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Johansson, Inga-Maj
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Publications (10 of 42) Show all publications
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, 98-105 p.Article 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
Keyword
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: 2017-11-30Bibliographically 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, 160-167 p.Article 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.

Keyword
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: 2018-01-10Bibliographically approved
Johansson, M., Agusti, A., Llansola, M., Montoliu, C., Strömberg, J., Malinina, E., . . . Felipo, V. (2015). GR3027 antagonizes GABA(A) receptor-potentiating neurosteroids and restores spatial learning and motor coordination in rats with chronic hyperammonemia and hepatic encephalopathy. American Journal of Physiology - Gastrointestinal and Liver Physiology, 309(5), G400-G409.
Open this publication in new window or tab >>GR3027 antagonizes GABA(A) receptor-potentiating neurosteroids and restores spatial learning and motor coordination in rats with chronic hyperammonemia and hepatic encephalopathy
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2015 (English)In: American Journal of Physiology - Gastrointestinal and Liver Physiology, ISSN 0193-1857, E-ISSN 1522-1547, Vol. 309, no 5, G400-G409 p.Article in journal (Refereed) Published
Abstract [en]

Hepatic encephalopathy (HE) is one of the primary complications of liver cirrhosis. Current treatments for HE, mainly directed to reduction of ammonia levels, are not effective enough because they cannot completely eliminate hyperammonemia and inflammation, which induce the neurological alterations. Studies in animal models show that overactivation of GABA(A) receptors is involved in cognitive and motor impairment in HE and that reducing this activation restores these functions. We have developed a new compound, GR3027, that selectively antagonizes the enhanced activation of GABA(A) receptors by neurosteroids such as allopregnanolone and 3 alpha, 21-dihydroxy-5 alpha-pregnan-20-one (THDOC). This work aimed to assess whether GR3027 improves motor incoordination, spatial learning, and circadian rhythms of activity in rats with HE. GR3027 was administered subcutaneously to two main models of HE: rats with chronic hyperammonemia due to ammonia feeding and rats with portacaval shunts (PCS). Motor coordination was assessed in beam walking and spatial learning and memory in the Morris water maze and the radial maze. Circadian rhythms of ambulatory and vertical activity were also assessed. In both hyperammonemic and PCS rats, GR3027 restores motor coordination, spatial memory in the Morris water maze, and spatial learning in the radial maze. GR3027 also partially restores circadian rhythms of ambulatory and vertical activity in PCS rats. GR3027 is a novel approach to treatment of HE that would normalize neurological functions altered because of enhanced GABAergic tone, affording more complete normalization of cognitive and motor function than current treatments for HE.

Place, publisher, year, edition, pages
American Physiological Society, 2015
Keyword
GABA(A) receptors, hyperammonemia, neurosteroids, hepatic encephalopathy
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:umu:diva-109375 (URN)10.1152/ajpgi.00073.2015 (DOI)000360687000012 ()26138462 (PubMedID)
Note

This study was financed by Umecrine Cognition AB

Available from: 2015-09-28 Created: 2015-09-25 Last updated: 2017-12-01Bibliographically approved
Holmberg, E., Johansson, M., Bäckström, T., Löfgren, M. & Haage, D. (2015). Repeated allopregnanolone exposure induces weight gain in schedule fed rats on high fat diet. Physiology and Behavior, 140, 1-7.
Open this publication in new window or tab >>Repeated allopregnanolone exposure induces weight gain in schedule fed rats on high fat diet
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2015 (English)In: Physiology and Behavior, ISSN 0031-9384, E-ISSN 1873-507X, Vol. 140, 1-7 p.Article in journal (Refereed) Published
Abstract [en]

