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Bäckström, Torbjörn
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Publications (10 of 155) Show all publications
Ekenros, L., Bäckström, T., Hirschberg, A. L. & Fridén, C. (2019). Changes in premenstrual symptoms in women starting or discontinuing use of oral contraceptives. Gynecological Endocrinology, 35(5), 422-426
Open this publication in new window or tab >>Changes in premenstrual symptoms in women starting or discontinuing use of oral contraceptives
2019 (English)In: Gynecological Endocrinology, ISSN 0951-3590, E-ISSN 1473-0766, Vol. 35, no 5, p. 422-426Article in journal (Refereed) Published
Abstract [en]

It is not clear whether oral contraceptive (OC) treatment affects premenstrual symptoms in women. The aim of the present study was to evaluate changes in premenstrual symptoms (PMS) in women starting to use or discontinuing the use of OCs. Twenty-four healthy women with no previous diagnosis of premenstrual dysphoric disorder were included in this study with a prospective crossover design. Nineteen women completed daily ratings of somatic and mood symptoms during two hormonally different cycles, during a normal menstrual cycle and while using OCs. The menstrual cycle phases were hormonally verified and the low-dose, monophasic OCs were used in a 21/7 regimen. The onset of OC use significantly decreased premenstrual somatic symptoms, but it did not affect mood symptoms. In the women who discontinued OC use, no significant changes in neither somatic nor mood symptoms appeared in the premenstrual phase.

Place, publisher, year, edition, pages
Taylor & Francis Group, 2019
Keywords
Cross-over design, female sex hormones, menstrual cycle, estrogens, hormonal contraception
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-159611 (URN)10.1080/09513590.2018.1534097 (DOI)000467731500011 ()30668208 (PubMedID)
Available from: 2019-06-17 Created: 2019-06-17 Last updated: 2019-06-17Bibliographically approved
Poromaa, I. S., Comasco, E., Bäckström, T., Bixo, M., Jensen, P. & Frokjaer, V. G. (2019). Negative Association Between Allopregnanolone and Cerebral Serotonin Transporter Binding in Healthy Women of Fertile Age. Frontiers in Psychology, 9, Article ID 2767.
Open this publication in new window or tab >>Negative Association Between Allopregnanolone and Cerebral Serotonin Transporter Binding in Healthy Women of Fertile Age
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2019 (English)In: Frontiers in Psychology, ISSN 1664-1078, E-ISSN 1664-1078, Vol. 9, article id 2767Article in journal (Refereed) Published
Abstract [en]

Allopregnanolone is a metabolite of the sex hormone progesterone, with suggested relevance for female mood disorders. While allopregnanolone and serotonin are known to influence psychological well-being, the molecular and psychological specifics of their relationship are to date poorly understood, especially in women of fertile age who experience regular fluctuations of progesterone across the menstrual cycle. Availability of serotonin in the synaptic cleft is regulated by the serotonin transporter (SERT), which can be imaged in the living human brain by use of positron emission tomography (PET) and the radiotracer [C-11]DASB. To evaluate sex-specific allopregnanolone-SERT interactions, the present study investigated the relationship between cerebral SERT availability, serum allopregnanolone levels and psychological well-being in women of fertile age. Brain imaging data, self-reported symptoms of mental distress and emotion regulation, and biobank material from ninety healthy women were available from the Center for Integrated Molecular Brain Imaging (CIMBI) database. Age, BMI, and daylight minutes were included as covariates in the analyses and SERT genotype (5-HTTLPR) was considered a potential confounder. Lower serum allopregnanolone levels were associated with higher SERT binding in the prefrontal cortex. Moreover, allopregnanolone levels were negatively associated with measures of alertness, although this finding was not mediated by prefrontal cortex SERT binding. These findings suggest a link between the typical psychological well-being experienced in the follicular phase when allopregnanolone levels are low and higher SERT in the prefrontal cortex, a region for higher cognitive functions and top-down regulation of emotions.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2019
Keywords
allopregnanolone, brain, mood, PET, serotonin transporter, women, 5HTT
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-155960 (URN)10.3389/fpsyg.2018.02767 (DOI)000455554400001 ()
Funder
Swedish Research Council, VR: 2015-00495
Available from: 2019-02-08 Created: 2019-02-08 Last updated: 2019-02-08Bibliographically approved
Holmberg, E., Sjöstedt, J., Malinina, E., Johansson, M., Turkmen, S., Ragagnin, G., . . . Bäckström, T. (2018). Allopregnanolone involvement in feeding regulation, overeating and obesity. Frontiers in neuroendocrinology (Print), 48, 70-77
Open this publication in new window or tab >>Allopregnanolone involvement in feeding regulation, overeating and obesity
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2018 (English)In: Frontiers in neuroendocrinology (Print), ISSN 0091-3022, E-ISSN 1095-6808, Vol. 48, p. 70-77Article, review/survey (Refereed) Published
Abstract [en]

