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Holm, Lovisa
Publications (10 of 13) Show all publications
Domi, E., Xu, L., Toivainen Eloff, S., Wiskerke, J., Coppola, A., Holm, L., . . . Heilig, M. (2023). Activation of GABA(B) receptors in central amygdala attenuates activity of PKC delta plus neurons and suppresses punishment-resistant alcohol self-administration in rats. Neuropsychopharmacology, 48, 1386-1395
Open this publication in new window or tab >>Activation of GABA(B) receptors in central amygdala attenuates activity of PKC delta plus neurons and suppresses punishment-resistant alcohol self-administration in rats
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2023 (English)In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 48, p. 1386-1395Article in journal (Refereed) Published
Abstract [en]

Alcohol use despite negative consequences is a core phenomenon of alcohol addiction. We recently used alcohol self-administration that is resistant to footshock punishment as a model of this behavior, and found that activity of PKC delta + GABAergic neurons in the central amygdala (CeA) is a determinant of individual susceptibility for punishment resistance. In the present study, we examined whether activation of GABA(B) receptors in CeA can attenuate the activity of PKC delta + neurons in this region, and whether this will result in suppression of punishment- resistant alcohol self-administration in the minority of rats that show this behavior. Systemic administration of the clinically approved GABA(B) agonist baclofen (1 and 3 mg/kg) dose- dependently reduced punishment-resistant alcohol self-administration. Bilateral microinjections of baclofen into CeA (64 ng in 0.3 mu l/side) reduced the activity of PKC delta + neurons, as measured by Fos expression. This manipulation also selectively suppressed punished alcohol self-administration in punishment-resistant rats. Expression analysis indicated that virtually all CeA PKC delta + neurons express the GABA(B) receptor. Using in vitro electrophysiology, we found that baclofen induced hyperpolarization of CeA neurons, reducing their firing rate in response to depolarizing current injections. Together, our findings provide a potential mechanism that contributes to the clinical efficacy of baclofen in alcohol addiction. Therapeutic use of baclofen itself is limited by problems of tolerance and need for dose escalation. Our findings support a mechanistic rationale for developing novel, improved alcohol addiction medications that target GABA(B) receptors, and that lack these limitations, such as e.g., GABA(B) positive allosteric modulators (PAM:s).

Place, publisher, year, edition, pages
SPRINGERNATURE, 2023
National Category
Neurosciences
Identifiers
urn:nbn:se:liu:diva-191971 (URN)10.1038/s41386-023-01543-1 (DOI)000926088900001 ()36739350 (PubMedID)
Available from: 2023-02-28 Created: 2023-02-28 Last updated: 2024-03-05Bibliographically approved
Paul, E., Schwieler, L., Erhardt, S., Boda, S., Trepci, A., Kämpe, R., . . . Samuelsson, M. (2022). Peripheral and central kynurenine pathway abnormalities in major depression. Brain, behavior, and immunity, 101, 136-145
Open this publication in new window or tab >>Peripheral and central kynurenine pathway abnormalities in major depression
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2022 (English)In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 101, p. 136-145Article in journal (Refereed) Published
Abstract [en]

Considerable data relate major depressive disorder (MDD) with aberrant immune system functioning. Pro inflammatory cytokines facilitate metabolism of tryptophan along the kynurenine pathway (KP) putatively resulting in reduced neuroprotective and increased neurotoxic KP metabolites in MDD, in addition to modulating metabolic and immune function. This central nervous system hypothesis has, however, only been tested in the periphery. Here, we measured KP-metabolite levels in both plasma and cerebrospinal fluid (CSF) of depressed patients (n = 63/36 respectively) and healthy controls (n = 48/33). Further, we assessed the relation between KP abnormalities and brain-structure volumes, as well as body mass index (BMI), an index of metabolic disturbance associated with atypical depression. Plasma levels of picolinic acid (PIC), the kynurenic/quinolinic acid ratio (KYNA/QUIN), and PIC/QUIN were lower in MDD, but QUIN levels were increased. In the CSF, we found lower PIC in MDD. Confirming previous work, MDD patients had lower hippocampal, and amygdalar volumes. Hippocampal and amygdalar volumes were correlated positively with plasma KYNA/QUIN ratio in MDD patients. BMI was increased in the MDD group relative to the control group. Moreover, BMI was inversely correlated with plasma and CSF PIC and PIC/QUIN, and positively correlated with plasma QUIN levels in MDD. Our results partially confirm previous peripheral KP findings and extend them to the CSF in MDD. We present the novel finding that abnormalities in KP metabolites are related to metabolic disturbances in depression, but the relation between KP metabolites and depression-associated brain atrophy might not be as direct as previously hypothesized.

