden||Swedish Research Council||Marianne and Marcus Wallenberg Foundation||

Available from: 2011-05-10 Created: 2011-05-10 Last updated: 2017-12-11Bibliographically approved
Gustafsson, S., Liang, W. & Hilke, S. (2011). Effects of voluntary running in the female mice lateral septum on BDNF and corticotropin-releasing factor receptor 2. International Journal of Peptides, 2011, 932361-932366
Open this publication in new window or tab >>Effects of voluntary running in the female mice lateral septum on BDNF and corticotropin-releasing factor receptor 2
2011 (English)In: International Journal of Peptides, ISSN 1687-9767, E-ISSN 1687-9775, Vol. 2011, p. 932361-932366Article in journal (Refereed) Published
Abstract [en]

Voluntary physical activities are known to modulate anxiety and depressive/like behaviors in both animals and humans. Brain derived neurotrophic factor (BDNF), has been reported to be elevated following exercise. BDNF, as well as type 2 corticotrophin releasing factor receptor (CRFR) 2, has been shown to mediate anxiety-like behavior. In the present study we examined the effects of long-term voluntary exercise on the transcripts for BDNF and CRFR2 in the lateral septum (LS) and for CRF in the central amygdala (CeA) in female mice. Thus, increased activity of CRF in the CeA is associated with anxiety-like behavior. Quantitative RT-PCR was employed to measure levels of mRNA in punch biopsies from LS and CeA. In addition, measurements of the concentration of corticosterone and leptin in plasma were employed. In the LS, we found a three-fold increase of BDNF mRNA (P < 0.05) but no significant change in CRFR2 mRNA. No changes in CRF in the amygdala were observed but we found a decrease in the levels of plasma corticosterone. Plasma leptin and the weight of perigonadal fat pads were decreased following exercise. In conclusion, these data show that BDNF gene expression in the LS is influenced by long-term exercise in females but not CRFR2.

Place, publisher, year, edition, pages
Hindawi Publishing Corporation, 2011
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-102016 (URN)10.1155/2011/932361 (DOI)21977046 (PubMedID)
Available from: 2013-11-26 Created: 2013-11-26 Last updated: 2017-12-06
Lundberg, K., Hilke, S., Nordin, C., Theodorsson, E. & Josefsson, A. (2010). Cholecystokinin in plasma and cerebrospinal fluid-A study in healthy young women. PEPTIDES, 31(8), 1625-1628
Open this publication in new window or tab >>Cholecystokinin in plasma and cerebrospinal fluid-A study in healthy young women
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2010 (English)In: PEPTIDES, ISSN 0196-9781, Vol. 31, no 8, p. 1625-1628Article in journal (Refereed) Published
Abstract [en]

Cholecystokinin (CCK) is widely distributed in the brain and is known to affect behavioral and physiological functions including anxiety and pain. The expression of CCK has been shown to be regulated by estrogen and to vary during the estrous cycle in rat brain. In the present study CCK was determined in plasma from 25 healthy women (age 25.0 +/- 3.5) during the menstrual cycle, in the late luteal phase and in the follicular phase. In the follicular phase, a lumbar puncture was performed at the same time that a plasma sample was taken in 15 subjects. The participants had fasted and were nicotine-free for at least 8 h preceding the sampling. We compared CCK-like immunoreactivity (CCK-LI) in plasma from 25 subjects in the late luteal phase (LLP) and the follicular phase (FP) and found that there was no difference during the menstrual cycle (n-25, R-2 =89.60%, p = n.s.). In the follicular phase no significant difference was found between CCK-LI in plasma and in cerebrospinal fluid (CSF) collected at the same time (n =15, R-2 = 55.32%, p = n.s.).

