scholarly journals Antidepressant-Like Effects of Chronic Guanosine in the Olfactory Bulbectomy Mouse Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Roberto Farina Almeida ◽  
Yasmine Nonose ◽  
Marcelo Ganzella ◽  
Samanta Oliveira Loureiro ◽  
Andréia Rocha ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Mouse Model ◽  
Memory Impairment ◽  
Time Course ◽  
Olfactory Bulbectomy ◽  
Major Depressive ◽  
Micropet Imaging ◽  
Fast Onset ◽  
Tnf Α

Major depressive disorder (MDD) leads to pervasive changes in the health of afflicted patients. Despite advances in the understanding of MDD and its treatment, profound innovation is needed to develop fast-onset antidepressants with higher effectiveness. When acutely administered, the endogenous nucleoside guanosine (GUO) shows fast-onset antidepressant-like effects in several mouse models, including the olfactory bulbectomy (OBX) rodent model. OBX is advocated to possess translational value and be suitable to assess the time course of depressive-like behavior in rodents. This study aimed at investigating the long-term behavioral and neurochemical effects of GUO in a mouse model of depression induced by bilateral bulbectomy (OBX). Mice were submitted to OBX and, after 14 days of recovery, received daily (ip) administration of 7.5 mg/kg GUO or 40 mg/kg imipramine (IMI) for 45 days. GUO and IMI reversed the OBX-induced hyperlocomotion and recognition memory impairment, hippocampal BDNF increase, and redox imbalance (ROS, NO, and GSH levels). GUO also mitigated the OBX-induced hippocampal neuroinflammation (IL-1, IL-6, TNF-α, INF-γ, and IL-10). Brain microPET imaging ([18F]FDG) shows that GUO also prevented the OBX-induced increase in hippocampal FDG metabolism. These results provide additional evidence for GUO antidepressant-like effects, associated with beneficial neurochemical outcomes relevant to counteract depression.

scholarly journals The time course of recognition memory impairment and glial pathology in the hAPP-J20 mouse model of Alzheimer's disease.

2018 ◽  
Author(s):  
Kamar Eleanor Ameen-Ali ◽  
Julie E Simpson ◽  
Stephen B Wharton ◽  
Paul R Heath ◽  
Paul Sharp ◽  
...  
Keyword(s):  
Recognition Memory ◽  
Mouse Model ◽  
Memory Impairment ◽  
Time Course ◽  
Neurovascular Unit ◽  
Disease Process ◽  
Short Term ◽  
Reactive Microglia ◽  
Term Memory

The role of cellular changes in the neurovascular unit is increasingly being investigated to understand the pathogenesis of Alzheimers disease. The aim of the current study was to determine the time course of recognition memory impairment in the J20 mouse model of AD, in relation to neuroinflammatory responses and the pathology of Aβ. Male hAPP-J20 and wild-type mice were assessed at 3, 6, 9, and 12 months of age. The spontaneous object recognition (SOR) task provided a measure of memory, with assessment of both a short delay (1 min) and a long delay (4 hrs). Immunohistochemistry was used to characterise Aβ-deposition, and quantify astrocyte and microglial responses. At all ages tested J20 mice had impaired long-term, but preserved short-term, recognition memory. Wild-types demonstrated preserved long-term memory up to 9 months of age, and preserved short-term memory at all ages tested. Plaque pathology in the J20 mice was present from 6 months onwards, with co-localisation of reactive microglia and activated astrocytes. Reactive microglia and astrocyte activation in the hippocampus were significantly greater in the J20 mice at 9 months, compared to wild-types. This study contributes to our understanding of the pathological and cognitive mechanisms at play in AD. J20 mice showed impairment in retaining information over longer periods from an early age, preceding the deposition of Aβ and glial activation. Defining early physiological changes in relation to cognitive decline could provide insight into new therapeutic targets early in the disease process, when intervention is most likely to effectively slow disease progression.

The Long-Term Effects of Mindfulness-Based Cognitive Therapy as a Relapse Prevention Treatment for Major Depressive Disorder

2010 ◽  
Vol 38 (5) ◽  
pp. 561-576 ◽  
Author(s):  
Kate L. Mathew ◽  
Hayley S. Whitford ◽  
Maura A. Kenny ◽  
Linley A. Denson
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Cognitive Therapy ◽  
Relapse Prevention ◽  
Mindfulness Practice ◽  
Long Term Effects ◽  
Major Depressive ◽  
Strong Negative Correlation ◽  
Group 3

Background: Mindfulness-based Cognitive Therapy (MBCT) is a relapse prevention treatment for major depressive disorder. Method: An observational clinical audit of 39 participants explored the long-term effects of MBCT using standardized measures of depression (BDI-II), rumination (RSS), and mindfulness (MAAS). Results: MBCT was associated with statistically significant reductions in depression from pre to post treatment. Gains were maintained over time (Group 1, 1–12 months, p = .002; Group 2, 13–24 months, p = .001; Group 3, 25–34 months, p = .04). Depression scores in Group 3 did begin to worsen, yet were still within the mild range of the BDI-II. Treatment variables such as attendance at “booster” sessions and ongoing mindfulness practice correlated with better depression outcomes (p = .003 and p = .03 respectively). There was a strong negative correlation between rumination and mindful attention (p < .001), consistent with a proposed mechanism of metacognition in the efficacy of MBCT. Conclusion: It is suggested that ongoing MBCT skills and practice may be important for relapse prevention over the longer term. Larger randomized studies of the mechanisms of MBCT with longer follow-up periods are recommended.