Obesity is strongly associated with ill health, primarily caused by consumption of excessive calories, and promoted (inter alia) by gamma-amino-butyric-acid (GABA) stimulating food intake by activating GABA(A) receptors (primarily with alpha 3 and alpha 2 subunits) in the hypothalamic arcuate nucleus and paraventricular nucleus. Allopregnanolone is a potent positive GABAA receptor modulating steroid (GAMS). As reviewed here, elevated allopregnanolone levels are associated with increases in food intake, preferences for energy-rich food, and obesity in humans and other mammals. In women with polycystic ovarian disease, high serum allopregnanolone concentrations are linked to uncontrolled eating, and perturbed sensitivity to allopregnanolone. Increases in weight during pregnancy also correlate with increases in allopregnanolone levels. Moreover, Prader-Willis syndrome is associated with massive overeating, absence of a GABA(A) receptor (with compensatory > 12-, > 5- and > 1.5-fold increases in alpha 4, gamma 2, and alpha 1, alpha 3 subunits), and increases in the alpha 4, beta x, delta receptor subtype, which is highly sensitive to allopregnanolone. GABA and positive GABA-A receptor modulating steroids like allopregnanolone stimulates food intake and weight gain.

Place, publisher, year, edition, pages
Academic Press, 2018
Keywords
Allopregnanolone, GABA, GABA(A) receptor, Satiety, Hunger, Obesity, Overeating
National Category
Nutrition and Dietetics
Identifiers
urn:nbn:se:umu:diva-145173 (URN)10.1016/j.yfrne.2017.07.002 (DOI)000424316800008 ()28694181 (PubMedID)
Available from: 2018-03-12 Created: 2018-03-12 Last updated: 2019-05-06Bibliographically approved
Bixo, M., Johansson, M., Timby, E., Michalski, L. & Bäckström, T. (2018). Effects of GABA active steroids in the female brain with a focus on the premenstrual dysphoric disorder. Paper presented at 9th International Meeting on Steroids and Nervous System, FEB 11-15, 2017, Torino, ITALY. Journal of neuroendocrinology (Print), 30(2), Article ID e12553.
Open this publication in new window or tab >>Effects of GABA active steroids in the female brain with a focus on the premenstrual dysphoric disorder
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2018 (English)In: Journal of neuroendocrinology (Print), ISSN 0953-8194, E-ISSN 1365-2826, Vol. 30, no 2, article id e12553Article in journal (Refereed) Published
Abstract [en]

Premenstrual dysphoric disorder (PMDD) afflicts 3%-5% of women of childbearing age, and is characterised by recurrent negative mood symptoms (eg, irritability, depression, anxiety and emotional lability) during the luteal phase of the menstrual cycle. The aetiology of PMDD is unknown, although a temporal association with circulating ovarian steroids, in particular progesterone and its metabolite allopregnanolone, has been established during the luteal phase. Allopregnanolone is a positive modulator of the GABA(A) receptor: it is sedative in high concentrations but may precipitate paradoxical adverse effects on mood at levels corresponding to luteal phase concentrations in susceptible women. Saccadic eye velocity (SEV) is a measure of GABA(A) receptor sensitivity; in experimental studies of healthy women, i.v. allopregnanolone decreases SEV. Women with PMDD display an altered sensitivity to an i.v. injection of allopregnanolone compared to healthy controls in this model. In functional magnetic resonance imaging (fMRI) studies, women with PMDD react differently to emotional stimuli in contrast to controls. A consistent finding in PMDD patients is increased amygdala reactivity during the luteal phase. Post-mortem studies in humans have revealed that allopregnanolone concentrations vary across different brain regions, although mean levels in the brain also reflect variations in peripheral serum concentrations. The amygdala processes emotions such as anxiety and aggression. This is interesting because allopregnanolone is detected at high concentrations within the region into which marked increases in blood flow are measured with fMRI following progesterone/allopregnanolone administration. Allopregnanolone effects are antagonised by its isomer isoallopregnanolone (UC1010), which significantly reduces negative mood symptoms in women with PMDD when administered s.c. in the premenstrual phase. This was shown in a randomised, placebo-controlled clinical trial in which the primary outcome was change in symptom scoring on the Daily Rating of Severity of Problems (DRSP): the treatment reduced negative mood scores (P<.005), as well as total DRSP scores (P<.01), compared to placebo in women with PMDD. In conclusion, the underlying studies of this review provide evidence that allopregnanolone is the provoking factor behind the negative mood symptoms in PMDD and that isoallopregnanolone could ameliorate the symptoms as a result of its ability to antagonise the allopregnanolone effect on the GABA(A) receptor.