Ingestion of energy rich high fat diets is one of the determining factors associated with the obesity epidemic. Therefore, much can be learned from studies of obesity-related substances given to animals fed a high fat diet.The progesterone metabolite allopregnanolone is a potent positive modulator of the gamma-aminobutyric acid(GABA)A-receptor, and both allopregnanolone and GABA have been implicated in evoking hyperphagia. In this study, food intake and body weight gain were investigated during repeated allopregnanolone exposure. Male Wistar rats were studied when fed chow ad libitum, with chow access for 4h per day or with 45% high fat pellets for 4 h per day. Rats on the high fat diet were separated into obesity prone and obesity resistant individuals.Subcutaneous injections of allopregnanolone were given once daily overfive consecutive days. Repeated exposure to allopregnanolone lead to increased weight gain, significantly so in schedule fed rats on a high fat diet. The increased weight gain was correlated to an increased energy intake. Both obesity resistant and obesityprone rats responded to allopregnanolone with increased weight gain. Obesity resistant rats treated with allopregnanolone increased their energy intake and ate as much as vehicle treated obesity prone rats. Their weight gain was also increased to the level of obesity prone rats injected with just the vehicle carrier oil. Thus, it appears that allopregnanolone may be one of the endogenous factors involved in weight gain, especiallywhen the diet is rich in fat.

Place, publisher, year, edition, pages
Elsevier, 2015
Keyword
Allopregnanolone Neurosteroid Weight gain Food intake Scheduled feeding High fat diet
National Category
Neurosciences Physiology Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-101793 (URN)10.1016/j.physbeh.2014.12.012 (DOI)000349588400001 ()
Available from: 2015-04-13 Created: 2015-04-13 Last updated: 2018-01-11Bibliographically approved
Bäckström, T., Bixo, M., Johansson, M., Nyberg, S., Ossewaarde, L., Ragagnin, G., . . . van Wingen, G. (2014). Allopregnanolone and mood disorders. Progress in Neurobiology, 113, 88-94.
Open this publication in new window or tab >>Allopregnanolone and mood disorders
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2014 (English)In: Progress in Neurobiology, ISSN 0301-0082, E-ISSN 1873-5118, Vol. 113, 88-94 p.Article in journal (Refereed) Published
Abstract [en]

Certain women experience negative mood symptoms during the menstrual cycle and progesterone addition in estrogen treatments. In women with PMDD increased negative mood symptoms related to allopregnanolone increase during the luteal phase of ovulatory menstrual cycles. In anovulatory cycles no symptom or sex steroid increase occurs. This is unexpected as positive modulators of the GABA-A receptor are generally increasing mood. This paradoxical effect has brought forward a hypothesis that the symptoms are provoked by allopregnanolone the GABA-A receptor system. GABA-A is the major inhibitory system in the brain. Positive modulators of the GABA-A receptor include the progesterone metabolites allopregnanolone and pregnanolone, benzodiazepines, barbiturates, and alcohol. GABA-A receptor modulators are known, in low concentrations to induce adverse, anxiogenic effects whereas in higher concentrations show beneficial, calming properties. Positive GABA-A receptor modulators induce strong paradoxical effects e.g. negative mood in 3-8% of those exposed, while up to 25% have moderate symptoms thus similar as the prevalence of PMDD, 3-8% among women in fertile ages, and up to 25% have moderate symptoms of premenstrual syndrome (PMS). The mechanism behind paradoxical reaction might be similar among them who react on positive GABA-A receptor modulators and in women with PMDD. In women the severity of these mood symptoms are related to the allopregnanolone serum concentrations in an inverted U-shaped curve. Negative mood symptoms occur when the serum concentration of allopregnanolone is similar to endogenous luteal phase levels, while low and high concentrations have less effect on mood. Low to moderate progesterone/allopregnanolone concentrations in women increases the activity in the amygdala (measured with fMRI) similar to the changes seen during anxiety reactions. Higher concentrations give decreased amygdala activity similar as seen during benzodiazepine treatment with calming anxiolytic effects. Patients with PMDD show decreased sensitivity in GABA-A receptor sensitivity to diazepam and pregnanolone while increased sensitivity to allopregnanolone. This agrees with findings in animals showing a relation between changes in alpha4 and delta subunits of the GABA-A receptor and anxiogenic effects of allopregnanolone. Conclusion: These findings suggest that negative mood symptoms in women with PMDD are caused by the paradoxical effect of allopregnanolone mediated via the GABA-A receptor.

(c) 2013 Elsevier Ltd. All rights reserved.