Place, publisher, year, edition, pages
Academic Press Inc - Elsevier Science, 2022
Keywords
Major depressive disorder; Kynurenine pathway; Inflammation; Central nervous system; Brain volumetry; Structural magnetic resonance imaging; Cerebrospinal fluid
National Category
Neurology
Identifiers
urn:nbn:se:liu:diva-183765 (URN)10.1016/j.bbi.2022.01.002 (DOI)000761260700005 ()34999196 (PubMedID)
Note

Funding Agencies|Johnson & Johnson Innovation; Swedish Medical Research CouncilSwedish Medical Research Council (SMRC)European Commission [2017-00875, 2013-07434, 2019-01138]; ALF Grants, Region Ostergotland; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01 CA193522, R01 NS073939]; MD Anderson Cancer Support Grant [P30 CA016672]

Available from: 2022-03-24 Created: 2022-03-24 Last updated: 2023-10-13
Mayo, L. M., Asratian, A., Lindé, J., Holm, L., Nätt, D., Augier, G., . . . Heilig, M. (2020). Protective effects of elevated anandamide on stress and fear-related behaviors: translational evidence from humans and mice. Molecular Psychiatry, 25(5), 993-1005
Open this publication in new window or tab >>Protective effects of elevated anandamide on stress and fear-related behaviors: translational evidence from humans and mice
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2020 (English)In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 25, no 5, p. 993-1005Article in journal (Refereed) Published
Abstract [en]

Post-traumatic stress disorder (PTSD) is a common, debilitating condition with limited treatment options. Extinction of fear memories through prolonged exposure therapy, the primary evidence-based behavioral treatment for PTSD, has only partial efficacy. In mice, pharmacological inhibition of fatty acid amide hydrolase (FAAH) produces elevated levels of anandamide (AEA) and promotes fear extinction, suggesting that FAAH inhibitors may aid fear extinction-based treatments. A human FAAH 385C-greater thanA substitution encodes an FAAH enzyme with reduced catabolic efficacy. Individuals homozygous for the FAAH 385A allele may therefore offer a genetic model to evaluate the impact of elevations in AEA signaling in humans, helping to inform whether FAAH inhibitors have the potential to facilitate fear extinction therapy for PTSD. To overcome the challenge posed by low frequency of the AA genotype (appr. 5%), we prospectively genotyped 423 individuals to examine the balanced groups of CC, AC, and AA individuals (n = 25/group). Consistent with its loss-of-function nature, the A allele was dose dependently associated with elevated basal AEA levels, facilitated fear extinction, and enhanced the extinction recall. Moreover, the A-allele homozygotes were protected against stress-induced decreases in AEA and negative emotional consequences of stress. In a humanized mouse model, AA homozygous mice were similarly protected against stress-induced decreases in AEA, both in the periphery, and also in the amygdala and prefrontal cortex, brain structures critically involved in fear extinction and regulation of stress responses. Collectively, these data suggest that AEA signaling can temper aspects of the stress response and that FAAH inhibition may aid the treatment for stress-related psychiatric disorders, such as PTSD.