Keywords
GABA, neuroactive steroids, premenstrual dysphoric disorder
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-145601 (URN)10.1111/jne.12553 (DOI)000425521300018 ()
Conference
9th International Meeting on Steroids and Nervous System, FEB 11-15, 2017, Torino, ITALY
Available from: 2018-03-29 Created: 2018-03-29 Last updated: 2018-06-09Bibliographically approved
Johansson, M., Månsson, M., Lins, L.-E., Scharschmidt, B., Doverskog, M. & Bäckström, T. (2018). GR3027 reversal of neurosteroid-induced, GABA-A receptor-mediated inhibition of human brain function: an allopregnanolone challenge study. Psychopharmacology, 235(5), 1533-1543
Open this publication in new window or tab >>GR3027 reversal of neurosteroid-induced, GABA-A receptor-mediated inhibition of human brain function: an allopregnanolone challenge study
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2018 (English)In: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 235, no 5, p. 1533-1543Article in journal (Refereed) Published
Abstract [en]

RATIONALE: GR3027 is a novel small molecule GABA-A receptor-modulating steroid antagonist, which in non-clinical studies has shown promise for treatment of human disorders due to allosteric over-activation of GABA-A receptors by neurosteroids, such as allopregnanolone. We here studied its safety, pharmacokinetics, and ability to inhibit allopregnanolone effects in humans.

METHODS: Safety and pharmacokinetics were studied in healthy adult males receiving ascending single or multiple oral GR3027 vs. placebo. GR3027-mediated reversal of allopregnanolone effect on maximal saccadic eye velocity (SEV), and self-rated somnolence was studied in a double-blind, placebo-controlled, three-part cross-over study in which 3 or 30 mg oral GR3027 preceded 0.05 mg/kg of i.v. allopregnanolone.

RESULTS: ]) varied linearly with dose; with dose-dependent accumulation ratios of 1.3-1.6. Allopregnanolone decreased SEV and induced somnolence in most, but not all subjects. By predefined analyses, 30 mg GR3027 significantly inhibited allopregnanolone-induced decrease in SEV (p = 0.03); 3 and 30 mg GR3027 non-significantly inhibited allopregnanolone-induced sedation. By post hoc analyses restricted to subjects with allopregnanolone-induced changes and the time period over which they occurred, GR3027 dose dependently inhibited allopregnanolone-induced decrease in SEV (p = 0.04 at 30 mg, non-significant at 3 mg) and allopregnanolone-induced sedation (p = 0.01/0.05 at 3/30 mg doses).

CONCLUSION: Oral GR3027 mitigates inhibition of brain function induced by allopregnanolone at doses which are clinically well tolerated and associated with linear pharmacokinetics.

Place, publisher, year, edition, pages
Springer, 2018
Keywords
Allopregnanolone, Clinical trial, GR3027, Saccadic eye movement, Sedation
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-148340 (URN)10.1007/s00213-018-4864-1 (DOI)000431034400018 ()29492615 (PubMedID)
Available from: 2018-06-04 Created: 2018-06-04 Last updated: 2018-10-29Bibliographically approved
Mahlck, C.-G. & Bäckström, T. (2017). Follow-up after early medical abortion: comparing clinical assessment with self-assessment in a rural hospital in northern Norway. European Journal of Obstetrics, Gynecology, and Reproductive Biology, 213, 1-3
Open this publication in new window or tab >>Follow-up after early medical abortion: comparing clinical assessment with self-assessment in a rural hospital in northern Norway
2017 (English)In: European Journal of Obstetrics, Gynecology, and Reproductive Biology, ISSN 0301-2115, E-ISSN 1872-7654, Vol. 213, p. 1-3Article in journal (Refereed) Published
Abstract [en]