Place, publisher, year, edition, pages
Elsevier Science B.V., Amsterdam., 2010
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-58776 (URN)10.1016/j.peptides.2010.04.028 (DOI)000280663600028 ()
Note
Original Publication: Kristina Lundberg, Susanne Hilke, Conny Nordin, Elvar Theodorsson and Ann Josefsson, Cholecystokinin in plasma and cerebrospinal fluid-A study in healthy young women, 2010, PEPTIDES, (31), 8, 1625-1628. http://dx.doi.org/10.1016/j.peptides.2010.04.028 Copyright: Elsevier Science B.V., Amsterdam. http://www.elsevier.com/ Available from: 2010-08-27 Created: 2010-08-27 Last updated: 2019-06-28
Josefsson, A., Theodorsson, E., Berg, G., Sydsjö, G. & Hilke, S. (2010). Complex Biphasic Changes of Neuropeptide Concentrations in the Rat Limbic System During Pregnancy and Parturition. The Open Neuroendocrinology Journal, 3, 45-51
Open this publication in new window or tab >>Complex Biphasic Changes of Neuropeptide Concentrations in the Rat Limbic System During Pregnancy and Parturition
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2010 (English)In: The Open Neuroendocrinology Journal, ISSN 1876-5289, Vol. 3, p. 45-51Article in journal (Refereed) Published
Abstract [en]

Sex hormones including estrogens affect brain areas involved in mood and cognition in addition to directly controlling reproduction and reproductive behavior. We studied the effect of pregnancy and puerperium on the concentrations of cholecystokinin (CCK), neuropeptide Y (NPY), substance P (SP) and galanin in tissue extracts from the rat striatum, frontal cortex and the hippocampal formation by means of radioimmunoassay. The most profound effects were found in the frontal cortex. Thus, cholecystokinin-like immunoreactivity (CCK-LI) was increased by 40 % during late pregnancy (p < 0.01) compared to estrous whereas SP-LI and galanin-LI decreased 25 % and 10 %, respectively. Postpartum, CCKLI decreased by 26% compared to pregnancy (p < 0.05) whereas SP-LI and galanin-LI were increased to a level above estrous (SP, P < 0.01; galanin, P < 0.05). No significant effect was observed in NPY-LI in this area. In the striatum during late pregnancy the concentrations of cholecystokinin-LI increased by 29 % (p < 0.05), NPY-LI by 22% (p < 0.05) whereas SP-LI slightly increased (not significant). Postpartum, cholecystokinin-LI decreased by 25 % (p < 0.01) compared to pregnancy and NPY by 16 % (p < 0.01). SP continued to increase postpartum by 33 % (p < 0.05) whereas no effect was observed on galanin-LI concentration. Surprisingly, we did not observe any changes in any peptide or groups measured in the hippocampal formation. The complex hormonal adjustments occurring during pregnancy and in the puerperium induce profound changes in the concentrations of several neuropeptides in regions of the rat brain involved in the control of mood and motor control.

Place, publisher, year, edition, pages
Bentham Open, 2010
Keywords
Rat, brain, neuropeptides, estradiol, postpartum depression
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-58932 (URN)10.2174/1876528901003010045 (DOI)
Note
Original Publication: Ann Josefsson, Elvar Theodorsson, Göran Berg, Gunilla Sydsjö and Susanne Hilke, Complex Biphasic Changes of Neuropeptide Concentrations in the Rat Limbic System During Pregnancy and Parturition, 2010, The Open Neuroendocrinology Journal, (3), 45-51. http://dx.doi.org/10.2174/1876528901003010045 Licensee: Bentham open http://www.bentham.org/ Available from: 2010-09-02 Created: 2010-09-02 Last updated: 2019-06-28
Hilke, S., Holm, L., Aman, K., Hokfelt, T. & Theodorsson, E. (2009). Rapid change of neuropeptide Y levels and gene-expression in the brain of ovariectomized mice after administration of 17 beta-estradiol. NEUROPEPTIDES, 43(4), 327-332
Open this publication in new window or tab >>Rapid change of neuropeptide Y levels and gene-expression in the brain of ovariectomized mice after administration of 17 beta-estradiol
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2009 (English)In: NEUROPEPTIDES, ISSN 0143-4179, Vol. 43, no 4, p. 327-332Article in journal (Refereed) Published
Abstract [en]