Short-term and long-term effects of major depressive disorder subtypes on obesity markers and impact of sex on these associations

2021 ◽  
Author(s):  
Clémentine Ottino ◽  
Marie-Pierre F Strippoli ◽  
Mehdi Gholam ◽  
Aurélie M Lasserre ◽  
Caroline L Vandeleur ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Long Term Effects ◽  
Short Term ◽  
Major Depressive

scholarly journals Perceived Impeding Factors for Return-to-Work after Long-Term Sickness Absence Due to Major Depressive Disorder: A Concept Mapping Approach

PLoS ONE ◽  
2014 ◽  
Vol 9 (1) ◽  
pp. e85038 ◽  
Author(s):  
Gabe de Vries ◽  
Hiske L. Hees ◽  
Maarten W. J. Koeter ◽  
Suzanne E. Lagerveld ◽  
Aart H. Schene
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Return To Work ◽  
Concept Mapping ◽  
Sickness Absence ◽  
Major Depressive ◽  
Mapping Approach

scholarly journals 50 Adjunctive Buprenorphine/Samidorphan Combination in Patients with Major Depressive Disorder: Phase 3 Long-term Extension Study Results

CNS Spectrums ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 203-204 ◽  
Author(s):  
Michael Thase ◽  
Arielle D. Stanford ◽  
Asli Memisoglu ◽  
William Martin ◽  
Amy Claxton ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Safety Profile ◽  
Rating Scale ◽  
Remission Rate ◽  
Term Treatment ◽  
Adjunctive Treatment ◽  
Major Depressive ◽  
Long Term Treatment

AbstractIntroductionBuprenorphine/samidorphan (BUP/SAM), a combination of BUP (a µ-opioid receptor partial agonist and κ-antagonist) and SAM (a sublingually bioavailable µ-opioid antagonist), is an investigational opioid system modulator for depression. BUP/SAM has shown efficacy versus placebo as an adjunctive treatment for major depressive disorder (MDD) and a consistent safety profile in previously reported, placebo-controlled clinical studies.1,2Study Objective(s)1. To characterize the safety profile following long-term treatment with BUP/SAM2. To explore depression symptoms and remission rates in patients with MDD following long-term treatment with BUP/SAMMethodsFORWARD-2 (Clinicaltrials.gov ID: NCT02141399) enrolled patients who had participated in 1 of 4 controlled studies as well as de novo patients. All patients had a confirmed diagnosis of MDD, had a history of inadequate response to standard antidepressant therapies (ADTs), and had been treated with an adequate dose of an established ADT for ≥8weeks before BUP/SAM initiation. ADT dosage could be titrated, but the ADT could not be changed. During the study, patients received open-label, sublingual BUP/SAM 2mg/2mg as adjunctive treatment for up to 52weeks. Safety (primary objective) was assessed via adverse events (AEs), vital signs, laboratory analytes, and electrocardiography. Suicidal ideation or behavior (SIB) was evaluated by the Columbia Suicide Severity Rating Scale. Abuse potential, dependence, and withdrawal were assessed by AEs and the Clinical Opiate Withdrawal Scale. Exploratory efficacy endpoints included mean Montgomery–Åsberg Depression Rating Scale (MADRS) scores and remission rate (MADRS ≤10).ResultsOf 1454 total patients, 49% completed the 52-week study, 11% discontinued due to an AE, and 40% discontinued because of other reasons as of the interim data cutoff date (April 30, 2017). Most AEs were of mild/moderate severity. Serious AEs were reported in 3.2% of patients. AEs occurring in ≥10% of patients were nausea, headache, constipation, dizziness, and somnolence. There was no evidence of increased risk of SIB with BUP/SAM. Incidence of euphoria-related events was low (1.2%). After abrupt discontinuation of BUP/SAM, there was little evidence of withdrawal. BUP/SAM was not associated with meaningful changes in laboratory or metabolic parameters or in bodyweight. The mean MADRS score decreased from 22.9 (±9.7) at baseline to 9.8 (±8.8) after 52weeks. The remission rate at 52weeks was 52.5%.ConclusionsLong-term treatment with BUP/SAM did not reveal any new safety findings and confirmed that the risk of abuse and dependence with BUP/SAM was low. BUP/SAM maintained an antidepressant effect for up to 52weeks of treatment in patients with MDD.Funding Acknowledgements: Alkermes, Inc.

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