Place, publisher, year, edition, pages
Nature Publishing Group, 2020
National Category
Neurosciences
Identifiers
urn:nbn:se:liu:diva-154914 (URN)10.1038/s41380-018-0215-1 (DOI)000529878300007 ()30120421 (PubMedID)2-s2.0-85052287102 (Scopus ID)
Note

Funding agencies: Swedish Research CouncilSwedish Research Council [2013-7434]; Canadian Institutes of Health Research (CIHR)Canadian Institutes of Health Research (CIHR); Alberta Innovates and BranchOut Neurological Foundation

Available from: 2019-03-05 Created: 2019-03-05 Last updated: 2021-05-07Bibliographically approved
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
Holm, L., Theodorsson, E., Hokfelt, T. & Theodorsson, A. (2011). Effects of intracerebroventricular galanin or a galanin receptor 2/3 agonist on the lesion induced by transient occlusion of the middle cerebral artery in female rats. Neuropeptides, 45(1), 17-23
Open this publication in new window or tab >>Effects of intracerebroventricular galanin or a galanin receptor 2/3 agonist on the lesion induced by transient occlusion of the middle cerebral artery in female rats
2011 (English)In: Neuropeptides, ISSN 0143-4179, E-ISSN 1532-2785, Vol. 45, no 1, p. 17-23Article in journal (Refereed) Published
Abstract [en]

Several studies have shown that injury to the central and peripheral nervous system can increase expression of galanin, a 29 amino acid neuropeptide. Moreover, there is evidence that galanin, especially through its galanin receptor 2 (GalR2) receptor, plays a neuroprotective role in different injury models. However, direct studies of a possible neuroprotective effect of galanin in experimental stroke models are lacking. Galanin, a GalR2/3 agonist or artificial CSF was continuously infused intracerebroventricularly (i.c.v.) in naive female rats after a 60 min transient and focal occlusion of the middle cerebral artery. The animals were sacrificed, and the ischemic lesion was visualized using 2,3,5-triphenyltetrazolium hydrochloride (TTC) staining. The lesion was 98% larger after i.c.v, administration of the GalR2/3 agonist (2.4 nmol/day) seven days after occlusion compared to artificial CSF (p = 0.023). No statistically significant differences were found after seven days in the groups treated with galanin in three different concentrations (0.24, 2.4 and 24 nmol/day; p = 0.939, 0.715 and 0.977, respectively). There was no difference in the size of the ischemic lesions measured after three days in the galanin-treated group (2.4 nmol/d) compared to artificial CSF (p = 0.925). The present results show, surprisingly, that a GalR2/3 agonist doubled the size of the ischemic lesion. Whether this effect primarily reflects the properties of the current model, species, gender and/or the mode of galanin administration, e.g. causing desensitization, or whether galanin indeed lacks neuroprotective effect of its own, remains to be corroborated.

Place, publisher, year, edition, pages
Elsevier Science B.V., Amsterdam, 2011
Keywords
Cerebral ischemia, Neuropeptide, Neuroprotection, Stroke
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-66126 (URN)10.1016/j.npep.2010.09.002 (DOI)000286857800003 ()
Available from: 2011-03-04 Created: 2011-03-04 Last updated: 2017-12-11Bibliographically approved
Holm, L. (2011). Focal ischemic reperfusion stroke model in rats and the role of galanin. (Doctoral dissertation). Linköping: Linköping University Electronic Press
Open this publication in new window or tab >>Focal ischemic reperfusion stroke model in rats and the role of galanin
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Stroke is the third most common cause for mortality in industrialised countries and amongst the major causes of long- time morbidity. While the mortality due to myocardial infarction has been dramatically reduced during the last 10-15 years, mortality due to stroke remains almost the same, despite the fact that the two share similar basic pathogenic mechanisms including atherosclerosis, hypertension and diabetes. Treatment modalities of reperfusion therapy for acute ischemic stroke, including the use of tissue plasminogen activator for thrombolysis and endovascular treatments, are eff ective if applied early after onset of the first symptoms. The more frequent use of reperfusion therapy, especially in the most common type of stroke aff ecting the middle cerebral artery (MCA), increase the clinical relevance and demand for experimental models of temporary and focal ischemia of the brain. The primary goal of the present work was to develop a model in rats for studying the mechanisms underlying focal and temporary ischemia in brain regions supplied by the MCA.