National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-87179 (URN)10.1016/j.pneurobio.2013.07.005 (DOI)000331508100007 ()
Available from: 2014-03-31 Created: 2014-03-24 Last updated: 2017-12-05Bibliographically approved
Holmberg, E., Johansson, M., Bäckström, T. & Haage, D. (2014). Allopregnanolone preferentially induces energy-rich food intake in male Wistar rats. Physiological Reports, 2(12), e12190.
Open this publication in new window or tab >>Allopregnanolone preferentially induces energy-rich food intake in male Wistar rats
2014 (English)In: Physiological Reports, E-ISSN 2051-817X, Vol. 2, no 12, e12190- p.Article in journal (Refereed) Published
Abstract [en]

Obesity is an increasing problem and identification of the driving forces for overeating of energy-rich food is important. Previous studies show that the stress and sex steroid allopregnanolone has a hyperphagic effect on both bland food and palatable food. If allopregnanolone induces a preference for more palatable or for more energy-rich food is not known. The aim of this study  was to elucidate the influence of allopregnanolone on food preference. Male Wistar rats were subjected to two different food preference tests: a choice between standard chow and cookies (which have a higher energy content and also are more palatable than chow), and a choice between a low caloric sucrose solution and standard chow (which has a higher energy content and is less palatable than sucrose). Food intake was measured for 1 h after acute subcutaneous injections of allopregnanolone. In the choice between cookies and chow allopregnanolone significantly increased only the intake of cookies.When the standard chow was the item present with the highest caloric load, the chow intake was increased and allopregnanolone had no effect on intake of the 10% sucrose solution. The increased energy intakes induced by the high allopregnanolone dose compared to vehicle were very similar in the two tests,120% increase for cookies and 150% increase for chow. It appears that in allopregnanolone-induced hyperphagia, rats choose the food with the highest energy content regardless of its palatability.

Place, publisher, year, edition, pages
Wiley Periodicals Inc., 2014
Keyword
Allopregnanolone, energy need, food intake, neurosteroids GABA
National Category
Neurosciences Physiology
Identifiers
urn:nbn:se:umu:diva-101791 (URN)10.14814/12190 (DOI)
Available from: 2015-04-13 Created: 2015-04-13 Last updated: 2018-01-11Bibliographically approved
Holmberg, E., Bäckström, T., Johansson, M., Löfgren, M. & Haage, D. (2013). Allopregnanolone induces a diurnally dependent hyperphagic effect and alters feeding latency and duration in male Wistar rats. Acta Physiologica, 208(4), 400-409.
Open this publication in new window or tab >>Allopregnanolone induces a diurnally dependent hyperphagic effect and alters feeding latency and duration in male Wistar rats
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2013 (English)In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 208, no 4, 400-409 p.Article in journal (Refereed) Published
Abstract [en]

Aim: Gamma-aminobutyric acid (GABA)-ergic transmission from the hypothalamus is essential for normal feeding regulation, and hyperphagia can be induced by local application of GABA(A)-receptor agonists to different feeding-associated brain areas. The food intake in rats varies diurnally and that may influence the effect of GABA(A)-receptor active compounds. The progesterone metabolite allopregnanolone is a highly potent endogenous positive modulator of the GABA(A) receptor. Therefore, it is easy to envisage that allopregnanolone would have a hyperphagic effect, but earlier reports in rat have given ambiguous results. However, a contributing factor for the discrepancy may be the time point of the diurnal cycle in which the experiments were performed. The aim of this study was to investigate the effect of allopregnanolone on intake of standard chow in male Wistar rats at different time points of the day.

Methods: Chow intake was measured after acute administration of allopregnanolone, and feeding behaviour was analysed to detect meal patterns.

Results: We found that allopregnanolone increased chow intake by up to four times in the dark part of the 24-h cycle. The rats ate significantly more, and the effect of allopregnanolone was more prominent in the active (dark) compared with the inactive (light) period. Allopregnanolone also reduced feeding latency and prolonged the meal duration compared with vehicle.

Conclusion: Allopregnanolone seems to act at several levels of feeding regulation, that is, to initiate feeding and to prolong the duration of a meal, thereby increasing the meal size, especially in the dark period of the 24-h cycle.