Estrogen alters excitability and changes synaptic morphology in the rat hippocampal formation. We have compared, by means of radioimmunoassay and in situ hybridization, the effects of short-term treatment with 17 beta-estradiol on neuropeptide Y (NPY) in the brain of ovariectomized mice. A highly significant reduction in concentrations of NPY-like immunoreactivity (LI) was observed in the hippocampal formation, some cortical areas and the caudate nucleus 1 h after administration of 17 beta-estradiol as compared to the control group. In contrast, NPY transcript levels increased in the hippocampal formation (dentate gyrus) and the caudate nucleus, possibly representing a compensatory increase of NPY synthesis following increased estradiol-induced NPY release. These data suggest that 17 beta-estradiol, via membrane-related mechanisms, increases NPY release and synthesis in forebrain areas involved in cognition, mood and motor functions.

Keywords
Estrogen, In situ hybridization, Limbic system, Neuropeptide, Radioimmunoassay
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-20329 (URN)10.1016/j.npep.2009.04.005 (DOI)
Available from: 2009-09-04 Created: 2009-09-04 Last updated: 2012-02-27
Hilke, S., Hökfelt, T. & Theodorsson, E. (2007). A short estrogen-responsive N-terminal galanin homologue found in rat brain and gut with antiserum raised against rat galanin(1-16). Neurochemical Research, 31(2), 177-188
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, p. 177-188Article 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.

Keywords
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
Hilke, S., Hokfelt, T., Darwish, M. & Theodorsson, E. (2007). Cholecystokinin levels in the rat brain during the estrous cycle. Brain Research, 1144(1), 70-73
Open this publication in new window or tab >>Cholecystokinin levels in the rat brain during the estrous cycle
2007 (English)In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1144, no 1, p. 70-73Article in journal (Refereed) Published
Abstract [en]

Cholecystokinin (CCK) is widely distributed in the brain, and its expression has been shown to be regulated by estrogen. In the present study we used radioimmunoassay to monitor CCK levels in rat brain during a normal estrous cycle. Compared to di-estrous and estrous, CCK-like immunoreactivity was significantly reduced in cingulate and frontal cortex, hippocampus, striatum and hypothalamus during pro-estrous, that is the phase with the highest plasma estradiol levels. These results provide further evidence that circulating steroid hormones in the female rat can influence expression of a brain peptide, in this case CCK, and primarily in the limbic system, which is interesting in the context that CCK has been associated with anxiety and depression in both animals and humans. © 2007 Elsevier B.V. All rights reserved.

Keywords
Estrogen, Limbic system, Neuropeptide, Radioimmunoassay, Steroid hormone
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-49777 (URN)10.1016/j.brainres.2007.01.107 (DOI)
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-12
Hilke, S., Theodorsson, A., Fetissov, S., Åman, K., Holm, L., Hökfelt, T. & Theodorsson, E. (2005). Estrogen induces a rapid increase in galanin levels in female rat hippocampal formation: possibly a nongenomic/indirect effect. European Journal of Neuroscience, 21(8), 2089-2099
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
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2005 (English)In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 21, no 8, p. 2089-2099Article 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.

Keywords
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
Hilke, S. (2005). Galanin and NPY in the rodent brain: rapid effects of 17beta-estradiol and possible roles in hippocampal plasticity. (Doctoral dissertation). Institutionen för biomedicin och kirurgi
Open this publication in new window or tab >>Galanin and NPY in the rodent brain: rapid effects of 17beta-estradiol and possible roles in hippocampal plasticity
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
Keywords
Sex-hormones, Brain, Neuropeptides
National Category
Neurosciences
Identifiers
urn:nbn:se:liu:diva-4152 (URN)91-85299-24-3 (ISBN)
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: 2018-01-13
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