We have modified the intracranial method of occluding the MCA originally described by Tamura et al. in the early 1980es by introducing a microclip to occlude the artery and induce reperfusion under direct visual control through an operating microscope. The goal was to create a mild ischemia model with low morbidity and mortality, optimizing conditions for the animals postoperatively and allowing longterm (weeks) observation periods of high relevance for human stroke. Morbidity and mortality in experimental stroke models are crucial confounders. Change of anesthesia from intraperitoneally administrated chloral hydrate to isoflurane inhalation anesthesia with endotracheal intubation and controlled ventilation reduced mortality markedly from 25% to ~10%. Improved overall skills in anesthesia and surgical techniques further reduced mortality to <3%.

Hypothermia reduces brain lesions caused by ischemia not only when administered before and during the ischemic episode, but also afterwards. Several studies have shown that galanin concentrations are increased in response to various types of lesions to the nervous system, and galanin may be amongst the factors supporting neuronal survival and functions. We therefore investigated whether or not hypothermia-induced alterations in galanin concentrations could constitute a part of the established neuroprotective effect of hypothermia in our rat stroke model. Hypothermia induced an overall increase in the concentrations of immunoreactive galanin (p < 0.001). The elevated galanin levels were predominantly found in the non-ischemic control hemisphere. The galanin concentrations were lower in the ischemic hemisphere in both the normo- and hypothermic animals compared to the corresponding contralateral intact hemisphere (p = 0.049). The hypothermia and not the ischemic/reperfusion lesions explained the major part of the observed changes in galanin concentrations. Hypothermia-induced elevation in galanin concentration is therefore not likely to be amongst the major protective mechanisms of hypothermia. Our results support the notion that hypothermia-induced increase in tissue concentrations of galanin in the brain are the result of changes from optimal homeostatic conditions – the hypothermia-induced stress – rather than the ischemic/reperfusion lesion- induced changes in galanin concentrations.

Whether the lesion-induced increase in galanin concentrations is primarily a signal that a lesion has occurred, a consequence of the lesion or a mechanism for facilitating neuronal survival is an open question. We therefore infused three different concentrations of galanin intracerebroventricularly in a direct attempt to investigate whether or not galanin has neuroprotective properties in a rat model of MCA occlusion. Furthermore, we infused the GalR2/3 agonist Gal(2-11) (AR-M1896) shown to subserve neuroprotective functions. The lesion was 98% larger seven days after a 60 min transient MCA occlusion and continuous administration of the GalR2/3 agonist Gal(2-11). No differences were found after seven days in the groups treated with galanin in three different concentrations (0.24, 2.4 and 24 nmol/day; p = 0.939, 0.715 and 0.977, respectively). There was also no difference in the size of the ischemic lesion measured after three days in the galanin-treated group (2.4 nmol/d) compared to artificial cerebrospinal fl uid (p = 0.925).

The expression of the galanin, GalR1, GalR2 and GalR3 receptor genes were investigated in the female rat brain seven days after a 60-min unilateral occlusion/reperfusion of the MCA. 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, and the GalR1 mRNA levels decreased by 35% in the cortex of the ischemic hemisphere. Thus, 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, supporting the notion that galanin may play a role in the response of the central nervous system to injury and have trophic effects.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2011. p. 92
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1242
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-68086 (URN)978-91-7393-185-4 (ISBN)
Public defence
2011-05-20, Berzeliussalen, Ingång 65, Campus US, Linköpings universitet, Linköping, 09:00 (English)
Opponent
Supervisors
Available from: 2011-05-10 Created: 2011-05-10 Last updated: 2020-02-03Bibliographically approved
Mutalifu, Y., Holm, L., Ince, C., Theodorsson, E. & Sjöberg, F. (2011). Multiple different laminar velocity profiles in separate veins in the microvascular network of brain cortex in rats. International Journal of Clinical and Experimental Medicine, 4(1), 10-16
Open this publication in new window or tab >>Multiple different laminar velocity profiles in separate veins in the microvascular network of brain cortex in rats
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2011 (English)In: International Journal of Clinical and Experimental Medicine, E-ISSN 1940-5901, Vol. 4, no 1, p. 10-16Article in journal (Refereed) Published
Abstract [en]