Place, publisher, year, edition, pages
John Wiley & Sons, 2013
Keyword
allopregnanolone, diurnal rhythm, food intake, Gamma-aminobutyric acid, hyperphagia, neurosteroids
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-79224 (URN)10.1111/apha.12100 (DOI)000321695000013 ()
Available from: 2013-09-16 Created: 2013-08-13 Last updated: 2017-12-06Bibliographically approved
Löfgren, M., Bengtsson, S. K., Johansson, M. & Bäckström, T. (2013). Allopregnanolone promotes success in food competition in subordinate male rats. Neuropsychobiology, 68(1), 15-23.
Open this publication in new window or tab >>Allopregnanolone promotes success in food competition in subordinate male rats
2013 (English)In: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 68, no 1, 15-23 p.Article in journal (Refereed) Published
Abstract [en]

Background/Aims: Allopregnanolone or 3 alpha-hydroxy-5 alpha-pregnan-20-one (AlloP) is normally sedative and anxiolytic, but can under provoking circumstances paradoxically induce aggressive behavior. Therefore, it is of particular interest to determine if there is a relationship between an anxiolytic effect and aggressive behavior following AlloP administration.

Method: Male Wistar rats were housed in triads comprising of 1 young rat (35 days) and 2 older rats (55 days), with the intent of producing a social hierarchy. The triads were sampled for total serum testosterone and submitted to a social challenge in the form of a food competition test (FCT), where the rats competed for access to drinking sweetened milk. At baseline, the younger rats were identified as subordinates. To test for the behavioral effect of AlloP, the subordinate rats were given intravenous AlloP injections of 0.5 and 1 mg/kg. To assess the optimal AlloP effect, 6 intervals (5, 10, 15, 20, 30 and 40 min) between injection and the FCT were used. In separate studies, AlloP was also given by subcutaneous and intraperitoneal administration at 10 and 17 mg/kg.

Results: AlloP (1 mg/kg, i.v.) increased drinking time and aggressive behavior in subordinate rats, with a positive correlation between these behaviors. The subcutaneous injection (17 mg/kg) also increased drinking time in subordinate animals. Serum testosterone concentration was higher in dominant compared to subordinate rats, and correlated with drinking time and weight.

Conclusions: AlloP increased drinking time and aggressive behavior, and the correlation indicates a relationship between an anxiolytic effect and aggressive behavior. Copyright (c) 2013 S. Karger AG, Basel

Keyword
Allopregnanolone, Anxiety, Behavior, Aggression, Hierarchy, Triad, Subordinate
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-79290 (URN)10.1159/000350478 (DOI)000321482500002 ()
Available from: 2013-08-23 Created: 2013-08-13 Last updated: 2017-12-06Bibliographically approved
Bengtsson, S. K., Johansson, M., Bäckström, T., Nitsch, R. M. & Wang, M. (2013). Brief but Chronic Increase in Allopregnanolone Cause Accelerated AD Pathology Differently in Two Mouse Models. Current Alzheimer Research, 10(1), 38-47.
Open this publication in new window or tab >>Brief but Chronic Increase in Allopregnanolone Cause Accelerated AD Pathology Differently in Two Mouse Models
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2013 (English)In: Current Alzheimer Research, ISSN 1567-2050, Vol. 10, no 1, 38-47 p.Article in journal (Refereed) Published
Abstract [en]

Previously, we have shown that chronic treatment with allopregnanolone (ALLO) for three months impaired learning function in the Swe/PS1 mouse model. ALLO is a neurosteroid, produced in the CNS and a GABA(A) receptor agonist. ALLO modulates the general inhibitory system in the CNS by enhancing the effect of GABA. Chronic treatment with other GABA(A) receptor active compounds, such as benzodiazepines, ethanol and medroxy-progesterone acetate has been associated to cognitive decline and/or increased risk for dementia. In this study, we sufficed with a treatment period of one month for the Swe/PS1 mouse, and included another Alzheimer's disease mouse model; the Swe/Arc model. We found that one month of chronic treatment with elevated ALLO levels within physiological range impaired learning and memory function in the Swe/Arc female and male mice. Male Swe/PS1 mice also showed marginally impaired function, while the female mice did not. Furthermore, the chronic ALLO treatment caused increased levels of soluble A beta in the Swe/PS1 mouse model while the levels were unchanged in the Swe/Arc model. Therefore, both Swe/Arc and Swe/PS1 mice showed signs of accelerated disease progression. Still, further studies are required to determine the mechanisms behind the cognitive impairment and the increased A beta-levels caused by mildly elevated ALLO-levels.

