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- Ardo, Jessica, et al.
(author)
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Codesign of a cardiovascular disease prevention text message bank for older adults
- 2021
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In: Patient Education and Counseling. - : ELSEVIER IRELAND LTD. - 0738-3991 .- 1873-5134. ; 104:11, s. 2772-2784
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Journal article (peer-reviewed)abstract
- Objective: Develop and validate a text message bank to support healthier lifestyle behaviors in older adults at risk for cardiovascular disease utilizing a codesign approach. Methods: Initially, the researchers, based on literature, developed a bank of 68 SMS text messages focusing on healthy eating (24 messages), physical activity (24 messages), and motivational feedback (20 messages), based on a scoping review of the literature on promoting behavioral change to engage in healthy lifestyle behaviors. In the next step, a panel of five experts analyzed every subset of SMS text messages. Further validation was conducted by nine older adults (>= 60 years). The user demographics, telephone literacy, understanding, and appeal for every SMS text message were evaluated using a 31-item questionnaire. Results: Participants provided an acceptable understanding of the critical concept found in the 49 SMS text message (physical activity M = 1.73 +/- 0.18; diet M = 1.73 +/- 0.26; motivation M = 1.85 +/- 0.25; range 0-2). The average ratings for physical activity (i.e., likability), healthy eating, and motivation were 8.62 +/- 0.64, 8.57 +/- 0.76, and 8.40 +/- 0.83, respectively (range 0-10). Conclusion: Co-designers were able to identify the technological and content requirements for each text message and infographic to enhance understanding and appeal. Practice implications: A feasibility study will need to be conducted as a next step to testing the effectiveness of text messages in a mobile-based intervention to promote healthy behaviors in older adults at high CVD risk. (C) 2021 Elsevier B.V. All rights reserved.
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- Bäckström, Torbjörn, et al.
(author)
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GABAA Receptor-Modulating Steroids in Relation to Women’s Behavioral Health
- 2015
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In: Current Psychiatry Reports. - : Springer Science and Business Media LLC. - 1523-3812 .- 1535-1645. ; 17:11
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Research review (peer-reviewed)abstract
- In certain women, increased negative mood relates to the progesterone metabolite, allopregnanolone (allo), during the luteal phase of ovulatory menstrual cycles, the premenstrual dysphoric disorder (PMDD). In anovulatory cycles, no symptom or sex steroid increase occurs but symptoms return during progesterone/allo treatment. Allo is a potent GABA(A) receptor-modulating steroid and as such is expected to be calming and anxiolytic. A relation to negative mood is unexpected. However, this paradoxical effect can be induced by all GABA(A) receptor modulators in low concentrations whereas higher concentrations are calming. The severity of the mood symptoms relate to allo in an inverted U-shaped curve at endogenous luteal-phase serum concentrations. Allo's effects on the GABA(A) receptor can be antagonized by isoallopregnanolone (ISO), an antagonist to allo. ISO has also been used in a preliminary clinical trial on PMDD ameliorating symptoms with good effect in PMDD patients.
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- Johansson, Maja, et al.
(author)
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GABAA receptor modulating steroid antagonists (GAMSA) are functional in vivo
- 2016
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In: Journal of Steroid Biochemistry and Molecular Biology. - : Elsevier. - 0960-0760 .- 1879-1220. ; 160:SI, s. 98-105
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Journal article (peer-reviewed)abstract
- 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.
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- Johansson, Maja, 1962-, et al.
(author)
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GR3027 antagonizes GABA(A) receptor-potentiating neurosteroids and restores spatial learning and motor coordination in rats with chronic hyperammonemia and hepatic encephalopathy
- 2015
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In: American Journal of Physiology - Gastrointestinal and Liver Physiology. - : American Physiological Society. - 0193-1857 .- 1522-1547. ; 309:5, s. G400-G409
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Journal article (peer-reviewed)abstract
- 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.
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- Löfgren, Magnus, 1979-, et al.
(author)
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Chronic subordination stress augments combined progesterone and estradiol withdrawal behavior
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Other publication (other academic/artistic)abstract
- Exposure to stress is a risk factor for developing pre-menstrual syndrome (PMS) and pre-menstrual dysphoric disorder (PMDD), and stress enhances the anxiogenic effect of female sex steroids in animals. This study examines the interaction between chronic subordination stress and withdrawal from progesterone (P4) and estradiol (E2) (PEWD) in producing behaviors analogous to anxiety and irritability in rats. At the start of the experiment, male Wistar rats were housed in triads consisting of one younger rat (~35 days) and two older rats (~50 days). The housing condition was aimed at producing chronic subordination stress in the younger animals. Chronic subordination stress was assessed by the elevated plus maze (EPM) and by corticosterone (CORT) analysis. A triad of three 35-day-old rats was used as age control. Social rank within the triads was determined using a food competition test (FCT) and the tube test (TT). The younger rats (subordinate) and the dominant rats were assigned to 10 days of treatment with 5 mg/kg progesterone combined with 10 µg/kg 17β estradiol. Twenty-four hours after the last injection, the subordinate and dominant animals were tested in the open-field test (OFT) and in the intruder test (IT). The IT consists of a 10-minute exposure to 3 unfamiliar rats. Chronic subordination stress reduced EPM open-arm time and altered the CORT response. It also made the subordinate animals more vulnerable to PEWD. The effects were increased locomotion in the OFT, increased defensive burying, and increased social anxiety in the intruder test (IT). Dominant animals did not react to PEWD. Thus, chronic subordination stress augments PEWD.
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