The orthogonal polarisation spectral (OPS) imaging technique is a method that enables intravital microscopy of the tissue microvasculature particularly including the erythrocytes and leucocytes. As a new finding we here report multi flow, i.e, several different laminar velocity profiles in each and separate veins (diameters < 200 μm) of the microcirculation of the rat brain cortex. The phenomenon was present in all 20 preparations studied and these different laminar velocity profiles were regularly maintained in length beyond 20 times the diameter of parent vessel. In single veins up to 9 different laminar velocity profiles were discernible, each with a different red blood cell velocity. These multi flow profiles may theoretically be anticipated based on what is known in rheological physiology as the Fahreus - Lindqvist effect. It may also be predicted in tissues that have both high and heterogeneous blood flows in conjunction with large local variations in metabolic activity as are present in the cortex of the brain. The new information is that the extent and magnitude of this multi laminar flow phenomenon especially in the venular network of the brain exceeds what has previously been known. The physiological importance of these finding warrants further studies.

Place, publisher, year, edition, pages
Madison, WI, United States: e-Century Publishing, 2011
Keywords
Dynamic structure of blood flow, Multi-laminar flow profiles, Orthogonal polarization spectral imaging
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-65641 (URN)000208701200002 ()21394281 (PubMedID)
Available from: 2011-02-15 Created: 2011-02-15 Last updated: 2023-10-04Bibliographically approved
Ström, J. O., Theodorsson, E., Holm, L. & Theodorsson, A. (2010). Different methods for administering 17 beta-estradiol to ovariectomized rats result in opposite effects on ischemic brain damage. BMC Neuroscience, 11, 39
Open this publication in new window or tab >>Different methods for administering 17 beta-estradiol to ovariectomized rats result in opposite effects on ischemic brain damage
2010 (English)In: BMC Neuroscience, E-ISSN 1471-2202, Vol. 11, p. 39-Article in journal (Refereed) Published
Abstract [en]

Background: Numerous stroke studies have controversially shown estrogens to be either neuroprotective or neurodamaging. The discordant results observed in rat brain ischemia models may be a consequence of discrepancies in estrogen administration modes resulting in plasma concentration profiles far from those intended. To test this hypothesis we reproduced in detail and extended an earlier study from our lab using a different mode of 17 beta-estradiol administration; home-made silastic capsules instead of commercial slow-release 17 beta-estradiol pellets. Four groups of female rats (n = 12) were ovariectomized and administered 17 beta-estradiol or placebo via silastic capsules. All animals underwent MCAo fourteen days after ovariectomy and were sacrificed three days later.

Results: In contrast to our earlier results using the commercial pellets, the group receiving 17 beta-estradiol during the entire experiment had significantly smaller lesions than the group receiving placebo (mean +/- SEM: 3.85 +/- 0.70% versus 7.15 +/- 0.27% of total slice area, respectively; p = 0.015). No significant neuroprotection was found when the 17 beta-estradiol was administered only during the two weeks before or the three days immediately after MCAo.

Conclusions: The results indicate that different estrogen treatment regimens result in diametrically different effects on cerebral ischemia. Thus the effects of estrogens on ischemic damage seem to be concentration-related, with a biphasic, or even more complex, dose-response relation. These findings have implications for the design of animal experiments and also have a bearing on the estrogen doses used for peri-menopausal hormone replacement therapy.

Place, publisher, year, edition, pages
BioMed Central, 2010
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-55058 (URN)10.1186/1471-2202-11-39 (DOI)000276444500001 ()20236508 (PubMedID)
Note

Original Publication: Jakob O Ström, Elvar Theodorsson, Lovisa Holm and Annette Theodorsson, Different methods for administering 17 beta-estradiol to ovariectomized rats result in opposite effects on ischemic brain damage, 2010, BMC NEUROSCIENCE, (11), 39. http://dx.doi.org/10.1186/1471-2202-11-39 Licensee: BioMed Central http://www.biomedcentral.com/

Available from: 2010-04-28 Created: 2010-04-28 Last updated: 2024-01-17Bibliographically approved
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
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