Objectives: A follow-up study was performed on women who had requested medical abortions in a rural hospital in northern Norway to compare clinical assessment with self-assessment of early medical abortion in terms of safety. Study design: During the three-year study period, 392 women requested termination of pregnancy. After excluding those who changed their mind, those who had a spontaneous miscarriage, those who were referred to a central hospital for a two-stage abortion, and those who had the abortion performed surgically, 242 cases remained, and all the medical files were reviewed. Five cases (2%) were lost to follow-up, so the study group consists of 237 cases. Results: Out of the 237 cases, in which a medical abortion was performed, 106 were performed at home with a self-assessment (44.7%), and 131 (55.3%) were performed at the department of Gynecology. The percentage of cases with self-assessment did not noticeably change during the three-year study period. The registered complications were infection, incomplete abortion requiring a surgical procedure and hospitalization due to severe pain. No significant difference in registered complications was found between medical abortions with self-assessment (n=9, 8.5% out of 106 cases) and medical abortions at the gynecological out-patient department (n=6, 4.6% out of 131 cases). Conclusion: According to this investigation, it is equally safe to perform a medical abortion at home with a self-assessment as it is to have a medical abortion at an outpatient clinic. These results could be useful for health care provision in rural areas where access to hospitals is impeded by logistical difficulties.

Place, publisher, year, edition, pages
Elsevier, 2017
Keywords
Medical abortions, Complications, Rural hospital
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-137393 (URN)10.1016/j.ejogrb.2017.03.034 (DOI)000403134500001 ()28384539 (PubMedID)
Available from: 2017-07-05 Created: 2017-07-05 Last updated: 2018-06-09Bibliographically approved
Lundqvist, A., Sandström, H. & Bäckström, T. (2017). The relationship between weight gain during pregnancy and allopregnanolone levels: a longitudinal study. Endocrine Connections, 6(4), 253-259
Open this publication in new window or tab >>The relationship between weight gain during pregnancy and allopregnanolone levels: a longitudinal study
2017 (English)In: Endocrine Connections, ISSN 2049-3614, E-ISSN 2049-3614, Vol. 6, no 4, p. 253-259Article in journal (Refereed) Published
Abstract [en]

Objective: Large weight gain during pregnancy is a risk factor for complications for mother and fetus. Hunger and satiety are regulated in the hypothalamus, where the gamma-amino-butyric acid system (GABA) has an important role. Allopregnanolone, a progesterone metabolite, increases during pregnancy and is a potent GABA-A receptor modulating steroid. Allopregnanolone has been shown to induce overeating in rodents. The aim was to investigate whether there is a relationship between weight gain and allopregnanolone concentrations during pregnancy in humans. Design: A longitudinal, cohort study. Methods: Pregnant women (n = 56) were recruited in primary care in northern Sweden. Allopregnanolone concentrations in plasma were measured using radioimmunoassay and weight was measured in gestational weeks 12 and 35. Results: Weight increase correlated significantly to allopregnanolone in late pregnancy increase (r(s) = 0.320; P = 0.016), indicating a positive relationship between weight increase and allopregnanolone increase. A positive relationship was also noted between allopregnanolone in the 35th gestational week and weight increase. Women who gained = 11 kg during pregnancy showed higher allopregnanolone concentrations in week 35 and higher increase compared to women who increased < 11 kg (P = 0.006 and P = 0.009 resp.). There was no difference in weight or allopregnanolone concentrations at the onset of pregnancy. Conclusions: The results show a relationship between weight gain during pregnancy and increase in allopregnanolone concentrations.

Place, publisher, year, edition, pages
Bioscientifica, 2017
Keywords
allopregnanolone, pregnancy, weight increase, longitudinal
National Category
Obstetrics, Gynecology and Reproductive Medicine Nutrition and Dietetics
Identifiers
urn:nbn:se:umu:diva-137986 (URN)10.1530/EC-17-0046 (DOI)000404927100012 ()28381564 (PubMedID)
Available from: 2017-08-01 Created: 2017-08-01 Last updated: 2018-06-09Bibliographically approved
Bixo, M., Ekberg, K., Poromaa, I. S., Hirschberg, A. L., Jonasson, A. F., Andreen, L., . . . Bäckström, T. (2017). Treatment of premenstrual dysphoric disorder with the GABA(A) receptor modulating steroid antagonist Sepranolone (UC1010)-A randomized controlled trial. Psychoneuroendocrinology, 80, 46-55
Open this publication in new window or tab >>Treatment of premenstrual dysphoric disorder with the GABA(A) receptor modulating steroid antagonist Sepranolone (UC1010)-A randomized controlled trial
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2017 (English)In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 80, p. 46-55Article in journal (Refereed) Published
Abstract [en]