Place, publisher, year, edition, pages
Bentham Science Publishers, 2013
Keyword
Allopregnanolone, Alzheimer's disease, beta-amyloid(1-42), beta-amyloid(1-40), cognition, physiological stress, transgenic
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-70364 (URN)10.2174/156720513804871363 (DOI)000317271800006 ()
Available from: 2013-05-16 Created: 2013-05-14 Last updated: 2015-11-11Bibliographically approved
Bengtsson, S., Johansson, M., Bäckström, T., Nitsch, R. & Wang, M. (2013). Brief but Chronic Increase in Allopregnanolone Cause Accelerated ADPathology Differently in Two Mouse Models. Current Alzheimer Research, 10(1), 38-47.
Open this publication in new window or tab >>Brief but Chronic Increase in Allopregnanolone Cause Accelerated ADPathology Differently in Two Mouse Models
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2013 (English)In: Current Alzheimer Research, ISSN 1567-2050, Vol. 10, no 1, 38-47 p.Article in journal (Refereed) Published
Abstract [en]

Abstract: Previously, we have shown that chronic treatment with allopregnanolone (ALLO) for three months impaired learning function in the Swe/PS1 mouse model. ALLO is a neurosteroid, produced in the CNS and a GABAA receptor agonist. ALLO modulates the general inhibitory system in the CNS by enhancing the effect of GABA. Chronic treatment with other GABAA receptor active compounds, such as benzodiazepines, ethanol and medroxy-progesterone acetate has been associated to cognitive decline and/or increased risk for dementia. In this study, we sufficed with a treatment period of one month for the Swe/PS1 mouse, and included another Alzheimer’s disease mouse model; the Swe/Arc model. We found that one month of chronic treatment with elevated ALLO levels within physiological range impaired learning and memory function in the Swe/Arc female and male mice. Male Swe/PS1 mice also showed marginally impaired function, while the female mice did not. Furthermore, the chronic ALLO treatment caused increased levels of soluble Aβ in the Swe/PS1 mouse model while the levels were unchanged in the Swe/Arc model. Therefore, both Swe/Arc and Swe/PS1 mice showed signs of accelerated disease progression. Still, further studies are required to determine the mechanisms behind the cognitive impairment and the increased Aβ-levels caused by mildly elevated ALLO-levels. learning function in the Swe/PS1 mouse model. ALLO is a neurosteroid, produced in the CNS and a GABAA receptor agonist. ALLO modulates the general inhibitory system in the CNS by enhancing the effect of GABA. Chronic treatment with other GABAA receptor active compounds, such as benzodiazepines, ethanol and medroxy-progesterone acetate has been associated to cognitive decline and/or increased risk for dementia. In this study, we sufficed with a treatment period of one month for the Swe/PS1 mouse, and included another Alzheimer’s disease mouse model; the Swe/Arc model. We found that one month of chronic treatment with elevated ALLO levels within physiological range impaired learning and memory function in the Swe/Arc female and male mice. Male Swe/PS1 mice also showed marginally impaired function, while the female mice did not. Furthermore, the chronic ALLO treatment caused increased levels of soluble Ab in the Swe/PS1 mouse model while the levels were unchanged in the Swe/Arc model. Therefore, both Swe/Arc and Swe/PS1 mice showed signs of accelerated disease progression. Still, further studies are required to determine the mechanisms behind the cognitive impairment and the increased Aβ-levels caused by mildly elevated ALLO-levels.

Place, publisher, year, edition, pages
Bentham Science Publishers, 2013
Keyword
Alzheimer's disease, beta-amyloid proteins, allopregnanolone, chronic stress, transgenic mouse models, synaptophysin, amyloid plaques
National Category
Neurosciences
Research subject
Obstetrics and Gynaecology; Neurology; Medical Pharmacology; Geriatrics
Identifiers
urn:nbn:se:umu:diva-66571 (URN)
Funder
Swedish Research Council, 4x-11198
Available from: 2013-02-28 Created: 2013-02-25 Last updated: 2018-01-11Bibliographically approved
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