Context: Allopregnanolone is a metabolite from progesterone and a positive modulator of the GABAA receptor. This endogenous steroid may induce negative mood in sensitive women when present in serum levels comparable to the premenstrual phase. Its endogenous isomer, isoallopregnanolone, has been shown to antagonize allopregnanolone effects in experimental animal and human models.

Objective: The objective was to test whether inhibition of allopregnanolone by treatment with the GABAA modulating steroid antagonist (GAMSA) Sepranolone (UC1010) during the premenstrual phase could reduce symptoms of the premenstrual dysphoric disorder (PMDD). The pharmacokinetic parameters of UC1010 when given as a subcutaneous injection were measured in healthy women prior to the study in women with PMDD.

Design: This was an explorative randomized, double-blind, placebo-controlled study.

Setting: Swedish multicentre study with 10 centers.

Participants: Participants were 26 healthy women in a pharmacokinetic phase I study part, and 126 women with PMDD in a phase II study part. Diagnosis followed the criteria for PMDD in DSM-5 using Daily Record of Severity of Problems (DRSP) and Endicott’s algorithm.

Intervention: Subjects were randomized to treatment with UC1010 (10 or 16 mg) subcutaneously every second day during the luteal phase or placebo during one menstrual cycle.

Outcome measures: The primary outcome measure was the sum of all 21 items in DRSP (Total DRSP score). Secondary outcomes were Negative mood score i.e. the ratings of the 4 key symptoms in PMDD (anger/irritability, depression, anxiety and lability) and impairment (impact on daily life).

Results: 26 healthy women completed the pharmacokinetic phase I study and the dosing in the following trial was adjusted according to the results. 106 of the 126 women completed the phase II study. Within this group, a significant treatment effect with UC1010 compared to placebo was obtained for the Total DRSP score (p = 0.041) and borderline significance (p = 0.051) for the sum of Negative mood score.

Nineteen participants however showed symptoms during the follicular phase that might be signs of an underlying other conditions, and 27 participants had not received the medication as intended during the symptomatic phase. Hence, to secure that the significant result described above was not due to chance, a post hoc sub-group analysis was performed, including only women with pure PMDD who completed the trial as intended (n = 60). In this group UC1010 reduced Total DRSP scores by 75% compared with 47% following placebo; the effect size 0.7 (p = 0.006), and for sum of Negative mood score (p = 0.003) and impairment (p = 0.010) with the effect size 0.6. No severe adverse events were reported during the treatment and safety parameters (vital signs and blood chemistry) remained normal during the study.

Conclusions: This explorative study indicates promising results for UC1010 as a potential treatment for PMDD. The effect size was comparable to that of SSRIs and drospirenone containing oral contraceptives. UC1010 was well tolerated and deemed safe.

Keywords
Premenstrual dysphoric disorder, Allopregnanolone, Isoallopregnanolone, GABA, Randomized ntrolled trial
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-136320 (URN)10.1016/j.psyneuen.2017.02.031 (DOI)000402352200007 ()28319848 (PubMedID)
Available from: 2017-06-26 Created: 2017-06-26 Last updated: 2018-06-09Bibliographically approved
Johansson, M., Strömberg, J., Ragagnin, G., Doverskog, M. & Bäckström, T. (2016). GABAA receptor modulating steroid antagonists (GAMSA) are functional in vivo. Journal of Steroid Biochemistry and Molecular Biology, 160(SI), 98-105
Open this publication in new window or tab >>GABAA receptor modulating steroid antagonists (GAMSA) are functional in vivo
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2016 (English)In: Journal of Steroid Biochemistry and Molecular Biology, ISSN 0960-0760, E-ISSN 1879-1220, Vol. 160, no SI, p. 98-105Article in journal (Refereed) Published
Abstract [en]

GABAA receptor modulating steroid antagonists (GAMSA) selectively inhibit neurosteroid-mediated enhancement of GABA-evoked currents at the GABAA receptor. 3α-hydroxy-neurosteroids, notably allopregnanolone and tetrahydrodeoxycorticosterone (THDOC), potentiate GABAA receptor-mediated currents. On the contrary, various 3β-hydroxy-steroids antagonize this positive neurosteroid-mediated modulation. Importantly, GAMSAs are specific antagonists of the positive neurosteroid-modulation of the receptor and do not inhibit GABA-evoked currents. Allopregnanolone and THDOC have both negative and positive actions. Allopregnanolone can impair encoding/consolidation and retrieval of memories. Chronic administration of a physiological allopregnanolone concentration reduces cognition in mice models of Alzheimer's disease. In humans an allopregnanolone challenge impairs episodic memory and in hepatic encephalopathy cognitive deficits are accompanied by increased brain ammonia and allopregnanolone. Hippocampal slices react in vitro to ammonia by allopregnanolone synthesis in CA1 neurons, which blocks long-term potentiation (LTP). Thus, allopregnanolone may impair learning and memory by interfering with hippocampal LTP. Contrary, pharmacological treatment with allopregnanolone can promote neurogenesis and positively influence learning and memory of trace eye-blink conditioning in mice. In rat the GAMSA UC1011 inhibits an allopregnanolone-induced learning impairment and the GAMSA GR3027 restores learning and motor coordination in rats with hepatic encephalopathy. In addition, the GAMSA isoallopregnanolone antagonizes allopregnanolone-induced anesthesia in rats, and in humans it antagonizes allopregnanolone-induced sedation and reductions in saccadic eye velocity. 17PA is also an effective GAMSA in vivo, as it antagonizes allopregnanolone-induced anesthesia and spinal analgesia in rats. In vitro the allopregnanolone/THDOC-increased GABA-mediated GABAA receptor activity is antagonized by isoallopregnanolone, UC1011, GR3027 and 17PA, while the effect of GABA itself is not affected.

Place, publisher, year, edition, pages
Elsevier, 2016
Keywords
Allopregnanolone, Neurosteroids, GABAA receptor, GAMSA, Cognition
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-118532 (URN)10.1016/j.jsbmb.2015.10.019 (DOI)000376840500013 ()26523675 (PubMedID)
Available from: 2016-03-22 Created: 2016-03-22 Last updated: 2018-06-07Bibliographically approved
Bengtsson, S. K., Johansson, M. & Bäckström, T. (2016). Long-term continuous allopregnanolone elevation causes memory decline and hippocampus shrinkage, in female wild-type B6 mice. Hormones and Behavior, 78, 160-167
Open this publication in new window or tab >>Long-term continuous allopregnanolone elevation causes memory decline and hippocampus shrinkage, in female wild-type B6 mice
2016 (English)In: Hormones and Behavior, ISSN 0018-506X, E-ISSN 1095-6867, Vol. 78, p. 160-167Article in journal (Refereed) Published
Abstract [en]

Chronic stress in various forms increases the risk for cognitive dysfunction, dementia and Alzheimer's disease. While the pathogenesis behind these findings is unknown, growing evidence suggests that chronic increase in neurosteroid levels, such as allopregnanolone, is part of the mechanism. We treated wild-type C57BL/6J mice with allopregnanolone for 5months, using osmotic pumps. This treatment led to moderately increased levels of allopregnanolone, equivalent to that of mild chronic stress. After an interval of no treatment for 1month, female mice showed impaired learning and memory function in the Morris water maze (MWM) in combination with diminished hippocampus weight and increased cerebellum weight, both correlating to MWM performance. Male mice showed a minor reduction in memory function and no differences in brain structure. We conclude that chronic allopregnanolone elevation can lead to cognitive dysfunction and negative brain alterations. We suggest that allopregnanolone could play a key role in the pathogenesis of stress-induced cognitive disturbances and perhaps dementia.

Keywords
Allopregnanolone, Memory and learning, Chronic stress, Mild cognitive impairment, Dementia, Brain tissue weight, GABA, Wild-type mice, C57BL/6J mice
National Category
Neurosciences Other Health Sciences
Identifiers
urn:nbn:se:umu:diva-118533 (URN)10.1016/j.yhbeh.2015.10.010 (DOI)000368962200020 ()26497250 (PubMedID)
Available from: 2016-03-22 Created: 2016-03-22 Last updated: 2018-06-07Bibliographically approved
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